in the open air. However, the velocity of the airstream through the chamber has considerable influence on the yields of individual compounds in SS (Klus and Kuhn 1982). To collect the particulate phase of MS and SS, the smoke aerosols are passed through a glass fiber filter (a Cambridge filter with a diameter of 45 mm) that traps more than 99 percent of all particles with a diameter of at least 0.1 pm (Wartman et al. 1959). The portion of the smoke that passes through the glass fiber filter is arbitrarily designated as vapor phase, although it is realized that this separa- tion does not fully reflect the actual physicochemical conditions prevailing in MS and SS. For the analysis of individual components or a group of components, specific trapping devices and methods have been developed (Dube and Green 1982). Human Smoking The standardized machine-smoking conditions used in the tobacco laboratory were set up to simulate the parameters of human smoking as practiced 30 years ago. The examination of current smoking practices suggests that machinesmoking conditions no longer reflect current practices. Human smoking patterns depend on a number of factors, one of which is the delivery of nicotine. Do&retry of smoke constituents has shown that low nicotine delivery (~0.6 to 1.0 m&cigarette) generally induces the smoker to draw larger puff volumes (up to 55 mL per puff), to puff more frequently (three to five times a minute), and to inhale more deeply (Heming et al. 1981). Furthermore, many smokers of cigarettes with perforated filter tips tend to obstruct the holes in these tips by pressing their lips around them; thus, they inhale more smoke than would he expected according to the machine-smoking data (Kozlow- ski et al. 1960). Smokers of cigarettes with a longitudinal air channel in the filter tip compress the tip in a similar manner so that the mainstream smoke delivery is increased over that measured with the laboratory methodology (Hoffