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UNITED STATES ENVIRONMENTAL PRC)TECTION AGENCY ENVIRONMENTAL TOBACCO ISMOKE: A COMPENDIUM OF TECHNICAL ]:NFORMATION COMMENTS OF THE TOBACCO ]:NSTITUTE February 5, 1990 Reviewers' Statements 1

Comments on Chapter 3 Prepared by: Dr. Deborah L. C. Kay Dr. James C. Walker Dr. Daniel B. Kurtz We have reviewed chapter 3, titled "The Odor and Irritation of Environmental Tobacco Smoke", by William S. Cain and feel that modif'.,cations in the document should be made in order for it to be scientifically credible and of optimum value for the stated audience, i.e., labor and management afficials concerned with workplace exposures, public health officials and corporate medical directors concerned with making health policy recommendations, educators, industrial hygienists and safety officers, ETS researchers, indoor air pollution investigators and legislators who are considering legislation to restrict smoking in.workplaces, restaurants, and public access buildinE;s. After reviewing the chapter, we were left with four general impressions: i. the author leads the reader to a number of conclusions regarding standards for ventilation in "real world" environments but: these conclusions rest entirely on a methodology for which the reli3vance to "real world" situations has not been demonstrated; ii. assuming this work is intended as a major review of studies in the area of odor and irritation of environmental tobacco smoke, we feel that many major and significant studies in this area were Dmitted; - iii. the chapter would be much improved if it placed ETS in some balanced prospective within the overall area of indoor air quality. iv. many statements in the paper are not clear. This first criticism is the most significant since a nuriber of these unsupported conclusions are assembled here to lead the reader to the implied conclusion that odor and irritation from ETS is a problem in real worLd environments, of such magnitude, that it requires measures more aggressive than simply adherence to recommended ventilation guidelines. We have detailed below a number of specific criticisms to illustrate our objections: 1. In paragraph 2 of the Introduction, the statemenl:s are made that "smoking has traditionally been pervasive" and "has accordingly received special• attention". We feel that these statements are simply unclear. If the intent is to "explain" the history of ETS concerns, at least two factors should be considered. These factors are: i. the tendency for buildings to be poorly ventilated consequent to the energy crisis of the mid 1970's (see e.g. Skov et al., 1987, Robertson, 1988, 1989); ii. the publication of a number of epidemiological studies (e.g. Uberla, 1988 and Hirayama, 1981, 1987) purporting to demonstrate a link between exposure to ETS and cancer. More recently, attention has been given to the ETS issue due to the report of the Surgeon General (1986).

Comments on EPA ETS compendium 2. In paragraph 3 of the Introduction, the statement is made that "a chemical analysis of ETS-containing air offers little o:` practical significance regarding the origin of its, odor or irritatiun". This statement is contrary to the recent recommendations of the Cortnnittee on Passive Smoking et al. (1986). This group pointed out that one of the key goals of future scientific research information should be a better understanding of the relationship between the chemical composition of ETS and its sensory properties. Understanding the relationship between ETS chemistry and human responses to ETS could aid air cleaner and veni:ilation system design. Finally, in the last paragraph of the Introduction, the author appears to contradict his dismissal of the importance of understanding ETS chemistry when he raises questions about the relative importance of the vapor and particulate phases of ETS for its sensory impact. 3. The second segment of the document is titled "Ventilation Requirements Based on Responses of the Visitor". This segment and the one to follow ("Responses of Occupants") need an introductory paragraph explaining to the reader the reasons for the experimental approach that investigators have taken to studying the sensory impact of ETS. In this paragraph the author could discuss the need for controlled environmental chambers and the need for a-distinction between visitors and occupants. Cain should discuss more extensively the work of other scientists who have emphasized: i. understanding the relationship between ETS cunstituents and irritation (Hugod et al., 1978, Weber-Tshopp et al., 1977a, 1977b, Marquardt e a ., 1986); 1A ii. investigating non-verbal physiological responses to ETS in an attempt to develop objective measures of the impact of ETS, e.g. Claussen et a., 1984, Muramatsu et a., 1983, Weber (or Weber-Tschopp) e al., 1976a, 1976b, 1978, 1979a, 1979b, 1982, 1984a, 1984b, Walker et a ., 1989); iii. studying the role of social factors as detezminants of the appraisal of ETS (Winneke et al., 1984). These other approaches should be discussed amply, since they address issues ::elated to the general question of the relevance of these kinds of experiments for understanding the role of ETS in indoor air quality in the real world. Equally important as an orientation of the re:ader to the methodology employed in chamber/sensory studies is a discuss::on of the ETS levels used in the sensory/chamber studies as compared to those found in the "real world". We are not aware -of any field study demonstrating significant le,vels of dissatisfaction among occupants of, or visitors to, "real world" smoking environments where proper ventilation practices are followed. If the author of this chapter is aware of such material, it should definitely be included. (We are aware of the paper by WebE:r et al.(1979a) in which laboratory studies of sensory responses to sidestream smoke (not true ETS) were related, using CO concentrations as a "bridge" marker, to sensory evaluation of ETS in a restaurant). Failing such a direct comparison between laboratory and field, the more appropri.ate approach would be to

Comments on EPA ETS compendium examine existing data concerning levels of ETS in the field in light of the levels typically employed in chamber studies. For example, a recent presentation of results of fifteen surveys of "roal world" environments, i.e., nonsmoking sections of aircraft, restaurants and offices (Oldaker, 1989) indicated that "real world" levels of nicot:Lne averaged 5Jag/m3. In a recent study (Walker et al., 1989) nicotine le-irels on the order of 140 xg/m3 were found when 8 cigarettes/hour were smoked in an 18-m3 ~ environmental chamber. This same smoking regime xesulted in CO elevations S of 3.4 ppm. These pieces of information -allow one to place the sensory/chamber studies in some "real world" pezspective. That is, one can reasonably calculate that a "ball park" estima-:e for the mean increment in CO to be expected from the rates of smoking in typical real world settings is 5/140 X 3.4 ppm - 0.12 ppm CO. This CO level is significantly lower than the 1.5 to 2 ppm ACO level which Cain proposes as a limit. Examination of Fig. 6 in the present report or, for that matter, the literature in general, demonstrates that levels this low are almost never investigated. The simple conclusion is that the:re has been little or no examination of sensory responses to ETS at concentrations that can realistically be expected in the enviro:unent. This point needs to be emphasized in this chapter. In paragraph 1 on page 30, the parenthetic sentezce is incomplete. 4. We feel that the quoted material from Yaglou, R:aey and Coggins (1936) (Note: author order not correct in Cain's chapter) on page 30, paragraph 4 does not illustrate shifting standards and i:> not relevant. In the second paragraph of the Introduction, Cain pointed out correctly that there is a great deal of subjectivity in people's responses to ETS. While individual differences and "aesthetic criteria" a-re likely to explain some of this variation, it is misleading to omit a d::scussion of the role of epidemiological reports (well-publicized by public health officials) purporting to demonstrate adverse health effects of ETS. Isn't this development the clearest determinant of the "shifting standards" that Cain describes? 5. Page 31, paragraph 1 refers to Figure 1. In thLs figure and in several other figures in the chapter the response measu:-e from subjects that is emphasized is the proportion of subjects tt•.:at are "dissatisfied". According to Figure l's caption, this result is abtained by simply asking subjects visitors "Is the air acceptable or ur.acceptable?". While we understand that this method was used to easily translate visitors' perceptions to the ASHRAE criteria, we suggest that the author discuss the many factors which influence acceptance measures. The following are a few of our particular concerns. i.- Great care must be taken when measuring and interpreting acceptance scores, such as those presented in this chapter and in Cain (1983). As demonstrated by Sheen and Drayton (1988) subjects' mental set plays a very important role in the scores. This mental set could be affected by social setting and the subjects's emotions. Therefore, one could envision different standards for bars, office buildings, bingo parlors and conference-rooms, etc.

Comments on EPA ETS compendium ii. Because the percent dissatisfied is relativel}• insensitive to changes in ventilation rate , i.e. the slope of Figure l's line for percent dissatisfied versus ventilation rate is very small, a shift of percent dissatisfaction of 10% due to lack of matching real world mental sets (i.e. if his 30% dissatisfaction level were only 10%) would reduce the ventilation requirements by at least 50% (Figure 1, p. 39a). Because acceptance scores can shift dramatically with demographic factors, a pool of respondents must be carefu.lly stratified to avoid bias. Both of these issues should be discussed by Cain. iii. One wonders, in light of the ASHRAE 20% criterion, what percentages of occupants in "real world" environments (smoking or nonsmoking) are dissatisfied. For example, what percentage of people are normally dissatisfied, in the "real world", with their environment? Are their any environments in which 100% of the occupants are consistently satisfied (Jaakkola and Heinonen, 1989; Andersson et a ., 1976)? In addition, can we expect subject's satisf,sction to ETS to be the same in a chamber as it would be to equivalent levels of ETS experienced in the "real world". 6. The author omitted a legend for the two depicted symbols in Figure 1. Figure 2 is unclear. 7. When reviewing paragraph 3 on page 31, we disagree with the use of the assumption, i.e. "10% of occupants would be would be smoking at any given time" to draw conclusions regarding the inability of current ASHRAE ventilation standards to meet the satisfaction nEeeds of nonsmokers (page 32 paragraph 2). This estimate of smoking rates is presumably based on some rather crude calculations by Repace and Lowl-ey (1980). Again, the reader would be greatly helped by the availability of "real world" smoking rate data if conclusions regarding ventilation standards are being made. The author should report the size of the chamber used in this study. 8. We were initially confused when we referred to Figure 5. This initial confusion may be eliminated by referring to the two odors in the figure's legend as "ETS" and "occupancy" as opposed to "nonsmoking" and "smoking". 9. On Page 33, paragraph 1, we share the author's isplied concerns regarding the use of CO as a marker of ETS in non-laboratory'environments, although this important point should be more explicitly stated. We disagree with the author's comments on page 33, paragraph 1 regarding the use of carbon monoxide.as the sole indicator of ETS levels. Although ETS levels within a given set of experimental conditions may possibly be related to each other by C0, use of this ETS constituent to compare ETS levels from study to study is faulty due to the different CO levels produced by various cigarette types and by different smoking condit:ions.. Data and-further

t Comments on EPA ETS compendium discussion supporting this argument is presented-by Nystrom and- Green - (1986). 10. Regarding page 34, paragraph 2, we do not understand Cain's contention that people should not be allowed to judge dissatisfaction based on perceptual irritation. 11. On page 34 in the indented section, referring to a Cain reference (year of publication missing), there is a statement "irritation would seen interpretable on grounds of health". We agreis that for some people, irritation may be a nuisance, but it has not been demonstrated that there is any health hazard related to perceived irritation of ETS. Without a demonstration of harm to the body, perceived il-ritation should only be considered a component of the subjects' percept,ial responses to the ETS stimulus. 12. On page 34, paragraph 4, the author misuses the word "Tar". "Tar" is the collection of mainstream smoke on a glass fiber filter pad. The use of the word "particles" would be more appropriate. 13. On page 34, in paragraph 5, the author should change the word "both" to "the majority of". 14. Based on the chamber data presented, we agree with Cain's statement on p. 35, paragraph 3, "ventilation has its limit3tions", but we strongly feel that Cain needs to emphasize that this conclusion has not been confirmed by analyzing real world situations where standard ventilation requirements are met. Comments regarding Cain's references: 1. Reference for Kerka (1956) is missing. 2. Reference to Cain (1986) is missing initials for co-author See. 3. Reference for Yaglou (1955) is missing.

Comments on EPA ETS compendium References Andersson, L.O., Frisk, P., and Wyon, D.P., (1976) Human Responses to Dry, Humidified and Intermittently Humidified Air in Large Office Buildings. Swedish Building Research; PB 257 903, Stockholm, Sweden. Cain, W. S., Leaderer, B. P., Isseroff, R., Bergland, L.G., Huey, R.J., Lipsitt, E.D., Perlman, D. and Dunn, J. D., (1983) Ventilation requirements in buildings - 1. Control of occupancy odor and tobacco smoke odor. Atmospheric Environment, 17, 1183-1197. Claussen, G.H., Nielsen, K.S., Sahin, F., and Fanger, P.O., (1984) Sensory irritation from exposure to environmental tobacco smoke. In: Proceedings of the 3rd International Conference o~}r Indoor i,r al t and C mate, Stockholm, Berglund, B., et a (Eds.) Swedish Council for Build:Cng Research, Stockholm, Sweden, pp. 52-56. Committee on Passive Smoking, Board on Environmental Studies and Toxicology, National Research Council (1986) Environmental Tobacco Smoke - Measurine Exposures and Assessing Health Effects, National Academ.j Press, Washington, D.C. Hirayama, T. (1981) Non-smoking wives have a higher risk of lung cancer, a study from Japan. Br. Med. J 282:183-185. Hirayama, T., (1987) Passive Smoking and Cancer: An Epidemiological Review, In: Changing Cancer Patterns and o ics in Cancer Wdemioloev. Kurihara, M., Ed., Japan Scientific Society Press, Tokyo; Plenum Press, NY, pp. 127-135 Hugod, C. Hawkins, L.H., and Astrup, P. (1978) Exposure of passive smokers to tobacco smoke constituents. Int. Arch. OccuR. Environ. Hlth. 42:21-29. Jaakkola, J.J.K., and Heinonen, O.P. (1989) Sick building syndrome, sensation of dryness and thermal comfort in relation to room t:emperature in an office building: Need for individual control of temperature. Environment. International 15:163-168. Marquardt, R., Christ, T., Blessing, A., (1986) Effect of nicotine on lacrimation and tear-film stability. Fortschr. Ophthalmol., 83:1CQ-104. Muramatsu, T., Weber, A., Muramatsu, S., and Akermann, F., (1983) An experimental study on irritation and annoyance due to passive smoking. Intl. Arch. Occu Environ. Health 51:305-317. Nystrom; C. W.nd Green, C. R. (1986), Assessing the impact of environmental tobacco smoke on indoor air quality: Current status. In: Proceedings of the ASHRAE Conference IA~ '86. Managing ndoo Air for ealth and Ener Conservation, American Society of Heating, Refrigerating and Air-Conditioning Engineers, Atlanta, GA. 0ldaker, C. B., (1989) Environmental Tobacco Smoke (ETS): How much is in the air? Presented at the_ International Tobacco_Conference!s mini-symposium on

Comments on EPA ETS compendium Environmental Tobacco Smoke and Scientific Affairs-, May 25, Winston-Salem, NC. Repace, J.L., and Lowrey, A.H., (1980) Indoor Air Pollution, Tobacco Smoke and Public Health, Science 208:464-472. Robertson, G., (1988) Source, nature and symptomology of indoor air pollutants. In: Indoor and Amb ent i~r Quality, R. Perry and P.';?. Kirk (Eds.), Selper, London. Robertson, G., (1989) Source, nature and symptomology of indoor air pollutants. Presented at the International Tobacco Conference's mini-symposium on Environmental Tobacco Smoke and Scientific Affairs, Mwr 25, Winston-Salem, NC. Sheen M..R., and Drayton, J.L. (1988) Influence of Brand Label on Sensory Perception In: Food Acceptabilitv, Thompson D.M.H. (Ed.) Elsevier Applied Science, London. Skov, P., Valbjern, 0., and DISG (1987) The "sick" building syndrome in the office environment: The Danish town hall study. Env lton. Int. 13:339-349. Uberla, K., (1988) Epidemiology: Its scope and lim:Ctations for indoor air quality. In: Indoor Air ualit , The National Acadeny of Sciences of Buenos Aires, Argentina, San Carlos de Bariloche, Argentina. - U. S. Department of Health and Human Services. 1986. 'he Hea Conseauences of Smokine. A e o of the Surgeon Ge era . DHHS Pub. No. (CDC) 87-8398. U.S. Department of Health and Human Services. Public Health Services Centers for Disease Control and Center for Health Promotion and Education. Office on Smoking and Health., Rockville, MD. Walker, J.C., Jennings, R.A., Morgan, W.T., Robinson, J.H., Griffith, D.W., and Reynolds, J.H. (1989) Sensory responses to environmental tobacco smoke from cigarettes that heat but do not burn tobacco. In: Proceedines 2f resen and Future of Indoor A_ir alit , Proceedings of the Brussels Conference 14-16 February 1989, Bieva, C.J., Courtois, Y., and Govae:rts, M., Eds., Excerpta Medica, Amsterdam. Weber-Tschopp, A., Fisher, T., Gierer, R., and Grandjean, E., (1977a) Experimentelle Reizwirkungen von Akrolein auf den Men:>chen. Int. Arch. Occuv. Environ, Hlth. 40:117-130. Weber-Tschopp, A., Fisher, T., and Grandjean, E., (1.977b) Reizwirkungen des Formaldehyds (HCHO) auf den Menschen Int. Arch. OccuR. Environ. Hlth. 39:207- 218. Weber, A., Fisher, T., and Grandjean, E. (1978) Passivrauchen unter experimentellen Bedingungen und in Feldversuchen. Sozi.ai- und Praventivmedizin 23 (4):261-262. , Weber, A., Fisher, T., and Grandjean, E., (1979a) Passive smoking in experimental and field conditions. Environ. Res. 20:205-216.

Comments on EPA ETS compendium Weber, A., Fisher, T., and Grandjean, E., (1979b) Passive smoking: Irritating effects of the total smoke and gas phase. Int. Arch. Occu Environ. Hlth. 43:183-193. Weber, A., Muramatsu, T., and Muramatsu, S., (1982) Akute und Chronische Auswirkungen des Passivrauchens. Sozia - und Preventivmed 27:262-263. Weber, A., (1984a) Acute effects of environmental tobacco smoke. European Jou Respiratory Disease 65 (Suppl. 133) 98-108. Weber, A., (1984b) Annoyance and Irritation by Passi-ie Smoking. Preventive Medicine 13:618-625. Weber-Tschopp, A., Fisher, T., and Grandjean, E., 1;1976a) Objektive und subjektive physiologische Wirkungen des Passivraucheris. Int. Arch. Occuv. Environ Hlth. 37:277- 288. Weber-Tschopp, A., Fisher, T., and Grandjean,E., (1976b) Luftverunreinigung und Belastigung durch Zigarettenrauch. Sozial- und Prevent:ivmedizin 21: 101-106. Winneke, G., Plischke, K., Roscovanu, A., and Schlipkoeter, H. (1984) Patterns and determinants if reaction to tobacco smoke in an experimental exposure setting. Proceedings of the 3rd International Conferer:ce on Indoor Air Quality and Climate, Stockholm, Indoo Air, Vol. 2. Swedis'1 Council for Building Research, Stockholm, Sweden, pp 351-356. Yaglou, C.P. (1955) Ventilation Requirements for Cigarette Smoke. Transactions Amererican Society of Heating and Air-Conditionin¢ Enzineers 61:25-32.

REVIEW OF: ENVIRONMENTAL TOBACCO SMOKE A COMPENDIUM OF TECHNICAL INFORMATION by Simon Turner, Healthy Buildings International, Inc. I Introduction Healthy Buildings International, Inc. (HBI) is a company that specializes in the study and assessment of indoor air pollution. Since we incorporated in ].981, we have studied in excess of 80 million square feet of buildings throughout the world, perhaps confirming us as the most experienced private company in that field. HBI seeks to identify the causes of indoor air quality problems -- the "sick building syndrome" -- and to recommend remedial steps. Our experiences are attracting widespread interest in the professional arena of those truly interested in indoor air quality. Clients include major banks, insurance companies, property developers, hospitals, colleges, and government agencies, including the U.S. Department of Health and Human Services, Social Security Administration, Longworth Congressional Building, Supreme Court, Government Services Administration Regional Head- quarters, United Nations Buildings in New York, Customs and Excise and Coast Guard Buildings. We were asked to comment upon the document entitled "Environmental Tobacco Smoke: A Compendium of Technical Information" based upon our extensive experience with indoor air quality problems. In addition to a number of specific substantive flaws contained in the document, this compendium

on environmental tobacco smoke (ETS) sanctioned by a body such as the U.S. Environmental Protection Agency (EPA) concerns us in that this single-minded focus on one pollutant, unique in EPA's policies on indoor air, will give the public the impression that its removal will solve al:. indoor air problems, thus giving an entirely false sense of security. We frequently investigate build'.ngs on account of complaints from occupants with symptoms such as eye and nose irritation, fatigue, coughing, rhinitis, nausea, headaches, sore throats and general respiratory prob:.ems. It is frequently assumed by our clients that these symptoms are due to ETS. However, it is clear that identical symptoms may be found in individuals exposed to formaldehyde, sulphur oxides, ammonia, oxides of nitrogen, and ozone. :Cn addition, similar symptoms are reported by those individuals with allergies to specific fungi such as aspergillus, cladosporium, and penicillium, among others, as well as to miscellaneous bacterial aerosols. Overlapping symptoms also can be caused . by exposure to household dusts, cotton fibers, fiberglass fragments, etc. Low relative humidities create similar problems and are on the increase. Surprisingly, after a detailed, scientific evaluation of these buildings, we have de-:ermined high levels of environmental tobacco smoke to be the immediate cause of indoor air pr6blems in only three percent of the 412 major U.S. buildings investigated by HBI between 1981 and 1989. This result has been corroborated. In a similar study of 203

buildings from 1978 to 1983., the National Institute for Occupational Safety and Health (NIOSH) found that only four of the buildings studied (two percent) had indoor ai-r-quality problems attributable to high concentrations of ETS. Significantly, in those few cases where we found high accumulations of ETS, we also discovered an excess of fungi and bacteria in the HVAC system. These microorganisms usually are found to be the primary causes of the complaints and acute adverse health effects reported by building occupants. Dirt in Duct Systems We have also found that HVAC systems are often poorly designed and negligently maintained. Excessive_dirt accumulations are common in ductwork, even in hospitals. Following the inspection of a number of buildings, hundreds of pounds of fungi, dust, and dirt have been removed from such ductwork. Bird, insect, and rodent carca:>ses and excess amounts of dust have been found in many buildings where employees have complained of eye irritation, headaches, fatigue, nausea, allergies, and general respiratory problems. Of course, since the ductwork is out of s'..ght, it is also invariably out of mind. Thus, it is common for the blame for these types of problems to be laid elsewhere. Energy Conservation Indeed, the complex of symptoms that we have mentioned - the "sick building syndrome" •- may result Go primarily from energy conservation efforts to seal buildings N W and reduce the infiltration/exfiltration of air.- Such efforts: N

have reduced the natural infiltration of Eresh air that previously existed in many buildings, exacerbating the often undiscovered problem of a poorl-y de-signed-or maintained HVAC system. In addition to tightening buildings and sealing windows, building managers have shut down air conditioning systems at night and on weekends in an efEort to lower energy costs. When the air conditioning is shut down in humid climates, condensation builds up and settles inside the ductwork. If dirt is present in damp ductwork, spores and microbes can flourish, only to be spread throughout the building once the HVAC system is -turned on the next mo-rning. This often results in Monday morning complaints of building odors or building sickness that disappear during the week, only to recur the following Monday morning. To save more energy, automatic temperature controllers are used to cycle fans on and off during the day. Vibrations from,the start-up of these fans can cause dirt and microbes trapped inside ductwork to be dislodged and carried into occupied areas. Another energy conservation effort that may contribute to sick building syndrome is the recirculation of indoor air, at the expense of fresh outdoor air. This may be the result of either a deliberate policy or*shortsightedness on the part of the designers. This results in the continuous redistribution of infectious microbes, allergenic dusts and spores from office to office and floor to floor. Improper ventilation can sometimes be ca-rried--to-extremes:----Typic-ally-:>

we find the fresh air dampers were.closed.completely_in over_ 35% of those buildings studied by HBI. Ore misguided engineer actually had bricked up -the fresh air vent.s -to save- energy-:- All of these buildings were operating witt, 100% recycled indoor air. The lack of an adequate frest air supply, coupled with dangerously low air exchange rates, 1-.as led to hazardous ventilation conditions in many of the buildings evaluated by HBI. Similarly, over 50%~of-the investigations conducted by NIOSH from 1978-1987 attributed the indooi air quality problems to inadequate ventilation. Poor Air Filtration Modern filter technology can easily cope with the numerous particulate matter that is routinely .carried in the indoor air. Unfortunately, however, there is far too much ignorance in this area. Frequently good filters are poorly installed allowing air bypass, but more frequently we see a move to cheaper, less efficient filters-: Many buildings attempt to clean the air with filters no better than butterfly nets. Compound this with the lack of maintenance given to the filter systems and the infrequent changes of filters and it is hardly surprising that airborne pollutants accumulate. Methodology of Dealing with Indoor Pollut'..on • Instead of a single-minded focus on specific pollutants, we believe very strongly in a generic engineering approach to deal with all pollutants at the same time. In our U.S. experience of over 80 million square feet of building studies, the major contributors to poor a.ir were threefo-ld: _-

(1) Poor Ventilation Inadequate ventilation 62% Zero fresh air intake 33% (2) Poor Filtration Inefficient air filters 43% (3) Dirt in Ventilation System; Contaminated air handlers 36% Contaminated ductwork 22% We are convinced that improving ventilation rates, upgrading filters, and cleaning up the air handling system will eliminate over 80% of indoor pollution problems. Such changes will improve worker productivity, enhance staff morale, and reduce absenteeism~owever, many managers have decided to ban smoking as an apparently cheap and easy way to solve indoor air quality problems. Unfori.unately, this simply does not work. HBI has determined that the pre:3ence of high concentrations of tobacco smoke indicates that a much more serious problem exists. Poor ventilation and improperly maintained ventilation systems are the pr.imary causes of poor indoor air. When such conditions prevail, all the invisible and odorless pollutants are also trapped. Many of these are potentially far more dangerous than ETS. Persistent indoor air quality complaints therefore can be resolved only if building managers and operators are prepared to focus on building air handling systems in an appropriate manner. High concentrations ~:)f ETS are s.5mptom, not a cause of these complaints. Its eli:nination can effect no cure.

.{ CRITIQUE OF COMPENDIUM There follows specific comments on selected chapters of this compendi.um,- either where we feel i;here are flaws or misconceptions, or where we have construci;ive contributions to make. General We feel that in many areas of this compendium the list of papers and authors referenced to i:ends to be selective; there is a broad range of research, findings and conclusions on this topic and we feel the compendium needs to reflect this breadth of information. Suggestions for additional authors are made where relevan: in each chapter. Chapter 3 Chapter 3 is entitled "The Odor and Irritation of Environmental Tobacco Smoke," by Dr. William S. Cain. Much of the premise on which this chapter is based is derived from chamber studies where visitors are asked to expose themselves to the air inside an experimental aluminum or steel space occupied by varying smoking activities in order to assess acceptability. The authors' basic conclusions are that impractically high levels of ventilation a,ould be required to provide acceptable conditions for non-smokers where smoking activity is in place, and they state "it would appear that where smoking occurs none of the recommendations of the ASHRAE (American Society of Refrigerating and Air Conditioning Engineers) standard will do for the non-smokers."

I i Unlike Dr. Cain, ASHRAE bases ii:s standards on real life feedback from architects, engineers, consumer organizations, health.officials,--medical researcher-s, bui-lding- owners and operators, and the interested public. There are significant differences in the use of real life versus chamber studies leading to very different conclusions about appropriate ventilation rates. For a number of reasons, a properly operated ventilation system works quite effectively in providing an environment not perceived as containing uncomfortable levels of ETS despite the conclusions of theoretical chamber studies. Dr. Cain justifies his reliance on chamber as opposed to real-life studies by attemptincI to portray environmental tobacco smoke (ETS) as a substance whose chemical complexity "likely exceeds that of emissions from bodies and as a consequence" analysis of EITS - containing air offers little of practical significance regarding the origin of odor or ir'ritation". This, Dr. Cain a:°gues, is because human beings perceive ETS differently thail certain other chemicals. In the case of formaldehyde, for example, Dr. Cain's own research (1) has shown that "prominen: characteristics of the sensations included growth of irritation with time for the lower concentrations and decay for the highest". In experiments (Y) on possible interaction bstween odor and OD m -3 irritation, "the odorous substance pyridiie was injected into N an environment containing 1 ppb-formaldehyde", and "the ~ Ch ~

irritation from formaldehyde decreased. :uch-sensor-y interactions may also result in environmentally realistic situations", Dr. Cain concluded. .Yet in.t:he case of ETS no-- such observations were made. Why is this: Dr. Cain does not offer an acceptable explanation. Dr. Cain also believes that "as ETS enters the atmosphere, its many chemical constituent:; react with each other and with surrounding materials both chemically and physically". Yet "irrespective of whatever chemical changes occur", Dr. Cain would have us believe th<<t "the odor of ETS behaves in the short run like a stable contaminant". Even after the source has been removed, Dr. Cain states that "ETS odor decays in a manner entirely predictable from ventilation rate" and "therefore" differs from occupany odor which has a half-life of 55 minutes presumably by slow oxidation of its chemical constituent into less odorous products" (2). Since the liquid aerosol of ETS" absorbs and so on, it becomes a source for Dr. strong].y to walls, fabrics odor Cain argues "the background odor of carries its own demands for ventilation from the typical amount of smoking in a fails to explain adequately how and why later". Consequently, the emitted products predictable in part space" (3). Dr. Cain this is so as well as how it affects the overall conclusions reyarding recommended ventilation rates. Reliance upon chamber versus real life studies also means that, as a practical matter, ASHRAE and Dr. Cain employ different definitions of acceptable indoor.--air quality:

ASHRAE Standard 62-1989 defines acceptable indoor- air- qu-ality- as "air in which there are no known contaminants at harmful concentrations as determined.by cognizant.-authorities-and_with which a substantial majority (80% or more) of the people exposed do not express dissatisfaction." Appendix C, (see page 17 of ASHRAE Standard 62-1898,) provides the "proper" or recognized definition' of acceptability to be used in establishing the 80% level, namely: "Many contaminants have odors or are irritants that may be detected by human occupants or visitors to a space. The air can be considered acceptably free of annoying contamina:nts if 80% of a panel of at least 20 untrained obse!rvers deems the air to be objectionable under representative conditions of use and occupany. An observer should enter the space in the manner of a normal visitor and should enter a judgment of acceptability within 15 seconds. Each observer should make the valuation independently of other observers and without influence from a panel leader. Users of this method are cautioned that the method is only a test for odors. Many harmful contaminants will not be detected by this test. Carbon monoxide and radon are two examples of odorless contaminants." The criteria employed by Dr. Cain in his odor and irritation tests appears far broader and nonspecific to be covered by the above, rather explicit defi.nition.(4) Dr. Cain did confirm that his own experimental findings suggested a ventilation requirement of "17.5 cfm per occupant and accordingly would meet ASHRAE visitor crii:eria", for several listed occupancies under Table 2 of ASHRAI; Standard 62-1989. Yet in returning to his climate chamber data, he continues to - argue that based on data from (his) "investigations suggests that under typical conditions of- smoking -occupany--(10$ smok=ing

at any given time) non-smokers would need over 100 cfm per occupant to hold dissatisfaction at only 20$." Also unlike Dr. Cain,.ASHRAE..St.andard 62-1989. makes no mention of non-smoker ventilation rates. To do so would r create an HVAC designers nightmare, as past experience with previously flawed ASHRAE Standard 62-1981 has shown. ASHRAE standards for ventilation of office space have varied from 20 cfm per person of outdoor air before the energy crisis to the recently replaced 5 cfm per person in non-smoking areas and 25 cfm per person in smoking areas set in*the mid-seventies. The new ASHRAE standard does not differentiate between non-smoking and moderate smoking areas, with 20 cfm per person being the recommendation in office spaces. Their experience, in real life situations, is that 20 cfm of outdoor air per person deals adequately with moderate smoking activities in buildings, and this should be reflected in any EPA position on the issue unless major new research shows this not to be the case. Environmental chamber data cannot generally be extrapolated to predict performance within actual occupied spaces. For example, Dr Cain reported employing a sniffing station where air from the chamber was passed through "an aluminum box of 0=11M3 which "eventually went back into a return duct. The box enabled persons to judge the air in the chamber without the need to enter it. After sniffing the air at the system, the visitor assigned the occupany odor a magnitude_estima.te from.the scale previously.generated-from

judgments of butanol". Dr. Cain then-stated-that "in view of- our findings that only 85% of visitors deamed the very weak butanol level of 1 acceptable, the ASHRAE-80$-rule seems rather stringent" (5). While this observation obviously reflects Dr. Cain's opinion, one can hardly expect these findings to be used by HVAC designers attempting to comply with the above specified ASHRAE 62-1989 "untrained observer" criteria provided under it's Appendix C as a guideline for implementation whenever concern for odors in buildings become a problem. Dr. Cain also pointed out some important problems in his published test results (5) which are not mentioned in this chapter. For example, in his tests "high humidity led to higher odor intensity and substantially lower acceptability". Furthermore, "agreement among visitors from one set of experiments to another suggests that visitors decided on acceptability on the basis of odor intensity without regard to quality". This alone in our opinion suggests some major uncertainties in Dr. Cain's basic premise. It is interesting to note that in a generally parallel research effort dealing with formaldehyde, Dr. Cain concluded that "a given concentration of formaldehyde may evoke quite different degrees of irritation, depending upon duration of exposure, fluctuations in concentrations, and the presence of other agents in the air".(l) Yet he fails to account for these same likely variables in his published ETS

I work (5)... Additional problems are also ccnveniently ignored; namely: (a) Laboratory experiments in a.cl.irrate chamber of small volume in which cigarettes were smoked with-a smoking machine (6) are hardly comparable to actual smokers moving about occupied spaces of considerably larger volume, and exposed surface area, etc. (2). Inside most buildings there are a wide range of absorptive surfaces such as carpets, wall coverings, particle board, and furnishings. These act as sinks for gas and particle phase emisEions from all indoor sources, reducing both the intersity and half-life of irritative substances in the air. This is in direct contrast to the non-absorptive surface of the smoking chambers used in these tests. (b) Effects of widely differing brands of tobacco often result in some variations in ga:;eous and particulate composition, a factor largely icinored by Dr. Cain in his remarks (6). (c) The effects of climatic (i.e., humidity) influence on perceived odor and irritation threshold levels is largely ignored. For example, iis pointed out by other researchers (6) threshold limit values are reduced for drier environments, e.g. naturally ventilated spaces in winter, etc.

(d) Variations in concentration--of czone and/or particulate matter in outdoor air (used in Dr. Cain's experiments) were not accounted-.for,-. (e) Recognizing that more than one-tYalf of the U.S. population reside in areas that have failed to meet the 120 ppbv natural Ambient Aii Quality ,Standard (NAAQS), (7) for ozone, a known irritant that is odorless. In reviewing his published work, we can find no evidence of any measurentents made to determine outdoor air ozone levels in Hew Haven during the period of his testinc (5). _ B (f) of Levels of ETS necessary to raise- the carbon monoxide concentration from 2 to 5 ppm are considerably higher than found in.typical modern office environments where smoking is discretionary. Absolute levels of ETS used in the laboratory studies versus real life situations, as well as frequency of occurrence. This is especially the case when carbon monoxide is used as an indicator ETS (as found in reference six in this chapter). Certainly any measurement of maintained particulate concentrations•(8) (i.e., attributable directly to tobacco ~ 07 smoke) should take into account the probable effects: ~ W W

(a) Of prevailing outdoor-air on indoor-air, any infiltration, internal deposition levels, and (b) That fan operations, HVAC systein filter efficiencies, infiltration, internal deposition sites, internal generation rates (of all known or suspected species including VOC's, particles, and ozone) and (c) their interaction would have a-Derceived odor and irritation levels. r As many other researchers have :oointed out (7) (8), such tests require (at a minimum) the determination of a mass balance model based on the characteristics of a specific building and site. Such information cannDt reasonably be extrapolated from data obtained from environmental test chamber without considerable speculation. Accordingly,-such methods are questionable particularly when establishing realistic ventilation rates for todays modern buildings in the manner suggested by Dr. Cain. In practice, the experience of HBI mirrors that of ASHRAE, in that where 20 cfm of fresh outside air is provided, complaints of excessive smoke are rarely found. The problem remains, however, that this level of ventilation tends to be ~ .~ the exception rather than the rule, and then-not only smoke ~ builds up, but_'all types of internally generated-pollutants; W .P

most less visible_than cigarette.smoke, a].though frequently just as irritative. References (1) Cain, W. S., See, Leaderer, B., and 7'oson, T. (1986). Irritation and odor from formaldehyde: chamber studies. In IAQ '86: Managing Indoor Air for Health and Energy Conservation. Atlanta: ASHRAE, pp., 126-137. (2) Clausen, G. H., Fanger, P. 0., Cain, W. S. and Leaderer, B. P. (1986). Stability of body odoi7 in enclosed spaces. Environment International, 12, 201-205. (3) Clausen, G. H., Moller, S.B., Fanger,. P.O., Leaderer, B. P., and Dietz, R. (1986). Background odor caused by previous tobacco smoking. In IAQ '86: Managing Indoor Air for Health and Energy Conversation. Atlanta: ASHRAE, pp. 119-125. (4) Clausen, G.H. (1988) Comfort and env:Lronmental tobacco smoke. In IAQ '88: Engineering Solutions to Indoor Air Problems. Atlanta, ASHRAE, pp. 267-274. (5) Cain, W.S., Leaderer, B.P., Isseroff, R., Bergland, L.G., ' Huey R. J., Lipsitt, E. D., and Perlman, D. (1983).

Ventilation requirements in buildings - 1. Control of occupany odor and tobacco smoke odor. Atmospheric Environment 17, 1183-1197. .(6) Weber, A. (1984). Annoyance and irritation by passive smoking. Preventative Medicine, 13, 618-625. (7) Weschler, C. J. and Shields, H.C. (1989). Indoor Ozone Exposures. JAPCA, 39 pp. 1562 - 1568. (8) Weschler, C.J. and Shields, H.C. (1989), The effects of ventilation, filtration and outdoor air on the - composition of indoor air at a telephone office building, Environment International, Vol. 15, pp. 593 - 604. (9) Yaglou, C.P., Riley, E.C., and Coggins, E. (1936). Ventilation requirements. ASHRAE Transactions, 42, 133-162:

REACTIONS TO ENVIRONMENTAL TOBACCO SMOKE:. A Compendium of Technical Information Chapter 4: Environmental Tobacco Smoke and Cancer Prepared by: Joseph L. Fleiss, Ph.D. I I have been a Professor and Head of the Division of Biostatistics at the Columbia University School of Public Health since 1975. In addition to my academic appointment at Columbia, I was until 1986 a senior research scientist in biostatistics at the New York State Psychiatric Institute, and from 1976 to the present I have been a consulting biostatistician at Presbyterian Hospital in New York City. I have been an officer, member, and award recipient of a number of professional societies and journals, and I have served on several expert and review committees for the National Institutes of Health, the Food and Drug Administration, and the American Public Health Association, among others. I have published four books, 16 chapters in books, and some 160 journal articles on statistical aspects of medical research,_ including epidemiologic issues. My curriculum vitae is attached. I have been asked to review "Environmental Tobacco Smoke and Cancer," by J.M. Samet, which is Chapter Four of an EPA•draft compendium of technical literature on environmental . tobacco smoke. CD

- 2 - In this chapter, Dr. Samet reviews the epidemiological evidence concern.ing an association-between environmental tobacco smoke (ETS) and lung cancer, and concludes that "involuntary smoking causes lung cancer" (p. 46). In my opinion, such a conclusion is unwarranted, given the almost uniformly poor quality of the epidemiological studies that have been published. There are numerous flaws in these studies; I will limit my comments to those that strike me as most serious from the point of view of a biostatistician. Poor quality in the form of inadequate control has characterized most of these studies from the very beginning, starting with Hirayama's initial study published in 1981. A flood of criticism followed the publication of the article, with responses by Hirayama that Dr. Samet asserts "satisfactorily answered most of these criticisms." I disagree strongly with this assertion. Hirayama never satisfactorily explained, for example, why he controlled in his first analysis for the age of the husband when it was the wife who was the study subject and thus her age that affected her risk for lung cancer. It was in 1984 that Hirayama finally reported the results of analyses that adjusted for the age of the subject herself. The age-adjusted risk for nonsmoking women married to a husband who ever smoked relative to that for nonsmoking women married to a nonsmoker dropped from 1.57 to 1.45, and its two-tailed p-value increased from=

3 0.02 to a barely significant 0.05. The strength and significance of the association were both attenuated-when the correct adjustment was made. The impact of Hirayama's original article would surely have been weaker had the data been properly analyzed. For all of its flaws -- in addition to the absurd control for the age of the husband, Hirayama's study failed to employ actuarial methods in analyzing the data, misstated the statistical significance of the association between exposure to ETS and lung cancer, and combined adenocarcinoma of the lung and bronchial alveolar cancer with o--her lung cancers more strongly linked statistically to cigarette smoking -- the study was prospective and therefore not p:rone to the kinds of systematic errors in ascertaining exposure to ETS that afflict retrospective case-control studies. Dr. ,3amet discusses the effects of misclassification errors on the estimate of relative risk. Even though he points out that nonrandom misclassification error may either exaggerate or reduce the magnitude of the estimate, most of his subsequent analysis of misclassification assumes that misclassification errors occur randomly and with equal probability in caSes and controls. The predictable effect of random misclassification is to underestimate, not overestimate the relative risk. What Ob concerns me, and what should have concerned Dr. Samet more ~ ~ ~ than it did, is the likelihood of nonrandom, systematic error, N W CO Cd

- 4 - r, with the possible consequence that the published relative risks are overestimates-of the true parameter.- I have in mind especially the bias produced in case-control studies by the nonblinded irquiry by the investigator into the patient's and the spouse's smoking history. It is not deliberate misrepresentation or falsification that is of concern so much as the unwitting application of different criteria in evaluating the report of a lung cancer patient or surrogate versus the report of a control. I have long argued that it is as essential for_ validity in a case-control study to blind the investigator as it is in a clinical trial (Fleiss, 1981, p. 206). Nevertheless, the investigators were kept ignorant of the status of the subject as case or control in, apparently, only three of the case-control studies that have been published (Garfinkel, et al., 1985; Akiba, et al., 1986; Brownson, et al., 1987). The nonblinded studies are, in my opinion, seriously and possibly fatally flawed. Similarly flawed are those case-control studies in which a surrogate reporter, someone other than the patient, was relied on for information about the patient's and spouse's smoking history. The Methods sections of the published articles do not always state whether surrogate reports were permitted, but my estimate is that at least half and possibly three quarters of the published case-control studies relied on

- 5 - the recollections of the next of kin when the patient had died. Consider as an example the 1985.study by Garfinkel et al. that Dr. Samet cited as providing supporting evidence for an association between exposure to ETS and lung cancer. The patient herself was the source of information in only 12 percent (16/134) of the cases. In approximately 65 percent of the cases the patient had died and a spouse or child was interviewed for information about the patient. In the remaining 20-25 percent of the cases, someone other than the patient, her spouse or her children supplied the neces-sary information! A body of knowledge exists to the effect that sizable fractions of subjects misreport, sometimes randomly but generally systematically, their lifetime history of smoking and that of their spouses. How much greater must the error rates be when it is the surviving spouse, or a child, or a sibling, or someone not even related, who is the source of information about the patient, or when it is a child, or a sibling, or someone unrelated who is the source for the spouse. In my opinion, it is still not known, nine years after the appearance of the first three articles on the subject, whether exposure to ETS is truly a risk factor for lung cancer. -•Perhaps the epidemiological studies that Dr. Samet mentions as being in progress are sufficiently tightly designed, with appropriate controls, to settle the-issue of

- 6 - whether or not an association exists. The epidemiological studies that have been published thus far, however, are inadequate for the task. *10.l

References Akiba, S., Kato, H., Blot, W.J. (1986). Passive smoking and lung cancer among Japanese women. Cancer Res. 46:4804-4807. Brownson, R.C., Reif, J.S., Keefe, T.J., et al. (1987). Risk factors for adenocarcinoma of the lung. Amer. J. Epidemiol. 125:25-34. Fleiss, J.L. (1981). Statistical Methods for Rates and Proportions. 2nd edition. New York: Wiley. Garfinkel, L., Auerbach, 0., Joubert, L. (1985). Involuntary smoking and lung cancer: A case-control study. J. Natl. Cancer. Inst. 75:462-469. Hirayama, T. (1981). Nonsmoking wives of heavy smokers have a higher risk of lung cancer: A study from Japan. British Med. J. 282:183-185. Hirayama, T. (1984). Lung cancer in Japan: Effects of nutrition and passive smoking. Chapter 14 in Mizell, M. and Correa, P. (eds.). Lung Cancer: Causes and Prevention. Deerfield Beach FL: VCH.

COMMENTS ON ENVIRONMENTAL TOBACCO.SMOKE: A Compendium of Technical Information Chapter 4:- Environmental Tobacco Smoke and Cancer Prepared by: Maxwell W. Layard, Ph.3. I am a partner in Layard Associates, a firm of consulting statisticians in-Alameda, California. I received the Ph.D. degree in Statistics from StanfDrd University in 1969. I was formerly an assistant professor of mathematics, University of California, Davis, a staff ::nember in the Biometry Branch of the National Cancer Institute, and a senior biostatistician in the Veterans Administration clinical trials program. My professional activities have involved statistical analyses of epidemiologic data, including data pertaining to studies of exposure to environmental tobacco smoke and disease incidence. My curriculum vitae is attached. I have been asked to review "Environmental Tobacco Smoke and Cancer," by J.M. Samet, which is Chapter Four of an EPA draft compendium of technical literature on environmental tobacco smoke. In this chapter, Dr. Samet cursorily reviews the epidemiologic evidence concerning exposure to environmental tobacco smoke (ETS) and lung cancer in humans, and discusses the conclusions of three review committees on this subject. He also briefly considers epidemiologic studies of ETS exposure and cancer at sites other than the lung. 1

In his introduction, the author states (p. 42) that.- the World Health organization (WHO), the U.S. Surgeon General,- and the National Research Council judged the evidence [i.e., reports of studies of ETS exposure and lung cancer] sufficient to support the conclusion that involuntary inhalation of tobacco smoke by nonsmokers causes cancer„ As regards the conclusions of the WHO IARC Working Group on tobacco smoking, that statement is not strictly accurate. The relevant passage from the report of the IARC Working Group (IARC, 1986, p. 314) reads: "The observations on nonsmokers that have been made so far are compatible with either an increased risk [of cancer] from 'passive'-smoking or an absence of risk. Knowledge of the nature of sidestream and mainstream smoke, of the materials absorbed during 'passive' smoking, and of the, quantitative relationships between dose and effect that are commonly ob:aerved from exposure to carcinogens, however, leads to the conclusion that passive smoking gives rise to some rLsk of cancer." Clearly the Working Group's conclusion was not based on the sufficiency of the epidemiologic evidence, but on considerations of biologic plausibility, ;3pecifically similarities between the composition of m,3instream smoke and ETS, and an a.9sumed absence of a dose threshold below which there is no carcinogenic effect. This point is acknowledged later in Chapter Four (p. 46), and is dis::ussed again-below. 2

) i It is pertinent to note that-in-an earlier review paper Samet- (1985) reached essentially the same.conclusion regarding the epidemiologic evidence.as did the'IARC Wo:rking Group, perhaps not surprisingly since he was a member of that group. In that paper it was stated that the observed association between ETS exposure and lung cancer did not yet meet the criteria for making causal inferences which were applied to smoking in the 1964 Surgeon General's Report, although he did consider that the criterion of biological plausibility l-iad been met. Apparently at the time of writing the earLier review Samet did not consider that biologic plausibility oE itself was - sufficient to warrant a causal inference. In the present review, Samet does not explicitly review the epidemiologic studies of ETS a:zd lung cancer in the light of the usual criteria for making•ca.i-sal judgments based on epidemiologic evidence. Instead, he briefly reviews some of the studies (pp. 44-45), and offers very little critical analysis of the overall evidence. Two taoles are presented (Tables 1 and 2, pp. 52a-52d), containing summary information about 3 cohort studies and 17 case-control studies. The review of the epidemiologic studies begins with a discussion of the Japanese cohort study reported by Hirayama (1981, 1984). The author states that Hirayama satisfactorily answered most'of the published criticisms of the study, but that assertion is debatable. The fact is that there is a remarkable.paucity of information of Hirayama's puk;~-lished ~ `. 3

reports about the design, conduct, and re:cults-of the study. Most seriously, no explicit information h<<s been published about the number of subjects lost to follow-up. Detailed analysis of the published results on ETS and lung cancer reveals serious internal and external inconsistencies in those results which raise questions about their validity. (See Layard and Viren, 1989.) The author next briefly describes the.Greek case-control study of Trichopolous et al. (1981, 1983), but does not mention the serious criticisms which have been made of that study, although those criticisms were discussed at some length in his own 1985 review. In the following paragraph (p.44), Samet states that the results of subsequently reported case-control studie:; also demonstrated a significantly elevated risk of lung cancer in nonsmokers exposed to ETS, and asserts that the more recent studies "greatly strengthen" the evidence from the earlier studies. It is not clear how he arrived at that conclusion, since he offers no explanation beyond a reference i.o Table 2. In fact, reports of 19 case-control studies have been published since the initial report of the Trichopolous et al. study. Most of those studies used spousal smoking as the index of ETS exposure, and based on comparisons between "non-exposed" and all "exposed"Isubjects, only three of the 19 reported a significant association between ETS exposure and lung cancer. (See the reviews by Layard, 1989,- and Lee, 1989.) The author 4

goes on to say that several of the newer studies- included relatively large numbers of nonsmokers. However, two of the five studies he lists following that remark, namely Akiba et al. (1986) and Gao et al. (1988) did not report a significant elevation in lung cancer risk. (The resu7.t given in Table 2 for one of the listed studies, that of Da7.ager et al., 1986, was based on an analysis of combined data, with 48 lung cancer cases of both sexes, from the Correa et aL., 1983, and Ziegler et al., 1984, studies.) Samet next refers to studies by Knoth et al. (1983) and Gillis et al. (1984) as having been interpreted as- showing an association between ETS and lung cancer, and remarks that both studies have limitations. The Knoth et al. study did not incorporate a control group, and for that reason was discounted by the NRC and Surgeon General's committees; it was not mentioned by the IARC Working Group. The Gillis et-al. cohort study'reported a- spousal smoking relative risk of 3.25 for males which was based on only six lunq cancer cases, and was not statistically significant; the re:lative risk for females was 1.0. These results can hardly be interpreted as showing an ETS-lung cancer association. In the next paragraph, the author notes that other investigations indicate lesser or no effects of ETS exposure Gn Cn on lung cancef risk. He goes on to say that these studies ~ ~ have relatively few subjects and large statistical ?J ~ uncertainty, so their. apparently_.negative-findings are m 0. 5

statistically compatible,with those-of the_"studies-judged-as- positive." It is not entirely clear whicll-studies-Samet is placing in the negative and positive categories. Following these remarks, he discusses, as having negative or weak findings, the case-control studies of Chan and Fung (1982), Koo (1987), Lee et al. (1986), Shimizu et al. (1988), Kabat and Wynder (1984), Wu et al. (1985), and 13rownson et al. (1987), as well as the American Cancer Society cohort study (Garfinkel, 1981). (Another negative study which is not listed in Table 2 is that of Buffler et a:L., 1984.) However, six of the other studies listed in Tables 1 and 2, which by implication Samet categorizes as "positivi~," reported nonsignificant relative risks. The implication that "negative/weak" studies had few lung cancer cases relative to "positive" ;studies is rather I U misleading. Four of the "negative/weak" studies listed above had more than 80 cases, and the Gao et al. (1988) study, surely "weak" with a nonsignificant relative risk of 1.19, had 226 cases. On the other hand, four of the remaining, implicitly "positive," studies had fewer than 30 cases. Apart from remarks, in connection with two of the studies, to the effect that exposure misclassification may have biased the results, Samet in this review offers no further comment on the quality of the epi3emiologic data or on potential biasing factors. (Later in the review he does mention the--NRC committee's analysis of-pDssible_sources_=of--- 6

S l1 I bias.) In fact the studies of ETS and lung cancer suffer from serious methodologic-flaws in their-design-and execution which- could well introduce bias into the results. There is good reason to suppose that biases and confounding factors may have inflated the observed relative risks in many of these studies. Detailed discussions of these points are presented in the recent reviews of Layard (1990) and Lee (1989), and are briefly summarized-here: The study results are weak and inconsistent, and thus do not offer convincing evidence that any observed association is not an artefact-produced by bias or confounding factors. Dose-response relationships are nonexistent or negative in some studies, and none of the studies demonstrates a significant dose-response when attention is restricted to exposed subjects. Some studies display.contradictory results with respect to the lung cancer cell type for which risk elevation with ETS exposure was observed. The results of epidemiologic studies are subject to distortion by various types of bias, and case-control studies in particular are susceptible to selective recall bias, due to the propensity of cases to recall exposure - more completely. None of the studies of ETS and lung cancer used objective ETS exposure measurements such as biologic or environmental markers. One important source of bias in these-studies is under-reporting of current or 7

i r past smoking by professed "never-smokers." This would result in over-estimation of relative risk, since the smoking habits of spouses, as well a:a smoking-and lung cancer incidence, are positively cor:-elated. This point is taken up again below. A number of studies have suggested a,3sociations between lung cancer and factors such as occupation, nutrition, and alcohol consumption. There is evidence that such factors are also correlated with ETS exposure, and they are therefore confounders which could well give rise to spurious associations between ETS and lung cancer. Few of the studies of ETS and lung cancer have controlled for potential confounding factors. Estimates based on epidemiologic data of the relative risk of lung cancer of nonsmokers married to smokers, such as the NRC committee's estimate of 1.25 referred to on page. 46 of Chapter Four, are much higher than would be expected from comparisons of biologi::al markers of smoke exposure between ETS-exposed persons and active smokers. In the case of respirable suspended :particulates, for example, such dosimetric comparisons, coupled with low-dose extrapolation from data on active smokers, lead to risk estimates which are two or mcre orders of magnitude smaller than estimates based on the epidemiologic data. Such huge discrepancies cast doubt on the__validity of-the observed association-between~ETS- 8

j ; r9 t and lung.cancer, and suggest that.the epidemiologic_- results are more_.likely_explained by-bias and.confounding than by an effect of ETS exposure.- On page 46 of Chapter Four, the author discusses the conclusions of the three review committees referred to earlier, namely the IARC, the NRC, and the Surgeon General's committees. He notes that the IARC committee reached its conclusion largely on the basis of biologic plausibility, and states that one factor cited by the committee was the nature of dose-response relationships for carcinogenesis, "which project some risk for any level of exposure." The quoted language, which was not used by the IARC committee, obscures the fact that a no-threshold carcinogenic dose-response is an assumption, not an experimentally verified principle. Samet next discusses the NRC committee's report, noting that after careful consideration of possible sources of bias the committee concluded that the asscciation observed in the epidemiologic studies could not be attributed solely to bias. The NRC committee did not attempt to estimate the possible effects of uncontrolled confounding factors, but did consider the possible effect of misclassification of current- or ex-smokers as nonsmokers, concluding tt.at it was likely to be relatively small. Lee (1988a, 1989) took issue with the NRC committee''s analysis, pointing out tha,t there was an error in their calculations and claiming that their.assumptions about smoking risk and the extent of-.misc]assification_.were- 9

unrealistic. Lee suggested that- miscl.ass:LE-ication-of smoking== habits could produce an apparent.ETS-1ung_,cancer-association. similar in magnitude to the average relatdve risk reported in the epidemiologic studies. In view of the dosimetric evidence referred to above, Lee concluded that misclassification bias is a more likely explanation of the observed association than is an effect of ETS. Samet briefly describes the reasoning behind the conclusion of the Surgeon General's Commi-:tee that ETS exposure is a cause of lung cancer, but makes no further comment on it. The Surgeon General's report discusses- dosimetric comparisons of ETS exposure and smoking, and the comparability of low dose extrapolation from smoking data with the epidemiologic results. It reaches quite different conclusions from those of Lee (1988a) and others, on the basis of estimates suggesting that the epidemioLogic data are similar to what would be expected from smoking dose-response models. However, those estimates used cigarette equivalents of ETS exposure, derived from urinary cotinine data, which were higher than those calculated by others (see the NRC report, for example). Moreover, dosimetric comparisons using respirable suspended particulates suggest cigarette equivalents which are far lower than those based on cotinine data (Lee, 19$8a, Robins et al., 1989, McAughey et al., 1989). T W The Surgeon General's report also briefly considers the ~ questions- of misclassif-ication of smoking status, but N GJ 10

dismisses it as unimportant on the ground:;.that_elevated risks-- were reported in studies conducted in countries where no social stigma against smoking exists. In view of the dat-a elicited by Lee (1988b) in his intensive examination of the smoker misclassification question, this argument appears to be facile and insubstantial. Finally, little attention was given :; in the Surgeon General's report to the important matter of uncontrolled confounding in the analysis of study results. Samet concludes his lung cancer discussion by mentioning three ETS-lung cancer risk assessments, which he says can provide insight into the magnitude of the problem in spite of the fact that they are subject to substantial uncertainty. He first refers to Repace and Lowrey's (1985) estimate of lung cancer deaths attributab:_e to ETS exposure, but offers no critical evaluation of its validity. Primarily because it was based on a comparison of mortality rates in two populations which could not be assumed to be comparable in respects other than ETS exposure, the Repace and Lowrey risk assessment has been strongly criticized and largely disregarded by the scientific community (i:he NRC report did not mention it, for example). The other -=wo risk assessments mentioned by Samet are those of Robins (in an appendix to the NRC-report) and Wells (1988). Both are biased on data from the epidemiologic•studies, and have no validi:y in view of the fact that it cannot be definitely concluded that the 11

associations repor-ted.in_those.-studies.reflect-a causal. - relationship. In the- last section of-his review, Samet discusses epidemiologic studies of ETS exposure and cancer other than of the lung. Surprisingly, he states that the Miller (1984) study linked ETS exposure to a generally increased risk of malignancy. That study showed an age-adjusted cancer mortality relative risk of 0.97 for all women, and a nonsignificant relative risk of 1.25 for women not employed outside the home. Samet does not mention the cohort study of Sandler et al. (1989), which reported all-site cancer - mortality relative risks of 1.01 and 1.00 for men and women respectively. Nor does he mention criticisms that have been made of other ETS cancer studies, for example that they failed to control for known risk factors for specific cancers, such as sexual activity in the case of cervical cancer. No review committee ha's concluded that ETS exposure is linked to an elevated risk of cancer at sites other ti-an the lung. Some ETS studies have reported increased risks for cancers not associated with smoking, and, as Samet notes, such findings are biologically implausible. Thus bias and confounding are likely contributors to these observed risks. There seems nb reason to suppose that these distorting factors have not also been present in the lung cancer studies themselves : -- 12

To summarize, _ this chapter prov'.des -a rather cursory_ and uncritical review of the epidemiologic-evidence-concerning ETS and cancer. It offers little in the way of systematic analysis or new insights, merely endorsiny the conclusions of some of the studies without considering the merits of opposing viewpoints. It falls short of being an adequate source of technical information on this important subject. V:O 13

ADDITIONAL REFERENCES (NOT LISTED IN 'PHE EPA DOCUMENT)-- Buffler, P.A., L.W. Pickle, T.J. Mason, and C. Constant (1984). The causes of cance•r in Texas. In: Lung Cancer: Causes and Prevention (Eds. Mizell and Correa). Verlag-Chemie International, New York. Layard, M.W. (1990). Environmental tobacco smoke and cancer: the epidemiologic evidence. In: Environmental Tobacco Smoke: Proceedings of the Interational Symposium at McGill University 1989 (Eds. Ecobichon and Wu). D.C. Heath & Co., Lexington, MA. Layard, M.W., and J.R. Viren (1989). Assessing the validity of a Japanese cohort study. In: Present and Future of Indoor Air Quality (Eds. Bieva et al.). Excerpta Medica, Amsterdam. Lee, P.N. (1988a). An alternative explanation for the increased risk of lung cancer in non-smokers married to smokers. In: Indoor Air and Ambient Air Quality (Eds. Perry and Kirk). Selper Ltd., London. Lee, P.N. (1988b). Misclassification of Smoking Habits and Passive Smoking. A Review of the Evidence. Springer-Verlag, Heidelberg. Lee, P.N. (1989). Passive smoking and lung cancer; fact or fiction? In: Present and Future of Indoor Air Quality (Eds. Bieva et al.). Excerpta Medica, Amsterdam. McAugtiey, J.J., J.N. Pritchard, and A. Black (1989). Relative lung cancer risk from exposure to mainstream and sidestream smoke particulates. In: Present and Future of Indoor Air Quality (Eds. Bieva et al.). Excerpta Medica, Amsterdam. Robins, J.M., D. Blevins, and M. Schneiderman (1989). The effective number of cigarettes inhaled daily by passive smokers: are epidemiologic and dosimet.ric estimates equivalent? J. Hazardous Materials 2].:215-238. Samet, J.M. (1985). Relationship between passive exposure to cigarette smoke and cancer. In: Indoor Air and Human Health (Eds. Gammage and Kaye). Lewis Publishers Inc., Chelsea, MI. Sandler, D.P., G.W. Comstock, K.J. Helsing, and D.L. Shore (1989). Deaths from all causes in non--smokers who lived with smokers. Am. J. Publ. Health 79::.63=167: 14

Wynder, E.L., and G.C. Kabat (1989). Health-care.and-society• environmental tobacco smoke and lung cancer. In: Present • and Future of Indoor Air Quality (Eds. Bieva-et-al.). Excerpta Medica, Amsterdam. Ziegler, R.G., T.J. Mason, A. Stemhagen, et al. (1984). Dietary carotene and vitamin A and risk of lung cancer among white men in New Jersey. J. Natl. Cancer Inst. 73:1429-1435. 15

CHAPTER 4: ENVIRONMENTAL TOBACCO SMOKE AND CANCER fl CARR J. SMITH, PH.D. SENIOR SCIENTIST L

ENVIRONMENTAL TOBACCO SMOKE: A COMPENDIUM OF TECHNICAL INFORMATION Section/Page/Line Specific Comments ETS and Cancer/Paae 41/Line 14 The phrase 'in the general population" needs to be clarified.- There are significant differences in histologic distribution between males and females (1)- ETS and Cancer/Page 41/Line 17 The sentence 'Bronchioloalveolar cell carcinoma represents about 5 percent of the remaining lung cancers' is incorrect. Five percent of ten percent is 0.5%. This cancer represents from 1.1 to 9.0% of lung cancers (2). ETS and Cancer/Page 41/Line 24 - The statement, 'Most of the early evidence indicated that tobacco smoke was a potent respiratory carcinogen" deserves comment. Toba,:co smoke has not been shown to induce lung cancer in experimental animals. 0D OQ ~ ~ N ~ 1 p

ENVIRONMENTAL TOBACCO SMOKE: A COMPENDItM OF TECHNICAL INFORMAT[ON Section/Page/Line Specific Conwents ETS and Cancer/Paae 41/Line 41-42 The statement "Agents other than tobacco smoke may also cause lung cancer, and cases occur in lifelong nonsmokers" implies that lung cancer is unusual in nonsmokers. M. A. Schneiderman and D. L. Davis, National Academy of Sciences, and D. K. Wagener, National Center for Health Statistics (3) recently made the following comment: "If these estimates are accurate, only colon and prostate cancers in men (mortality rates, 21.4 and 23.5 per 100,000, respectively) and colon and breast cancers in women (15.7 and 27.3 per 100,000, re;:pectively) had higher mortality rates than did non-smoking-attributable lung cancer for both blacks and whites.` Further, blacks might be at higher risk than whites for non-smoking-_ attributable lung cancer, the computed residual "rate" being 67% higher in black men than that in white men and 16% higher in black women than that in white women. As computed herein, non-smoking-attributable lung cancer is one of the most common causes of cancer mortality.... " 2

ENYIRONMENTAL TOBACCO SMOKE: A COMPENDIUM OF TECHNICAL INFORMAT[ON Section/Page/Line Specific Comwents ETS and Cancer/Page 41LLine 48 Line 48 states that "many other occupational agents are suspect respiratory carcinogens'. The list of occupational exposures not mentioned that have been associated with increased lung cancer risk includes: Welding (4) Painting (5) Pesticides (6) Diesel Exhaust (7) Working in foundries (8-10) Ceramic and pottery workers (11-12) Rubber workers (13) Herbicides (14) t r. 0, 3 L.

ENVIRONNENTAL TOBACCO SNOKE: A CONPENDIUN OF TECHNICAL INFORMAT[ON ` Section/Page/Line Specific Coments ETS and Cancer/Pa4e 42/Line 2 The statement "a clear pattern of genetic susceptibility to lung cancer has not been demonstrated" is incorrect. Tokuhata and Lilienfeld (15,16) first observed the familial aggregation of lung cancer in 1963. In the absence of smoking, they 1'ound.the relative lung cancer mortality rate among first-degree relatives of lung cancer patients to be 2.7 times higher than that among relatives of controls. 0oi et al. (17) reported a 2.4-fold greater.risk among relatives of probands after controlling for the effects of age, sex, and environmental factors„ Samet et al. (18) have shown a 5.3-fold increase in adjusted risk in individuals with a parental history of lung cancer. A recent study by NcDuffie et al. (19) also demonstrated a two-fold increase in lung cancer risk fur relatives of probands in a Canadian population. Further evidence for a potential familial link was provided by Joishy-et al. (20) in 1977. They reported the occurrence of alveola'r cell carcinoma in a pair of male identical twins. The cancers in these twins presented with strikingly similar ages of onset, histopathologic features, and sites of metastasis. After adjustment for age, sex, race, and smoking, the first-degree relatives of lung-cancer patients and of patients with chronic obstructive pulmonary disease have been shown by Cohen et al. (21) to have significantly higher rates of impaired forced expiration than first-degree relatives of patients with non-pulmonary disease. Similarly, Guirgis, et al. (22) reported an increased frequency•of pulmonary diseases in the relatives of lung cancer patients. These findings suggest*that lung cancer and chronic obstructive pulmonary disease may share a common familiar component. There may be genetically determined metabolic differences between lung cancer patients and matched controls. Ayesh et al. (23) have reported differences in the metabolic pathway of debrisoquine 4-hydroxylation in a white English population. They demonstrated that lung cancer patients showed a preponderance of probable homozygous dominant extensive metabolizers (78.8%) with a few recessive poor metabolizers (1.6%) compared with matched controls (27.8% and 9.0% respectively). These authors concludE:d that the gene controlling debrisoquine 4-hydroxylation may be a genetic determinant of susceptibility to lung cancer. Caporaso et al. (24,25) have recently confirmed these observations in a group of white and black American patients. They have estimated that extensive metabolizers are al; 4.5 times the risk for developing lung cancer compared with poor metabolizern. 4

ENVIRONMENTAL TOBACCO SNOKE: A CONPENDItN OF TECHNICAL INFORMATION V Section/Page/Line Specific Co=ents ETS and Cancer/Page 42/Line 2 (Continued) Kellermann has reported that the inducibility of aryl hydrocarbon hydroxylase (AHH) in human lymphocytes is correlated with an increased risk of the occurrence of bronchogenic carcinoma (26). The use of lymphocyte AHH induction as an indicator of genetically controlled metabolic activation of chemical carcinogens in the lungs is based on the assumption that induction is similarly regulated in different tissues. Dosaka and colleagues (27) have studied the inducibility of sister chromatid exchanges (SCEs) by benzo(a)pyrene in cultured peripheral blood lymphocytes from 15 untreated lung cancer patients and 25 healthy persons including 11 high - and 14 low - cancer-risk individuals as classified by family history. After exposure to benzo(a)pyrene, the lymphocytes of lung cancer patients and high-risk individuals exhibited significantly increased SCE rates than those of low-risk persons. These authors have suggested that lymphocytes of high- risk individuals may be more susceptible to benzo(a)pyrene induced DNA damage and therefore to cancer. The spontaneous transformation of human skin fibroblasts from three lung cancer patients was observed by Azzarone et al. (28) in 1976. Rudiger et al. (29) have also reported spontaneously increased SCE r<<tes in the fibroblasts from lung cancer patients. Several studies have shown differences in HLA frequenc':es between lung cancer patients and the normal population. Ford, Newman, and Mackintosh (30) found a high relative risk of being HLA-BW22-positive and having lung cancer. Markman et al. (31) found individuals with the HLA-BW44 (HLA-Ba2) allele to be significantly over-represented in a patient population with small cell carcinoma of the lung compared to a control population (52% versus 25%, N.001). Mottironi and Banks (32) showed that AW33 had a significant difference in antigen frequency between a lung cancer population and controls. However, none of these correlations has been strong ernwgh to use HLA typing to screen patients for susceptibility to lung cancer. Heighway et al. (33) investigated the influence of polymorphic variants of the human c-Ha-ras gene on predisposition to lung cancer. They found an abnormal allele distribution of the c-Ha-ras gene in individuals with non-small cell carcinoma of the lung compared to both control and small cell carcinoma of the lung patients. These authors have suggested that this difference may represent a"degree of genetic predisposition" to non-small cell carcinoma of the lung. Another way to study the question of genetic predisposition to lung cancer 5

ENVIRONMENTAL TOBACCO SMOKE: A COMPEHDIUN OF TECHNICAL INFORMATION I U Section/Page/Line Specific Comments ETS and Cancer/Page 42/Line 2 (Continued) involves the identification and isolation of oncogenes i:apable of inducing malignant transformation. Yokota et al. (34) showed that the c-erbB-2 gene was amplified in 5 of 63 adenocarcinomas and in one of -the 38 other types of tumors studied. These authors have suggested that the arotein products of the amplified c-erbB-2 gene may play a role in the evolution of adenocarcinomas. Whang-Peng et al. (35) have reported a nonrandom chromosomal abnormality (a common deletion of the short arm of chromosome #3) in human small cell lung cancer. The expression of proteins encoded by ras oncogenes was examined by Tanaka et al. (36) in several types of lung cancer. PrDteins related to ras genes were detected in squamous cell carcinoma, small cell carcinoma, and adenocarcinoma. Individual differences in oncogene activation as a response to environmental insult may be an important determinant of susceptibility to lung cancer. The National Cancer Institute currently has a major research program on genetic typing and lung cancer. NCI Director Samuel Broder has formed a committee to bring this gene research to clinical practice as quickly as possible (37,38). In summary, the evidence for the existence of a genetic predisposition for the development of lung cancer comes from several sources: family histories, case studies, epidemiology, biochemical measurements and geretic studies. ETS and Cancer/Page 42/Line 6 The statement "Animal and human studies suggest that law consumption of Vitamin A or its precursor, beta-carotene, may also increase lung cancer risk" downplays a significant body of literature on the assoc:iation between diet and lung cancer risk. Zeigler (39) has recently written a literature review on the association between low levels of serum or plasma beta-carotene and lung cancer risk. Several of these dietary studies have reported relativc risks for lung cancer much larger than those reported in ETS studies. For example, Menkes et al. (40) reported that "A strong inverse association between serum beta-carotene and the risk of squamous-cell carcinoma of the lung wa:: observed (relative adds, 4.30: 95 percent confidence limits, 1.38 and 13.41)". Dietary factors other than beta-carotene levels have also been associated with lung cancer risk. Irv 1987, Wynder et al. (41) reportei that in an international comparison study "calories from dietary fat were highly 6 ~

ENYIRONMENTAL TOBACCO SMOKE: A CONPENDIIAN OF TECMiICAL INFORMATION iJ h i Section/Page/Line Specific Comments ETS and Cancer/Page 42/Line 6(Continued) significantly associated-(P<.001) with lung cancer mortality. This finding was obtained after accounting for disappearance data for tobacco (P<.001)..." In addition, Goodman et al. (42) have reported a"sign-ificant positive association of dietary cholesterol and the risk of lung cancer in men, but not in women". Therefore, dietary fat intake is a risk factor for lung cancer. ETS and Cancer/Page 42LLine 26-34 This paragraph states that epidemiologists "determine the causes of disease by studying populations" and "identify the causes of disease". Epidemiologists study "associations" of risk factors with diseases. They do not determine "causes". Sir Richard Doll (43) has commented on this inherent limitation of epidemiology, "Two methods have been commonly used - the retrospective, starting from affected patients and unaffected controls, and the prospective, starting from subjects with varying degrees of exposure to the agent under study. Both methods have their advantages and disadvantages; but neither can overcome completely the difficulty that any relationship that is found may be a secondary one and that the suspected agent may itself be associated with another which is, in fact, the true carcinogen." ETS and Cancer/Page 43/Line 22 This paragraph on the misdiagnosis of lung cancer omits the important work of McFarlane, Feinstein, and Wells (44-46). ETS and Cancer/Page 43-45LSection entitled "EDidemiolaaical Evidence on Involuntary Smokin4.and Lung Cancer" There are significant differences in lifestyle between smokers and nonsmokers. Smokers consume a diet significantly higher in saturated fat and lower in fruits and vegetables than nonsmokers (47-49). Smokers exercise significantly less than nonsmokers (50). They also sleep less than nonsmokers (51). There are also significant differences in lifestyle between the spouses of smokers and the spouses of nonsmokers. The following abstract is excerpted from Perusse et al.'s (52) paper entitled "Familial Aggregation in Physical 7

ENVIRONMENTAL TOBACCO SMOKE: A COMPENDIUM OF TECHNICAL INFORMATION :NO Section/Page/Line Specific Coo~nents ETS and Cancer/Page 43-45/Section entitled "Eaidemiological Evidence on Involuntary Smoking and Lung Cancer" (Continued) Fitness, Coronary Heart Disease Risk Factors, and Pulmmary Function Measurements": "In order to test for the presence of familiar aggregation in physical fitness and coronary heart disease risk factors, body fat, subnaximal power output, muscular strength, muscul-ar endurance, blood pressure, pulmonary functions, and several blood biochemical variables were measured in 304 nuclear families living in the Quebec city area. Analysis of variance indicated a larger between-family than within-family variation for all the variables. When all members of nuclear families were considered, intraclass correlations ranged from 0.21 to 0.34 (P < 0.01). Interclass correlations computed for various pairs of relatives revealed significant parent-child and sibling correlations for all the variables (0.14 <_ r<_ 0.55; P<_ 0.01). On the other hand, spousal correlations tended to be lower but significant (0.10 < r< 0.30; P< 0.05) for all variables except subcutaneous fat and hemoglobin concentration. These results suggest that heredity and common lifestyle shared by members of nuclear families are responsible for the familial aggregation of physical fitness, coronary heart disease risk factors, and pulnionary functions. The findings also support the notion of considering the nUclear family as a unit of intervention in the application of preventive measures aimed at the reduction of several risk factors." Sidney et al. (53) recently reported that the self-reported mean dietary intake of carotene is lower in nonsmokers exposed to ETS at home than in nonsmokers not exposed to ETS at home. These authors stated, "We know of no studies that have controlled for blood levels of caroi:enoids in the analysis of this relation...". In addition, Miyamoto et al. (!i4) has reported decreased levels of serum selenium and Vitamin E in the families of lung cancer patients. All of the studies described in this section and in the next section (ETS and cancer at other sites) suffer from the same limitation - the inability to control for the contribution of confounding variables to relative risk estimates. As previously described in this review, there are a large number of risk factors for lung cancer which exceed the National Research Council's 259'o risk increase estimate for exposure to ETS. The risk factors already discussed include occupational exposures, genetic predisposition, high saturated fat intake, and low intake of beta-carotene and other antioxidant vitamins. There are many other reported risk factors for lung cancer: tuberculosis, reproductive history in female adenocarcinoma patients, periodontal disease, and even owning pet birds. Lifestyle differences between 8

ENYIRONNENTAL TOBACCO SNOKE: A CONPENDIUM OF TECFWICAL INFORNATION Section/Page/Line Specific Comments ETS and Cancer/Page 43-45/Section entitled 'Epidemioloaical Evidence on'' Involuntary Smoking and Lung Cancer" (Continued) , smokers and nonsmokers are significant. Lifestyle differences between the spouses of smokers and the spouses of nonsmokers also appear to be significant. None of the studies associating exposure to ETS with cancer have controlled for these lifestyle differences. JJ I ii L ~ ~

References 1. Watkin S. Temporal demographic and epidemiologic variation in histologic subtypes of lung cancer: a literature review. Lung Cancer 5: 69-81, 1989. 2. Robbins S., et al. Pathologic Basis of Disease 755. Third edition. Saunders, 1984. 3. Schneiderman M, Davis D. Letter to the editor: Lung cancer that is not attibutable to smoking. JAMA 261(18): 2635-36, 1989. 4. Table on welding and lung cancer risk (attached). Referencing: Lerchen M, Wiggins C, Samet J. Lung cancer and occupation in New Mexico. JNCI 79(4): 639-645, 1987. Buiatti E, Kriebel D, Geddes M, Santucci M, and Pucci N. A case control study of lung cancer in Florence, Italy I; Occupational risk factors. J. Epidem. & Comm. Health 39: 244-250, 1985. Buiatti E, Kriebel D, Geddes M, Santucci M, and Pucci N. A case control study of lung cancer in Florence, Italy II; Effect of migration from the south. J. Epidem. & Comm. Health 39: 251-255, 1985. Tola S, et al. Cancer incidence among shipyard and machine shop workers. Scand. J. Work. Environ. Health 13(2): 180, 1987. Hull C, et al. Case-control study of lung cancer in Los Angeles County welders. Am. J. Indust. Med. 16: 103-112, 1989. Sjogren B, Gustavsson A, Hedstrom L. Mortality in two cohorts of welders exposed to high- and low-levels of hexavalent chromium. Scand. J. Work. Environ. Health 13: 247-251, 1987. 5., Table on painting and lung cancer risk (attached). Referencing: Zahm S, Brownson R, Chang J, Davis J. Study of lung cancer histologic types, occupation, and smoking in Missouri. Am. J. Indus. Med. 15: 565-578, 1989. Lerchen M, Wiggins C, Samet J. Lung cancer and occupation in New Mexico. JNCI 79(4): 639-645; 1987. 10

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t ~. I 30. 31. i 32. 33. 34. 35. ,, ? Ford CHJ, Newman CE, Mackintosh P. F[LA frequency and- prognosis in lung cancer. Br. J. Cancer 43: 610-614, 1981. Markman M, Braine HG, Abeloff MD. Histocompatibility antigens in small cell carcinoma of the lung. Cancer 54: 1943-1945, 1984. Mottironi VD, Banks S. HLA and survival in lung cancer. FASEB Proceedings 42: 404, 1983. Heighway J, Thatcher N, Cerny T, Has].eton PS. Genetic predisposition to human lung cancer. Br. J. Cancer 53: 453-457, 1986. Yokota J, Toyoshima K, Sugimura T, et: al. Amplification of c-erbB-2-oncogene in human adenocarcinomas in vivo. The Lancet, April 5: 765-766, 1986. Whang-Peng J, Bunn PA, Kao-Shan CS, et al. A nonrandom chromosomal abnormality, del 3p (14-23), in human small cell lung cancer (SCLC). Cancer Genetics and Cytogenetics 6: 119-134, 1982. 36.* Tanaka T, Slamon DJ, Battifora H, Cline MJ. Expression of p21 ras oncoproteins in human cancers. Cancer Research 46: 1465-1470, 1985. 37. Genetic Typing and Lung Cancer. Arti.cle excerpted from New York Times, 5/16/89. 38. Minna J. Genetic events in the pathogenesis of lung cancer. Proceedings at the 5th World Conference on Lung Cancer., Chest 96: 17s-23s, 1989. 39. Ziegler R. A review of epidemiologic evidence that carotenoids reduce the risk of cancer. Symposium -- Biolgocial actions of carotenoids: 1:.6-122, 1988. 40. Menkes M, et al. Serum beta-carotene, vitamins A and E, selenium, and the risk of lung cancer. New Engl. J. Med. 315(20): 1250-1254, 1986. 41. Wynder E, Hebert J, Kabat G. Association of dietary fat - and lung cancer. JNCI 79(4): 631-637, 1987. 42. Goodman M, Kolonel L, Yoshizawa C, and Hankin J. The effect of, dietary choloesterol and fat on the risk of lung cancer in Hawaii. Am. J. Epidern. 128(6): 1241-1255, 1988. 43. Doll,.R. Prevent.ion -of Cancer.: Pointers from-.. Epidemiology 17. 1967. 13 ~ ~

44. McFarlane M, Feinstein A, Wells C. Dlecropsy-evidence of detection bias in the diagnosis of lL.ng cancer. Arch: Intern. Med. 146: 1695-1698, 1986. 45. McFarlane M, Feinstein A, Wells C, Cr.an C. The epidemiologic necropsy: unexpected detections, demographic selections, and changing rates of lung cancer. JAMA 258(3): 331-338, 1987. 46. Wells C and Feinstein A. Detection bias in the diagnostic pursuit of lung cancer. Pn. J. Epidem. 128(5): 1016-1026, 1988. 47. Whichelow M, Golding J, Treasure F. Comparison of some dietary habits of smokers and nonsmokers. Br. J. Addiction 83: 295-304, 1988. 48. Shibata A, et al. Serum concentration of beta-carotene and intake frequency of green-yellow vegetables among healthy inhabitants of Japan. Int'l J. Cancer 44: 48-52, 1989. 49. Hirayama, T. Dietary habits in smoke!rs. In: Statistical Methods in Cancer Research 93-94 (Blot W, Hirayama T, and Hoel D, eds.) 1984. 50. Lazarus N, et al. Smoking and body mass in the natural history of physical activity: prospective evidence from the Alameda County Study, 1965-1974. Am. J. Prev. Med. 5(3): 127-135, 1989. 51. Edington, D. Smoking and habits. Study reported by the University of Michigan News and Information Services Department, June 29, 1988. 52. Perusse L, et al. Familial aggregation in physical fitness: coronary heart disease risk factors, and pulmonary function measurements. Prew. Med. 16: 607-615, 1987. 53. Sidney S, et al. Dietary intake of carotene in nonsmokers with and without passive smoking at home. Am. J. Epidem. 129(6): 1305-1309, 1989. 54. Miyamoto H, et al. Serum seleniuni arid vitamin E concentrations in families of lung eancer patients. Cancer 60: 1159-1162, 1987. * -- Copy of article not provided. 14

-'STATEMENT Irving I Kessler, M.D., Dr. P.H. Department of Epidemiology & Preventive Medicine University of.Maryland School.of Medicine- Baltimore, Maryland I am a physician and epidemioloclist who has been active in cancer research for many years. My academic affiliations are with the University of M<<ryland School of Medicine, where I have been Professor of F:pidemiology and Preventive Medicine since 1978 and Chaifm<<n of the Department until 1988. Previously, I served as Professor of Epidemiology at the Johns Hopkins University. My profe!ssional expertise is in research on disease of humans, health regulation, medical administration and clinical education. My curriculum vitae is attached. I have been asked to comment on "Environmental Tobacco Smoke and Cancer," Chapter 4 in "F:nvironmental Tobacco Smoke: A Compendium of Technical Information" recently issued in draft form by the U.S. Environmental Protection Agency. Cancer in general, and lung cancer in particular, are relatively prevalent conditions which provoke concern among scientists, public health officials, health regulators, the corporate community and the general public. All share an earnest desire that the causes of these diseases be elucidated, that effective treatments or preventive measures be developed, and that individual risks be substantially reduced or eliminated. However, the achievement of these objectives can only follow the acquisition of the requisite

i etiological knowledge and the subsequent formulation of clinical and public policies taking the ne!w knowledge into account. Regulatory.actions-.initiated on any.basis other than that of the hard facts, however well intentioned, must inevitably fail. - -At a time like the present, when good health is widely regarded as a right rather than a privilege, activism by individuals or political bodies responding to public pressures is not uncommon. It is fair to say that activist efforts sometimes even succeed in changincf established government policies, typically diverting f'unds and public attention from one disease or condition to another of more current interest. AIDS, asbestos-related disease, DES, saccharine, the Dalkon Shield, and the lat:est neoplasm befalling a prominent public figure are among examples that may be cited. In recent years, environmental tobacco smoke has attained similar notoriety as a controversial issue raised to an intensely high level of public concern through activist pressure, media attention, and the subsequent reactions of governmental agencies and other public bodies. The EPA document is described in its preface as "intended to be useful for a diverse audience including: decision makers such as labor and management officials con-cerned with workplace exposures, public health officials and corporate•medical directors who are concerned with making health policy recommendations, educators, industrial hygienists and safety officers, ETS researchers, indoor air

pollution investigators and legislators who are considering legislation to restrict smoking in workplaces, restaurants and public access.buildings . . . . It is hoped that the technical information in this document, written by experts in the field, will provide information necessary to allow the public, government agencies, and the building industry, to make well-informed choices regarding exposure to ETS." Implicit in this statement is that the facts concerning the relationship between envircnmental tobacco smoke and cancer have been fully established and that public policy can now be modified to take these facts into account. Accordingly, the statement is addressed tc scientists, educators, public health officials, corporations and legislators, whose cooperation would be required to implement changes in health policy regarding environmental tobacco smoke and cancer. In reality, definitive or even reasonably convincing evidence on the biological relationship between passive exposure to environmental tobacco smoke ard cancer has not been assembled. There are no conclusive facts for the biomedical scientist to consider, for the public health official to regulate, for Corporate America to acknowledge or for the general public to understand. In no way can evidence of the quality presently available enable interested parties "to make we11-;informed choices regarding exposure to ETS". In fact, the author of Chapter 4 freely admits to the limitations of the evidence, including-substantial deficiencies in-most of

the published studies. The reader is therefore quite unprepared for the author's ultimate agreement with the conclusions of the three consensus confere!nces of.the World Health Organization, the National Research Council, and the Office of the U.S. Surgeon General, conclusions which ignore the scientific evidence in a rush to consensus. The general public is, by and large, ignorant of the methods of epidemiologic study, particularly the manner in which these differ from the experiments of basic medical scientists. In the laboratory, the reactions of biologically identical animal clones exposed and unexposed to a test - treatment are compared. The results serve as the basis on which to accept or reject the scientific hypothesis in question. By way of contrast, the epidem'.ologist studies heterogeneous human subjects, facing almost insurmountable ethical and judgmental problems in exposing them to the test treatment and other essentially unavoidab:.e methodological difficulties: At the completion of the si:udy, the laboratory scientist can attribute the experimental outcome to the test treatment without undue concern for methodological bias or confounding by the subject's gender, prior disease history, behavior, diet, environment, methods of selection, motivation or extent of cooperation. On the other hand, the epidemiologist is usually left with these problems incompletely resolved and thus confronts .influential roadblocks to a full understanding of the biological significance of the investigation. The basic problem.-of the

laboratory scientist is generalizing the-.experimental...- conclusions from the test animals to man. The fundamental prQblem of the epidemiologist -is deriving:-scientifically."- justified conclusions on the biological phenomena that are being studied. The "significance" alluded to throughout the chapter is statistical rather than biological, anc the critical distinction between the two should not be ignored. It can be affected by the number of cases studied ar.d the appropriateness of the statistical test us.ed as well as by the underlying biological reality under investigation. Most of the cited studies are deficient in respect to the - representativeness of the cases and controls utilized. None has resolved the basic problem of defininci ETS and measuring it quantitatively in human subjects who m<<y be exposed at home, at work, and at leisure throughout t:heir lifetime. Most fail to show a dose-response relationship between ETS and cancer, and odds'ratios are not often greater than 2.0, i.e., well within the range of biological insignificance as understood by experienced epidemiologists, Some of the studies do not take into account the histopathological distinctions of lung neoplasms, each of which may be subject to a specific etiology. Response rates anong the human subjects, an important desideratum for evaluating all epidemiological studies, are poorly documented in a number of the studies.

L, The author's discussion.of the epidemiologic literature on environmental tobacco smoke and lung cancer is reasonable and objective. He is forthright in pointing-out many deficiencies and limitations in the existing studies. His conclusion that there is a proven eticlogical relationship between lung cancer and environmental tobacco smoke therefore follows almost as a non sequitur. For example, a large paragraph is devoted to the study of Hirayama and its limitations which have been widely discussed, debated and publicized. An objective reader could not reasonably conclude that such a study contributes substantialiy to the positive evidence on the relationship between environmental tobacco smoke and lung cancer. The same applies to all of the other published studies which are flawed to one extent or another. By no means are these comments intended as, an indictment of Hirayama's study or those of the other investigators cited in this chapter. Epidemiological studies are notoriously susceptible to methodological difficulties because of their reliance on the voluntary participation of' human subjects. One must retain a modicum of understandincl for these difficulties while, at the same time, insisting upon objectivity with respect to any causal inferences that are adduced from the studies. None of the investigations cited in the chapter are capable of serving as a sulid scientific foundation fof the conclusion.that environmental tobacco smoke ik' O'f` ~ .l is etiologically related to lung cancer. If this,is true of the individual. studies, it is also--true -of: all:, of =the studies W CD

considered jointly, notwithstanding the claims of the meta-analysis. It has been noted that the.author relies substantially on the conclusions of panels commissioned by three public bodies (the World Health Organization, the National Research Council, and the U.S. Surgeon General's Office ) to buttress his evidentiary argument. The conferences which generated these reports were consensual and quasi-political rather than unequivocally scientific. This brings to mind an earlier conference sponsored by a worldwide health organization on the prevention and control of cervical cancer. For reasons having nothing to do with the scientific issue at hand, the panel members were informed that exfoliative cystological screening for ceivical cancer prevention could not be recommended in the final document. Accordingly, the members deliberated for three days on techniques for controlling or preventing cervical cancer without being able to discuss the technique which has been proven the most effective, viz. the Pap Smear. Those in attendance at the three ETS conferences understood the need to arrive at consensual recommendations aimed primarily at public health action (i.e. disease prevention) rather than at scientific elucidation of the etiological agents. The author's comment that "consensus among the thre'e groups in spite of differ'_ng-methodology, stresses the determination that involuntary smoking causes lung cancer'.' is unconvincing if only because=the panels-did

i not organize themselves primarily as scientists seeking. truths, but rather as synthesizers of existing information and supporters of public health measures in the absence of definitive scientific truths. The World Health Organization "reached its conclusion. . . largely on the basis of b'_ological plausibility". The National Research Council "based its views on a pooled analysis of the epidemiological data adjusted for . bias." The U.S. Surgeon General's conclusion "was based on the extensive information already availab:=e". These bodies were limited in their deliberations by the studies available to them, with all of their inherent diver:aity, variability, and inconsistency. None of the three consensus reports adds new information to the issue at hand. The author concedes that "the published epidemiological studies provide varying and imprecise measures of the risk, and that exposures to environmental tobacco smoke have not been characterized for large and representative population samples." Clearly risk assessments for involuntary smoking•and lung cancer are subject to substantial uncertainty. Scientists are-comfortable working in uncertainty, and their studies are designed to reduce the degree of uncertainty. On the other hand, decision-making public bodies are unaccustomed to working with uncertainty which, by their nature, they attempt to minimize in order to achieve consensus on the policy and regulatory outcomes of their daliberations. It is in this context that one-may understand-tie-implications-of

the author's statement that-"while_the results-of these new- studies will provide needed information fcr scientific purposes, the available data-and the conclusions of-the scientific community already provide a conpelling rationale for reducing involuntary exposure to environmental tobacco smoke." In other words, while it is essentially conceded that the hard biological evidence is not at hand, it is deemed prudent at the level of the lay public to conclude that indirect tobacco smoke is a cause of lung cancer. Many scientists, especially those concerned with the scientific facts rather than with serving the needs cf public health activism, would insist that prudence (or Folitics) should not play a decisive role in biomedical research. The evidence on involuntary smoking and cancer at sites other than the lung is, by the authcr's own statement, extremely weak: "Associations of involuntary smoking with cancer at diverse sites cannot be readily supported with arguments for biological plausibility." in other words, except for the lung, the author concedes that substantial evidence on associations of passive smokir.g with neoplasms does not now exist.

CRITIQUE OF THE REPORT ENTITLED Environmental Tobacco Smoke:. A Compendium of Technical Information U.S. Environmental Protection Agency Chapters 5-8 Prepared by: Mark J. Reasor, Ph.D. , L 7 Ii I received the B.S. (1967) and M.A. (1969) degrees in Biochemistry from Purdue and Duke Universities, respectively. I received the Ph.D. degree in Biochemical _Toxi-cology from <the.-Johns =Hopkins--Univers~.ty in 1975. In 1975-76, I performed postdoctoral work in pharmacology- at the National Institute of Environmental Health Sciences, North Carolina. I then became an Assistant Proi:essor of Pharmacology and Toxicology at West Virginia University in 1976, and achieved tenure at that institui:ion in 1984. I am certified in general toxicology by the American Board of Toxicology. Since 1969, I have published 66 research articles in the fields of pharmacology and toxicology. I am an Editorial Board member of Toxicology and Applied Pharmacology, an .official journal of the Society of Toxicology, and am an Associate Editor of Journal of Toxicology and Environmental Health. I have published one book chapter and one review article on environmental tobacco smoke: (1) Biological markers in assessing exposure to environmental tobacco smoke. In: Environmental Tobacco-Smoke: Proceedings_.of the

- 2 - International Symposium at..McGi11 UniversiLy (D. Ecobichon-.and J.M. Wu, eds.), Lexington Books, Lexington, MA, pp. 69-77, 1990; (2) The composition and dynamics-of environmental tobacco smoke. J. Environ. Health 50: 20-24, 1987. A copy of my curriculum vitae is attached. I have been asked to review Chapters Five through Eight of an EPA draft compendium of technical literature on environmental tobacco smoke. OVERVIEW •As•presented, the four chapters addressing aspects of exposure to ETS do not effectively present the issues associated with this topic. This is due, in part, to the omission of cer,tain information and redundancy among the chapters. One way to remedy this situation would be to reorganize this section with the addition of another chapter. A suggested framework for this reorganization is presented in this introductory overview. The remaining sections of this critique will provide specific comments on individual chapters. The first chapter in the series on exposure should be concerned with the chemical compositiorr of ETS. This chapter would provide a basis for discussing the issues related to exposure. Without an appreciation of the problems inherent in analyzing the composition and properties of ETS, a discussion of the assessment of exposure cannot be fully evaluated. Aspects of composition are sczttered throughout - ob. T ~ N ~ rA ~A

- 3 - r i J LI the four chapters-; thus. the -reader never- iecei-ves :a comprehensive analysis of the subject. Azeas that should be- discussed include the-results and limitations-of controlled laboratory studies examining sidestream smoke as a surrogate for ETS, a critique of the use of mainstream to sidestream smoke ratios in the comparison of exposure to ETS with active smoking, and field studies on the composition of ETS. The role of aging in determining the chemical composition and particle sizes of ETS should also be carefully considered. A chapter examining the significance of ETS in indoor air pollution-should be the second chapter in the series. This chapter should include a more general discussion of indoor air pollution, in which the overall contribution of ETS is put in a proper perspective.. Chapter 6, "Exposure to Air Pollutants," does not succeed in this respect; the chapter's singular focus on ETS gives the reader the impression that it is the only significant: source of indoor air pollution. The chapter on "Measuring Exposure to Environmental Tobacco Smoke" would follow, expanded to provide an in-depth discussion of the problems inherent in specifically measuring exposure to ETS. Considerations of poteni:ial airborne markers and their limitations, proper experimenta:L design, and appropriate equipment to measure the various ETS constituents should be included. At present, Chapter !i does only a fair job on part of this topic.

- 4 - f- I Next, the Compendium-,might- include--a-chapter- on - mathematical modeling, which may present a usefuI approach to exposure estimation under appropriate.cirtumstances:- However,-. the contribution of this approach to a better understanding of ETS exposure can only be assessed if the limitations of modeling are clearly discussed. At present, Chapter 7 fails to address these limitations, particularly the heavy reliance on existing data and the necessity of making certain assumptions of questionable validity. As presented, Chapter 7 should be retitled to more correctly reflect the nature of the material_presented. -For example, a title of "Assessment of Exposure to ETS: Use of Mathematical Mode!ls" is more - descriptive of the author's presentation. The final chapter of this section would discuss the use of biological markers for assessing exposure to ETS. The present Chapter 8 provides a good general overview of the subject, but the evaluation of the literature could be more comprehensive. Overall, I found the chapters superficial in places, somewhat redundant (particularly regardin(.1 the composition of ETS and the use of biological markers),*contradictory on certain topics (use of carbon monoxide as a marker for ETS: Chaps. 5 & 6; use of cigarette equivalents: Chaps. 6 & 8), and not very effective in achieving the goal stated in the title of the document. The individual chapters were of widely varying quality, and except for Chapter 5 and parts of Chapter 8, did a poo-r job- of present-ing,a balanced==ana1_ys-is.-of- the--

- 5 - issues. At the least, each :chapter- shoul9.=contain-.a. section..- dealing with future needs to give the rea9er an idea of where deficiencies exist and how-they can-be ad3ressed.-.With these general comments in.mind, the following.discussion-will focus on the problems associated with each chapter. Suggestions for improvements will be made where appropriate. The page on which an item of attention is located will be noted in brackets, e.g., [p.54]. Additional relevant references will be cited at the end of the discussion of each chapter. C<~S

- 6 - Chapter 5 Measuring Exposure to Environmental Tobacco Smoke Br.ian P. Leaderer In general, Dr. Leaderer presents a reasonably balanced analysis of this topic. In particular, he is careful to list the limitations associated with the use of certain substances as markers for ETS. The author should discuss and reference recent studies from the laboratcry of Dr. Delbert Eatough (Eatough et al., 1989, 1990; Tang et al., 1988) that - have-, examined:tobacco-specific chemicals Euch as solanesol, 3-ethenylpyridine, and particulate phase ricotine, for_use as markers. These are significant studies ir this field, and should be thoroughly reviewed in any chapter on exposure. Eatough et al. utilized 'the annular denuder system for measuring vapor phase nicotine; therefore, in light of the discussion on this technique [p.62], the <<uthor should be familiar.with this research. Ultraviolet particulate matter (UV-PM) may have value in monitoring the particulate phase of ETS (Carson and Erikson, 1988). The use of tobacco-specific nitrosamines as markers For ETS would be of particular value because of their potential health effects, However, they have not been detected in room air (Klus et al,, 1985). - Personal monitoring can provide an integrated measure of an•individual's exposure since all of the material collected by a sampler is retained for analysis. In contrast to what the author states [p.54], biomarkers- are not

- 7 - necessarily effective in providing= an--integrated-measure of - exposure. Since biomarkers decay with time from tissue and fluids, a person heavily exposed to an airborne contaminant- may show no detectable level of the biomarker if sampling occurs long after exposure is terminated. In this circumstance, an integrated measure of exposure would be impossible to obtain. In general, statements made by the author could be better referenced. For example, in Table 1, it would be valuable to provide citations of studies ahere these --techniques formeasur-ing-RSP have been used. This would enable the interested reader to evaluate the statement that all of the methods have been used with success in chamber and field studies [p. 60-61]. By referencing articles, it would be possible to obtain more detailed technical information on the technique. A general problem throughout the chapter in evaluating statements was that no references were included in the copy I received. REFERENCES Carson JR and Erikson CA: results from survey of environmental tobacco smoke in offices in Ottawa, Ontario. Environ. Tech. Lett. 9: 501-508, 1988. Eatough DJ, Benner CH, Bayona JM, Richards G, Lamb JD, Lee ML, Lewis EA, and Hansen LD: Chemical composition of. environmental tobacco smoke. I. Gas--phase acids and - bases. Environ. Sci. Technol. 23:, 679-687, 1989. Eatough D.J.,•Hansen LD, and Lewis EA: The chemical characterization of environmental tobacco smoke in Environmental Tobacco Smoke, Proceed'.ngs of the International Symposium at McGill Un:.versity of 1989, Ecobichon DJ and--Wu-JM, edi-tors-, Lex'..ngton--Books, DC-- Health and Co., Lexington, Mass., pp,. 3-50, 1990

- 8 - Klus H, Begutter H, Nowak A, Pinterits= G, -Ult-sch-, •and •Wihli~dal- H: Indoor air pollution due to tobacco smoke under real conditions. Preliminary results. Tokai J. Exp. Med. 10: 331-340, 1985. Tang H, Richards G., Gunther K, Crawford J, Lee ML, Lewis EA, and Eatough DJ: Determination of ga:>-phase nicotine and 3-ethenylpyridine and particulate phase nicotine in environmental tobacco smoke with a collection bed capillary gas chromatography system. J. High Resol. Chromat. Chromat. Commun. 11: 775-782, 1988. ~..

- 9 - I i Chapter..6 Exposure to Air Pollutants John McCarthy,_ Elizabeth Miesner,.arid -John Spengler.- This chapter does not present a balanced picture of the subject. The title of the chapter is misleading; the authors do not discuss exposure to air pollutants, rather they limit their presentation to ETS. The reader does not obtain an impression of the relationship of ETS to the overall problem of indoor air pollutants. In fact:, as Dr. Spengler has discussed in a previous publication (;tpengler and Sexton, 1983),.indoor.air pollution,can arise from a multitude of sources. The authors should be encouraged to discuss this relationship in an effort to provide a more balanced pre- sentation of the topic. The authors do not discuss the ].imitations or qualifications associated with the statements they make on a number of issues. For example, their discussion of the composition of ETS [p. 76] is much too siriplistic and misleading. The studies and values cited in Table 3 relate to freshly generated sidestream smoke and noi: to ETS. It is also important to point out that these values were generated under .standardized laboratory conditions and may have little relationship to ETS as it exists in the arabient environment. The-reasons for this include: 1) ETS is composed of both sidestream smo,ke and exhaled mainstream smoke, the latter of which has not been characterized. The re:lative contribution of each of these types.of-smoke to ETS-has not-been.measured - c.r

under laboratory or ambient_conditions; and 2) the process of= aging markedly affects the composition-of ETS, making simple sidestream smoke. values -difficult, if not impossible-,--to interpret. The aging of ETS should be discussed in detail, since an appreciation of this process is essential in -evaluating da,ta on ETS. For example, Pritchard et al., (1988) reported that a significant fraction of the particulate matter in ETS evaporates under ambient conditions. Benner et al., (1989), reported that particles in ETS -coagulate as they age. Tang et al., (1988),•=demonstrated that constituents of ETS decay at different rates in a ventilated indoor laboratory. Also, ultraviolet light caused marked changes in the phase distribution of nicotine in ETS. Vu Duc and Huynh (1987) observed that the half-lives of particles from sidestream smoke vary as a function of size. It should follow that an additional problem is the use and interpretation of ratios of sidestream smoke to mainstream smoke to compare levels of chemicals in each type of smoke. Considering the problems of using sidestream smoke as a surrogate for ETS, such values are virtually meaningless. Furthermore, the amounts of each type of smoke generated are dependent on the smoking patterns of individuals; the deeper the inhalation (leading to increased deposition) and the more frequent the puff ( leading to increased production.of mainstream smoke), the less ETS will be generated from a cigarette. I

i ; i _: For the_ sake o£-balance-,--the-_aul;.hor-s..-should--discuss._ the published studies indicating that ETS does not appear to make a major contr-ibution-to indoor~air pollution.: In studies in the United States and Canada, Sterling et al., (1987-) and Sterling and Mueller, (1988) concluded that ETS does not make a significant contribution to either indoor air quality or health and comfort symptoms associ-ated with the "sick building syndrome." Since 1978, NIOSH has conducted numerous investigations of buildings with health and comfort complaints. Nearly half of the complaints were associated with-,;i-nadequate,ventilation (Mehlius et al., 1984). Only 2% of the complaints involved ETS. _ Another problem area is the sec:ion in which the authors present data on levels of RSP in homes [p.68-69]. What conclusions are to be drawn from the results of these studies? In the article by Spengler et aL., (1981), the actual amount of smoking was not reported, thus the reader has no way of assessing the limitations of the conclusions regarding levels of RSP per smoker. It would be appropriate for the authors to discuss problems in interpreting such data, and to indicate how particular levels relate to health effects. Certain conclusions in the Summary section are not supported by information presented in the text or in the literature. For example, the statement that "Environmental ~ tobacco smoke is the primary contaminant causing elevated RSP C?~ ~ levels in enclosed spaces.°- is too-absolute-:- A more-accu-rate- .F _tV ~ U1 W

~1d statement would_be "In enclosed spac.es--in which smoking occurs,. ETS may be a major cause of elevated RSP levels." Certainly, there are many enclosed spaces in which ETS makes- no contribution to RSP because smoking is not occurring. Even where smoking does occur, not all studies have been properly controlled to permit such an absolute statement. For example, in the study by Weber and Fisher (1980) cited by the authors, baseline values of particles were determined at a time when the rooms were unoccupied. These values ;aere subtracted from values obtained when the rooms were occupied and smoking was occurring. -To control for particles generated by occupancy, the proper condition to establish the baseline is wherL the only variable is the occurrence of smoking. Occupancy and other human activity should be the same during the baseline and experimental conditions. In summary statement #2, the authors are in conflict with the conclusions of Dr. Leaderer in Chapter 5[p.56]. Evidence has•not been provided which allows this statement to be made. In fact, it is well established that carbon monoxide levels do not change very much due to ETS (Carson and Erikson, 1988; Hugod, 1985; Proctor, 1988; Sterling and Mueller, 1988). None of the other chemicals mentioned in the statement have been•studied thoroughly enough to support this conclusion. If the authors have references in support of these statements, they should be provided. Generally, the authors should te more comprehensive in citings references for statemen.ts- they make- throughout- the; -

LJ chapter. Further.,. there -are several point:s.-.on_ whi-ch_ .the - authors have presented inappropriate information, not . thoroughly referenced- statements, or have.-cited --studies -thart are not contemporary and omitted those that are contemporary. For example, inclusion of the work by Wallace et al. (1987), [p.71], is inappropriate, since that study's conclusion that cigarettes are a major source of benzene is relevant only to active smoking and not e:cposure to ETS. Another example is the citation to Dzubay and Stevens, 1975, as support for the statement that at leasi: 75$ of the sulfur, zinc,-bromide-and lead are •found •in the s:.ze range of <2.5 um. [p.66]. Based on one reference from that long.ago, it_ is not valid to make such a definitive statement. It is not clear that the data collected in 1981 and presented in Figure 3 are an accurate ref:lection of present exposure conditions [p.68]. Since this document deals with. technical information, it would be an app::opriate place to discuss the proper experimental design fo:- studies measuring the contribution of ETS to RSP or any other constituent of indoor air. For example, as mentioned ea:lier, the proper controls in such studies should be measurements in the same environment with the same number of peopl,2 and the same level of activity, but with no smoking occurring. It is appropriate to critique the studies of Weber and Fiscler, (1980) [p.69], Quant et al.,'(1982) [p.69], and others on the basis of design flaws, and to question the conclusions that can be drawn if proper experimental design is not utilize3-.-

,J A number. of articles more recent -than those- cited--in - Tables 5 and 6 have been reported where particulates and nicotine have been measured under--realist_i::-conditions: For- example: Sterling et al., 1987; Mattson et al, 1989; Henderson et al., 1989; Sterling and Mueller, 1988. These articles should be cited and reviewed. Comments on future directions that should be taken in this area would be appropriate. REFERENCES L .Benner CL,.--Bayona JM, Caka FM, Tang H, Lewis L, Crawford J, Lamb JD, Lee ML, Lewis EA, Hansen LD, and Eatough DJ: Chemical composition of environmental tobacco smoke. 2. Particulate-phase compounds. Environ. Sci. Technol. 23, 688-698, 1989. - Carson JR and Erikson CA: Results from survey of environ- mental tobacco smoke in offices in Ottawa, Ontario. Environ. Tech. Lett. 9: 501-508, 1988. Eatough DJ, Hansen LD, and Lewis EA: The chemical characterization of environmental tobacco smoke in Environmental Tobacco Smoke, Proceedings of the International Symposium at McGill University 1989, Ecobichon DJ and Wu JM, editors, Lexington Books, DC Heath and Co., Lexington, Mass. pp. 3-50, 1990. Henderson FW, Reid HF, Morris R, Wang O-L, Hu Pc, Helms RW, Forehand L, Mumford J, Lewtas J, Haley NJ, and Hammond SK: Home air nicotine levels and urinary cotinine excretion in preschool children. Am. Rev. Resp. Dis. 140: 197-201, 1989. Hugod C: Exposure to smoke constituents by passive smoking. Tokai. J. Exp. Med. 10: 401-405, 1985. Mattson ME, Boyd G, Byar D, Brown C, Callahan JF, Corle D, Cullen JW, Greenblatt J, Haley NJ, Hammond SK, Lewtas J, and Reves.W: Passive smoking on commercial airline flights. JAMA 261: 867-872, 1989. Mehlius J, Walingford R, Keenlyside R, et. al.: Indoor air quality; the NIOSH experience.- Meeting-of -the-=American-= - Congress of Government Hygienists, 1984.

Muramatsu M, Umemura S,.Fukui_J-, Arai T, and-Kira S: Estimation of personal exposure to ambient nicotine in daily environment. Int. Arch. Occup. Environ. Health 59: 545-550, 1987. Pritchard JN, Black A, and McAughey JJ: The physical behavior of sidestream tobacco smoke under ambient conditions. Environ. Tech. Lett. 9: 545-552, 1988. Spengler JD and Sexton K: Indoor air pollution: A public health perspective. Science 221: 9-17, 1983. Sterling TD, Collet CW and Sterling EM: Environmental tobacco smoke and indoor air quality in modern office work environments, J. Occup. Med. 57-62, 1987. Sterling TD and Mueller B: Concentrations of nicotine, RSP, CO and CO in nonsmoking areas of offices ventilated by air recirgulated from smoking designated areas. Am. Ind. Eya. Assoc. J. 49: 423-426, 1988. Vu Duc TV and Huynh CK: Deposition rates of sidestream smoke particles in an experimental chamber. Toxicol. Lett. 35: 59, 1987.

Chapter 7 Exposure Assessment in Passive! Smoking James L. Repace---- {1 In this Chapter, the author relies extensively on modeling to assess exposure to ETS. While modeling may be useful under appropriate circumstances, the author's approach to it here oversimplifies a complex exposure problem. For the presentation to be balanced, it should be pointed out that there are limitations to modeling, such as the heavy reliance on published data and the need to make nurierous assumptions that might not be valid. The lack of qua:.ifications gives the reader a misleading impression of the nature of such an approach. In many instances, the author has relied on reviews of the literature, such as the reports by the Surgeon General, the National Research Council and IARC. ~'he primary literature sources, rather than these rev::ews, should be cited. The statement is made that ETS :Ls the dominant contributor to indoor levels of RSP [p.801. What is the evidence to support that statement? A mo:-e correct statement would be "that in certain indoor environments, ETS may be the dominant contributor to RSP levels." A strong case can be made that RSP is not the best measure of air contamination due to ETS []?.80], principally due to its lack of specificity for ETS. Nicotine may be a better marker because of its tobacco-specificity and ease of measurement (Eatough et al., 1990). However, because of its U

r Lii rapid decay during ag.ing,_ severe limitationsn exist. in the.use_= of nicotine as a surrogate for ETS (Eatoucih et al., 1990). It is-not clear that the author is correct in assuming that it is almost impossible for nonsmokers to avoid some exposure to ETS, [p.80). This is too strong of a generalization. While there may be some data to support this statement, it is clear that many nonsmokers can avoid exposure to ETS, particularly with all of the present smoking restric- tions. For a balanced presentation, the ZLuthor should cite and discuss other work that indicates that, ETS may not contribute significantly to indoor RSP (Sterling et al., 1987). In places, the author relies on data that were obtained as long as 20 years ago. For exzimple, the author cites a 1970 reference to support an assertion about the number of homes containing children and smokers [p.86]. There is no reason to-believe that these figures are accurate, particularly•with the decline in cigarette! smoking. The author should cite more contemporary research in this area or qualify his statements. The same comments apply to the data in Table 10. A number of publications have ai:tempted to quantitatively compare exposure to ETS wit:h that of active smoking through the use of "cigarette equ:.valents." While alluding to the limitations of using such a value, the author should comment more thoroughly on the ovel-a11 validity of this concept in order-to have a balanced presentation-of the -

r subject [p.89].. Cons.ideri-ng-the-chemical complexity and.. dynamics of ETS, the concept of cigarette equivalents has little util.ity. This is particularly true when-.values are based upon a single component of ETS such as nicotine or cotinine levels in biological fluids. The presentation contains a numter of misleading statements, assumptions, and omissions. For example, in contrast to what the author claims [p.89], there is evidence that nicotine is cleared from the body at different rates in smokers and nonsmokers (Kyerematen et al., 1982). Further, in addressing:the use of-nicotine as a marker for ETS exposure [p.89], the author states that "it has been calculated- that a nonsmoker would inhale volatile nitrosamires equivalent to 10 nonfilter cigarettes or 35 filter cigaretts." The term "calculated" implies that there is no question of the validity of the data from which the calculations were made. The term "estimated" would be more accurate here since the data being relied on are only estimates to begin with. It is also inappropriate for the author to use the term "typical nonsmoker" in making generalizations about: body burden nicotine [p. 91-92]. A more accurate typology would be "nonsmokers who work with smokers." Another example is the author's use of the term "ETS carcinogens" [p.92]. This statement assumes that ETS is carcinogenic, but this has not been proven. Finally, the citation for Kuller et al., (1986) [p.90] should be provided.

It would- als-o- be useful. to incLx,de:-a sect.i.on.-on- future needs in this area. REFERENCES Eatough DJ, Hansen LD, and Lewis EA: The chemical characterization of environmental tobacco smoke in Environmental Tobacco Smoke, Proceedings of the International Symposium at McGill University 1989, Ecobichon DJ and Wu JM, editors, Lexington Books, DC Heath and Co., Lexington, Mass. pp. 3-50, 1990. Kyetematen GA, Damiano MD, Dvorchik BHT, and Vessell ES: Smoking-induced changes in nicotine disposition: Application of a new HPLC assay for nicotine and its metabolites. Clin. Pharmacol. Ther. 32: 769-780, 1982. Sterling TD, Collet CW and Sterling EM: F,nvironmental tobacco smoke -and -indoor air quality in modern office work environments, J. Occup. Med. 57--62, 1987. - t

E: Chapter 8 Absorption of Smoke Constituents by Nonsmokers Dietrich Hoffmann, Klaus- D. Brunnemann; and:=Nancy J. Haley The authors have presented a reasonably balanced discussion of the use of biological marke::s in the assessment of exposure to ETS. Several points should be expanded upon or clarified in order to more completely evaluate the authors' statements. These will be addressed in the following para- graphs. The authors have not provided a citation in support of their statement that exhaled mainstream smoke makes few contribution to ETS [p. 95]. In fact, there are little quantitative data on which to base any co-iclusions on this question. For example, the more frequent the puffs and the more shallow the inhalation (the less deposition), the larger the contribution of exhaled mainstream smoke to ETS. Additionally, the type of tobacco being s:noked will influence the contributions of each. The authors snould acknowledge the fact that little information exists in this area. The authors should more fully discuss the problems associated with interlaboratory comparisons of nicotine and cotinine in human serum and urine as presented in the ref-erence by Biber et al. [p.98]. These investigators found that absolute_,values for these parameters show large interlaboratory variations which are particularly high in the samples from subjects exposed to ETS. In addition, in another study (Letzel et al., 1987), it was reported that estimating

low level ETS exposure_by._measur-ing urinary_:_cotinine..is highly-._ susceptible to-uncontrolled-variations and errors. In light of these problems; standardization of procedures and Ii methodology would permit more meaningful correlations to be established among various studies. If the authors are making the point that there is a relationship between urinary nicotine/cotinine levels in infants and respiratory infections, they r:eed to discuss the link more clearly [p.100). They also neecd to discuss the limitations of such studies. For example, both prenatal .exposure-from,women-who=smoke dur-ing pregnancy and exposure to tobacco-derived chemicals during breast feeding are substantial confounding factors. Unless exposure through these routes can be ruled out, interpretat.ion of studies involving infants may be difficult. The authors do not make a clear case for the significance of genotoxicity in physiological fluids [p.104], particularly•at the low levels of activity that have been reported. There is no evidence that bacterial mutagens in the urine at such low levels are a reflection of any health consequences, particularly cancer. What evidence is there that the refinements presented in refs. 86 & 88 will enable more sensitive measurements of urine to be made [p.104]? Further, it is an unwarranted as,sumption that upon refinements of the methodology, the assay for urinary mutagenicity will reflect the uptake of genotoxic ETS constituents by nonsmokers.-= As

- 22 - the urine of involuntary smokers can already be.assayed for genotoxic agents, the last sentence of this paragraph does not represent what the authors-intend: - The authors should discuss the strengths and weak- nesses associated with the use of macromolecular adducts in assessing exposure to ETS [p. 104j. A potential advantage of such a marker in blood or tissue is the atility to monitor exposure on a more chronic basis than witt other markers (e.g., hemoglobin his a lifespan of 120 days). However, cessation of smoking in humans (Bryant et al., 1987) or termination of:e_xposure of-animals to carcinogens (Belinsky et al. 1986), results in a more rapid loss of adducts than would be expected, making their value in monitoiing long-term exposure questionable. A problem with studies using BaFl or 4-aminobiphenyl adducts is that neither is tobacco-specific. Since alleged increases in adduct formation are quite small in persons exposed to ETS (Maclure et al. 1989; Perera et al., 1987), it is not possible to state, with certainty, that the adduct arose from ETS. A similar lack of specificity exists in the use of hemoglobin adducts of alkenes as an assessment of exposure to ETS (Persson et al., 1988). A more useful approach would be to have a DNA or protein adduct originating from a tobacco--specific chemical. NNK, a nitrosation product of nicotine, has been shown to form DNA and protein adducts when injected into animals (Hecht and Trushin,--19.88). Measurement- of. the methy:iguanine.= and -_

- 23 - f 7-methylguanine_moieties occu.r.ring- in-.tissues- or. -cells-may--be useful in assessing exposure to NNK and ETS. Nicotine is bioactivated to a species that binds macromolecules (Shigenaga et al., 1988). Little information exists as to the feasibility of using nicotine-derived adducts to monitor exposure to ETS. Finally, it is not appropriate to cite unpublished and non-peer reviewed data to support a pcint [p.99, Haley]. REFERENCES -Belinsky SA, White CM, Boucheron J, Richardson FC, Swenberg J and Anderson MA: Accumulation and persistence of DNA adducts in respiratory tissue of rats following multiple administrations of the tobacco-specific carcinogen 4-(N-methyl-N-nitrosoamino)-1-(3-pyridyl)-1-butanone. Cancer 46: 1280-1284, 1986. Bryant, M. et al.: Hemoglobin Adducts of 4-Aminoloiphenyl in Smokers and Nonsmokers. Cancer Research 47: 602-608, 1987. Hecht SS and Trushin N: DNA and hemoglobin alkylation by 4-(methylnitresamino)1-(3-pyridyl)-1-butanone and its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanol'in F344 rats. Carcinogenesis9: 1665-1668, 1988. Letzel H, Fischer-Brandies A, Johnson LC, Uberla K, and Biber A: Measuring problems in estimating the exposure to passive smoking using the excretion of cotinine. Toxicol. Lett. 35: 35-44, 1987. Maclure, M., et al.: Elevated Blood Levels of Carcinogens in Passive Smokers. A.J.P.H. 79: 1381-]384, 1989. Perera FP, Santella RM, Brenner D, Poirier MC, Munshi AA, Fischman NH, and Van Ryzin J: DNA aciducts, protein adducts and sister chromatid exchange! in cigarette smokers and nonsmokers J. Nat. Cancer 79: 449-456, 1987. Persson KA, Berg S, Tornqvist M, Scalia-Tomba G-P, and Ehrenberg L: Note on ethene and othE!r low molecular weight hydrocarbons in environmental tobacco smoked. Acta Chem. Scand. 42: 690-698, 1988.

- 24 - Shigenaga MK,..Trevor.-AJ, and Castagnoli N,. Jr.:. Metabolism-dependent covalent bindinq of (S)[5-H] nicotine to liver and lung microsoma:. macromolecules. Drug Metab., Dispos. 16: 397-402, 19F38.

ENVIRONMENTAL TOBACCO SMOKE: A COMPENDIUM OF TECHNICAL INFORMATION Technical Review - Michae). W. nrrden, Ph.^= Chapters 5 ("Measuring Exposure to Environnu.ntal Tobacco Smoke"), 6 ("Exposures to Air Pollutants"), and 7("]sxposure Assessment in Passive Smoking") all deal with essentia:lly the same subject matter. Although the approaches taken represent the various author's individual viewpoints, it would be in the best interest of this Compendium to combine these three chapters into one comprehensive review of "Exposure to Environmental Tobacco Smoke". This reviewer will address each chapter individually with emphasis on omissions, redundancies, and cnntradictio:«s. - Chapter 5 - "Measuring Exposure to Environmontal Tobacco Sraokell Chapter 5 is in a form which makes it 3ifficult to review adequately. Specifically, there are numerous misspellings, incomplete or awkward sentences, and the list of literature references is unavailable. The subject matter of biomarkers is not really.addressed at all. The limitations of nicotine and RSP are not adequately portrayed. There are ways to make RSP a much more useful marker of ETS: through the use of apportionment techniques such a~= t::e published methods tor UVPM (ultraviolet particulate * matter, references" below) and solanesol ( j73 ]..and references below) and the presented but not yet published method for FPM (fluorescent * particulate matter) [751. At a minimum, the pul:)lished methods must *"[]" refers to Chaps. 5-8 Index.

6 t. i be included. p. 53 - The opening sentence is misleading. It st?*_p-- that measuring exposure to ETS is an exact science when in fact it can only be estimated. Replace "assessing" with "estimating". p. 54 - The author states that "models can be developed. and validated to predict concentration" implying that this has been done. This reviewer knows of no adequately validated models for this purpose, including those referenced in Chapter 7. p. 55 - The opening sentence is misleading. It states that "(ETS) is -a complex mix of over 4,000 air contaminantF". This is speculation based on what is known about mainstream and sidestream tobacco smoke. Nowhere near 4,000 tobacco smcke derived components have ever been measured at true ETS concentrations. In fact, this reviewer is unaware of more than 100 or so. p. 56 - Although RSP and nicotine are widely used as markers, this chapter (indeed, all three chapters) neads to address the appropriateness of their use. The author states they are used because of "their relationship to other ETS contaminants". This reviewer is unclear as to what is meant by this statement, when in . _ ~b ~ appropriate documentation. ~ ~ tJ ~ ~ p. 57 - "The EPA standard is for particle mass, 10 µm." What does ~ fact,-the relationship between nicotine and PSP is highly variable across environments Thi!z section needs eiaboration with 2

i [l this mean? Ten µm is a unit of particle diameter, not mass. The author needs to clarify what is meant by "reasonably consistent RSP to vapor ph%~kse ratio(*:" . _`or ETS" and "nicotine, for some applications, may vary with ETS related RSP". While nicotine and RSP are almost always correlated in field studies (i.e., there is a statistically significant slope), the corre].ation (i, e. , goodness of fit) is almost always very poor. This reviewer questions how this supports the statement that nicotine ca:ri be used to estimate RSP attributable to ETS. p. 58 - The author incorrectly states that there are no health standards for exposure to nicotine. 0!SHA has one (500 µg/m3). A further drawbac;t ot nicotine as an ETS m<<rker that should be included is the fact that in environments w:Cthout active smoking activity (but which have a history of smokiiig activity) there is the very real possibility of a nicotine background due to * adsorption/desorption from room furnishings, etc. t74}. In these cases, measurement of nicotine indicates expo:aure to nicotine only, and not ETS (other less-adsorptive components have decayed to zero). The author raises this issue at the bottom of the page and states that "background levels of nicotine might also be indicative of outgassing from surfaces of other volatile ETS components". This latter statement is purely speculation <<nd should be omitted. p. 61 - In the discussion of short-term me,==ement methods for ETS RSP, the ultraviolet absorption method reported by Ingebrethsen * et al. [49] needs to be included. This UV method is the only methodology widely-used in field surveys i.o indicate some ETS *"[]" refers to Chaps. 5-8 Index. 3

* apportionment of RSP [.15,70,75,92].- rl The author states incorrectly that "}hic tXA.D-4; method has been evaluated for sampling periods up to one hour with...detection limit of 0.1 µg/m3". The method has been evaluated for periods up to 8 hours with LOD of 0.02 µg/m3. LOD for 1 hour sampling is 0.17 µg/m3 [77]* pp. 61-62 - It is not true that particle phase nicotine can be determined by analyzing the first filter. Particle phase nicotine will impact the first filter but is stripped from the particles and collected on the second filter as vapor phase nicotine. This method cannot give separate i:.forinaiion on vapor phase and-particle phase nicotine; it can only give total ETS nicotine if both filters are analyzed and the results summed (i.e., the first filter underestimates particle phase nicotine and the second filter overestimates vapor phase nicotine). Although passive samplers are useful in field surveys under certain constraints, they generally show much worse ;precision than active sampling systems and, in some cases, severely overestimate nicotine concentrations [76]*. p• 63.- Delete the gratuitous statement that "ETS is a complex mix of ~pveral thousand chenicals..." for the raasons outlined comment to p. 55. The author states that RSP and vapor phase nicotine * "[]" refers to Chaps. 5-8 Index. 4 are

r "reasonable" markers. How is reasonable defined? This is solely the authors opinion and should be stated as such, if not deleted. Chapter 6 - "Exposures to Air Po].lutants's The title for Chapter 6 listed in the Table of Contents does not agree with the actual chapter title. It appears the title listed on p. 65 is more indicative of the chapter contents and implies that this chapter was actually written for some other purpose. This is further supported by the numerous irrelevant comments attributable to air pollution in general. As stated previously, this chapter should be combined with Chapters 5 and 7 for a more comprehensive and useful review. pp. 66-67 - What is-the relevance of the information relating to sulfur, zinc, bromide, lead, silicon, calcium, and iron? should be deleted. This The definition of mainstream smoke is circuitous and needs revision. This reviewer disagrees with the authors' statement that exhaled mainstream tobacco smoke adds little to ETS. Exhaled mainstream smoke can easily aa:' 1c? -20°s to true ETS In addition, the chemical composition of exhaled mainstrean smoke is markedly different from sidestream smoke due to absorption in the smoker. 5

i t- L These authors have included the same gratuitous comments regarding the "several thousand chemical compounds" in ETS as was included in Chapter 5_ These c.om?aents should be del eted for the reasons outlined previously (comments to pp. 55 & 63). p. 68 - The authors state that the "large numibers of constituents in ETS make it impossible to assess overall exposure based on...each one" when in fact this is not true. The reason exposure is not assessed on each constituent is because the vast majority of tobacco-smoke chemicals have never been detected in ETS! In fact, validated analytical methods exist for only a very few. Although this may seem a trivial pursuit, the authors are implying "ovPn•::elming ccrupiexity" is the relevant issue when in realit~, "extremely dilute concentration" is more pertinent. The authors should strive to make a more objective presentation of the issues. Of the possible measures of ETS, why do the authors choose RSP, nicotine, cadmium and nitrosamines? RSP and nicotine form the major theme of Chapters 5 and 7. Cadmium and nitrosamines are not generally useful ETS tracers because of the ultra-trace quantities present. (Is this a scare tactic?) Cadmium and nitrosamine related information should be deleted and the remainder with Chapters 5 and 7. integrated p. 69 - The statement is made that "each --:oker in the home raised the mean respirable particle level by 20 lag/m3". What is the relevance of this increase? In relation to 'the OSHA standard for dust of 2000 Ecg/m3, this increase seems a.inuscule. The data 6

i i I+ ii I presented in the next paragraph (0.88 and 2.11 µg/m3) are considerably lower. This reviewer fails to see the relevance or significance of these dat?.. M^ro information (with references) needs to be presented or this discussion eliminated. Because of the fact that RSP is not selective for ETS, it is impossible to infer that the 962 µg/m3 measured (or any of the other data) is attributable to ETS. p. 71 - The authors contradict themselves by stating that "Indoor cadmium levels were below the detectable limit" followed by "cadmium levels were highly correlated with...particulate measurements". If 7ad:uium was undetected, how could it be correlated with anything else? The relevance of any discussion of cadmium data is unclear and should be omitted. The relevance of the information presented on nitrosamines is unclear and appears to be taken out of context [9]. While true that Brunnemann et al. detected nitrosamines, they were not directly attributable to ETS (i.e., they were not tobacco-specific nitrosamines). Brunnemann et al. state that "...the assessment of traces of established animal or human carcinogens, possible thrqugh advanced instrumentation, does not imply increased cancer risk for man. _ The human risk can be established only through appropriate epidemiological investigations." They go on to state =~...no Go epidemiological data exist linking human respiratory cancers to pp ~ volatile nitrosamines." The entire discussion of nitrosamines N should be omitted from this chapter and left to the experts ~ rV 7

L.J r ~ ~ (Hoffmann et al., Chapter 8). What is the relersnce of the breath concen' r=* i c:: of benzene in i! smokers? This paragraph must be deleted. pp. 71-72 - What appear to be trivial increases in RSP (29 to 56 µg/m3) and nicotine (0.3 to 2.5 µg/m3) values; are presented. What is the significance of these increases? Likewise, the statement is made that "exposu::-e was increased by 20 llg/m3" • Z ~N What is the relative magnitude and significance of this increase? . The two paragraphs presented on cotinine measures are hardly adequate. They should be deleted or covered in much greater detail. Summary statement #2 declares that ETS is a substantial contributor to indoor air of benzene, acrolein, nitrusamines, pyrene, and carbon monoxide. With the exception of bens,ene and nitrosamines, the other compounds are not discussed within this chapter. The data presented for benzene relate only to smokers and the nitrosamine data are not specific to ETS. 7'his summary statement is unfounded, unwarranted, and should be de].eted. 8

Chapter 7-O'Exposure Assessment in Passive Smoking" The 1.Yt5!rature cita_tions for Chapter 7 are incomplete (e.g., IA.RC, 1987; Williams, 1985). The frequent use of "persortal communication" citations is inappropriate. If this information is not included in the scientific literature or other public domain, it must be deleted. Considering the scope and content of Chapters 5 and 6, this reviewer sees no real need for this information to be presented as a separate chapter. What new information is presented here should be incorporated with Chapters 5 and 6 for a more comprehensive and cohesive review. p• 7y - This reviewer agrees with the author that exposures tu ETs can be assessed by personal air contaminant zaonitoring (presuming appropriate contaminants are monitored); however, this reviewer strongly disagrees that exposures can be assessed by modeling. This is a common misstatement in Chapters 5, 6, and 7: assessment implies an actual determination. Modeling can, at best, provide an estimate, i.e., in place of an actual measurement. In reality, modeling is still only a crude estimate and needs to be portrayed as such. p. 80 - It is not true that the "two most proa.ising markers for ETS are respirable suspended particles...and nicotine". While these are currently the most widely uscd, :aany resaarchers in the field are actively pursuing identification of other markers specifically to overcome the significant-limitations of-taiese two. i 9

The author offers several unsubstantiated opinions as fact: "the substantial emission of RSP", "ETS is the daminant contributor", "RSP...found to be subc}antially elevated", etc. If this Compendium is to be a scientific document, these loosely defined qualifiers (substantial, dominant, etc.) need replaced with quantifiers and appropriate literature citat:.ons added. kJ I L L*~ U The author states that the presence and number of smokers lacks specificity for tobacco smoke. What does this mean? Assuming the author means that RSP lacks specificity for tobacco smoke, this is a true statement. However, the author continues throughout the rest of the chapter blatantly ignoring this :aevere limitation. Again, the author incorrectly states that "RSP is currently the best...to represent ETS". This is opinion and should be stated as such, if not deleted. The author states that "nicotine and ...cotinine...derive exclusively from tobacco products". This is incorrect. Nicotine has been determined in a substantial number of foodstuffs including tomato, potato, eggplant, pepper, and instant tea [13,100]* . This reviewer agrees that tobacco smoke*is the most important source; however, the possibility for nicotine and co-tinine in body fluids arising from dietary sources cannot be ignored. It is unclear how the statement "Generally, the mean concentrations c:fi -'~cotine and cotinine in...nonsmokers exposed to ETS under natural conditions" can be used to support the claim that "smokers are present in nearly all environments". This section needs rewritten. * "[]" refers to Chaps. 5-8 Index. 10

The assumption (statement) made in the last paragraph on p. 80 (and later in the chapter) that "the averaRe...=!*cyer...emit about 22 mg of RSP per cigarette" is totally unjust:Lfied. This reviewer must assume that the IARC reference gives an average sidestream 'tar' of 22 mg/cigt (which is not unreasonable). How is it possible to justify the equation that 22 mg SS 'tar' = 22 mg ETS RSP? Even the author recognizes the fact that "almost all nicotine shifts from the particulate phase in MS and fresh SS smoke to the vapor phase in ETS". It must be assumed thai: this same phenomenon occurs for other tobacco-smoke constituents. The weight of ETS RSP must be substantially less than the 22 mg predicted from SS 'tar'. However, it is not known what the r.^latiunship is. p. 81 - It is only correct to state that "Nonsmokers are exposed to ETS in indoor spaces" where smoking occurs. statement accordingly. Please modify p. 84 - The author states that "The utility cf Eq. 4 depends on the assumption of an air exchange rate" when in reality Eq. 4 depends on many more assumptions (no. of smokers, R:;P/cigt., sinks, etc.) The appropriateness and limitations of these assumptions are never clearly defined and they impact heavily on the usefulness of the proposed models. Gb (Z This reviewer fails to see how the example presented "illustrates -1 ~ the utility of models". Having data from one experiment which are N ~ 17, then fit to a model which has been adjusted Eor variables measured -1 11

in the experiment can in no way be used as validation of the general applicability of the model. Even i:n this case, when the actual air exchange is used, the model predicts 130% of the RSP actually determined. Combined with the observation that, on * average, RSP overestimates ETS by an additional 50% [T0;110],these facts severely hinder the general applicability of this model. The second example is equally flawed. The entire difference between daytime and evening RSP concentrations is erroneously attributed to ETS. The impact of persona]. activity other than smoking on the daytime RSP concentration i,s completely ignored. This so-called "pig-pen" effect (espoused pr:imarily by the authors of C hapter 6) should be explained as a further conforndcr of these data. The author "implies that ETS may diffuse throughout a large office building, exposing nonsmokers even in private offices" and offers * the data of Williams, 1985 [123]; as "support". The data of Williams et al., in fact, do not support t:ais implication. The results (Williams et al.) were miscalcu:lated and originally published incorrectly; corrections to the calculations were made * and subsequently published [34]. These corrected data were overlooked or ignored by the author and actually refute the observation. Assuming the analytical method of Williams et al. is sound, tneir data suppor` ey.:eedingly clean air in the office complex surveyed. p. 85 - The author states that from "li:mited field tests of * "[]" refers to Chaps. 5-8 Index. 12

the...model...it is clear that both models and observations based ,r1 on...monitoring...yield consistent results". This could not be further from the }~ ~t::- Simpl l stated, this; model has certainly not been validated and has yet to be used in even one incidence to provide reliable data in advance of actual air monitoring. p. 86 - What is the relevance of the narrative concerning the Mormons and the Seventh Day Adventists? p. 88 - The author correctly states that "In the •absence of...data...exposures can be estimated by models or by extrapolation from biological markers". The key word here is ~a "estimate" and it needs to be realized that the existing models have' yet to provide any indication of -re:producible, reliable estimates. In other words, the quality of these estimates is still ~ very much in question among scientists. This reviewer reiterates the comment provided to p. 79. ETS exposures can be assessed by air monitoring but only estimated by modeling, questionnaires, and the like. The statement "there are models in use...which can predict the concentrations of RSP from ETS to a reasonable degree of accuracy" is the opinion of the author and is not a generally held opinion. p. 89 - The author (inadvertently?) providea further evidence of the inappropriateness of calculated exposurEas- by stating "it has been calculated that a nonsmoker would inhale volatile nitrosamines 13

equivalent to...35 filter cigarettes." What evidence exists that this magnitude of exposure has, in fact, occu:cred? What the author alsc fails to include is the f?^_t that "no ep;c?emiological data exist linking human respiratory cancers to volatile nitrosamines." * ([g]; see also comment to Chapter 6, p. 71) The author makes further statements based on "the assumption that formation of cotinine...and clearance from the body does not differ substantially from smokers to nonsmokers". It is known, however, that formation of cotinine and clearance from the body do differ * substantially [2,45]. What is the relevance of the :.ote ddded regarding the RSP/nicotine ratio and the resulting calculated RSP? RSP/nicotine ratios are known to vary from 2:1 up to 100:1 across normal environments. This calculation serves no useful purpose. If you want to know RSP with any degree of confidence, you must measure it. This note should be deleted. p. 90 - The author presents a one-sided viewpoint ("may substantially underestimate") on the ability :)f nicotine absorption to predict exposure to other ETS constituents. It is at least equally likely (and never mentioned by this author) that nicotine absorption would overestimate exposure to other ETS constituents k,aGFc'. on possibilities of nicotine in the di.et: (see comment to p. 80) and of a detectable nicotine background in the absence of other ETS constituents (see comment to p. 58 [Ch. 5]). * "[]" refers to Chaps. 5-8 Index. 14

The author attempts to support his view of the appropriateness of RSP measurements for ETS exposure with a reference to the Surgeon General's report: "...*_:±e relationships of RUSP mea=»rPneTt.z to ETS are quite accurate". This comment is taken out of context and appears to be slanted solely for the author's purpose. The actual quotation from the Surgeon General's report is "At a practical level, the technology for measuring nicotine levels and RSP levels is available and accurate." The author should strive to remain objective in presentation of the relevant issues. p. 91 - It is not a consensus among researchers in the field that RSP is the best atmospheric marker of ETS exposure. This is the author's opinion. It is incorrectly stated that the cotinine measures reflect the actual dose of an ETS constituent. The confounding factors (diet, background nicotine) were never presented. The statement that cotinine measures "may substantially underestimate exposures to other constituents of ETS" is totally unfounded. As stated previously, it is equally likely (if not more so) that these measures will overestimate actual ETS exposures. It is presented as an advantage that RSP-based estimates are model- based_ In reality, this is its second most serious drawback (the first being that,RSP 41 ._ not specific to ETS). In discussing the GE) Qn drawbacks, the author fails to point out these limitations or the .~ .~ fact that RSP in nonsmokers is not absorbed in the same manner as N ~ 4D it is in smokers [2]. ~-A 15

REVIEW OF: ENVIRONMENTAL TOBACCO SMOKE A COMPENDIUM OF TECHNICAL INFORMATION= by Simon Turner, Healthy Buildings International, Inc. L LI Introduction Healthy Buildings Internationa:l, Inc. (HBI) is a company that specializes in the study and assessment of indoor air pollution. Since we incorporated in 1981, we have studied in excess of 80 million square feet of buildings throughout the world, perhaps confirming us as the most experienced private company in that field. HBI seeks to identify the causes of indoor air quality problems -- the "sick syndrome" -- and to recommend remedial s~=eps. Our building experiences are attracting widespread interest in the professional arena of those truly interested in indoor air quality. Clients include major banks, insurance companies, property developers, hospitals, colleges, and government agencies, including the U.S. Department of Health and Human Services, Social Security Administration, Longworth Congressional Building, Supreme Court, Government Services Administratioi Regional Head- quarters, United Nations Buildings in New York, Customs and Excise and Coast Guard Buildings. We were asked to comment upon the document entitled "Environmental Tobacco Smoke: A Compendium of Technical rX Information" based upon our extensive experience with indoor ~ .1 air quality problems. In addition to a number of specific N ~ ~ substantive flaws contained in the document, this compendium t~

rI L on environmental tobacco-- smoke ( ETS )- --sarrc:t-ionedr-by-a body°- such - as the U.S.. Environmental Protection Agency--(EPA)-concerns us - in that this single-minded focus on one pollutant, unique in EPA's policies on indoor air, will give t:he public the impression that its removal will solve a].1 indoor air problems, thus giving an entirely false sense of security. We frequently investigate buildings on account of complaints from occupants with symptoms such as eye and nose irritation, fatigue, coughing, rhinitis, nausea, headaches, sore throats and general respiratory problems. It is frequently assumed by our clients that these symptoms are due to ETS. However, it is clear that identical symptoms may be found in individuals exposed to formaldehyde, sulphur oxides, ammonia, oxides of nitrogen, and ozone. In addition, similar symptoms are reported by those individua:ls with allergies to specific fungi such as aspergillus, cladosporium, and penicillium, among others, as well as to miscellaneous bacterial aerosols. Overlapping symptom;3 also can be caused by exposure to household dusts, cotton fibers, fiberglass fragments, etc. Low relative humidities create similar problems and are on the increase. Surprisingly, after a detailed, scientific evaluation of these buildings, we have determined high levels- of environmental tobacco smoke to be the immediate cause of indoor air problems in only three percent of the 412 major U.S. buildings investigated by HBI between 1981 and 1989. This result has.been corroborated. In a similar study of 203

buildings from-1-978 to 1983,_-the Nationa-1--Insti=tube=-for -- ~ Occupational Safety and Hea-lth- ( NIOSH} _ found that -.onl.y. four of-. the buildings studied (two percent) had indoor air quality problems attributable to high concentrations of ETS. Significantly, in those few cases where we found high accumulations of ETS, we also discovered an excess of fungi and bacteria in the HVAC system. These microorganisms usually are found to be the primary causes of the complaints and acute adverse health effects reported by building occupants. Dirt in Duct Systems We have also found that HVAC systems are often poorly designed and negligently maintained. Excessive dirt accumulations are common in ductwork, even in hospitals. Following the inspection of a number of buildings, hundreds pounds of fungi, dust, and dirt have been removed from such ductwork. Bird, insect, and rodent carcasses and excess amounts of dust have been found in many buildings where of employees have complained of eye irritation, headaches, fatigue, nausea, allergies, and general respiratory problems. Of course, since the ductwork is out of sight, it is also invariably out of mind. Thus, it is common for the blame for these types of problems to be laid elsewhere. Energy Conservation Indeed, the complex of symptoms that we have mentioned - the "sick building syndrome" - may result primarily from energy conservation efforts to seal buildings and reduce the i-nfiltration/exfiltration of air. Such efforts

1J U, have reduced -the. natural -infiltration--of~ Eresh--air- that previously existed in:many buildings-,-exacerbating.the oftem- undiscovered problem of a poorly designed or maintained HVAC system. In addition to tightening buildings and sealing windows, building managers have shut down air conditioning systems at night and on weekends in an effort to lower energy costs. When the air conditioning is shut down in humid climates, condensation builds up and settles inside the ductwork. If dirt is present in damp ductwork, spores and microbes can flourish, only to be spread throughout the building once the HVAC system is turned on the next morning. This often results in Monday morning complaints of building odors or building sickness that disappear during the week, only to recur the following Monday morning. To save more energy, automatic temperature controllers are used to cycle fans on and off during the day. Vibrations from the start-up of these fans can cause dirt and microbes trapped inside ductwork to be dislodged and carried into occupied areas. Another energy conservation effort that may contribute to sick building syndrome is the recirculation of indoor air, at the expense of fr•esh outdoor air. This may be the result of either a deliberate policy or shortsightedness on the part of the designers. This results in the continuous redistribution of infectious microbes, allergenic dusts and spores from office to office and floor tc floor. Improper ventilation can sometimes be-carrit-d to extremes. Typically

we find the_ fresh.-ai-r :.damper%.:-we-re .closed-_ completely-- in- over - 35% of those buildingsd studied by. HB:I. One misguided engineer- actually had bricked up the fresh air vents to save energy. All of these buildings were operating wil:h 100% recycled indoor air. The lack of an adequate fre;3h air supply, coupled with dangerously low air exchange rates, has led to hazardous ventilation conditions in many of the buildings evaluated by HBI. Similarly, over 50% of the investigations conducted by NIOSH from 1978-1987 attributed the indoor air quality problems to inadequate ventilation. Poor Air Filtration Modern filter technology can easily cope with the numerous particulate matter that is routinely carried in the indoor air. Unfortunately, however, there is far too much ignorance in this area. Frequently good filters are poorly installed allowing air bypass, but more frequently we see a move to cheaper, less efficient filters. Many buildings attempt to clean the air with filters no better than butterfly nets. Compound this with the lack of maintenance given to the filter systems and the infrequent changes of filters and it is hardly surprising that airborne pollutants accumulate. Methodology of Dealing with Indoor Pollution Instead of a single-minded focus on specific pollutants, we believe very strongly in a generic engineering approach to deal with all pollutants~at the same time. In our U.S. experience of over 80 million square feet of building studies, the maJor contributors.to poor air were threefold:

(1) Poor Ventilation Inadequate ventilation 62% Zero fresh air intake 33% (2) Poor Filtration • Inefficient air filters 43% (3) Dirt in Ventilation Systems Conta nated air handlers 36% Contaminated ductwork 22% I We are convinced that improving ventilation rates, upgrading filters, and cleaning up the air handling system . will eliminate over 80% of indoor pollut.Lon problems.. Such' changes will improve worker productivity, enhance staff morale, and reduce absenteeism however, inany managers have decided to ban smoking as an apparently cheap and easy way to solve indoor air quality problems. Unfortunately, this simply does not work. HBI has determined that the presence of high concentrations of tobacco smoke indicates that a much more serious problem exists. Poor ventilatioz and improperly maintained ventilation systems are the primary causes of poor indoor air. When such conditions.prevail, all the invisible and odorless pollutants are also trapped. Many of these are potentially far more Persistent can be resolved only pr-epared to focus on appropriate manner. not a cause of these no cure. dangerous than ETS. indoor air quality complaints therefore if building managers and operators are building air handling systems in an High concentrations o.f ETS are sumptom, complaints. Its elimination can effect

r+) i c CRITIQUE.OF COMRENDIUM. There follows specific comments on selected chapters of this compendium, either where we feel there are flaws or misconceptions, or where we have constructive contributions to make. General We feel that in many areas of ttiis compendium the list of papers and authors referenced to tends to be selective; there is a broad range of research, findings and conclusions on this topic and we feel the compendium needs to reflect this breadth of information. Suggestions for additional authors are made where relevant in each chapter. Chapter 5 We do not have any major philosophical.bones of contention with this chapter, except that a better author who has published extensively in this specific field might have been Delbert Eatough, of the University of Utah. One technical point where we would take issue is the contention that 2.5 µg/m3 should be used as the cutoff point for respirable sized particles. The American Conference of Governmental Industrial Hygienists (ACGIH) clearly specify that collection devices for respirable particulate mass should have a medium cutoff size of 3.5 um. (AFpendix D, Threshold Limit Values and Biological Exposure Indices for 1989-90). Thef use of 2.5 µg/m3 instead of a commonly accepted value of 3.5 µg/m3 will artificially increase the percentage of ETS derived particulate present.in incoor RSP, since ETS

particles are almost ail.be_low-.2:5 µg/m3 in size:----There is a t t. Ii 4 . large body ofa data on indoor_RSP taken-at 3.5 um,.including Repace and Lowry's own work with piezobalances. A portion of the size fraction between 2.5 µg/m3 and 3.5 µg/m3 does indeed enter the respirator tract, and there is no evidence to suggest this size fraction is ,physiologically-significant. Of the nicotine sampling method, Healthy Buildings International (HBI) has been using the XAD-4 sorbent method for the past two years and has collected over 500 nicotine samples this way. It has proven robust, sensitive and reproducible; we support the acceptance of this method. Finally, the statement concerning the lack of health standards for controlling exposures to nicotine (p. 58) is not entirely true.' There are indeed health standards specifically meant for controlling airborne nicotine levels, published both by the ACGIH and by the British Health and Safety Executive of 500 µg/m3. Chapter 6 The paragraph on page 66 and 67 (size distribution and composition of particulates) is flawe-d -- the data they refer to on both size distribution and composition refers specifically to the outdoor case. One large area of research still to be explored in indoor air quality science is particle characterization. There is very little ].ikelihood that particle size distribution indoors is the~ same as outdoors, and even less likelihood that elemental composition of --particles indoors and• outdoors.. is. the same. For instance,

there are more sources of.-:iron, fibers-;.= aotton__dus-t:,..paper-;:. r In , mites, and organic mat-erial-s..indoors:.than outdoors.- - Specifically, Dzubay and Steven's work on particle size fractionating was primarily on outdoor air samples. ASTM are.currently exploring the possibility of developing a dust which more accurately approximates indoor particles for calibration of particle mass monitoring equipment. EPA will be asked to assess the feasibility of developing such a dust. Much of the remainder of the chapter concerns particle measurement results from different authors. Many of these samples were taken using the piezomicrobalance, and HBI has much experience using this instrument in thousands of locations,in the hundreds of buildings across the world. For instance, in 1989, in 26 office buildings in Switzerland, HBI found mean RSP values from between 26 and 63 µg/m3 (Environmental Technology Letters; in preparation). Smoking was discretionary in most of these buildings. Examining the data presented in this review, we find that in general this range is consistent with other workers' findings for this type of building. The chapter is confusing, however, because under the heading of "particulate concentraticn in offices" (in which much of the debate on control of ETS is currently centered) we find reference to Repace ard Lowry's work ten years ago in'non-smoking libraries and churches, compared to premises allowing smoking, namely bars and grilles, bowling alleys, cocktail lounges, barbecue restaurants,. all areas

-which by their nature_are-heavily-polluted.:env:ironments.--(Table' - 5). Not surprisingly,.-RSP values--measured-by the-same piezobalances tend to be an order of magnitude higher in these environments. Yet this data is presented as evidence of high levels of RSP to be found as a result of smoking i.n offices. Given recent measurements made in offices at today's levels of office smoking, it should be accepted that RSP levels, even where smoking is allowed, do not reach levels claimed by Repace et al. The selection of nicotine levels quoted in Table 7 is also not representative of most workplace environments. HBI Inc. has over the last three years been measuring nicotine in some six hundred office locations and the mean value to date approximates to 4.0 µg/m3. Overall, the chapter is selective in its choice of references; once more, Eatough's work should have been referenced in this section. Furthermore, other more recent work on measurement of ETS exposure in offices apart from our own is available which has been ignored - this includes authors such as Sterling (Theodor D. Sterling & Associates Ltd., Vancouver, Canada) who has published extensive data on ETS levels in buildings and Kirk (Imperial College, London) who has data on British ETS levels. Chapter 7 . The estimation of human exposure levels of a pollutant based either on modelling or measurements of some supposedly rep.resentative parameter depends-crucially on -the

i Vl I L, accuracy of the=original assumption..or-,the representativeness- of the measurements made.- That is why.- -measurement--methods- development for ETS is so important. Unfortunately, much of James Repace's,exposure estimations are riot based on realistic original data or assumptions. This critique will demonstrate areas of this chapter where this is the case. A prime example of this poorly conceived initial assumption is found on page 85. Repace picks measurements from 42 "smoking" buildings; a substantiaLl number of which are those bowling alleys, casinos, bars, barbecue restaurants and cocktail lounges referenced to in the previous chapter we reviewed, and compares them with twenty-one non-smoking buildings (such as churches and libraries) and concludes that about 85% of the indoor RSP is due to ETS. Reference to Eatough's work where he reviews exposure assessment methods shows he estimates about 50% of indoor RSP due to ETS. The difference is explained because Repace did not compare like buildings with similar activities in each, which generated equivalent amounts of non-ETS derived RSP. In Section D, in support of hi:; modelling assumptions, he states, "Field studies of` RSP in buildings where smoking occurs suggest that RSP from ETS contributes 80 to 90 percent of the particulate load during the period of smoking,-and that it persists for long pe!riods after smoking ends at typidal building air exchange rat:es, thus prolonging nonsmokers' exposures." Of course he is referring once more to his-unique collection=of bui-ldings., and-the statement---

, fl concerning the pers-istenc.e, of ETS -is - in--di-rect_- contrast with our -own work on the topic •of office_ environments-. - In Section C he also mentions t:hat exposures on aircraft can be considerable. This contrasts with the FAA and NIOSH findings of mean RSP levels of only 40 µg/m3, and maximum of 120 µg/m3. Measurements by Drake found a mean level of 14 µg/m3 and a maximum of 41 µgfm3. . Repace goes on to explore the concept of cigarette equivalents. This concept has to be used with care -- the basis on which such estimations are made must be carefully stated. For instance, based on his assurnptions, he estimates nicotine uptake in non-smokers to be equivalent to between 1/6 and 1/3 of a cigarette per day. However, in our previous studies of approximately 600 offices sampled on a worldwide basis where smoking was allowed, the ave::age airborne concentration of nicotine was 4.0 µg/m3. Using breathing rates as publi;3hed by ASHRAE, the average individual in an office inhales 3.6 liters of air per minute or 4.13 cubic meters of air per eight hour day. If the average nicotine content of that air was 4.0 µg/m3, each individual could inhale 16.52 micrograms of nicotine through- out the course of each day. Since the average smoker in the USA inhales 880 micrograms of nicotine per cigarette, the non- smoker exposed to 16.52 micrograms per day could inhale 0.019 QC "cigarette equivalents" per eight hour day, in contrast to ~ -IT Repace's estimates of 0.17 to 0.33 nicotine cigarette equiva- ~ lents.' ~

Finally, RSP is defined early on in this•chapter--as that portion of the particles below -2.5 um:. For reasons-_ discussed in the review of chapter 6, this figure should be 3.5 um. The piezobalance used for Repace's own work to which he refers is equipped with a size selectiv.e inlet of 3.5 um. In sui~mary, the assumptions on which exposure assessment models are based must be carefully examined since they will have such a strong influence on the outcome of such an exercise, and the policy decisions on which they are based. In our opinion, much of the data from which Repace's assumptions are derived are unrealistic, and not representative of the typical workplace environment, yet the workplace is where much of the smoking policy decision making is currently taking place.

Comments by Dr. Guy B. Oldake^ III on CHAPTER 5 MEASURING EXPOSURE TO ENVIRONMENTAL 1'OBACCO SMOKE INTRODUCTION 0 U U Ii General Comments Chapter 5 "Measuring Exposure to Environmental Tcbacco Smoke" (ETS) in its present form is an incomplete rough draft which cannot be expected to address adequately the needs of decision makers, public health officials, corporate medical directors, etc. in their efforts to malce well-informed decisions regarding the assessment of exposure to ETS. Because of the chapter's limited ;;.opa a.:d i;egl ect of a l arge amount of publ i shed 1 iterature, i t i s~^c;:,:~ ~~teni with thp theme of a compendium of technical information. The autnui., may wi~;h to consider using as a guide the document produced by Nagda and Rector ("Guidelines for Monitoring Indoor Air Quality," I:PA-600/4-83-046, September 1983) as they pursue revisions. This document provides a wealth of technical information regarding the measurement of indoor air cuality as well as a thorough review of available methods and instruments for assessing indoor air quality. The copy available to this reviewer lacked a listing of literature citations; consequently, the extent of review is severely limiti2d. Without such citations, the chapter has inadequate technical support. This reviewer recommends that additional drafts submitted contain the necessary references to facilitate adequate review. Specific Comments The Introduction, which is inordinately lengthy and reaches the point only at its very end, presents the Chapter's objectives: ~ GD ~ ~ ~ ~ 1 CD C!T

"This chapter will present a discussion of' the issues to be considered in air sampling for ETS with emphasis on air sampling in enclosed spaces rather than on personal monitoring. Selection of ETS contaminants to be monitored, available methods of sample collection and analysis, operating principles for each method, relative advantages and disadvantages of each mathod and sources for purchase of sampling equipment will be covered." Although adequately identified, these objectives are not met by the chapter in its present form.- This set of topic sentences is probably best placed at the beginning of the Introduction. In this place, it would offer the author a guide for the-revision of the Introduction, which contains much information that is not germane to the discussion. SELECTION OF ETS CONTAMINANTS FOR NIONITORING , The author on p. 55 states that ETS contains over 4,000 compounds in the particulate and vapor phases. This statement is apt to confuse most users of the document bec?use 'It suggests that these compounds have been measured in ETS, which is not tne case. The author should note that this statement derives from information on mainstream and sidestream smoke and i3 assumed to extend to ETS. Although the author lists many of ETS markers which have been used or proposed, the author fails to list several which provide apportionment for RSP and which have found wide use for assessing exposure to ETS. Thus, the author neglects to identify ultraviolet particulate matter (UVPM, a measure providing an upper estimate of exposure to ETS respirable suspended par-:icles (RSP) (Ingebrethsen, 1988, Carson, 1988; Conner, 1990; Proctor, Environ. Technol. Lett., 1989), solanesol (which provides a direct measure of ETS RSP (Ogden, Environ. Sci. Technol., 1988; Ogden, TCRC 1989)), 3-vinylpyridine (which provides a measure of exposure to the gas phase of ETS (Ogden, TCRC 1989), and fluorescent particulate matter (which complements UVPM (Ogden, "CRC 1989)). The author's discussion of ETS indicators on page E6 is misleading because it fails to distinguish between practical indicators z.nd impractical indicators. In addition, the author's reference to tables in Chapter 6 is imprecise, and therefore, also misleading. On page 56 the author :;tates: QD Co ~ .1< N 2 rA CD a~

l.: k "Carbon monoxide, nitrogen oxides, acroleir, benzene, toluene, tobacco specific nitrosamines, vapor and particle phase nicotine, isoprene, pyridine, particle phase nicotine and cotinine, respirable suspended particles, polonium-210 and benzo[a:lpyrene are among the many air contaminants that have been used or proposed for use as indicators of the presence of ETS. Tables in chapter 6 show the range of concentrations measured in a number of indoor environments were [sic] smoking occurred." Most of the substances listed are either impractical or unreliable because they occur at trace levels and because they originate from sources other than ETS. Tables in Chapter 6 suamarize data for sidestrean to mainstream ratios of various substances and results from surveys of nicotine and total suspended particles (TSP) in indoor environments under realistic conditions. Of these tables, only those presenting nicotine and RSP results are germane- to the discussion; however, these present information available in previously published documents and represent but a small portion of the data now available. The author should revise this paragraph to address practical ETS indicators. (This recommendation is consistent with thp author's statemsnt: "This chapter will focus on the use of RSP and nicotine os markers for ETS ...." The authors of Chapters 5 and 6 should coordinate their efforts to ensure that literature citations are accurate and up to date. On page 56 the author states that tobacco combustioi has a major impact on the mass of RSP, and that ETS RSP is detectable above background levels in occupied environments even under conditions of low smoking rates. These statements are ambiguous, unsupported, and to some extent, inaccurate. Because RSP is not specific for ETS, an RSP measurement in itself provides an ambiguous result for ETS'RSP without some means of apportionment. Although tobacco consumption can have a major impact on the mass of RSP, such is not typically the situation; if this were the situation, there would be no interest in the development of methods to apportion RSP. (This concern speaks also to item 2, of page 56.) The ongoing efforts to develop methods for apportioring RSP respond directly to the first of the five criteria the author lists on page 55 (for example see Ogden, Environ. Sci. Technol., 1988). The author should define "low smoking , rates," because detection of ETS RSP depends strongly on this parameter. Detection also depends on the method employed and tFe circumstances under which ~ it is employed, as is the case for integrated methods of sampling where J N 3 CD ~

{J f-' r detection is greatly affected by sampling time and therefore sample volume. Indeed, the author recognizes this limitation in Table I. Some of the methods referenced by the author will not detect ETS RSP urder typical circumstances; the author should identify these. Also on page 56, the author states: "... methods are available to accurately and inexpensively measure RSP levels ...." Accuracy needs to be addressed more fully and quantitatively within the body of the chapter, if this subject is be raised, as it should. At the end of page 56 and continuing to page 57, the author notes that "there are outdoor particle health standards established by the U.S. EPA which provide a frame of reference in interpreting measured RSP levels associated with ETS." This statement should be omitted from the text, because the "frame of reference" assumes that the reader will understand and appreciate the numerous attending assumptions that must be understood for making informed, intelligent interpretation. If this "frame of reference" is to be offered, the author should inform the reader of the technical, politica'I, institutional, economic, :nd regulatory issues which affected promulgation of the Nat'.;,,all Ambient Air Qii?l ity Standards (NAAQS) . At a minimum, the author must aaor a.s tnr imrort?nca of averaging time for interpretation. To be complete, the author should identify the standards of the Occupational Safety and Health Administration for RSP and nicotine, 2 mg/m3 and 500 µg/m3, respectively. On page 57 the author states: Some recent'field studies have found a reasonably consistent RSP to vapor phase ration [sic] between for ETS in the. residential and non- industrial occupational environments (11, 12) [references unavailable], suggesting that vapor phase nicotine, for some applications, may vary with ETS related RSP and thus be used to estimate the RSP attributable to ETS." Results from the greater number of field studies, including offices, restaurants, and passenger cabins of commercial aircraft, discount the broad applicability of this "suggestion" (Oldaker, Excerpta Medica International Congress Series 1989). Nonetheless, it might be that these results are not covered by the qualifier "some applications." The author of Chapter 5 should 4 i_

provide the reader with specific examples of situations where the suggested relation might hold and be useful. C] On page 57 the author states that nicotine provides a link between air concentrations of ETS and internal dose. Because the relations between nicotine and ETS constituents have not been characterized, this statement is speculation and should be either revised or omitted. On page 58 the author states that there are no health standards controlling exposures to nicotine. This'statement is false; the OSHA standard is 500 µg/m3. MEASUREMENT OF RSP AND NICOTINE IN AIR f: L fl The author states correctly that concentrations of RSP, nicotine, and other ETS constituents in an enclosed space can exhibit a pronounced spatial and temporal distribution. This statement directly contradicts the fundamental assumptions made by the author of Chapter 7 for the equilibrium RSP model. The authors of the respective chapters should address and resolve this contradiction. The aut.i,G:' t.ur r-cck'?y rerogai zes several of disadvantages associated with use of RSP for assessing exposure to ETS. These disadvantages need to be integrated with Chapter 7 by Mr. Repace who uses RSP in his arguments to support (invalidated) models. The fundamental, unstatel issue is that RSP will overestimate exposure to ETS RSP. The question the author of Chapter 5 must address is: to what extent and under what circumstances will RSP overestimate ETS RSP? The importance of nicotine outgassing is not adequately stressed at page 58; this issue is critical to current interpretation of determinations of nicotine exposure and dose. Most investigators assume that the outgassing does not contribute significantly to measures of exposure and dose as inferred by nicotine. Results reported by Eudy (1987) and RSP to nicotine ratios reported by Oldaker (Excerpta Medica International Congress Series 1989) indicate that such background levels caused by outgassing can represent a substantial portion of the nicotine actually measured in the air, and tierefore presumably, in body fluids. 5

MEASUREMENT METHODS FOR RSP The author defines RSP to include particles ranging below 2.5 Am; however, a11 the measurement methods listed in the table have cut points greater than this. How can use of such methods be supported? This reviewer questions whether some of the methods should be included. In addition, the concentration ranges of the methods are shown to depend on sampling time. For the integrated methods, sampling time is only one limitation. The author shuuld provide the reader with information on detectionn as controlled by the sensitivity of the balances available-for the integrated methods employing gravimetry. The author fails to recognize the availability of the portable air sampling system (PASS), which has been used to determine levels of RSP, UVPM, carbon monoxide, and nicotine in indoor environments as part of field surveys (McConnell, 1988; Carson, 1988; Drake, 1988; Proct3r, Environ. Technol. Lett. 1989; Crouse, 1988, 1989). In addressing the "detailed comparative study" (Ingebrethsen, 1988), the author neglects to mention the methotf-for dei:erodning ultraviolet particulate matter (UVPM), whi ch al so• vras d-i scua:;cd i n the ttud,.7 The UVPM method shoul d be addressed to ensure completeness. MEASUREMENT METHODS FOR NICOTINE The author provides but scant information on the XAD-4 based method, which has been used to provide the greatest amount of inforination on exposures to ETS nicotine. In addition, the author fails to recognize use of Tenax for collecting nicotine (Jenkins, 1988; Thompson, 1989). The author should omit the discussion dealing with "small annular denuder systems," because papers on this subject have not been published. GD Qn J ~ lU 6 p O

i I L Comments with references on "Measuring exposure to Environmental Tobacco Smoke" Submitted by: Dr. Paul R. Nelson, R.J. Reynolds Tobac:co Co. A major problem with this text is the omission of the references. Without these, it is impossible to verify that the claims mada about selected pieces of research are indeed representative of the work t:hat has been performed. Additionally, it makes judgements about the completeness and balance of background research impossible. Overall, this chapter does not contain a full set of references for statements made throughout the chapter. Specific references which are missing are included with this document, and passages of text which the author should be required to substantiate with references or deleteare also indicated. In the introduction, the author makes refelrence to measurements of hydroproline, N-nitrosoproline, aromatic amines, genotoxicity, and protein or DNA adducts in biological fluids as indicators of exposure to ETS or mainstream smoke. As this chapter deals with measurement of exposure to ETS, only those methods which can be used to assess exposure to ETS should be included. Without access to the specific references, it is not possible to asses the relevance or specificity of these measures to ETS, and this shouLd be done by the author. Additionally genotoxici,ty of and DNA adducts in biological fluids may also be caused by non-ETS sources. This may render the use of these tests inappropriate for consideration or mention in this chapter. The validity of self reported data on questionnaires (p. 52, para. 2) should be taken into account. References•should be provided to demonstrate the validity of self-reported exposure to ETS. The modeling approach described on page 54 and detailed in chapter 7 is not based upon representative sampling, and its app:.icability to this chapter is questionable. Additionally there are many questions about the validity of the model and its underlying assumptions, which are tD be dealt with elsewhere. Furthermore, it should be pointed out that the model. of Repace et: al., is not the only model which had been proposed to model ETS behavior. Several additional models have been advanced [(Rickert,1988) (Robinson,1988) (Nazaroff,1989,2 refs.)] and these are included in the appendix 'to this text. Before any model is advocated (as on p. 54) the relative merits and applicability of the models to a wide variety of sampling conditions must be performed. The reference to over 4000 air contaminants in the gas and particulate phase of ETS requires reference and clarification. First (First,1985) reports that >2300, or perhaps >3000 compounds have been idi~ntified in tobacco smoke; however, in order to state that >4000 contaminants are present in ETS requires that positive confirmation of this many compounds in ETS be documented in the literature. The presence of these compounds at trace levels in mainstream and sidestr-eam smoke does not justify the conclusion that all are present in ETS, nor does the actual number bear particular relevance to measurement of ETS. Relatively few compounds are present in sufficient coilcentration to permit their measurement in ETS. A balanced selection of references should be provided for the compounds measured in ETS presented at the top of page 56. Since this chapter deals with exposure measurement to ETS, multiple references 1:o each analyte should be

L1 I L provided which include sensitivity, detection-limits, possible interferences and concentrations typically encountered in real world settings. Discussion of and proper references to the analysis of these compounds in ETS and the environment in general is relevant to this chapter, and it should be included in more detail. It should also be noted that the tables in chapter six referenced in the same paragraph are incomplete. Only nicotine and RSP measurements are reported in the tables for ETS measurements. Sterling et al. hare prepared an excellent review of results reported prior to 1982 (Sterling,198?.), which includes tables of many compounds measured in ETS, and also provides available information on sampling conditions as well. The author should either prepare similar tables based upon all available data generated to date, or seek Dr. Sterling's permission to include his table in this document. It :ahould also be noted that the data presented in the tables in chapter 6 represen-: only a small segment of the total amount of ETS research which has been performe:d to date. (For example, see references in review by Sterling et al.) Additionally, several recent developments in ETS markers have been overlooked. Solanesol has been proposed as a marker for the particulate phase of ETS [ (Ogden, 1988) (Benner,1989)]. This compound has an advantage in that it is tobacco specific, and can be used to estimate the contribution of ETS to RSP. UVPM and FPM have also been reported as being reasonably specific markers of ETS particulate [(Conner,in press), Dr. Michael Ogden has presented this several places also]. Additionally, ethenylpyridine has been used as a marker for the vapor phase of ETS [(Thome, 1986) (Eatough,1988,EPA/APCA)]. This compound is also tobacco specific, and does not suffer from son:e of the decay problems associated with nicotine [(Baker,1988) (Eatough,1988,Indoor&Ambient Air Quality)]. Other markers have also been evaluated by Eatough et al. (Eatough,1989). Item 2 in the section of page 56 on the use of RSP as a marker requires reference. Specifically, what compounds of health concern are found in the particulate phase of ETS, who found them, and how do those concentrations compare with exposure limits. If the concentrations are "insignificant" by comparison to exposure limits item two should be dropped from thi: text. Items 3 & 4 in the same section also require reference. These statements cannot be considered general knowledge, and specific re::erences which prove their veracity must be provided. If they cannot be substantiated, then they should be dropped from the manuscript. On page 57, items one and two under the heading drawbacks with the use of RSP are related and should be combined under one heading. Additionally it should be noted from the data in figure 3 and table 4 of chapter 6 that tobacco smoke generally contributed less than 50% of the respirable suspended particles detected in homes. RSP levels in homes with no smoker:: were only 33% lower that in homes with one smoker, and 50% lower in homes with 2+ smokers (based on table 4). On page 57, Item two in the discussion of nicotine needs a reference. Once again, this is not a"point of common knowledge. Also, smokers smoke cigarettes on a per cigarette basis, not a on gram of tobacco basis. Therefore it is important to relate emission of nicotine to the smoking of a number of cigarettes, not just to the actual mass of tobacco consumed.

Item four in the discussion of nicotine is untrue, and it is not supported by the balance of available literature. When Kentucky reference cigarettes were smokel in a static cham~er by Ogden et al. (Ogden,1988,), the ratio of RSP (µg/m ) to nicotine (µg/m ) was found to be 14.7. When the same cigarettes were smoked in the same chamber under different conditicns, a ratio of 5.5 was obtained by Nelson et al. (Nelson,1989) In the work by Dgden et al. (Ogden,1988) 5 different types of cigarette were smoked under identical conditions, and RSP/nicotine ratios varied between 13 and 23. When one examines field studies, the variation in nicotine/RSP ratios continues to increase. In offices and bars in which smoking had taken place, Kirk et al. (Kirk,1988) found RSP/nicotine ratios which varied from 11.5 to 53. Oldaker et al.(Oldaker,1989), found that ratios in offices, restaurants and airplane passenger cs.bins were 30.8:1 (n-118), 22.5:1 (n-153) and 4.4:1 (n-44). Additionally, for the case of restaurant and office data, the correlation coefficient between RSP a1d nicotine were .236 and .198 respectively. These results indicate that any relationship between RSP and nicotine concentrations in smokey atmospheres is tenuous at best. Based upon the above referenced literature, nicotine does not vary with ETS related RSP as stated in item four of the nicotine discussion. Other researchers have examined the decay rates of nicotine and other ETS constituents in environmental chambers [(Heavner,1986) (Baker,1988) (Tang et al, 1989 APCA,in press)] and found that nicotine does not behave in a manner similar to other ETS constituents. These results also contradict the con:lusion in item 6 of the nicotine discussion. Because nicotine is not truly z.ssociated with other ETS constituents, nicotine and cotinine in physiological fluids do not provide a link between air concentrations of ETS and internal dose. Item two in the discussion of drawbacks of the ratio of nicotine to other vapor and particulate phase ETS constituents under a variety of conditions does not take the large amount of data in the literature ii.z which a large number of constituents have been measured into account. Sterling's (Sterling,1982) review gives data for a large number of constituents, and same relationships between nicotine and other compounds can be derived from his report. Additionally, multiple components have been measured in a number of other literature reports. [(Proctor,1989) (Sterling,1989)] In the section on the measurement of nicotine ani RSP in the air on p. 58, the statement that nicotine may be indicative of out:gassing from surfaces of other volatile ETS components is speculative, anc. not backed up by the literature. On P. 60, it is stated that "Gravimetric particles mass measurement methods are considered a standard method on particle mass measurement." References to this statement should be given. no The review annular denuder method outlined on page 62 is not yet published, of its effectiveness had been made by indeDendent laboratories. and It is likely that there are a great number of unpublished methods for many ETS analytes, however, this document should be concerned only with those which have 'M been presented in the literature, and for which there Ls good agreement on their effectiveness. Cn ~ .~ N O W

REFERENCES All references in this section are cited in detail in the bibliography associated with responses prepared at R.J. Reynolds. R.R. Baker, et al., Indoor & Ambient AIr Quality, p.121 (1988) C.L. Benner, et al, Environ. Sci. Technol., 23, 688 (1989) D.J. Eatough, et al., Proceedings of the 1988 EPA/AP:A International Symposium on Measurement of Toxic and Related Air Pollutants, p. 739 (1988) D.J. Eatough, et al., Indoor Air & Ambient Air Qualii_y, p. 131 (1988) D.J. Eatough, et al., Environment International, 15, 19 (1989) M.W. First, Indoor Air and Human Health, p. 195 (1985) P.W.W Kirk, et al., Indoor & Ambient Air Quality, p. 99 (1988) D.L: Heavner, et al., Proceedings of 79th annual APCA meeting, 86-37.9 (1986) W.W. Nazaroff, et al., Environ. Sci. Technol., 23, 157 (1989) W.W. Nazaroff, et al., Environment International, 15, 567 (1989) P.R. Nelson, et al., Present and Future of Indoor Air Quality, p. 277 (1989) G.B. Oldaker, et al., Present and Future of Indoor Air Quality, p. 287 (1989) C.J. Proctor, et al., Present and Future of Indoor Air Quality, p. 169 (1989) W.S. Rickert, et al., Can. Journal of Pub. Health, 79, S33 (1988) D.P. Robinson, et al., Indoor & Ambient Air Quality, 1>. 67 (1988) T. Sterling, et a1.; J. Air Pollution Control Assoc., 32, 250 (1982) T. Sterling, Indoor & Ambient Air Quality, p. 89 (1988) F.A. Thome, et al., Proceedings of the 79th APCA confe.rence, 86-37.6 (1986)

IL ii , I I 17' F L F II Comments by Dr. Guy B. Oldaker III on CHAPTER 6 EXPOSURES TO AIR POLLUTANT> General Comments Chapter 6 is in rough draft (as distinguished from final draft) form. The title of the chapter is inconsistent with the subject of text and the Compendium. Several key references are unavailable. The chapter.relies too much on work done by the Harvard School of Public Health in the residential environmental category and neglects the literature dealing with assessments of exposure in public places, which are the clear interests of the stated, intended users of the Compendium: "decision-makers such as labor and management officials concerned with workplace exposures, public health officials and corporate medical directors who are concerned with making health policy recommendations, educators, industrial hygienists and safety officers, ETS researchers, indoor pollution investigators, and legislators who are considering legislation to restrict smoking in workplaces, restaurants, and puElic access buildings." If this chapter is to be useful, it must be revised and expanded substantially. The chapter needs an Introduction. Specific Comments Time Activity Patterns The time-activity data reported by Quakenboss et a1. and summarized in Tables I and II is, in its present form, of questionable representativeness because roughly half the subjects included are students. 'The authors should provide representati-ve time-activity data or address how their reported data relate to the population.

i_ The paragraph dealing with time-activity patterns of infants that appears on pages 65 and 66 shoul.d be omitted since it provides assentially no information j' useful for the intended users of the Compendium. Figure 1 also should be omitted for the same reason. Environmental Tobacco Smoke 'i co On page 67 the authors define ETS as a mixture of exhaled mainstream smoke and sidestream smoke. The following definitiop is more accurate and therefore is recommended: ETS is the diluted, aged mixture of exhalesi mainstream smoke and sidestream smoke that occurs in spaces occupied by smokers. Composition of ETS The use of sidestream data, and by extension sidestream to mainstream ratios, suffers from too many assumptions to justify inclusion within the chapter. Discussions based upon these concepts should be omitted. The relations between sidestream data and ETS levels are currently unknown. Scientific ignorance reflects two problem areas: (a) methods for sampling and analyzing sidestream smoke components have not been applied consistently, and (b) currently available data from,sidestream measurements are of either unkrown or inadequate quality. Research has shown that the method of sample collection can have a profound effect on results from sidestream analyses. As a final note, the table refers to data for the analysis of nonfilter cigarettes, clearly, a nonrepresentative portion of the U.S. market. Measurement of ETS L L L The authors state correctly that most researchers have measured one or more compounds to estimate total exposure to ETS. The text, however, is inconsistent with this statement inasmuch as it neglects most of the literature where more than one compound was measured. Similarly, the authors point to the need to estimate ETS exposure by measuring more than one indicator, yet they present results from but one investigation involving the measurement of more than one indicator. The authors address "possible" measures of ETS, namely, particles, nicotine, cadmium, and nitrosamine. They fail to identify. that cadmium and nitrosamine 2 R : ~

f are impractical and non-specific. Discussions dealing with these two substances should be omitted. The Compendium needs better coordination among chapters, as these two possible measures are inconsistent with t)ose identified in Chapter 5 by Leaderer. Exposures to Environmental Tobacco Smoke P Overall ETS exposure will depend on the proximity of an individual to the source of the smoke. This statement, which is obvious to the layperson, is seemingly overlooked by Repace in his presentation of (invalidated) equilibrium models. The authors of the two chapters should revise their work to~ address this inconsistency. S The second paragraph of- this section contains information important to the stated users of the Compendium, namely, that :.moking between different demographic groups can vary widely. The authors should elaborate on this issue, particularly with respect to how it might affect'expusures in public places and the workplace. This reviewer recommends that the authors of Chapter 6 work with the author of Chapter 7 in addressing how this issue affects one of the main assumptions of the equilibrium model. MICROENVIRONMENTAL MEASUREMENTS OF CONCENTRATIONS Concentrations of Particles and'ETS I L The authors state that numerous studies have been conducted using RSP as a marker of ETS arrd that the number of cigarettes smoked have shown to be correlated well with RSP. These studies need to be identified and the strengths of correlations and significance levels need to be provided. On page 69, first paragraph, the- last sentence would not be misleading if rewritten to read: "Each smoker in the home was associated with an increased RSP level of 20 ug/m3.° On page 69, second paragraph, the last sentence is speculation; should consider revising it to read: "The cause of this increase however, one hypothetical cause is recirculation of indoor air conditioning system that reduced dilution of cigarette smoke." 3 the authors is unknown; ab by the air CZ) .~ ~ US O a

The authors note that results of the [Six City Study] indicated that each smoker in the home raised the mean RSP level by 20 ug/m3. The significance of this increase in terms of expected health effects should be addressed. In addition, descriptive statistics quantifying the quality of these calculated results should be provided. The same follows for discussions deriving from work reported by Dockery and Spengler (1981), Spengler and colleagues (1986), and McCarthy et a1. (1987). C i. Particulate Concentration in Offices The selection of literature citations, which are relai:ively old, shows only that the authors relied on their own publications or ised previously published reviews from 1986. These reviews ignore the review prepared by Sterling and coworkers (1982) which is more complete. In citing work by Weber and Fischer (1980) the au-:hors fail to address the representativeness of the results. Weber and Fischer described an investigation done in Switzerland where heating ventilating and air conditioning. systems differ from those in the U.S. Nor do the authors recognize that the piezoelectric balance used by Weber and Fischer (as well as Quant, 1982) provided biased RSP results because the cut point was 3.5 gm, rather than the 2.5 um defined by the authors of the chapter. The authors summarize results reported by Quant (1982) and provide Figure 4 showing "Aerosol Mass Concentration in R&D Office." The paragraph contains insufficient information to allow interpretation o-F the results and figure. The authors should revise the paragraph to address the significance of the results. They also should consider adjusting results for background levels of RSP; otherwise, the reader is apt to be misled. The authors' presentation of results reported by Miesner (1988) is inconsistent with the treatment given for those reported by Weber and Fischer (1980) and Quant (1982). Thus, ranges are presented rather than means as was the case for the earlier paragraphs. In addition to being inconsistent, this manner of presentation conceals from the reader the general observation that exposure distributions are lognormally distributed and consequently that extreme values are generally rare'occurrences. 4

Particulate Concentration in Offices [sic] [page 70] r r i:< The reviewer assumes here that the title should have read: "Particulate Concentrations in Public Places other than Offices." The authors cite only work by Repace and Lowery (1980) and Miesner et al. (1988). The authors have overlooked most of the pu')lished work in this area. For reasons described above, the RSP results reported by Repace and Lowrey are biased high because they used a piezoelectric balam:e. -(Questions of quality assurance still remain.) In the first paragraph of this section, the last sentence needs to be corrected. , The authors state that particulate levels were low, usually less than 30 ug/m3. In the same paragraph they state that a concentration of 63 ,Lg/m3 is slightly higher. Later, they note that higher concentrations still were found in smoking areas such as bars, restaurants and a public smoking ^oom with a mean integrated measurement of 79 µg/m3 and a standard deviation of 44 µg/m3. These statements are critical to the entire Compendium because they provide quantitative results and statistics along with a discussion that provide readers with some perspective on the interpretation of results. Two issues are important here: (a) quantitatively, what constitutes "low," and (b) the variability shown by real-world measures of ETS constituents. The authors of Chapter 6 should address the results they review based upon levels less than or equal to 30 Ug/m3 being "low" and levels at 63 ,tg/3 being "slightly hiqher." Likewise authors of other chapters containing concentration data should do the same to ensure consistency. Additionally, the authors of Chapter 6 should discuss more fully in this section the-practical significance of the relative standard deviation they find: 56 %. Finally, the author of Chapter 7 should consider the implications of this relative standard deviation on attempts to construct equilibrium models of ETS exposure. Concentration of Other Components of ETS U The authors state that McCarthy et al. (1987) found average nicotine concentrations of 4.2 ug/m3 in smoking households. The authors should address the significance of this result. In its present form the paragraph is 5 X_

ambiguous; thus, if 0.1 Kg/m3 is "low," what does a concentration of 4.2 Ag/3 imply? The authors provide a "selection of ... studies [where integrated readings were used to determine nicotine levels in offices and puElic buildings] in Table 7. This "selection," because it contains relatively old citations and ignores most of the research done in this area, provides an inaccurate view of results. The authors should revise this section and the Table to provide the reader with useful information. In addition, Table 6 should Ee revised to exclude some results reported. The results reported by Hinds and First (1975) and Weber and Fischer (1980) rely on invalid methods (Badre et a1., 1978). The results reported by Badre et a1. (1978) for the "Room" and the "Car" were not obtained under realistic conditions. Following discussions dealing with determinations of' ETS nicotine, the authors provide three paragraphs touching upon measurements of cadmium, nitrosamines, and benzene. These paragraphs do not address the subjects adequately and speculate on the validity of the substances as indicators of ETS; because of these deficiencies, the paragraphs should be omittei. The work of Lebret and coworkers (1987) figures prominently in the section as well as the Chapter; however, the literature citations contain no mention of this work. The significance of the results from determinations of cadmium are never stated nor is any information given relative to the reliability of this marker for assessing exposure to ETS. A similar situation exists with respect to nitrosamines (Brunnemann et al., 1978), the methodDlogy for which has yet to be used to assess exposures in the context of surveys. The work of Wallace et al. (1987) is cited in connection with exposures to benzene. Although the text indicates that the exposures of nonsmokers during the fall and winter (but not during the spring and summer) were elevated relative to nonsmokers not reporting ETS exposure, the magnitude of this elevation and the biological significance of this.elevation are not addressed. Furthermore, ro information is presented regarding the practical utility of benzene as an indicator of ETS exposure. Personal Exposures L The authors note that results reported by McCarth;f et al. (1987) show that children from nonsmoking families show mean exposure to RSP 27 µg/m3 higher than that for those of Smoking households. The significance of this difference is 6

L:J I I L L not addressed;•-thus, is this mean exposure "low," "medium," or "high."? Based upon the authors' previous discussions, this 27 µg/m3 exposure might be presumed to be "low." A similar situation exists for the case of nicotine exposures. This reviewer notes that the RSP to nicotine rati3s for these two exposure categories are 97:1 and 22:1, respectively. These ratio values are inconsistent with speculations made in the Compendium to the effect that RSP might be predicted from nicotine and vice versa. The author cif Chapter 7 evaluates data such as these assuming a 13:1 ratio between RSP and nicotine (Repace, Environ. Sci. Technol. 1988). Applying this evaluation approiLch to the results reported by McCarthy et al. would lead to the following conclusions: (a) the RSP method is biased high, causing RSP results to overestimate ETS exposure substant•ially; (b) the nicotine method is biased low; or (c) the 13:1 ratio, which is derived from measurements of unrealistically high levels of ETS in an environmental chamber, does not generally apply to real-world settings. This reviewer recommends strongly that the authors of chapters a.ddressing RSP to nicotine ratios revise their work to produce discussions consistent with experimental results. The authors cite work by Spengler et al. (1985;1 in connection with 101 nonsmoking volunteers and state that results showed that personal exposure to RSP was not correlated with outdoor concentrations but that ETS significantly increased an individuals [sic] personal concentration profile. The authors should provide quantitative results for the measurements and the statistics. The concluding sentence of this paragraph is probably more accurate if phrased: "... reported exposure to ETS was associated with a statistically significant increase in personal concentration profile." The authors also should define "personal, concentration profile." The authors present results in connection with deti!rminations of cotinine in body fluids. Because the subject is treated superficially, users of the Compendium can be expected to derive little benefit from its current inclusion in the chapter. The authors should either expand on this subject or omit it from the text. The authors note that they measured cotinine in urine and saliva of ch.ildren and found a high correlation with reported exposure. The magnitude and strength of this association need to be provided. They follow this presentation with results which cause ambiguity: Coultas et al. (1987) measured 7 d

cotinine in a significant number of subjects claiming no ETS exposure. What does this mean? Summary In summarizing the chapter, the authors conclude that ETS can be a substantial contributor to the indoor air pollution concentratioi of benzene, acrolein, N- nitrosamine, pyrene, and carbon monoxide; however, their text supports the "substantial contribution" of none of these. They also conclude that measured exposures to RSP are higher for nonsmokers who report exposure to ETS; however, they address neither the magnitude nor the significance of this higher exposure. REFERENCES The text does not cite all the references in this chapter. L

Comments by Dr. Guy B. Oldaker III on CHAPTER 7 EXPOSURE ASSESSMENT IN PASSIVE SMOKING f -a General Comments This chapter presents a model for estimating exposures to respirable suspended particles associated with ETS. This model has as its major assumption that ETS in rooms being modeled is in an equilibrium sti,te. This assumption of equilibrium has not been demonstrated with experimental measurements nor is it consistent with common experience. Thus, the model aisumes that smoke is evenly distributed, ventilation likewise is even, there are no drafts, and there are no temperature gradients from floor to ceiling. Anyoie who has observed a smoke plume rising from a cigarette knows these assumptions are not generally true in real-world settings. Despite the author's assertions that the model has been validated, this is not the case for the application of the model to field measurements. The literature shows only that the model can be fit to data obt<<ined in nonrepresentative experimental settings where unrealistically high levels of ETS RSP are produced with ventilation conditions maintained to ensure thorough mixing and therefore the necessary equilibrium condition. Thus, when equilibrium conditions are forced, the model applies, as it should based upon elementary physical principles. The author seemingly overlooks the basic scientific paradigm for validating a model. According to this paradigm, the model and its assumptions are defined for the experimental setting to be modeled. The model is then used to predict the results of experimental measurements. Then, the experimental measurements are performed after which these are compared to the predictions of the model. The validity of the model is established based upon quantitative, measures of agreement for the experimental settinas of interest. Gr) Ch . ~ I L W

The author's model has not been through this paradigm. Instead, the author approaches the validation process in reverse so that the model is, in effect, used to postdict rather than to predict results from measurements performed in the field. Because the input parameters of the model contain so many assumptions and admit such wide ranges of reasonable values (NAS, 1986), the model can be easily (and "reasonably") adjusted to produce results that agree with any set of environmental measurements. A model that predicts everything, predicts nothing. L L U L- The author provides several examples of experimental results for which he.can adjust the model to produce similar results. A subAantial body of research, including more reliable RSP data, exists providing results which are inconsistent with the some of the fundamental parameters assumed for the model. The author fails to recognize this research. To those who would use this chapter, Mr. Repace is potentially doing a great disservice, because he has neglected to address adequately the assumptions of the model. By its very nature, modeling is the cost effective alternative to measurement; thus, the many of the potential users of this compendium would be expected to perform modeling in lieu of making measilrements themselves. Such users will probably not recognize the assumptions a,:tending use of this model and will instead calculate numbers and assume that Mr. Repace has done the thinking for them. In his exposition, Mr. Repace has not adequately developed and presented his assumptions nor has he presented the logical pathways connecting his selection of values for input parameters, their calculation, and their interpretation. Moreover, Mr. Repace has presented a model which represents the ideal, rather than the real. Some information presented by the author of Chapter 7 is inconsistent with information presented by the authors of Chapters 5 and 6. This reviewer recommends that Mr. Repace consult with these authors to ensure that the Compendium is internally consistent. Some of Mr. Repace's literature citations are not sufficiently specific, thus, making it impractical for the reader to return to the original source to obtain suppofting or supplementary information. The author should at a minimum provide page numbers in connection with: "NRC, 1986"; "IARC, 1987"; and "SG, 1986." The author also should consider citing the IARC publication in greater detail. Mr. 2 L

Repace is the author of the chapter in-the IARC publication that contains most if not all of the material being cited in Chapter 7 of the Compendium. Although brevity and modesty are important considerations he're, it would be far better to identify the author, since some readers may be apt to assume incorrectly that the literature citation constitutes approval of the model by that organization rather than simply publication. Indeed, the IARC (1987, page ii) makes it clear that they do not necessarily support the model: "The authors alone are responsible for the views expressed in the signed articles in this publication." This reviewer strongly recommends that Chapter 7 be omitted from the Compendium because the model, which is the basis for the Chapter, has neither been validated nor.is it consistent with results from aasessments of ETS exposure done in real-world settings. Specific comments for each of the sections of Chapter 7 are provided below. Specific Comments Introduction L u The first sentence of the Introduction accurately presents the current situation regarding•assessment of exposure to ETS: There are currently no direct measures of the dose of ETS absorbed in a population under study; however, expo:;ures to ETS can be assessed by personal air contaminant monitoring, modeling of concentrations (based upon air sampling, time activity patterns, and questionnaires), or biological markers. (NRC, 1986) This sentence, however, does.not include the use of modeling by itself. Mr. Repace states that the concentration [of ETS] is directly proportional to the product of the number of smokers, smoking rate, and emissions per tobacco product, etc. This statement represents the theoretical rather than the real 3

world situation. The author should revise the paragraph to make this distinction. The author states that it has been shown that those nonsmokers who report exposure to ETS at home tend to have higher non-domes-tic exposures as well. The author should identify how the non-domestic exposures were assessed. Mr. Repace states that a majority of studies has used RSP as the indicator of ETS exposure. This is not supported by the record of the scientific literature. In fact, RSP, because of its lack of specificity foi•.ETS has been used in the minority of studies. The author fails to recognize tliose surveys which have not used RSP as the indicator nor does he make it clear to the reader why the majority of studies did not use RSP as the inJicator: RSP will always overestimate ETS exposure unless some means is takel to apportion for sources of RSP other than ETS. Other indicators include ultraviolet particulate matter (UVPM, an upper estimate of the contribution of ETS to RSP (e.g., Carson, 1988), fluorescent particulate matter (FPM, a complement to UVPM (Ogden, TCRC 1989), and solanesol ((Ogden, Environ. Sci. Technol. 1989), an indicator specific to ETS RSP). Results from surveys including these indicators show that ETS RSP constitutes on average approximately 50 9'e of the indoor RSP (Oldaker, 1987), significantly and substantially less than the 85 % assumed by the author throughout the text. In addition, the author defines the size range of RSP to be < 2.5 gm; this size range is inconsistent with the size range used by the methods of the "majority of studies" referred to by the author: 3.5 um. By this definition, the experimental method used by the author and Dr. Lowrey (Repace and Lowrey, 1980) is inappropriate for determining RSP. Although Mr. Repace recognizes that the currently accepted cutpoint for defining RSP is 2.5 µm, he fails to inform the reader that the method used Mr. Lowrey and him were performed with a device having a cutpoint of 3.5 µm. The accuracy of 'this device is critically important because it provided all the supporting data from the field for the model. Additionally, Repace and Lowrey (1980) failed to address quality assurance activities taken when measurements of RSP were made. Ingebrethsen and coworkers (1988) have demonstrated that quality assurance activities are a necessary condition for obtaining reliable data froi devices such as the type 05 used by Repace and Lowrey. The author should addre::s the effect of the 3.5 ,im ~ ~ N ~ 4

iji C ( cutpoint on the model and the quality assurance measures taken in connection with the original measurements. At he bottom of page 79, Mr. Repace presents an ideal approach to assessing exposure which involves quantifying "the several thousand compounds in tobacco smoke"; he adds that the enormity of this task has led to simpler approaches. These statements misrepresent the science. An estimated 100 compounds have been identified in the ETS matrix. Because most of these compounds exist at but trace levels they are unsuited for use as indicators, thus simplifying the task of exposure assessment. The author should revise these sentences to present accurately the current science relative to assessing exposure to ETS. A. Sources of ETS t In presenting examples supporting the model, the author employs an argument that is logically incomplete and seemingly inconsistent. Mr. Repace presents results from measurements of nicotine or cotinine in body f'iuids, and by manipulating assumptions he is able to show that the model can "predict" RSP concentrations that are comparable to those from measurements of nicotine and cotinine in body fluids. If this relationship between RSP and nicotine and cotinine in body fluids is valid, then a similar relationship must exist between RSP and airborne ETS nicotine, thus implying that nicotine should be an ETS indicator on equal footing with RSP. If the example including nicotine and cotinine measurements is to be used, the author should address the relationship between RSP and airborne nicotine. Readers of Chapter 7 cannot use the model intelligently because the text does not provide enough detail about the parameters appearing in the model and the assumptions attending the parameters. For example, Mr. Repace states as fact that the average U.S. smoker smokes 32 cigarettes per day at a rate of 2 cigarettes per hour. This statement appears to be only the result of simple arithmetic. This smoking rate is one critical inpLt parameter to the model. In view of its importance it is absolutely essential that the*reader know: (a) the origin of data used for calculation, (b) the deriaation of the smoking rate, and (c) assumptions made and the likely effect on results. It is this reviewer's understanding that these values are obtained through elementary arithmetic operations drawing from the reported number of smokers in the U.S. in 1986, the number of cigarettes sold that year, and the number of hours 5 dD ~ N G't N ~

available in an average day in'which the cigarettes can be smoked, specifically, 16 hours. If this understanding is correct, the z;uthor is assuming that a cigarette sold is a cigarette smoked; common experienc:e tells us that the former will be greater than the latter. The effect of sales practices employed by the industry on these values is unknown. Additionally, the author is assuming that smokers and, more importantly, nonsmokers will report their status accurately. Again, common experience tells us that the number of actual smokers will be greater than the number reported. Based upon these considerations, one can assume that smoking rates assumed for the model might be biased high. However, without additional information; this reviewer and Mr. Repace can only speculate on the quality of the assumed estimates of smoking rates. Furthermore, Mr. Repace assumes that the average smoker consumes cigarettes at a constant'rate be it on the basis of times figured yearly, daily, or hourly, and that this constant rate of consumption is scaled proportionally to a sixteen-hour day. Information on the temporal variability of smoking rates in the U.S. population is not provided; the reviewer is unaware of such information. f L u Next Mr. Repace uses the observation that the average person spends 90 9'e of their time indoors and by extension the average sm3ker smokes 90 % of their cigarettes indoors. No information is available reyarding where people smoke be it indoors or out. Again, common experience suggests that. because of social concerns, smoking frequency will tend to be shiftec to outdoors. Assuming a homogeneous smoking population is inaccurate. Demographics tell us that smoking i s more preval ent among l ower and l ower middl e i ncome groups than among the upper middle and upper income groups. These groups where smoking is expected to be more prevalent are those also where we can expect a greater probability of occupations th'at entail outdoor work. In contrac'iction to this exposition, the author fails to adjust the smoking parameter for the fraction of time the population spends indoors. From these assumptions Mr. Repace derives a parameter that predicts that in any indoor setting with more than nine occupants and where smoking is permitted, 0.111 cigarettes should be observed smoking per person at any instant when observations are made. The author fails to provide any visual observations made to confirm this assumption in spite of the fact that this parameter is critical to the model and is easily measured. Much additional effort needs to be expended to assess the distribution of the values of this parameter for the microenvironments of interest. 6 L

Mr. Repace also notes that the percentage of the smoking population .has decreased over the last 30 years and then speculates that the increase in smoking rate may tend to offset the trend to lowering nonsmoker exposure to ETS. Mr. Repace has no data to address this issue. In the absence of such data, Mr. Repace should inform the reader that the smoking rate used by the model must be calculated from data for the year of interest. B. Indoor air transport of ETS L. ~. The author states that equilibrium models are best suited to evaluating and predicting ETS concentrations in field studies, particularly when average concentrations over a period of days or longer are of interest. This statement implies that equilibrium models are not particularly suited for applications with time frames less than "days." The author must provide the reader with quantitative criteria describing the time frames for which the model is suited. Scientifically, the implication that the model is unsuited for short time frames implies that the model is either invalid or suffers from great imprecision. Mr. Repace should address these issues. The use of an equilibrium model for evaluation purposes assumes that the model*.has been validated to the extent that it has been demonstrated to show agreement with results from field studies: the model employed by Mr. Repace has yet to be evaluated in this context. Indeed, common sense says this is so, for otherwise there would be no justification for the ongoing field studies being done to assess exposure to ETS. Mr. Repace states that Leaderer (1984) has given 3 detailed review of [the equilibrium] model. Leaderer did not. The NRC (1986) is the best reference and should be used instead. The author states that the most extensive use of the mass-balance equation for assessing RSP levels due to ETS in occupied spaces ias been due to Repace and Lowrey. To this reviewer's knowledge, only Repace arid Lowrey have applied this model outside of chamber settings. The author should make this clear. The au-thor notes that the model assumes equilibrium conditions and that errors are introduced when any of the generation or removal terms are intermittent. The generation of ETS is fundamentally an intermittent process. Such 7

intermittency is fundamental because the productior of ETS derives from two discrete parameters: (a) a smoker must exist, and (b) the smoker smokes but one cigarette at a time. Hence, the equilibrium model is fundamentally in error unless the number of smokers and number of cigarettes smoked per unit time is sufficiently large. To this end, Mr. Repace assume:: that nine occupants in a room will produce the condition required for equilibrium, specifically, that at any instant, one cigarette is burning. No error analysis has been presented in connection with the equilibrium model. Logically, t1is condition implies that the model is applicable only to rooms occupied by nine or more people, otherwise, the model will predict erroneously. The author should provide the reader with- estimates of the probable errors which would be introduced if fewer than nine persons were in the room to be modeled. Firthermore, this condition implies that the "derivative equations" presented by the author will predict erroneously. (This reviewer suspects that the utility of the model is severely limited because the number of places occupied by nine or more people is relatively few.) L1 The model presented by the author at equation (2) has no derivation for the constant term, 650. Derivation is important to the user because without it the user is unaware of assumptions being made. Thus, the term includes assumed smoking rates, RSP emission rates, mixing factors, ventilation rates, and sink rates. As noted previously, quality data on smoking rates are unavailable; such rates, however, could be determined experimentally ir each setting of interest. The users of the model could determine this information themselves, rather than assuming that the value given by Mr. Repace was accurate. RSP emission rates have not been established, primarily because the methods necessary for determining this parameter have not been applied consistently. Sink rates for RSP also have not been quantified; the absence of this information explains why investigators are researching this area. Finally, raixing factors are for all practical purposes the greatest, and therefore the most important, unknown. Common experience tells us that smoke is seldom distributed homogeneously within an air space. This lack of homogeneity explains why Leaderer and McCarthy in Chapters 5 and 6, respectively, correctly recognize that ETS concentrations (including RSP) exhibit temporal and spatial va-iability. This spatial variability has bearing on another issue relating to RSP exposure. Put simply, many persons potentially exposed can and do move away from the source of the smoke, an action which directly reflects the importance of the mixing factor in interpreting predicted exposures. This reviewer strongly recommends that the 8

author provide equations which allow users to supply values for as many of the input parameters as possible. The author speculates that gathering data on ... smoking rates or volume can substantially reduce the variability of the estimated RSP levels. This statement must be supported by an error analysis performed on the model. Additionally, Mr. Repace does not provide the reader with the means of applying such data to the equilibrium model. Users of the Compendium can be expected to forgo such measurements for convenience and instead rely on the model as presented in equation (2). Of all the parameters, the mixing factor is probably the only one which, if• refined with experimental measurements, would effect substantial reductions inn the variability of prediction. As those who assess exposure by measurement (as distinguished from modeling) know, actual measurement of exposure is far more easily performed than measurement of the mixing factor. Again, this explains why researchers continue to pursue exposure assessment rather than modeling. The National Research Council (NRC, 1986) correctly recognizes these limitations when they conclude that a better understanding of the variability of the input parameters is needed. Mr. Repace states that the International Agency for Research on Cancer (IARC) has published derivatives of equation (2) which incorporate advances in understanding. Readers may be misled into believing that publication reflects adequacy and acceptance. The author should provide a more complete citation, which would inform the reader that the author of this publication is Mr. Repace, presenting only elaborati.ons on the same theme. The author's statement that the derivatives of equation (2) incorporate advances in understanding is incorrect. In the IARC publication, the author has used only :;imple arithmetic to scale equation (2) for the number of observed smokers; such scaling violates the condition necessary for equilibrium and therefore is scientifically invalid. Mr. Repace attempts to show the "validity" of his model through use of data reported by Spengler and coworkers from the "Six City Study." Because his model includes so many assumptions with undefined ranges of values he is able (as anyone would) to use simple arithmetic to show agreement. He assumes that two "habitual smokers" in a household would double the ISP level from 20 ,%g/m3 to 40 µg/m3. He then assumes that if the 24-hour RSP average concentration is 40 ug/m3 then the 16-hour average would be 60 gg/m3. Wext, he assumes an average air exchange rate for the heating season for typical middle income housing and 9

asks the reader to trust a personal communication. This air exchange rate derives from a study of "older middle class homes" as distinguished from "typical middle income housing." (The reader must assume that the "Six City Study" included middle income housing.) He notes that these air exchange value were obtained during tests when the occupants were asked to keep windows and doors closed. Besides being nonrepresentative, these conditions would reduce measured ventilation rates thus leading the model to predict higher concentrations of RSP. ( L L Mr. Repace refers to time-budget studies in connection with assuming the number of cigarettes smoked per day in the homes. A citation to these studies should be provided. _ Mr. Repace next shows that by assuming that the air exchange rate is "only a third of a standard deviation from the 14-city mean' the RSP levels can be fit exactly. The author concludes by stating: "This example illustrates the utility of models in estimating nonsmokers' exposures to ETS." No; rather, this example illustrates only that by making a host of assumptions, agreement can be achieved. Mr. Repace does not provide enough information for the reader to understand the steps taken in the arithmetic. Mr. Repace should provide the 'process by which,he arrives at the value for the density of habitual smokers, Dhs, as well as the attendant assumptions. For example, it is unclear how the volumes within the household were obtained and what he means by a "two smoker" home. Mr. Repace states that the utility of equation 4 depends on the assumption of an air exchange •rate. This statement is misleading as well as untrue. The utility of equation 4 depends on a host of assumpticns many of which are buried in the "constant coefficient." In this same vein, Mr. Repace concludes that "this example illustrates the utility of models in estimating nonsmokers' exposure to ETS." Logically, the reader must return to the topic sentence of the paragraph; in so doing the reader is confronted with a circular argument, namely, that the illustrated utility of the model depends on the assumption of an air exchange rate. The circular argument illustrates only one truth: the model predictions can be fit to experimental data provided enough assumptions can be made. 10

Mr. Repace also concludes that his illustration provides results consistent with those shown in figure 5 for the "Six City Study." Without some quantitative information the subject of consistency admits broad interpretation, with one possible interpretation being that there. is no adequate degree of consistency to justify use of the model. One can reasonably assume that the heating season includes the months from October to March. To be valid and therefore useful the model must be able to predict the large variability shown in the results for the cases of one smoker and more than one smoker. It is important to note that the categories for the field results differ from those of the model results thus constraining the ability to compare between the two. Taking March 1978 as an example, field measurements show a mean RSP level of 35 µg/m3; by contrast the model predicts 44 µg/m3, a bias of 26 %. Mr. Repace apparently attaches significance to his prediction of 84 ug/m3 for his :,cenario of three "habitual smokers." How this result is consistent with a measured result for "greater than one smoker" (whether this average smoker is "habitual" is unknown) is unclear. 6 Mr. Repace provides another example to "validate" the model. He starts by noting the "large impact" caused by smoking on the levels of RSP. This "large impact" is 10 ug/m3 for an assumed occupation of the room by one "habitual smoker." If the author is to make such a statement it would be instructive to know what represents a "low impact." Mr. Repace next proceeds to calculate the RSP level for the case of a chain smoker, one, who according to Mr. Repace, is consuming cigarettes at a rate of six cigarettes per hour. The reader can only assume the purpose of this example, since its representat'iveness is unknown and since it delves into the world of the bizarre. Is the reader to assume that this smoking rate continues (as it must if the model is to be appropriate as defined by Mr. Repace)? If this assumption is taken to its illogical end, the reader must conclude that the person is smoking almost five packs of cigarettes per day and gobbling food between puffs. In the same paragraph Mr. Repace notes that ETS can be very persistent, taking, for example, 3 hours for 95 % removal. The reader can only speculate why this factor was riot taken into account when Mr. Repace "modeled" RSP in the forgoing example dealing with homes. Instead he assumes that RSP exists only during the 16 hours he associates with the "habitual smoker" being awake. . Cb Mr. Repace then shares with the reader "several interesting factors" revealed ~ by recent research. He relies on a personal communication to provide this N Ctt 11 W

i information. Although it is certainly possible that floor-to-floor communication of RSP can occur, the significance of such communication and its representativeness are unknown. Mr. Repace is specul,iting; the paragraph should either be omitted or the above issue should be addressed with scientific data. The paragraph discussing work by Williams and coworkers should be omitted. Green and coworkers (1985) published a letter (In the same journal that contained the paper by Williams and coworkers) that discredited the method, results, and conclusions reported by Williams and coworkers. Following his citation- of the paper by Williams and coworkers, Mr. Repace presents results from surveys of air exchange rates done in offices. This information does not fit within the paragraph. P: can be assumed that the author might be attempting to make a point about values for air exchange rates in offices; however, the information he provides, specifically, only mean air exchange rates, is insufficient to be useful for one interested in assessing the assumption of his model. The information on air exchange rates might be useful if ranges and standard deviations were provided. Mr. Repace's summary to Section B is unsupported. To his credit he notes that "limited" field tests of the general equilibrium mcdel have been done. This reviewer is concerned that Mr. Repace may be statirn3 that the two examples he provides in the section represent the limited field i:ests. If these indeed are the limited field tests, then Mr. Repace is not applying the scientific paradigm, which would require that the model predictions be performed before the field measurement rather than after as he has done in all his manuscripts where the model is used. On the contrary, the model does not predict RSP levels reasonably well, rather, the model can be manipulated so that its "predictions" agree with results from field studies selected by author. Rather than being "clear that both models and observations ... yield consistent results," it is clear that whether they can or cannot is open to question. Mr. Repace's concluding statement in this paragraph is at odds with the data he uses to "validate" his model. If the statement "RSP levels wnen smoking is allowed will result in substantial increases over RSP levels ir nonsmoking occupancy" is true, how can it be that the Data of Figure 5 show essentially no differences among RSP levels in June 1977 for "outdoor," "indoor," "no smokers," and "indoor one smoker"? The reader deserves to know the meaning of "substantial" in quantitative terms. 12

I C. Measured concentrations of RSP From ETS t L 0 L Figure 8, which shows results from RSP measurements arid predictions and National Ambient Air Quality Standards (NAAQS) is inappropri<<te and should be omitted. Users of the Compendium can be expected to misunderstand and misinterpret this presentation. While there are several reasons why inclusion of NAAQS levels is inappropriate, the major one deals with averaging times. Assuming all other factors the same, the averaging times for the measurements and the standards must be the same for comparisons to be meaningful, as distinguished from appropriate. The U.S. EPA has algorithms which the author should use to adjust for averaging times. Even if all information was Fresented on the same time scale, discussions of exceedances would be meaningless, since from a regulatory standpoint criteria documents, standards, and reference methods do not exist. The data reported by Repace and Lowrey are on the timia scale of minutes. If the standards were adjusted to that same basis, it is reasonable to assume that all these data would be below adjusted "standards." If this presentation is to be included in the Compendium, the standards should be adjusted to time scales equivalent to those of the measured RSP values. Associating the Table with IARC is unnecessary and misleading; only the first published reference need be identified: Repace and Lowrey, 1980. The quality of the data reported by Repace and Lowrey in Figure 8 is unknown; nonetheless, it is known that these results are biased high because no apportionment was made for sources of RSP other than ETS. The degree of Has also is unknown. The representativeness of the sample population is qui!stionable. Results from surveys conducted since 1980 (Repace and Lowrey's experimental approach cannot properly be categorized as a survey) indicate that '2epace and Lowrey's sample population is probably nonrepresentative. Mr. Repace infers from his few measurements of questionable quality and representativeness that "the bulk of the RSP found in buildings where there is smoking is due to ETS." By selective referencing he is able to suggest that 85% of the indoor RSP in those buildings is due to ETS. Since 1980, surveys done in offices show mean RSP levels of approximately 125 µg/m3, a result indicating that Repace and Lowery's data base is probably biased. In addition, methods capable.of apportioning ETS have shown that less than half of the RSP found from surveys can be attributed to ETS (Ogden, TCRC 1989). Again, the data base of Repace and Lowrey is indicated to be biased. 13 L

Table 8 contains mostly old literature citations. Many more investigations have been conducted since this table was published in 1986. In addition, the reference to the U.S. Department of Transportation study done in aircraft cabins is incomplete since results were provided in that report. The mean level of RSP in cabins before smokers were segregated was only 40 ug/m3. (The reviewer recommends that Mr. Repace address this result with the equilibrium model.) Mr. Repace notes that in a setting such as a work environment, where the average exposure is several hours, ETS would be expected to disseminate throughout the airspace where smoking is occurring. Inasmuch as no data are available to support this speculation, the author should drop thi> statement from the text. Similarly, 'Mr. Repace speculates about exposures in transit and selectively references his paper (Repace, 1988) in connection with ETS in aircraft. Mr. Repace omits all otfier references surrounding his paper (Oldaker, Environ. Sci. Technol. 1987, 1988) and fails to inform the reader i:hat his position is based on an assumed relationship between RSP and nicotine. Specifically, Mr. Repace assumes that a constant ratio exists between the two indicators thereby allowing him to predict RSP from nicotine. Oldaker (Environ. Sci. Technol. 1988) has addressed some of the assumptions contained in this approach and Oldaker and coworkers (Excerpta Medica Interantional Congress Series 1989) have presented results showing that ratios have no predictive value. D. Exposure of Nonsmoking populations to ETS U The first paragraph of this section addresses risk, a subject which is inappropriate for•inclusion in view of the absence of risk assessment results. Mr. Repace identifies the Seventh Day Adventists as a subpopulation where few of its members are nonsmokers. The connection between this population and lung cancer incidence is unclear; the author should clarify the importance of this subgroup within the discussion. The author identifies cotinine as an indicator of exposure to ETS. Although cotinine is related to nicotine exposure because cotinine is a nicotine metabolite, the relation between cotinine levels in body fluids and exposure to ETS, as distinguished from nicotine, is currently unknown. Some investigators assume that the presence of cotinine in body fluids provides a lower estimate of exposure to ETS because of results from experiments in environmental chambers 14 Vv

that show nicotine to decay more rapidly than RSP. Although Eudy and coworkers (1987) have found appreciable background levels of nicotine in the absence of ETS in one setting, systematic investigations of this phenomenon have not been performed. Nonetheless, because nicotine can adsorb as well as desorb from surfaces of rooms, it is reasonable to assume that appreciable background levels of nicotine might exist in typical real-world settings, thus admitting the possibility that nicotine might overestimate exposure to ETS. In addition, it is known that this background can persist in the absence of RSP from ETS (Eudy, 1987), the implication being that cotinine might indicate only that exposure to nicotine has occurred, or, stated another way, tha1: nonsmokers have occupied spaces where smokers have been but where no ETS currently exists. The author notes: "The forgoing illustrates that exposure to ETS is very widespread in the population."•Based upon the uncertainties raised in the above paragraph, it is perhaps more accurate to state that exposure "appears" to be widespread. The author notes: "However, additional data on the Jistribution of smokers in the nonsmokers' environment as well as the distribLtion of ETS levels in the environment are needed in order to characterize the <<ctual ETS exposures of the population." This statement, which represents an a:curate description of the current understanding of ETS exposure, directly speaks to one of the assumptions of the equilibrium model: the distribution of smokers in nonsmokers' environments is unknown (this information is contained in the assumed term Mr. Repace identifies with Dhs). In addition, this statement speaks to the quality of the equilibrium model: if estimates provided by the model provided results of adequate quali'ty, then characterization of actual ETS exposures would be unnecessary. The author follows with the statement that in the absence of such data, population exposures can be estimated by models or by extrapolation from biological markers. Clearly both these approaches are valid, but only within the context of the statement; however, the quality of such estimates remains vague because the issue is not addressed within the text. The reviewer recommends that the author provide some information addressing the quality of such estimates. 15

E. Integrated Exposure Analysis 1J, L L I The author states: "Estimating the magnitude of the passive smoke dose is difficult, and it is of doubtful validity to extrapolate from the uptake of one marker to another." This statement, which correctly describes current understanding, contradicts many of the statements made earlier by the author. In sections above, the author states that estimates of the exposure of the population to ETS can be estimated by extrapolation from biological markers. Both these statements cannot be true. The author states: "under extreme conditions of incloor air pollution, it has been calculated that a nonsmoker would inhale volatile nitrosamines equivalent to 10 nonfilter cigarettes or 35 filter cigarettes." The significance of this statement is unclear and consequently it should either be revised or omitted. The extreme conditions are not described, thus admitting the possibility that they are unrealistic as is the case for most experiments addressing the uptake of ETS components. (ETS levels are typically made unrealistically high to enable'detection of ETS components in body fluids.) In addition, the author's choice of words implies fact, "would," rather than extrapolation and assumption, which would require use of "possibly might." The author's assumption that formation of cotinine from nicotine and clearance from the body does not differ substantially from non:,mokers to smokers need not be an assumption, because research indicates that this is false. The remainder of the paragraph is not supported and therefore should be omitted. Mr. Repace uses an RSP to nicotine ratio of 13:1 to calculate RSP levels which might have accompanied a mean nicotine concentration of 15 gg/m3. Use of ratios for predictive purposes is invalid (Oldaker and coworkers, Excerpta Medica Interantional Congress Series 1989). In addition, a 13:1 ratio is unjustified because the value was computed from results of an experiment done in an environmental chamber where the ETS levels were unrealistically high. Mr. Repace continues to address the ratio approach through mainstream and sidestream smoke. These are not ETS. The quality of sidestream data varies from unknown to poor. The use of ratios derived from these data is unsupported. The paragraph containing these speculations should tie omitted. 16 L

Because the paragraph going from page 89 to paqe 90 relies on so many assumptions, its message is speculation; the paragraph should be omitted. The author notes that these estimates must be interpreted with caution because they may substantially underestimate exposure to other components of ETS. In view of the assumptions made, the estimates should not be -interpreted at all. As for the cautionary note, this is pure speculation and therefore should be omitted-. L :. I The author correctly states that RSP lacks specificity for ETS; however, the extent of this lack of specificity is not given. The author also states that "the prevalence of smokers correlates well with RSP levels in homes and other enclosed areas." Descriptive statistics relating to this correlation should be included. Without such statistics, the reader may misunderstand the author by thinking that correlation implies prediction, which for the data provided by the "Six City Study" is not the case. The author also states that the "Six City Study" demonstrated that ETS exposures in the home ard at work were significant contributors to personal exposure to RSP. This statement should include statistics that quantify the significance of such exposures. Finally, the author states: "In general,'measurements in a large number of locations using measures of smoke generation such as the number of people smoking or the number of cigarettes being smoked have shown a definitive relationship of smoke generation to particulate levels." This statement is vague and therefore misleading. First, the conclusion is not-a generalization, because, as the author as stated several times before, the relationships have been assessed from a limited number of studies, where the author's analysis employed only the summary results from those studies. Thus, while the limited studies to which the author refers included a large number of locations, analysis was performed only on the summary results of the studies. The author chose not to include results of the majority of studies in his analysis. Finally, the author's use of the "phrase definitive relationship" is unclear since it is accompanied by no quantitative information. Although correlation can be interpreted as a "definitive relationship," correlation does not mean that the relationship can be used for prediction. The author also makes the blanket statement that "in U.S. homes, there are few other sources of RSP, and therefore, the relationships of RSP measurements to ETS are quite accurate." This statement is untrue and insupportable. Spengler and coworkers concluded that 50 % of the RSP in the studies of homes could be attributable to ETS. The accuracy of these relationships is, ,from the standpoint of prediction, not supported, again, 17 'L

because while correlation may be "accurate," the strength of correlation is too poor to allow predictions to be made. On page 90, Mr. Repace summarizes efforts in conne,:tion with the model. He states that the model was validated. The paper by Repace and Lowrey shows only that the model could be fit to data from experiments (lone in artificial settings as distinguished from real-world settings. Equilibrium conditions were imposed on these spaces and levels of RSP were excessive. Finally, these "demonstrations" did not address all the input parameters of the model, such as the number of habitual smokers, the smoking rate, the smoke generation rate, etc. To support the validity of the model, the authur cites work by Kuller and coworkers, which is not included with the references. Mr. Repace's discussions relating to probability-weighted exposures to ETS that appear in Table 13 cannot be followed. The reviewer recommends that the two paragraphs be revised to include literature citations supporting the values assumed as well as a development of the arithmetic used to obtain the estimates. In addition, the paragraphs should present the issumptions precisely and describe the extent to which the assumptions would be expected to affect the final results. In summarizing this section, Mr. Repace notes the disadvantages of the model and states that the NRC, Surgeon General, and IARC have utilized this data base ["the RSP-based estimates "] for exposure assessment purposes. Although this reviewer recognizes that the equilibrium model has been described in these documents, he is unaware that any of these organizations has used the model. The author should'cite publications describing use of the model. 18

Comments on Chapter 7: Exposure Assessment in Passive Smoking By: Dr. S. Keith Cole The statement is made that the RSP concentration is directly proportional to the product of the number of smokers, - smoking rate, and emmissions per tobacco product and inversely proportional to the product of the space volume and the removal rate. This is correct only in terms of the single compartment equilibrium model which assumes the gases are thoroughly and uniformly mixed. Th:Ls assumption has not been proven or even tested. Flow-dynam:Lc models might be more appropriate (see Horstman or Siurna and Bragg). It is stated that RSP and nicotine are i.he two most promising markers for ETS. Unless all sources of RSP can be accounted for RSP is not a good or even legitimate marker of ETS. Other sources may be present and iaay vary in time, creating unrealistic measures of RSP. Recent experiments have shown nicotine to decay rapidly in smoking environments due to adsorption to surfaces then to desorb over long periods of time. This makes measuremeni: of nicotine possible when there may not be any other ETS_components in the air, thus overestimating ETS exposure. The statement that RSP is the single largest component of ETS by weight is incorrect. Carbon dioxide and carbon monoxide are generated in larger quantities. The model proposed for predicting ETS exposures is only valid in the limit of a uniformly mixed gas. This limits application of the model to conditions where the residence time of the particular component (which depends upon details of the ventilation system, space geomet:_y, and physical characteristics of the component such as diffusion coefficient, etc.) is long compared to the decay time, whether this be due to chemical reaction, exhaust through the ventilation system, or a physical p:rocess such as adsorption or evaporation. The basic model is: Ceq = G / [m(Nv+Ns)V] where Ceq is the equilibrium concentration, G is the rate of generation of RSP in micrograms per hour, Nv is the ventilation or infiltration rate in air changes per hour (ACH), Ns is removal rate of RSP due to adsorption in ACH, and m is a mixing factor. A condensed Eorm of this.equation is presented as: Ceq = 650 Ds/Nv

where Ds is the density of active smokers per 100 m3 volume. The constant term is derived from average values assumed for RSP emission rates, building ventilatior. rates, mixing factors, and sink rates. Other derivative equations are provided which are supposed to adjust for intermittant smoking rates. Several questions arise from this presentation. What are these average values? Do any of the ave:rage values represent a realistic environment? For instance, the smoking rate used is presumably 2 cigare:ttes per hour per smoker as the author has used this value: in most previous publications. This is derived from the total number of cigarettes sold and the total number of smokers in the US. The author implies that since 90% of the: average persons time is spent indoors that 90% of all'ci.garettes are consumed indoors. Is this verifiable? If eight hours of sleep are allocated then the ammount of time indoors awake is reduced to 58% of a 24 hour day. Also, the•impression is given that all blue collar and white co].lar employment is indoors. Is it? How many cigarettes are smoked outdoors or in automobiles? Since the model is linear in all the variables it is extremely sensitive to such factors as smoking rate. In field studies conducted in aircraft, smoking rates of at most 0.5 to 0.6 cigZirettes per smoker per hour were observed (Drake and Johnson, submitted for publication to Aviation, Space, and Environmental Medicine, 1989). This lower smoking rate would reduce the estimated RSP concentration by 75%.' Perhaps more care should be taken in estimating or measuring smoke generation rates. In the field studies referenced such parameters as mixing factor and ventilation rate were not measured but were assumed. Since these factors are critical to the "predictive" power of the model they should be measured. The only validation of this model has been in controlled settings, i.e. chamber studies, where the air is mixed by fans. To my knowledge the model has noi: predicted RSP concentrations using accurately measured input parameters in the field. Regarding pathways for distribution of ]:TS through building ventilation systems the author is refer::ed to a publication by James Axley from the National Bureau of Standards that was prepared for the EPA and DOE (Indoo:: Air Quality Modeling - Phase II Report, NBSIR 87-3661). The treatment of recirculated air is presented for homes and could be extended to other mechanically ventilated structures. The following references are reported i;z the text but are missing from the reference list at the and of the chapter: Persily and Grot, 1986; Williams et al., 1985, IARC (1987).

In section C the author reports measured concentrations of RSP from ETS and states that the size r<inge of particles is less than.2.5 um. In the publications referenced (Repace and Lowrey, Science, 1980) the piezoelec:tric balance used was stated to have 100% efficiency for particles from 0.1 to 3.0 um diameter, 50% efficiency at 3.5 um, and 10% efficiency at 4.0 um. Was a device usec[ to restrict - measurements to particles less than 2.5 um diameter? If so, state what device was used and how it w<<s implemented. The author states that the weighted average RSP levels (taken from various publications) in buildings where smoking is permitted is 262 ug/m while in buildings with no smoking allowed it is 36 ug/m . The suggestion is then made that 85% of RSP in the buildings where smoking is allowed is due to smoking. First, what is the weighting procedure used to calculate the average, i.e. by occupancy or volume? Secondly, comparison of RSP levels between various buildings does not allow for such correlations as to the,origin of RSP. The author states that "under extreme conditions of indoor pollution, it has been calculated that a nonsmoker would inhale volatile nitrosamines equivalent to 10 nonfilter cigarettes or 35 filter cigarettes". The reference, which is missing from the reference list, is F[offmann and Hoffmann, Significance of Exposure to Sidestream Tobacco Smoke, in IARC, vol. 9 (1987), p.6. The more appropriate reference is to the original work of Brunnemann and Hoffmann, IARC Scientific Publications, No. 19, pp. 343-356. Review of this paper brings the statement referred to above into doubt. The only volatile nitrosamine detected in ambient air in the study by Brunnemann <<nd Hoffmann was NDMA. This compound is not specific to tobacco and is found in various substances in the environment. No other "ETS markers" were measured in the study. Also, the exposure to NDMA was given as a range of cigarette equivalents (9-10 nonfilter cigarettes, 17-35 filter ciga3-ettes) which depended on respiratory rate. Presenting only the upper bound of this range is misleading.

Review of Chapter 8 by D. Hoffmann, K. D. Brunnemann, and N. J. Haley of the draft Compendium of Technical Information on ETS edited by the Environmental Protection Agen.cy. L H Primary Reviewer: J. Donald deBethizy, Ph.D., D.A.B.T. Secondary Reviewers: Riley A. Davis, M.S. and David W. Eaker, Ph.D. Overall, Chapter 8 entitled "Absorption of smoke constituents by nonsmokers" by D. Hoffmann, K. D. Brunnema:ln, and N. J. Haley is well written and informative. The authors provide a concise and critical perspective on the many markers. that have been reported in the literature. However, the chapter can be improved considerably by addressing the following criticisms: . 1. Introduction. This section is somewhat anecdotal and needs to be tied to the literature better. For example, the definition of ETS in the first paragraph should be referenced. In addition, the discussion at the top of p. 96 about the SS smoke yield of ultra low and low yield cigarettes needs to ba referenced and more specific. The paper by Nelson et al. (1989) compares the ETS generated by smokers smoking cigarettes that vary in MS smoke yields. In fact, using this reference the a-.ithors could state that RSP, nicotine, formaldehyde, and acetaldehyde were 20 % lower in ETS generated by smokers smoking ultralow "tar"-yielding cigarettes compared to an equal number of full flavo::- low "tar" cigarettes (1R4F) instead of saying "a somewhat lower yield of SS is expected from the low-yield cigarettes". 2. Table 1. The tobacco-specific nitrosamine numbers reported in Table 1 may be artifactually high. The authors should point out that these data were collected prior to a report by Connors and Caldwell (1989) which reported artifactual nitrosamine formation on the Cambridge filter pads used to collect the SS smoke. These authors describe a method for eliminating artifactual formation of TSNA's by impregnating the pad with ascorbic acid. This paper should be referenced. 3. p. 96. lines 11, 12, 16, 22. These sentences should be rewritten to avoid the use of "polluted". This word conjures images of smokestacks belching black soot <<nd is not necessary in this document. 4. p. 96. lines 11 - 12. The authors should be specific about how much dilution of SS smoke takes place in indoor environments. It is important for readers of this chapter to realize that even though the yield of some chemicals from cigarettes is higher in the SS than in the MS smoke on a per cigarette basis (See Table 1 of the chapter), the dilution of the SS smoke in the environment is considerable. The dilution of these SS conponents in air reduces the exposure of nonsmokers by orders of mag:zitude when compared to L

the exposure of smokers to these same chemicals. For example, the SS yield of nicotine per cigarette is reported in Table 1 to be 2.5 to 21 times higher than the MS yield. However, the exposure to nicotine from ETS is generally 200 to 300 fold lower than smokers (See conclusion in Jarvis et al., 1984, ref. 41 in this chapter and summarized in Table 3 of this chapter). These data indicate that there is considerable- dilution of SS smake components in the environment and that its important to stress this fact.when presenting data shown in Table 1. Otherwise:, the public is done a disservice when reports appear in the lay prass that SS smoke is 10 times more toxic than MS smoke. r U L* I L 5. 'p. 96. line 25. The optimal assessment of ETS exposure would include bot analysis of physiological fluicls and the environment; not just fluids as suggested by the authors. It is important that the biomarker concentrations observed in the passively exposed individual be related to the environmental concentrations. Since the half-life of some of the biomarkers is very long (e.g. cotinine t 1/2 = 15 to 25 hr), there is the danger that ETS exposure could be attributed to the wrong environment if the relationship between environmental concentrations of ETS components and the physiological fluid concentrations are not confirmed. The limitations of saliva and blood for discriminating non-smokers and passive smokers has been discussed by Wall, et al-., 1988. These autors conclude that saliva and serum are nat appropriate matrices for discriminating non-smokers and passive smokers, but could be used to define active smokers. Factors which contribute to this lack of discrimination include: a) variance in nicotine metabolism, b) the time of day for sample collection, c) under-reporting of active smoking, d) adjustment of cigarette consumption for nicotine content, and e) over- and under-reporting of passive cigarette smoke exposure. 6. p. 96. The statement that the presence of nicotine and/or its metabolites in biological fluids is entirely due to the exposure to tobacco smoke may not be true. Sheen (1988) and Castro and Monji (1986) have demonstrated that nicotine is present in solanaceous vegetables such as potato, egg plant, tomato, and green pepper which are commonly consumed by humans. The contribution that nicotine in the diet makes to the baseline nicotine/cotinine in physiblogic fluids remains to be determined. However, with this data in the literature one cannot assume nicotine is "entirely" derived from tobacco. The statement should be modified to include references to these results. 7. p. 97. The statements about HPLC an<<lyses of nicotine and cotinine should be updated to include recent: literature. Cummings et al. (1989) used the Machacek and Jiang (1986) HPLC method to screen the urine of 663 never and ex-smokers for nicotine and cotinine. However, the mean cotinine concentrations were unusually

{ I L: .r high (9.5 ng/ml) for people who claimed to :not be exposed to ETS. One explanation for these high concentrations of cotinine may be interference of cotinine with caffeine using this HPLC method. Thuan et al. (1989) found that caffeine eluted between cotinine and the phenylimidazole internal standard causing interference with the cotinine determinations. This section should be expanded to include statements that describe the use of HPLC for nicotine and cotinine and point out its potential pit falls (Hariharan, et al., 1988). 8. p. 97. line 16. 3-hydroxycotinine must be derivatized because it is not sufficiently volatile for GC analysis and not readily soluble in organic extraction solvents. The line stating " not readily soluble" should be rewritten. 9. p. 97. The section on RIA techniques should address the concerns about the use of RIA for nicotine and cotinine at concentrations found in nonsmokers exposed to ETS which have been raised by Van Vunakis et al. (1987). The:se investigators have questioned the accuracy of the RIA, which wa.s optimized for use in active smokers, at the low concentrations encountered in the ETS exposed population. They state that cotinine concentrations below 10 ng/ml require the use of large sample volumes and data from a sub-optimal portion of the standard curve (< 5% inhibition by the antibodies). These limitations of the assay should be discussed and referenced. The detection limit for the RIA is frequently stated as being between 350 to 390 pg/mi for nicotine and cotinine, respectively. However the more important Limit of Quantitation has not been defined statistically. By definition there is a 30% chance of inaccuracy at the 95% confidence interval at the value of the Limit of Quantitation in any analytical technique. It is not unreasonable for the Limit of Quantitation to be stated for the application of,the RIA by the investigators reporting the data and the conditions from which the LOQ was derived. According to Van Vunakis, et al. (1987) increased sensitivity can not be derived from increasing the sample volume above 20 ul for urine samples and 0.2 ml for plasma samples. 10. p. 98. line 9. This statement should be expanded to include the reported cross reactivity of the cotinine antibody used in the RIA analyses with 3'-hydroxycotinine (301:; Schepers and Walk, 1988). 11. 1 p. 98. lines 10-11. It is unlikely that there is loss of cotin-ine during extraction prior to GC ana:lysis since all of the commonly used methods employ internal standard that would correct for losses. Thi,s statement should be delets:d or modified to point this out.(Davis, 1986; Curvall, Kazemi-Va:1a, and Enzell, 1982; Jacob, Wilson, and Benowitz, 1981). 12. p. 98. References to reference 33 in the second paragraph should probably be reference 32. 13. p. 98. Last paragraph. There is a broad range of values for

c t Ii L U L the half-life of cotinine in smokers and nonsmokers reported in the literature as implied by the authors. Since this paper will be read by those interested in using cotinine as a marker, the range of values reported in the literature shoL.ld be provided. The authors also imply that the difference in the cotinine half-lives between nicotine gum users and smokers is significant without providing some assurance that the difference is statistically significant. The statement on page 98 that.the longer half-life of cotinine in nonsmokers suggest that the residence time of nicotine and its metabolites are longer in nonsmokers: is overstated. There is very little 'difference, if any, in 'the rate of nicotine elimination between smokers and nonsmokers (Kyerematen et al., 1982). Thus the residence time of nicotine atself is not likely to be significantly longer in nonsmokers. The statement should be limited .to cotinine unless evidence of a longer half-life for nicotine is presented in the paper. The statement that the longer residence time of nicotine metabolites in nonsmokers could "conceivably increase the possibility of endogenous formation of carcinogenic tobacco-specific N-nitrosamines" is unsupported. Cotinine and its metabolites are very unlikely candidates for nitrosation and when cotinine is nitrosated, the resulting product is not a mutagenic/carcinogenic N-nitrosamine (See report from Brunnemann's laboratory at the 1989 TCRC meeting). In addition, there is no evidence for the in vivo formation of tobacco-specific nitrosamines from.nicotine or any of its metabolites. Since this statement is speculation, it should be either modified to include the latest information or eliminated from this type of document. 14. p.99. last paragraph and p. 101 second paragraph. A criticism of this work was described in Van Vunakis et al. (1987). This should be discussed and referenced at both of these points. The discussion on p. 101 about creatinine should reference p. 322 of the Van Vunakis paper. 15. The sections on carbon monoxide and th.iocyanate are accurate and well balanced. 16. The sections on hydroxyproline, N-nitroso-amino acids, aromatic amines, thioethers in urine, genotoxicity of physiological fluids, and adduct formation should all be grouped under a heading Indirect Markers of Uptake similar to how these authors treated this same material in another paper on the same subject (Haley et al., 1989). This would reduce the importance of these assays for assessing ETS exposure in the context of this chapter. Collectively these assays suffer from a lack of specificity for ETS constituents and a lack of sensitivity. Specific comments about these assays are listed below: p. 103. Aromatic amines. Even though the yield of some aromatic amines may be higher fro:n the SS than from the MS of some cigarettes, one shou.1d not imply that the exposure will be greater. SS is highly diluted in air before it is breathed by nonsmokers (See discussion in point #3 above). The amount of these aromatic amines

contributed by ETS compared to the amount being excreted in urine is a very small percentage. This section should be deleted because the contribution from other dietary and environment sources would confound this assessment. r f ; p. 103. Thioethers. These data are too preliminary to include in this document. The study can be referenced, but thioether excretion is notoriously insensitive to exposure to low doses. There are too many other xenobiotics that could react with glutathione in vivo and alter thioether excretion in the urine. p. 103. Items 4 and 5. It is, unlikely that either hydroxyproline or N-nitrosoamino a:cids could ever be used to assay personal dosimetry of ETS exposure. The paragraph on p. 8 discussing the use of hydroxyproline could include the recent finding that the diets of nonsmoking women married to smokers is different than the diet of nonsmoking women not married to smokers. These differences in diet could exp:lain the "surprising" differences in hydroxyproline excretion. These sections should be eliminated from the paper. p. 104. Urine mutagenicity. This should.be eliminated from the paper. The contribution of the diet to urinary mutagens is large enough to preclude the use of this assay for monitoring ETS exposure. p. 104. Adduct formation. The statement that urinary mutagenicity could be utilized to assess uptake of ETS should be removed from paragraph 1 of section C for the reason stated above. 17. p. 106. Site Ogden and Maiolo, 1988 and 1989 papers here along with reference 101. 18. Table 3. This table is a composite of Table 1 and 2 from the cited reference. The plasma concentrat:Lons for nicotine and cotinine in the plasma in the nonsmokers is below the limit of quantification for the assay. This leads to an erroneously high value relative to smoker's plasma. The authors of the original paper state "The average concentration of cotinine, whether measured in plasma, saliva, or urine, lay between one-third to one- half of 1 % of the levels found in the smckers in this study and migYit therefore be regarded as trivial". The statement on p. 99 referencing this table should reflect the conclusion drawn by the original authors. The statement used in this paper on line 13 of p. 99 is not consistent with the conclusion in the original paper. L

REFERENCES 1. Castro, A. and N. Monji. Dietary Nicotine and Its Significance in Studies on Tobacco Smoking. Biochemic3l Archives 2, 91-97, 1986. 2. Connor, J. M., and W. S. Caldwell. Artifact Formation during Smoke Trapping. An Improved Method for the Determination of N-nitrosamines in Cigarette Smoke. Presente:d at the 43rd Tobacco Chemists' Research Conference, Richmond, VA, October, 1989. 3. Curvall, M., E. Kazemi-Vala, and C. R. Enzell. Simultaneous Determination of Nicotine and Cotinine in ]?lasma using Capillary Gas Column Chromatography with Nitrogen-Sensitive Detection. J Chromatog 232, 283-293, 1982. 4. Curvall, M. and C. R. Enzell. Monitoring Absorption by Means of Determination of Nicotine and Cotinine. Archiv. Toxicol. Suppl., 88-102, 1986. 5. Davis, R. A. The Determination of Nicotine and Cotinine in Plasma. J Chromatog. Sci. 24, 134-141, 1986. 6. Haley, N. J., D. W. Sepkovic, K. E. Brunnemann, and D. Hoffmann. Biomarkers for Assessing Environmental Tobacco Smoke Uptake. Presented at the Air Pollution Control Association Specialty Conference on Combustion Processes and the Quality of the Indoor Environment, Niagra Falls, NY, September, 1988. 7. Hariharan, M., T. VanNoord, and J. F. Greden. A High Performance Liquid-Chromatographic Methcd for the Routine Simultaneous Determination of Nicotine and Cotinine in Plasma. Clin. Chem. 34, 724-729, 1988. f 8. Jacob III, P., M. Wilson, and N. L. Benowitz. Improved Gas Chromatographic Method for the Determination of Nicotine and Cotinine in Biologic Fluids. J Chromatog. 222, 61-70, 1981. 9. Kyerematen, G. A., M. D. Damiano, B. U. Dvorchik, and E. S. Vesell. Smoking-Induced Changes in Wicotine Disposition: Application of a New HPLC Assay for Nicotine and Its Metabolites. Clin. Pharmacol. Ther. 32, 769-780, 1982. ~. ~. 10. Machacek, D. and N. Jiang. Quantifi.cation of Cotinine in Go Plasma and Saliva by Liquid Chromatography. Clin. Chem. 32, Go s 979-982, 1986. ' ~ c1i W co

11. Nelson, P. R., D. L. Heavner, and B. B. Collie. Characterization of the Environmental Tobacco Smoke Generated by Different Types of Cigarettes. In Present and Future of Indoor Air Quality, Proceedings of the Brussels Confe::ence, 14-16 February, 1989, edited by C. J. Bieva, Y. Courtois, and M. Govaerts. Excerpta Medica, Amsterdam. Pps. 277-282. 12. Ogden, M. W. and K.C. Maiolo. Gas Chromatographic Determination of Solanesol in Environmental'Tobacco Smoke(ETS). J High Res. Chromatogr. Chromatogr. Comm. 11, 341-343, 1988. 13. Ogden, M. W. and K. C. Maiolo. Collection and Determination of Solanesol as a Tracer of Environmental Tobacco Smoke in Indoor Air. Environ. Sci. Technol. 23, 1148-1154, 1989. 14. Schepers, G. and R. A. Walk. Cotinine Determination by Immunoassays May Be Influenced by Other Nicotine Metabolites. Arch. Toxicol. 62, 395-397, 1988. 15. Sheen, S. J. Detection of Nicotine in Foods and Plant Materials. J Food Sci. 53, 1572-1573, 1988. 16. Thuan, N. T. L., M. L. Migueres, D. Roche, et al. Elimination of Caffeine interference in HPLC Determinat:.on of Urinary Nicotine and Cotinine. C1in..Chem. 35, 1456-1459, 1989. 17. Van Vunakis, H., H. B. Gjika, and J. J. Langone. Radioimmunoassay for Nicotine and Cotinine (Method 16). Environmental Carcinogens Methods of Analysis and Exposure Measurement, Volume 9-Passive Smoking. IARC Scientific Publications No. 81. eds. O'Neill, I. K., Brunnemann, K. D., Bodet, B. and Hoffmann, D. Oxford University Press, New York. Pps. 317-330. 1987. 18. Wall, M. A., J. Johnson, P. Jacob, and N. L. Benowitz. Cotinine in the Serum, Saliva, and Urine of Nonsmokers, Passive Smokers, and Active Smokers. Amer. J Puba. Health 78, 699-701, 1988.

CRITIQUE OF ENVIRONMENTAL TOBACCO SMOKE; A COMPENDIUM OF TECHNICAL INFORMATION Chapter 9: The Effects of Passive Sraoking and on Respiratory Illnesses in Children Day Care Prepared by: Ronald D. Hood, Ph.D. I- U c L I have.been a Professor of Bio:.ogy in the Cell, Molecular, and Developmental Biology Section, Department of Biology, The University of Alabama, since 1978. I hold a concurrent appointment as Adjunct Professor of Environmental Health Sciences in the School of Public Health, University of Alabama at Birmingham. I am also the Pr'.ncipal Associate in Ronald D. Hood and Associates, Toxicology Consultants. Since 1983, I have served as a Special Consultant to the EPA's Science Advisory Board. Since 1978, I have acted as a professional consultant in the areas of environmental, developmental and reproductive toxicology for a number of industrial clients and for government agencies, including the EPA, the Veterans Administration, and the Congressional Office of Technology Assessment. My curriculum vitae is attached. I have been asked to review "The Effects of Passive Smoking and Day Care on Respiratory Illnesses in Children," by Glen Bennett, which is Chapter Nine of an EPA draft compendium of technical literature on environmental tobacco smoke. Mr. Bennett's chapter on day care attendance and respiratory illnesses in children takes note of the many L

- 2 - L e problematic aspects of the epidemiologic studies.that have found a statistical association between parental smoking and the occurrence of certain respiratory diseases in children. Nevertheless, he appears to accept that an increased risk of such diseases is attributable to exposure to environmental tobacco smoke ("ETS"). He goes on to.suggest that smoking by day care workers -- a factor that he recognizes has not yet actually been studied -- may present a comparable risk. this basis, he proposes both that parents be alerted to a On possible danger in this area and that day care providers be educated about a possible compounding effect of ETS exposure and day care attendance. As an initial matter, I note that studies on parental smoking have been widely criticized. For example, a 1988 study by Rubin and Damus (14) re-examined the 30 extant studies on parental smoking and observed that "most studies had significant design problems that prevent reliance on their conclusions'." Additionally, a workshop sponsored by the NIH in 1983 (10) emphasized the importance of confounding factors for parental smoking studies; such factors include cross-infection in the home, proximity of the home to industry, general nutrition, and family access to medical care. Furthermore, at a recent international symposium on ETS at McGill University in Montreal, which I attended, Professor R. Witorsch (20) reached the following conclusions on the basis of a comprehensive review of the relevant literature: The association between parental smoking and increased incidence of respiratory symptoms L

3 and diseases in young children is provocative. However, the mechanism for this association remains unexplained. Among the possibilities to be considered are ETS, socioeconomic factors and effects of maternal smoking during pregnancy and/or lactation. The increased inconsistency of this association as the child ages is also unexplained. Amcng the possibilities to be considered for this apparent age-dependent change are changes in the susceptibility to or intensity of ETS exposure, inaccuracies in the data obtained from questionnaires (e.g. unvalidated clinical data and smoking misclassification) and confounding variables. L L Clearly a great deal of further research needs to be conducted before one could conclude with confidence that parental smoking itself is a causal factor for respiratory illnesses in early childhood. By the same token, it appears premature at best to employ an assumpticn about parental smoking as a basis for action by parents, day care providers or regulators with regard to smoking by day care workers -- particularly when our knowledge of the role of the day care environment itself is as yet so rudimentary. Ih the following review, I consider epidemiologic studies involving either parental smoking or day care attendance with regard to the only nexus between the two groups of studies, namely, the incidence of otitis media. Preliminary Observations Children in day care centers (DCCs) have significant health problems of various kinds, and sc it is important that any potential contributing factor be accurately identified. Children in DCCs have increased rates of many infectious diseases (2), including ones such as diarrhea, hepatitis, and

4 r Ii i meningitis that are by no stretch of the imagination related to ETS exposure. Children in DCCs also have an increased rate of colonization with antibiotic-resistant bacteria (3). There is, however, little evidence of high risk for respiratory illness, with the possible exception of Dtitis media. This infection problem is deemed moderate at::nost, and I agree that ". .. there is no need for a clarion call against day care or on behalf of major new federal or state regulation" in this situation (2). Some additional observations about DCC clientele are germane to the evaluations of studies conducted therein. It must be remembered (and controlled for in studies, if possible) that the reason for the child's being in a day care center may itself be an independent risk factor. Many mothers work because of financial need, and lower socioeconomic status is a known r•isk factor for infections. Lower socioeconomic status may also entail poorer nutrition, apartment (as opposed to single family home) dwelling, city (as opposed to suburban) living, and crowding, all of which are.pctential risk factors. It is also possible that DCC children may visit a doctor more often, perhaps because the mother becomes more concerned upon being presented suddenly with a sick child at the end of the day (as opposed to the mother gradually becoming aware of a child's illnesse while caring for it all day at home), or because DCC personnel influence the mother to seek medical attention for her child. Thus, at least some conditions may be more likely to be diagnosed in DCC children than in control L

- 5 - children, and this would exaggerate the ,apparent risk shown in -epidemiologic studies. Many of the available epidemiologic studies of DCC children have relied upon answers to questionnaires given by the day care provider. In the DCC the clzild is seen every day by someone knowledgeable about children, and this may lead to more diagnoses being identified •than would be the case with other types of care, again a factor that would falsely magnify the apparent risk. Additional potential confounders will be discussed later. Relationship to Respiratory Infections Otitis media is the only upper respiratory disease reported in the literature as being associated with ETS exposure, and it is the only one that ha,s been extensively studied in connection with DCC. Bennett'cited five such studies as being positive (see his references 3, 20, 21, 30, 34) and four as being negative (see his :ceferences 39, 45-47). It seems appropriate to review in greate:r detail the various studies that were cited and several addi:ional ones that were not. To facilitate comparison and evaluation, such standard. statistics for epidemiologic studies as -:he relative risk and its 95 per cent confidence intervals and probability (P) were calculated and are presented in Table 1. Table 1 summarizes the studies cited by Bennett of DCC or parental smoking and their association with otitis media or various of its parameters, plus some additional studies that were not cited by him. Four of the five studies

6 characterized by him as being positive*- reveal an increased incidence-of otitis media or its parameters that is statistically significant. Three of these are small case control studies, one was a retrospective cohort study, and there were no prospective studies. The Kraemer study (7) considered only smoking in the home and not day care use. That study found no effect with a single smoker or the smoking of fewer than three packs per day in the home, but did find an effect with two smokers or more than three packs -- factors not likely to prevail in a day care center, even if it were staffed with a smoker. The Said study's (15) reliability is open to serious question because it relied upon the subjects' remembering at age 10 to 20 what happene3 before age three, and it did not control for potential conEounders. The Black study (1) was the only one that controlled extensively for potential confounders or independent risk factors, but it had a probable detection bias. The diagnosis of "glue ear" in controls was based on parents' recounting of their physicians' diagnoses whereas subjects' diagnoses were confirmed by the investigators. If one considers that the disorder in many subjects was remarkably asymptomatic and that four controls had to be excluded because they had had surgery for glue ear, it becomes evident that the diagnosis was_more likely to be */ Bennett stated that there were six "positive" studies, hut listed only five. L_

Ld 7 missed in controls than in subjects. -This would have the effect of exaggerating the relative risk. All of these "positive" studies considered also (or in two cases, only) parental smoking, which in two studies was not associated with the difference noted with DCC, and in two instances the difference said to be assc-ciated with parental smoking was essentially similar to or greater than that associated with DCC. Of the four "negative" studies, only three concerned DCC; the remaining study (Van Cauwenberge, 17) dealt only with parental smoking and found no effect. Gne case control study (19) found a statistically significant increase in the incidence of otitis media in children with DCC, but the comparison was with much younger control subjects who may not have yet experienced their first bout of otitis -- predisposing to otitis media at the time of.examination -- which would exaggerate the relative risk. The others found no significant difference with DCC, and one (16) found with DCC a higher relative risk for fever or antibiotic use than for otitis media. Again, in this group of studies, those that considered parental smoking found no difference for that factor, including the study (19) that found a significant difference with DCC.

8 t I Especially noteworthy-among the-remaaining-studies are the lack of-control for parental smoking in most,*/ the almost universal lack of evident control for other confounders (Table 1), and the tendency for significant associations with DCC to be restricted to severe complications of otitis media. Yet here again a similar effect was not associated with parental smoking in those studies that included such an evaluation. One prospective study (4) found nearly a.50 per cent lower incidence of one to four'bouts of otitis-media.with DCC than with home care. This statistically highly significant difference ceased to exist only when five or more bouts of otitis media were considered. Then, the incidence was the same with DCC as with home care. Confounders Most studies of this issue have significant design problems (14). For reasons mentioned above, studies at day care centers may have a built-in bias toward reporting elevated ill.ness rates (2). The DCC studies presently fail to control for (though many studied the effect of) parental smoking, and there are as yet no studies that consider the smoking habits of the day care workers. All studies fail to control fully for confounders or independent risk factors, and */ It shouid be noted that looking for an effect of parental smoking is not the same as controlling for it. The latter requires matching of subjects and controls with regard to parental smoking or use of other procedures not possible to apply to the data as presented.

- 9 - many make no effort at all to control for even the most obvious ones (Table 1). Detection biases have already been mentioned. In many DCC studies there is also a substantial potential for misclassification bias caused by erroneous reporting of I parental smoking. Such misclassification biases are very important, because they can affect both index and control groups; occurrence in the former causes exaggeration, and in the latter causes dilution, of the apparent relative risk. Additional confounders that deserve consideration, but rarely have been controlled for in DCC studies, include outdoor air quality, home heating, air conditioning, and humidity. The failure of an experimental design to detect the same or a greater effect of parental smoking as compared with DCC attendance suggests very strongly that the DCC effect being measured is not due to smoking by DCC personnel. It is unlikely that one or even more smokers caring for a group of children in•a DCC setting would typically produce a concentration of ETS that would exceed that generated by a smoking, non-working parent. Such a parent would be likely to be in closer proximity to the child for larger portions of the week than would the day care worker. I suggest that what increase there might be in the incidence of otitis media and its parameters with DCC is merely a reflection of the increased incidence of various infections with crowding of children at very early ages, an observation that has been almost universal. If, as-Chapter 9 states, the total burden

of respiratory illness is actually similar for day care _ children and controls, any apparent differences in the incidences of otitis media probably reflect differences in either: (a) detection/diagnosis, or (b) the relative age at which children contract respiratory diseases. Conclusions Given the questionable conclusions of those studies that have found a statistical associaticn between parental smoking and childhood respiratory disease, one is not justified in extrapolating by means of a crude analogy from parental smoking to smoking by day care workers. In fact, day care attendance in general -- irrespective of whether day care workers smoke -- could well be a significant confounding factor in those parental smoking studies that have found a positive correlation. Furthermore, a review of those studies involving otitis media, which is both-the only upper respiratory disease that has been associated with ETS exposure and the only one that has been extensively studied in connection with day care attendance, strongly suggests that smoking by day care personnel is not a relevant factor. Finally, there are as yet no studies that actually consider smoking by the day care work-ers. This state of affairs points clearly to a need for conducting further research before the EPA disseminates a document such as the Bennett chapter. Otherwise, the public will very likely be misled to conclude that smoking in day care centers has already been established

as a risk factor for childhood respiratory disease, and to overreact accordingly. V t L L

ADDITIONAL CITATIONS 1. Black, N. The Aetiology of Glue Ear: A Case-Control Study. Intern. J. Pediat. Otorhinolaryng. 9(2): 1985. 2. Haskins, R. & Kotch, J. Day Care and Illness: Evidence, Costs and Public Policy. Pediatrics 77(Supplement): 951, 1986. - Henderson, F.W., Gilligan, P.H., Wait, K. & Goff, D.A. Nasopharyngeal Carriage of Antibiotic-Resistant Pneumococci by Children in Group Day Care. J. Infect. Dis. 157:256, 1988. I*, t L 4. Ingvarsson, L., Lundgen, K. & Olofsson B., in Lim, D.J. (ed.) Recent Advances in Otitis Media with Effusion, Philadelphla, 1984, B.C. Decker, p. 19. 5. Ingvarsson, L., Lundgren, K. & Olofsson, B. Incidence and Risk Factors of Acute Otitis Media in Children: Longitudinal Cohort Studies in an Urban Population. Ref. 8, p. 6. 6. Iverson, M.; Birch, L., Lundqvist, G. & Elbrond, O. Middle Ear Effusion in Children and the Indoor Environment: An Epidemiological Stidy. Arch. Envir. Health 40:74, 1985. 7. Kraemer, M.J. Risk Factor for Persistent Middle Ear Effusions. J.A.M.A. 249: 1022, 1933. 8. Lim, E.J. Recent Advances in Otitis Media, Toronto, 1988, B.C. Decker. 9. Marchisio, P., Bigalli, L. Massironi, E. & Principi, N. Risk Factors for Persisting Otitis.Kedia with Effusion in Children. Ref. 8, p.3. 10. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health."Report of Workshop on Respiratory Effects of Involuntary Smoke Exposure: Epidemiologic Studies, May 1-3, 1983," December, 1983. 11. Pukander, J., Luotonen, J., Timonen, M. & Karma P. Risk Factor Affecting the Occurrence of Dtitis Media Among 2-3 Year Old Urban Children. Acta Otolaryng. 100:260, 1985. 12. Pukander, J.S. & Karma, R.H. Persistence of Middle Ear Effusion and its Risk Factors After an Acute Attack of Otitis Media with Effusion. Ref. 8, p.8. 13. Rockley, T.J. Family Studies in Serious Otitis Media. Ref. 8, p. 22. L

14. Rubin, D.H. & Damus, K. The Relationship Between Passive Smoking and child Health: Methodologic Criteria Applied to Prior Studies. Yale J. Biol. Med. 61:401, 1988. 15. Said, G., Zalokar, J., Lellouch, J. & Patuis, E. Parental Smoking Related to Adenoidectomy and Tonsillectomy in Children. J. Epidamid. Commun. Health 32:97, 1978. 16. Stahlberg, M.R. The Influence of Form Day Care on the Occurrence of Acute Respiratory Tract Infections Among Children. Acta Pediat. (Supplement) 282: 1, 1980. 17. Van Cauwenberge, P.B. & Kluyske.ns, :?.M. Some Predisposing Factors in Otitis Media with Effusion, in Lim, D.J. (ed.) Recent Advances in Otitis Media with Effusion, Philadelphia, 1984, B.C. Decker, p. 28. 18. Vinther, B. & Elbrond, C.B. A PopuLation Study of Otitis Media Childhood, Acta Otolaryng. (Supplement) 360: 135, 1979. 19. Vischer, W., Mandel, J.S., Batalden, P.B., Russ, J.N. & Giebink, G.S. A Case Control Study exploring Possible Risk Factors for Childhood Otitis Medica, in Lim, D.J. (ed.): Recent Advance in Otitis Media with Effusion, Philadelphia, 1984, B.C. Decker, p. 13.. 20. Witorsch, R., Parental Smoking and :2espitory Health and Pulmonary Function.in Children: A:.4eview of the Literature, in Ecobichon, D. and Wu, J. (eds.) Environmental Tobacco Smoke: Proceedings of the International Symposium at McGill Uziversity~ Lexington, 1990, D.C. Heath & Co., pp. 205-226.

EVALUATION-.OF APPENDIX--'10: - ECONOMIC JUSTIFICATION FOR NO SMOKING POLICIES AT THE WORKSITE ITI t i. U C t., I. INTRODUCTION My name is Dr. Walter R. Holman; I am a financial economist and associate professor of finance at the Sellinger School of Business and Management, Loyola College. I have been asked to review and comment on an al-ticle by Ruth Behrens entitled, "Economic Justification For No Smoking Policies at the Worksite." I received a Ph.D. in economics and finance from Syracuse University and also hold two degrees in industrial engineering. I have served as the dean of the Sellinger School of Business and Management and as chairman of the department of finance. Prior to joining Loyola's faculty, I was a principal in the international management consulting firm of Booz, Allen & Hamilton, Inc., where I also served as the Director of Financial and Economic Studies for the firm's Environmental Division. At Booz-Allen, I conducted numerous regulatory analyses and economic impact -analyses for the U.S. Environmental Protection Agency (EPA) in:luding an evaluation of all of the Agency's economic impact methodologies relating to water and hazardous wastes. - The cover letter from Mr. Bob Axelrad (Director, Indoor Air Division) to the document entitled, "Environmental Tobacco Smoke: A Compendium of Technical Information," states that this document is an integral component of EPA'.s U

Environmental. Tobacco _Smoke_ (ETS); policy.. _Thee document-'-s --- preface states that this document has been written by experts in the field and is intended to provide information necessary to allow the public, government agencies and the building industry to make well-informed choices regarding exposure to ETS. It is, therefore, within this context that I reviewed the article which'constitutes Appendix 13 of the EPA document. (1) SUMMARY OF FINDINGS . In summary, I find the Chapter 10 Appendix woefully inadequate with respect to EPA's stated Dbjectives. The article does not meet the standards of cDmprehensive and objective research prevalent in the fields of science and economics. Frankly, it doesn't come close to achieving the label of "good research." Amongst the many shortcomings of the article, the following are most prominent: o failure to consider most of the relevant literature, especially studies which provide evidence contrary to the "conclusions" reached by the author. o incomplete discussions of the serious methodological problems and significant data deficiencies which continue to plague research efforts to identify and scientifically measure the costs of smoking. o failure to present objectively the limitations and ~ ~ lack of generalizability of some of the studies N cited and discussed. ~ C,lt G^

failurp to address key- aspects of the topic such as-: - company costs (direct, indirect and intangible) associated with smoking limitation or cessation programs; - benefits/cost analysis of smoking cessation programs from the perspect:ive of the company, society and the individua7_; - capturing the benefits of company smoke cessation programs: methodology, problems, findings from prior studies. o frequent reliance on anecdotal information whose relevant context (e.g., validity, representative- ness) is neither identified nor discussed. o complete•failure to utilize a research and writing format appropriate for a serious research paper: lack of stated objectives; incomplete ref erences; failure to cite and/or discuss the majority of relevant literature; absence of clear, testable L_ hypotheses; absence of tightly drawn and supportable conclusions; and lack of any in-depth discussion of the limitations. of the research presented or cited. (2) APPROACH OVERVIEW A three step approach was utilized in the review and Up ~ evaluation of the article; these steps a:~e as follows: ~ ~ tJ W Ut 0)

o summarize-the paper-'s scope-, objectives---and-= conclufr- sions. o identify significant deficiencies in each of the paper's four principal sections. discuss in detail the reasons that.the paper does not meet the standards of good research. Section II, which follows, critiques the Chapter 10 Appendix's substantive assumptions and cDnclusions. Section III addresses the significant shortcomings which qualify the Appendix as poor research. 4 t

II. CRITIOUE OF CHAPTER 10 APPENDIX: SUBSTANCE L t. UT r t (1) SUMMARY DESCRIPTION Appendix 10 addresses the topic of the economic justification for worksite smoking polic:.es, smoking bans in particular. It focuses on four aspects of the topic. These four aspects represent the four primary sections of the article and are as follows: o Section 1: Costs of Smoking to i:he Nation o Section 2: Differing Methodologles Make Pinpointing Worksite Costs Hard o Section 3: Economic Impact of Smokers On the Worksite o Section 4: Individual Companies Document Costs, Consequences of Smoking The Appendix reaches specific conclusions in each of the four sections and several overall conclusions. The more specific conclusions are as follows: o Section 1: the economic impact of smoking on the nation is staggering... . (T]hree key studies provide simiLar estimates of large costs. o Section 2: differing methodologies make pinpointing worksite smoking cost hard (but, the two cited studies, Kristein (1983) and Weis (1981), estimate large costs). o Section 3: substantial evidence exists demonstrating - 5 -

the important types.--of economic_impacts-- smokers exert on bus:.ness. o Secti-ion 4: individual companies have documented the costs and consequences of smoking; these studies offer further insights into the (high) price businesses pay for their .smoking employees. The author's more comprehensive conclusions are the following: o U.S. businesses are paying heavily for'their smoking employees through productivity losses and increased health care and other costs. o implementation of policies tha': restrict or eliminate smoking within businesses are one inexpensive, yet effective step that companies can take to discourage smoking and to vividly illustrate their concern for health, as well as for their bottom line. (2) KEY PROBLEMS IN PAPER'S FOUR SECTION3 In this part of the memorandum, the reviewer identifies the primary problems -in each of the four sections of Appendix 10. A comprehensive discussion of these problems and their implications is presented subsequently in this memorandum.

Section Primary Problems and,/or Shor-tcomings -= - 1 o author cites only 3 of a large number of studies which address the question of what smoking is costing the nation. o conclusion is drawn :hat the similarity of the estimates of tota1 costs from the 3 studies underscores that smoking does cost the nation a staggering amount. - As discussed in the next section of this memorandum, a closer review of the cited Rice, et al (1984) paper indicates (as do Rice and his colleagues) that there are huge dif- ferences among the 3 studies in the estimates of costs for each of the three diseases studied. - These huge differences accidentally cancelled out when aggregating the individual disease costs to arrive at an overall cost of smoking. The reported "similarity of costs" among the 3 studies was a fortunate accident which raises serious questions about the true comparability of the estimat-es and highlights several crucial

il L U L i 4,- t 2 3 methodological ' ssues-wh•ich are- - subsequently discussed in the Rice paper. o author alludes to methodological difficulties in pinpointing worksite costs but then proceeds to cite the high costs provided by two studies (Kristein, 1983 and Weis, 1981) with no further discussion of the large number of serious methodological problems and no reference to the large body of research literature addressing this subject. o author cites a wide variety of information concerning the economic impacts smokers exert on businesses over their nonsmoking counterparts. - author does not, however, address the significant proDlems which researchers continue to struggle with. - the primary problem is the inability to develop valid methods for apportioning the differential economic impacts of smoking (smoker versus nonsmoker costs) between - 8 -

smoking and other- soc-ioeconomic;.- genetic, and other characteristics of smokers which may be responsible for much of the referenced economic impacts of smokers. the studies cited by the author do, however, address this important methodological problem and its implications--making cost estimation extremely difficult. I- I L G L 4 o author states that studies by companies to document the costs and consequences of smoking have varying degrees of validity but then proceeds to present anecdo.tal information from the experiences of two companies. - the author provides no indication as to the validity, comprehensiveness, or representativeness of these two anecdotal data points. - the author claims, however, that they offer insights into the price businesses pay for their smoking • employees. - 9 - a"k

III. CRITIQUE OF CHAPTER 10- APPENDIX; -RESEARCH SHORTCOMING6 --- i L f (1) OVERVIEW OF RESEARCH DEFICIENCIES In this section of the memorandum, the reviewer identifies and discusses the numerous and substantial shortcomings of the Chapter 10 Appendix which qualify it as very substandard research. These shortcomings can be - categorized as follows: o failure to review the majority of relevant research studies, especially in the following 3 areas: - costs of smoking to the n<<tion; - impact of long-run reductions in smoking on the economy; - capturing the benefits of smoking cessation programs. o failure to present and discuss all the relevant research findings embodied in 1.he rich literature, especially: - findings which are inconclusive or do not support the author's expressed conclusions about smoking costs and the benefits of smoking cessation policies; - findings relating to the 3erious methodological problems and data deficiencies which make estimation of smoking costs and no smoking policy benefits difficult if not impossible to estimate.

I L L G (2) FAILURE TO REVIEW--.MAJORITY-' OF -RELEVANT- RESHARCH-' (2.1) Costs of Smoking to the Nation The author fails to cite and/or discuss a large number of important studies which address the issue of the possible cost of smoking to the nation. These include:: Simon (1968), Hendrik (1971), Williams and Justus (1974), Boden (1976), Freeman, et al (1976), Forbes and Thompson (1983), Vogt and Schweitzer (1985), Oster, Colditz and Ke::ly (1984), Leu and Schaub (1983),Schultz (1985) and National Interagency Council on Smoking and Health (1980). The absence of any consideration of these studies is significant as illustrated by the following considerations. Schultz (1985) concluded that while there are a number of studies of the costs of smoking, no one has addressed all the relevant aspects. Leu and Schaub (1983) concluded that lifetime medical care expenditures of smokers are not higher, and possibly are even lower than those o:= non-smokers. The National Interagency Council on Smoking and Health (1980) found in a survey of 3,000 companies, th,3t less than 1 percent had calcu~ated costs due to smoking. Rice, et al (1984) concluded that the results of the major :3tudies on the costs of smoking cannot be compared since the types of costs, diseases and categories of smokers included, and the methodology employed vary among the studies. OD ~ ~ C!T 0) W;~b

(2.2) Impact of _ Long Run Reducrt ions-- in Smok ing on--- the Economy The author fails to cite and/oi discuss any of the [ studies which have attempted to measure the impact of long run reductions in smoking on the economy (Atkinson and Townsend (1977) and Gori and Richter (1978)). Gori and Richter used the Wharton Long Term Econometric Model to forecast certain economic effects of the reduction in smoking. They concluded that the direction of changes in important economic variables was uncertain, and that their results were extremely sensitive to the input assumptions. Rice (1984), :.n commenting on this and other long term effects studies, concluded that "a good deal more analysis is required before we can be confident about long-run effects of changes in smoking patterns." (2.3) Capturing the Benefits of Smoking Cessation The author of the Chapter 10 Appendix does not address this particularly important aspect of the workplace costs of smoking. In fact, she fails to cite and discuss the research presented in one of her key citations, K::istein (1983). Kristein lays out a five step methodology for estimating the benefits of a workplace smoking cessation program. He divides the costs into two categories: shortterin (1 to 3 years) and long-term (greater than 3 years). Short term costs include absenteeism, productivity losses, fire losses, etc., while long-term losses include health insurance, life insurance, etc. Kristein says that the capture of t:ie long-term costs of smoking reduction may take 10 to 15 years;; he presents this as R -

a conclusion of the -literature in the fteld. He also notes- that the literature attempting to link smoking cessation and health promotion to improvement in the health and-non-health outcomes is "unfortunately, weaker than one would prefer." Finally, Kristein says that in order for companies to recapture the short and long-term costs of workplace smoking, labor turnover rates must be less than 33% (short-term.) and 10% (long-term). (3) FAILURE TO PRESENT AND DISCUSS ALL RELEVANT RESEARCH FINDINGS (3.1) Findings Which are Inconclusive or Don't Support Author's Views The author cites the Rice, et al (1984) paper and L its presentation of smoking costs estimates from three key studies. She says that these "three key studies ... demonstrate enough similarity (costs estimates are close) to underscore that smoking does cost the nation a staggering amount." However, what she fails to cite from the Rice study is crucial. The referenced three key studies estimated smoking costs by applying "attributable risks" to the direct arld indirect costs of three diseases: neoplasms, circulatory diseases, and respiratory diseases. Rice states that, "the Go (P apparent similarities of these (aggregate cost) estimates ma.sk ~ the substantial differences in estimated costs of the three ~ C11 ~ component diseases. There is, in general, a lack of ~ I

I I L consistency- among the studies -in --terms--of the- magni-tudes- of the estimated proportions for a given medical condition." Rice concludes that the substan,tial differences among the three studies with respect to the costs of smoking associated with each of the three disease categories studied tended to cancel out in the aggregate and resulted (as the author of Appendix 10 states) in three estimates of: total smoking costs which were very similar. Because of the fortunate cancelling out effect, which is purely accidental, t:he aggregate cost numbers for each of the three cited studies were close in magnitude. Viewed in this light, one must strongly refute the author's conclusion that the closeness of: total cost estimates among the three studies underscores that smoking costs the country a staggering amount. (3.2) Findings Related to Serious Methodological Problems and Data Deficiencies Appendix 10 fails to address the vast differences in the categorization and definition of smoking costs which are observed in the research literature. It is very likely, that the observed differences in cost definit:.ons are a major source of the extreme difficulty encountered by researchers in their attempts to derive consistent and scientifically-based estimates. Identified from the articles cited by the author in Appendix 10, the following list of cost definition (Z ~ alternatives demonstrates the disparity encountered: N U1 ~ 0 prevalence-based versus incidence-based costs. ~

o long-term versus-shor-t-term-co:3-ts: o direct, indirect and intangible costs. o company costs, individual costs (smoker versus nonsmoker) and societal costs. o current dollar versus nominal dollar costs. o present value costs versus non•-discounted costs. The most serious omission, however, is the author's profound failure to address the comprehe»sive discussions found in the literature, including the research she cited, (Kristein; Rice, et al) concerning the a:lmost insurmountable problems associated with the measurement of workplace smoking costs. Kristein (1984) states the implications of this problem as follows: I- I i f 1. "[Flor managers used to dealing wit],i hard numbers it is difficult to think of developing a ~~ompany (smoking) po.licy based on inferences from estimates. Many of them believe that true proof of the net 3ain of adopting a company smoking policy is missing, l:)ecause there is no smoking gun type of evidence that smoking employees involve a net cost to their employers that can be eliminated through nonsmoking policies." Kristein (1983) concisely summarized the current state-of-the-art in smoking cost measurement and its profound dilemma as follows: "[W]e lack meaningful 'case-controlled' company comparisons of experience with smoking versus nonsmoking versus ex-smokers and the impact on company costs. Therefore, we must work from aggregste national epidemiological data on illness and other costs associated with smoking and attempt to apportion a realistic share to smoking employees.... . To attempt a scientifically-based answer to the question of how much employee smoking is actually costing the typical American business-and by how--much this cost-zan be_reduced would require studies and data we do not now -- and most likely

will never -- possess.- Thus-, it-° wou-ld -be--necessary-=to have data reflecting at least a 20-year follow-up of at least one case-control led study comparing a company with several thousand employees that had pursued a smoking cessation effort with a similar company that has not pursued such a program... . Nothing in the literature even approaches such data. There have been aggregative and special epidemiological studies and estimates of overall extra-illness rates of smokers versus nonsmokers and versus ex-smokers, however, in addition, there is extensive literature on the relationship between chronic diseases and smoking based on population and laboratory epidemiology. Also there are studies, generally with serious research limitations, of various populations dealing with measures of -productivity, absent'eeism, involuntary smoking, and smoking and occupational health." Rice, et al (1984) discuss the substantially different assumptions made by prior researchers (Luce and Schweitzer, 1978; Leu and Schaub, 1983; Boden ,1976; and.OTA, 1985) concerning attributable risk, which is the proportion of differences in disease rates between smokers and nonsmokers which can be attributed to smoking as opposed to other socio-economic, genetic characteristics of smokers. Although the author of Appendix 10 cites the Rice article as important because it updates (puts in 1984 dollars) the estimates from three "key" studies of costs of smoking to the nation and finds the three estimates close, she fails to cite and/or discuss perhaps the most important finding of that research. As previously discussed in this memorandum, significant differences in assumptions concerning attributable risk led the three groups of researchers to arrive at substantially different cost estimates for the three diseases studied. These differences fortuitously and..accidentaLly cancel-led out-

r when-aggregating -the: costs. across the.thi-ee: diseases .to-arri-ve= at estimates of the total cost of smoking.

BIBLIOGRAPHY I I L t Atkinson, A.S., and J.L. Townsend. 1977. "Economic Aspects of Reduced Smoking." Lancet 8036:492-95. Boden, L.I. 1976. "The Economic Aspects of Environmental Disease on Health Care Delivery." Journal of Occupational Medicine 18:467-72. Forbes, S.F., and M.E. Thompson, 1983. "Estimating the Health Care Costs of Smokers." Canadian Journal of Public Health 74:183-90. Freeman, R.A., C.R. Rowland, N.C. Smith, 5. Cabell Schull, and D.D. Garner. 1976. "Economic cost of Pulmonary Emphysema: Implications for Policy on Smoking and Health." Inquiry 13:15-22. Gori, G.B., and B.J. Richter. 1978. "Macroeconomics of Disease Prevention in the United States." Science 200:1124-30. Hendrik, J.I., 1971. "The Economic Costs of Cigarette Smoking." HSMHA Health Reports 86:179-82. Kristein, M.N., 1983. "How Much Can Business Expect to Profit from Smoking Cessation?" Preventive Medicine 12:358-81. Kristein, M.N., 1984. "Wanted: Smoking Policies for the Work Place." Business and Health. Leu, R.E., and T. Schaub. 1983. "Does Smoking Increase Medical Care Expenditure?" Social ,3cience Medicine 17:1907-14. Luce, S.R., and S.O. Schweitzer. 1978. 'Smoking and Alcohol Abuse: A Comparison of Their Economic Consequences," New Enaland Journal of Medicine 298:569-71. National Interagency Council on Smoking ,3nd Health, 1980. "Smoking and the Workplace." Office of Technology Assessment. 1985. "Smoking-related Deaths and Financial Costs." OTA Staff Memorandum. Health Program, U.S. Congress. Oster, G., G.A. Colditz, and N.I. Kelly. 1984. "The Economic Costs of Smoking and Benefits of Quitting for Individual Smokers." Preventive Medicine 13:377-89.

Rice, D.P., T.A. Hodgson,.. P. Sinsheimer-,- W.: Browner_.-and A.N.._ Ropstein. 1984. "The Economic Cost:; of the Health Effects of Smoking." The Milbank Quarterly, 64: (4). Schultz, J.M. 1985. "Perspectives on the Economic Magnitude-of Cigarette Smoking." New York State Journal of Medicine 85:302-6. Simon, J. 1968. The Health Economics of Cigarette Consumption." Journal of Human Resources 3:111-17. Vogt, T.N., and S.O. Schweitzer. 1985. "Medical Costs of Cigarette Smoking in a Health Maintenance Organization." American Journal of Epidemiology 122:1060-66. Weis, W.L. 1981. "No Ifs, Ands or Buts: Why Workplace Smoking Should be Banned." Management World 339-44. Williams, J.R., and C.G. Justus. 1974. "Evaluation of Nationwide Health Costs of Air Pollution and Cigarette Smoking." Journal of the Air Pollui:ion Control Association 24:1063-66. ~

Economic Justification for Worksite Smoking Policies by Robert D. Tollison and Richard E. Wagner 1 L We are Dr. Robert D. Tollison and Dr. Richard E. Wagner of George Mason University in Fai::fax, Virginia. Dr. Tollison is presently Director of the Center for Study of Public Choice and Duncan Black ]?rofessor of Economics at George Mason University. Dr. Tollisoil received his doctoral degree in economics in 1969 froin the University of Virginia. Since that time, he has taugh-: at Cornell University, Texas A&M University, Virginia Tech, Clemson University, and now at George Mason Univiarsity. He has also served as a'Senior Staff Economist on the President's Council of Economic Advisers and as Director of -:he Bureau of Economics at the Federal Trade Commission. Dr. Tollison is the author of numerous scholarly books a>>d articles, and is the past president of the Southern Economic Association. Dr. Wagner is presently Chairm,in of the Department of Economics and Harris Professor of Economics at George Mason University. Dr. Wagner completed his Ph.D. in economics at the University of Virginia in 1966. Since that time, he has taught at the University of California ar. Irvine, Tulane University, Virginia Tech, Auburn Univer3ity, Florida State University, and now at George Mason University. Dr. Wagner also spent a year as a resident scholar at the Urban 1

Institute. He has published widely in economics, including two textbooks on public finance, numerou;3 scholarly papers, L L'i r i and a treatise on democracy with James M. Buchanan, 1986 recipient of the Nobel Prize in Economic;3. We have been asked to comment upon Chapter Ten and Chapter Ten's Appendix of a document entitled "Environmental Tobacco Smoke: A Compendium of Technica:L Information." Chapter Ten's Appendix, "Economic Justification for No Smoking Policies at the Worksite," by Ruth Behreas claims that smokers are particularly costly employee;3, as they raise costs to American businesses as much as $100 bLllion per year. The implication of this claim is that stringent anti-smoking policies in workplaces are good for busiaess and the American economy. However, we find the arguments in support of the author's thesis to be utterly without merit. At best, those arguments can be said to confuse accountLng for economics, in that the accounting-based claims the aut:zor makes about costs are misrepresented as being costs to busLness when, as a modicum of economic understanding would 3how, they are really costs to smoking workers. But it is also questionable how accurate those claims of cost are, even when considered from an accounting point of view. Th& author presents a number oE estimates on the alleged added cost of smokers to American business. For 2

instance, studies by Luce and Schweitzer (1978), the Office of Technology Assessment (1985), and Rice et al. (1978), all provide cost estimates per year of between $52.8 billion and $62.2 billion in 1984 dollars. These studies isolate three main categories of cost (p. 174): (1) lost earnings due to early death, which accounts for about 40 percent of the estimated totals; (2) medical and hospital expenses attributed to smokers in excess of what is attributed to nonsmokers, which also accounts for about 40 percent of the estimated totals; and (3) lost earnings attributed to smoking-related ill- nesses, which accounts for about 20 percent of the estimated totals. I [ In addition, the author cites a study by Kristein (1983) that estimates the added cost to business to be in the range of $336 to $601 per smoker per year, as well as one by Weis (1981) that estimates that added cost to be around ten times higher, in the vicinity of $4,500. Many of the cost categories discussed in these latter two studies duplicate one of the three noted above, but a few of them do not, or at least do not appear obviously to be duplications. For instance, the claim in Weis and in Kristein that smokers increase the costs of life and disability insurance for businesses is related to category #1 abcve; the claim that 3

--smokers-increase health insurance-costs is related to category #2; and the claim that smokers increase costs through increased absenteeism is related to category #3. What remains are a few miscellaneous categories in which it is alleged that smokers increase costs to business: (a) a claim that smokers are responsible for increased property damage and lead to increased costs for fire, liability, and accident insurance; (b) a claim that smokers increase costs for ventilation and air-conditioning, and (c) a claim that smokers increase costs through the time they spend smoking on the job. A consideration of these various alleged cost elements shows that there are six separable cost categories concerning the alleged higher cost of smoking: (1) life. insurance costs, (2) health insurance costs, (3) missed work through absenteeism, (4) missed work through smoking breaks, (5) property damage, and (6) costs for ventilation and air-conditioning. We shall examine each of these categories in turn, explaining why none of them create any legitimate issues of public policy, as well as showing why several of them are dubious even as accounting propositions. 1. Life insurance costs. Life insurance companies charge lower premiums to nonsmokers than to smokers for the same type of coverage. But nonsmokers are not harmed by the purchase of life insurance by smokers, for each pays an actuarially fair price for the relevant risk category. By the 4

same token, the lifetime earning losses noted by Behrens (p. 174) are lost by smokers and do not represent losses to nonsmokers. What about employers who provide life insurance to their employees? An employer with a greater proportion of smokers would seem to incur a higher cosi; in doing so than an employer with fewer smokers--at least if the insurance were i i I i I provided free of direct charge to the employees. This would be so in the situation described, but it should be noted in this case that it is the employer (i.e., the owner or owners of the firm, really) who is bearing this higher cost and not the nonsmoking workers. But_this is a cost the employer could avoid by passing on the extra cost of coverage fo)- smokers to smokers. There is no reason why smokers and nonsmokers have to be offered the same terms under group life ansurance. If an insurance company charges a company higher premiums for smokers, then the company may choose to ]?ass on the additional costs to smokers just as they can charge more for medical insurance for people who elect to have maternity coverage than for those who do not. 2. Health insurance costs. The claim that smokers are higher cost employees for purposes o.` health insurance is 00 C7) related to the claim that their annual medical expenses are ~ .~ more than $20 billion per year beyond wh,at they would be if N UT 5

they were nonsmokers. This claim is problematical on both accounting and economic grounds. On accounting grounds, those who make the claim that smoking employees have higher health insurance costs base their assertion on adding up cases where smokers supposedly have higher medical expenses than nonsmokers, and attributing the difference to smoking. But there are also cases where smokers have lower medical expenses, and these could likewise be attributed to smoking. For instance, Parkinson's disease is apparently rare among smokers, and it would be possible to impute a cost saving to smoking in this ::espect, due to the lower incidence of Parkinson's disease among smokers. Larger in magnitude but similar in spirit, smokers have a lower incidence of various geriatrical-related illnesses and diseases, and this cost saving could likewise be attributed to smoking. The result of a more complete accounting is unknown, but at the very least it would reduce the accounting cost attributed to smoking, and could even eliminate it. Economically, the situation is much the ;same as with employer-provided life insurance. If a company makes health insurance available on equal terms to bo:h smoking and nonsmoking workers, and if smokers are more costly to serve, it is the employers-owners who lose. Ani9 they could seek to pass on some of that added cost to smoki:lg employees, by 6

charging them for the added cost of their_premiums. But, as with life insurance, this is essentially a matter of compensation policy within companies, an3 not a matter of public policy. 3. Missed work due to absenteeism. One aspect of the claim that smokers have poorer health than nonsmokers is the claim that they miss work more often than nonsmokers. Some data allege that smokers on average miss about 2.2 days more work per year than nonsmokers. Based on this assumption, it might appear that smokers are more costly workers than nonsmokers. But the same type of data also show that pipe and cigar smokers miss less work than nonsmokers. Consistency would seem to require the conclusion that productivity might be enhanced by getting people to start s:.noking pipes and cigars! Another possible conclusion is that these accounting data are misleading, if not wrong. Smokers are relatively heavily concentrated in blue collar occupations with hourly pay and compensated sick leave. Smokers are less represented in white collar occupations with salary and without formal sick leave provisions--and which are generally occupations with a greater degree of on-the-job fun and recreation. There is no evidence that supports claims that, allowing for type of occupation and form of compensation, smokers miss work more often than nonsmokers. In fact, there is some evidence that 7

I r when such factors are taken into_account, smoking per se has no impact on worker absenteeism (Ault, Ekelund, Jackson, Saba, and Saurman 1988). To be sure, should smokers mis;a more work than non- smokers, this would show smokers to be hLgher cost employees than nonsmokers. But who bears this cos-=? We would.generally expect such higher cost workers to earn :Less, as, for example, in being promoted less quickly than lowe:: cost employees. In any event, smokers who might have relatively high rates of absenteeism would be a burden to their employers only to the extent the employers agreed to accept that burden--which is to say, only to the extent they decided to act charitably. 4. Missed work due to smoking breaks. This category is analytically identical to the preceding one. The accounting exercise is quite simple. Suppose smokers take four smoking breaks per day, of 15 minutes each. If the standard working day were eight hours, smokers would be viewed as working only seven hours. This would make smokers 12 percent more costly than nonsmokers--assuming that this was the only difference between smokers and nonsmokers. While this assumption informs ;;uch accounting efforts, it is surely without foundation. This assumption would have us believe that smokers and nonsmokers work equally diligently for seven hours per day, and =hat nonsmokers continue in the same manner for the eigh-:h hour while smokers 8

sit back and smoke for that eighth hour. Yet experience in any business establishment will show all kinds of ways that nonsmokers can also take what might be called on-the-job leisure: drinking coffee, making shopping lists on a computer, talking about sports with a co:lleague, and L daydreaming while appearing to be thinking, are a few of many possible illustrations. Smoking is simp:ly more visible and explicit, particularly in workplaces tha: allow smoking only in particular areas and times. But it is far, far from the only source of on-the-job leisure in workplaces throughout the land. 5. Property damage. It is claimed that smokers damage property in such forms as burned carpets and higher costs for cleaning draperies. This accounting fiction is based on a presumption that nonsmokers do not do such things. But it is totally illegitimate to add up such smoking-att'ributable costs as cigarette burns and call this an excess cost of having smoking workers, wathout also trying to consider the costs that nonsmoking worke::s might incur. Many nonsmokers drink coffee o:: soft drinks, and which on occasion are spilled--sometimes even onto, or into, such expensive office equipment as compul:ers and copying machines. Another nonsmoking employee may have failed to place a ladder securely in its position In a store room, with the result being that vibrations from a nearby fork lift L

r t I caused the ladder to fall and crash into some chemicals stored on a shelf, that in turn fell and broke open. This in turn shorted out the electrical system in the building, causing the loss of much computer work. Employers, of course, have incentives to mitigate accidental damage to property, whether by smokers or nonsmokers. But the kinds of accounting statistics reported by EPA give no basis for concluding that smokers are a source of excess property damage. And in any event, the issues created are ones of individual business policy and not of public policy. 6. Ventilation and air-conditioning costs. The claim that smokers increase costs of vent:ilation and air-conditioning is the same kind of claim as the preceding one that smokers are sources of property damage. Indeed, in many cases there may be no added ventilat:ion cost that can be reasonably attributed to smoking. To be sure, the inadequacy of ventilation in modern buildings is coming increasingly to be recognized. But in a great many case~s, and probably in most, there is no assignable cost of vent:ilation for particular items. To illustrate, suppose the only two things to be removed from the air are cigarette smoke and formaldehyde. It is doubtful rf a less expensive ventilati.on system would be installed if there were no cigarette smoke to remove. And 10

t once it is recognized that indoor air contains numerous other things, the relative significance of cigarette smoke diminishes even further, which in turn makes even less plausible the claim that smoking is a sionificant source of ventilation costs, in most cases. In sum, there is no economic justification for workplace smoking rules, except those ru:les which have been voluntarily adopted by firms and workers in the absence of government policy. Firms have clear incentives to produce their output at least cost. In this respect, even if smokers are more costly employees (a point of view with which we disagree), they will be employed because they add more to a firm's revenues than to its cost, i.e., !:hey are productive workers. To focus on the alleged costs of hiring a particular. type of worker is totally beside the point. The point is to hire the best workers, among which will often be found smokers. Whether through open competition for workers or through collective bargaining, the prope:- approach to workplace smoking is to allow companies and employees to decide upon the appropriate smoking policy on a company-by-company basis. Government is not required to solve this problem. 11

I Reference s 1. Ault, R.W., R.B. Ekelund, J.D. Jackson, R.S. Saba and D.S. Saurman, "Smoking and Abse Study," Auburn, Alabama (1988). nteeism: An Empirical r 1 2. Luce, B.L. and S.O. Schweitzer, "Smoking and Alcohol i Abuse: A Comparison of their E conomic C onsequences," New England Journal of Medicine 298, 569-571 (1978). 3. Kristein, M.M., "How Much Can B usiness Expect to Profit From Smoking Cessation?" Preve ntive Medicine, 12: 358-381 (1983). 4. Office of Technology Assessment , U.S. Congress, "Smoking-Related Deaths and Fin ancial Costs." Washington., D.C. (OTA Staff Mem orandum 1985). 5. Rice, D.P., T.A. Hodgson, P. Si nsheimer, W. Browner and A.N. Kopstein, "The Economic Costs of the Health Effects of Smoking, 1984" The Milbank Quarterly, 64: (4) Cambridge University Press (1986). 6. Weis, W.L., "No Ifs, Ands or Buts: Why Workplace Smoking Should Be Banned," Management World, 339-44, (Sept. 1981). i 12 t

REVIEW OF: ENVIRONMENTAL TOBACCO SMOKE A COMPENDIUM OF TECHNICAL INFORMATION by Simon Turner, Healthy Buildings International, Inc. Introduction Healthy Buildings Internatioaal, Inc. (HBI) is a company that specializes in the study 3nd assessment of indoor air pollution.. Since we incorporated in 1981, we have studied in excess of 80 million square feet of buildings throughout the world, perhaps confirming us as the most experienced private company in that field. HBI seeks to identify the causes of indoor air quality problems -- the "sick building syndrome" -- and to recommend remedial steps. Our experiences are attracting widespread interest in the professional arena of those truly interested in indoor air quality. Clients include major banks, insurance companies, property developers, hospitals, colleges, and government agencies, including the U.S. Department of Health and Human Services, Social Security Administration, Longworth Congressional Building, Supreme Court, Government Services Administration Regional Head- quarters, United Nations Buildings in New York, Customs and Excise and Coast Guard Buildings. We were asked to comment upon the document entitled "Environmental Tobacco Smoke: A Compe!ndium of Technical Information" based upon our extensive experience with indoor air quality problems. In addition to a number of specific substantive flaws contained in the document, this compendium

4 4 14 # ~ IN w A rn .n on environmental tobacco smoke (ETS) sanctioned by a body such as the U.S. Environmental Protection Agency (EPA) concerns us in that this single-minded focus on one pollutant, unique in EPA's policies on indoor air, will give the public the impression that its removal will solve all indoor air problems, thus giving an entirely false sense of security. We frequently investigate buildings on account of complaints from occupants with symptoms.such as-eye and nose irritation, fatigue, coughing, rhinitis, nausea, headaches, sore throats and general respiratory problems. It is frequently assumed by our clients that these symptoms are due to ETS. However, it is clear that identical symptoms may be found in individuals exposed to formaldehyde, sulphur oxides, ammonia', oxides of nitrogen, and ozone. In addition, similar symptoms are reported by those individuals with allergies to specific fungi such as aspergillus, cla3osporium, and penicillium, among others, as well as to miscellaneous bacterial aerosols. Overlapping symptoms also can be caused by exposure to household dusts, cotton fibers, fiberglass fragments, etc. Low relative humidities create similar problems and are on the increase. Surprisingly, after a detailed, scientific evaluation of these buildings, we have determined high levels of environmental tobacco smoke to be the immediate cause of indoor air problems in only three percent of the 412 major U.S. buildings investigated by HBI between 1981 and 1989. This result has been corroborated. In a similar study of 203

buildings from 1978 to-1983; the Naticnal Institute-for Occupational Safety and Health (NIOSH) found that only four_ of the buildings studied (two percent) hz.d indoor air quality problems attributable to high concentrations of ETS. significantly, in those few cases where we found high accumulations of ETS, we also discovei-ed an excess of fungi and bacteria in the HVAC system. The:ae microorganisms usually are found to be the primary causes of the complaints and acute adverse health effects reported by building occupants. Dirt in Duct Systems We have also found that HVAC systems are often poorly designed and negligently maintained. Excessive dirt accumulations are common in ductwork, even in hospitals. Following the inspection of a number of buildings, hundreds of pounds of fungi, dust, and dirt have been removed from such ductwork. Bird, insect, and rodent carcasses and excess amounts of dust have been found in many buildings where employees have complained of eye irritation, headaches, fatigue, nausea, allergies, and general respiratory problems. Of course, since the ductwork is out of sight, it is also invariably out of mind. Thus, it is common for the blame for these types of problems to be laid e7.sewhere. Energy Conservation Indeed,.the complex of symptoms that we have mentioned - the "sick building syndrome" - may result primarily from energy conservation e.Eforts to seal buildings and reduce the.infiltration/exfiltration of air. Such efforts

i is a- . go Am p have reduced the natural infiltration of fresh air that previously-existed in many buildings, exacerbating the often undiscovered problem of a poorly designed or maintained HVAC system. In addition to tightening buildings and sealing windows, building managers have shut down air conditioning systems at night and on weekends in an effort to lower energy costs. When the air conditioning is shut down in humid climates, condensation builds up and settles inside the ductwork. If dirt is present in damp ductwork, spores and microbes can flourish, only to be spread throughout the building once the HVAC system is turned on the next morning. This often results in Monday morning complaints of building odors or building sickness that disappear during the week, only to recur the following Monday morning. To save more energy, automatic temperature controllers are used to cycle fans on and off during the day. Vibrations from the start-up of these fans can cause dirt and micrcbes trapped inside ductwork to be dislodged and carried into occupied areas. Another energy conservation effort that may contribute to sick building syndrome is the recirculation of indoor air, at the expense of fresh oL.tdoor air. This may be the result of either a deliberate policy or shortsightedness on the part of the designers. This re!sults in the continuous redistribution of infectious microbes, allergenic dusts and spores from office to office and floor to floor. Improper ventilation can..sometimes be carried t.o extr.emes._ Typically

*4 A R4 IN L:~ W4 we find the fresh air dampers were-closed completely-in over 35% of those buildings studied by HBI. One misgu-ided engineer- actually had bricked up the fresh air vents to save energy. All of these buildings were operating with 100% recycled indoor air. The lack of an adequate fresh air supply, coupled with dangerously low air exchange rates, has led to hazardous ventilation conditions in many of the buildings evaluated by HBI. Similarly, over 50% of the investigations conducted by NIOSH from 1978-1987 attributed the indoor air quality problems to inadequate ventilation. Poor Air Filtration Modern filter technology can easily cope with the numerous particulate matter that is routinely carried in the indoor air. Unfortunately, however, there is far too much ignorance in this area. Frequently good filters are poorly installed allowing air bypass, but more frequently we see a move to cheaper, less efficient filters. Many buildings attempt to clean the air with filters no better than butterfly nets. Compound this with the lack of maintenance given to the filter systems and the infrequent changes of filters and it is hardly surprising that airborne pollLitants accumulate. Methodology of Dealing with Indoor Pollution Instead of a single-minded focus on specific 'pollutants, we believe very strongly in a generic engineering approach to deal with all pol-lutants at the same-time. In our U.S. experience of over 80 million square feet of building studies,-the major contr-ibutors to poor air were threefold:

I" A (1) Poor Ventilation Inadequate ventilation 62% Zero fresh air intake 33% (2) Poor Filtration Inefficient air filters 43% (3) Dirt in Ventilation Systems Contaminated air handlers 36% Contaminated ductwork 22% We are convinced that improvirg ventilation rates, w 14 upgrading filters, and cleaning up the air handling system will eliminate over 80% of indoor pollution problems. Such changes will improve worker productivity, enhance staff morale, and reduce absenteeism however, many managers have decided to ban smoking as an apparently cheap and easy way to solve indoor air quality problems. Unfortunately, this simply does not work. HBI has determined that the presence of high concentrations of tobacco smoke indicates that a much more serious problem exists. Poor ventilation and improperly maintained ventilation systems are the primary causes of poor indoor air. When such conditions prevaLl, all the invisible and odorless pollutants are also trapped. Many of these are potentially far more dangerous than ETS. Persistent indoor air quality complaints therefore can be resolved only if building managers and operators are prepared to focus on building air handling systems in an appropriate manner. High concentrations of ETS are sumptom, not a cause of these complaints. Its elimination can effect no cure.

of this CRITIQUE OF COMPENDIUM There follows specific comments on selected chapters compendium, either where we feel there are flaws or misconceptions, or where we have construetive contributions to make. General We feel that in many areas of this compendium the list of papers and authors referenced to tends to be selective; there is a broad range of research, findings and conclusions on this topic and we feel the compendium needs to reflect this breadth of information. Suggestions for additional authors are made where relevant in each chapter. Chapter 10 This entire chapter, by its title, examines "no smoking policies" at the work site. It is obvious, however, that there are many options which will deal with the issue of smoking in the workplace. In our opinion, smoking can comfortably be tolerated in offices employing the ventilation rates as defined in ASHRAE Standard 62-• 1989. In the event that dedicated smoking lounges are specified, we again draw attention to RSHRAE's ventilation rates for these areas and suggest that all such lounges should be equipped with local area exhaust capability. Policies For Dealing with Smoking in the Workplace Attempts to solve a tobacco smoke problem alone without dealing with ventilation as a whole could leave - signif_icant =env-i=ronmental-.pr-oblems unsolved. Evidence of this

is shown in work by NIOSH and our-own published--work--which- found 2% - 4% of bui-ldings-investigated for indoor air quality problems respectively had ETS as their major pollutant source. An example of a potentially misplaced smoking ban was shown in a building owned by a majoi bank with indoor air quality complaints recently. An occupant questionnaire commissioned by the management resulted in a proposed smoking ban. On investigation of the subject building, however, the .HVAC system was found to be operating on 100% recycled air, with the outdoor air dampers closed. Even when they were open, the system was capable of deliver;.ng only 2 to 5 cfm outdoor air per occupant. The filters were found to be inefficient, and excessive fungal growths were found inside the ductwork with correspondingly high numbers of their spores in the air of the office area. Once ventilation, filtration, and hygiene were improved, complaints were reduced and the proposed smoking ban was subsequently found to be unnecessary. Designated Smoking Areas are often a practical political solution which balances the objectives of non-smokers with the smokers' wishes. laith some thoughtfulness in the selection of the smoking areas with respect to prevailing ventilation conditions, the policy of designating smoking areas works very satisfactorily. However, problems with designated smoking areas have frequently been found in indoor air quality investigations due to careless- ness. Cafeteria areas are often designated as smoking areas by management, despite ventilation systems there which are

I I- 1, ( clearly-unable to cope. A fundamental p.itfall of the_ desig- nated smoking area concept, as-a.whole, is that in a large building served by many air handling uni-=s, it concentrates all the smokers into an area served by oaly one unit. The capacity of this unit to dilute this more concentrated smoke load is now often exceeded, delivering more, not less, ETS to non-smokers also served by this unit. If there is a requirement to establish non-smoking areas within a building, we recommend the designation of many small smoking areas throughout the building ensuring that no individual air handling unit is required to cope with more smokers than it has the capacity to handle. Air Cleaning equipment marketed specifically for removal of ETS components from room air is another option. These include electrostatic precipitators, activated charcoal filters and HEPA filter units. All three have their place in removing respirable dust from the air. Dnly activated charcoal systems will deal with odor, however. We have found that all types of retrofitted air cleaning equipment frequently are left unserviced and dirty, resulting in poor or no air cleaning capacity. The most effective devices for removal of perceived signs (both olfactory and visual) of ETS appear to be a combination of good quality filters, such as HEPA, or equivalent, followed by chemical sorption of odorous Gr) I gases with activated charcoal or other proprietary media. -1 N C!T "Dilution Ventilation" is another solution. This Cd W term refers to "-dilution of contaminated air with

- uncontaminated air- in a general ar.ea,-room-, or building-, for the purpose of health hazard or nuisance control." Those who feel that dilution v.antilation is an inadequate-solution to ETS exposure include Repace and Lowry. They maintain that for adequate protection from lung cancer, a standard of 0.75 µg/m3 RSP from ETS should be adopted in the office workplace environment. They then calculate that this would require as much as 5,400 cubic foot per minute per person of fresh air brought into the building to dilute ETS generated particulates to this level. Our data shows this figure of 0.75 µg/m3 to be an unrealistic goal. This will be I the case even in non-smoking offices. Since even dry outside air might have an RSP value of between 10 and 60 µg/m3, any attempt to attain a 0.75 µg/m3 standard when outdoor air is at these levels is clearly impractical. ASHRAE base their ventilation standard on achieving control of moderate amounts of smoking. The most practical long term solution to eliminating most ETS related problems, along with a wide range of other commonly found indoor pollutants, is to ventilate office buildings, whether or not smoking is allowed, to this standard of 20 cfm per person of outdoor air in office areas. Finally, Exhaust Ventilation offers another workable approach. This policy involves the designation of smoking areas in buildings and the retrofitting of exhaust systems to those areas. When properly installed, the advantages to this ~ -system are clear - no -reentrainment of ETS into-the return

system of the building . and a mi.nimum--of-•overall--air movement-- is required. From the point of view of basia industrial. hygiene principles, this approach is sound. Poor design or direct exhaust into the return system, however, can result in more problems than it solves, such as over pressurized ceiling voids, imbalancing of the main air handl:Lng system, and short-circuiting of the exhaust outlet into outdoor air intakes. A fundamental problem is the touted "advantage" of minimum air movement throughout the building once exhaust systems for specific air pollutants are :installed. This flies in the face of arguments for adequate overall ventilation in buildings. A less obvious but winning a::gument for proper ventilation rates is a comparison of bui..lding running costs- versus absenteeism costs. Absenteeism will far outrun the costs of maintaining a building's HVAC s.ystem responsibly with regard to adequate ventilation, good filtration and high standards of hygiene. Conclusions The experience of HBI in assessing indoor air quality as a whole demonstrates the value of adequate ventilation, at least to accepted building standards, along with proper HVAC maintenance. Attention-to these points is crucial to, and effective in, reducing ETS exposure, along with exposure to a whole series of other irritating indoor pollutants.

BIBLIOGRAPHY + Eatough, D.J., C.L. Benner, J.M. Bayona, F.M. Caka, G. Richards, J.D. Lamb, E.A. Lewis and L.D. Hansen (1989a). The chemical composition of environmental tobacco smoke. I. Gas phase acids and bases. Environ. Sci. Technol. 23: 679-687. Eatough, D.J., C.L. Benner, H. Tang, V. :Landon, G. Richards, F.M. Caka, J. Crawford, E.A. Lewis., L.D. Hansen and N.L. Eatough (1989b). The chemical composition of environmental tobacco smoke. III. Identification of conservative tracers of environmenta1 tobacco smoke. Environ. Inter. 18: 19-28. Eatough, D.J., L.D. Hansen and E.A. Lewis (1990) The Chemical characterization of environmental tobacco smoke. In: Environment Tobacco Smoke: Proceedings of the International Symposium at McGill University, Lexington Books, 3-39. Eatough, D.J., Methods for Assessing Exposure to Environmental Tobacco Smoke. In: Trans. Combustion Processes and the Quality of the Indoor Environment. Int. Spec. Conf., A&WMA TR-15, Pittsburgh, PA (1989). Kirk, P.W.W., Hunter, M., Back S.O. et al; Environmental toba,cco smoke in indoor air. In: Indoor & Ambient Air Quality, Selper, London, 1989. Kurtz, D.B., Savoca, M.R. A facility for the sensory Evaluation of Environmental Tobacco Smoke. In: Indoor and Ambient Air Quality, Selper London, 1988. Robertson, G. (1990) Indoor pollution sources. Sources, effects and mitigation strategies. In: Environment Tobacco Smoke: Proceedings of the International Symposium at McGill University, Lexington Books, 333-356. Sterling, T.D., Mueller, B. (1988). Concentration of Nicotine, RSP, CO and CO2 in non-smoking areas of offices ventilated by air recirculated from smoking designated areas. J. American Industrial Hygiene Assoc. 49: (9)423-426.

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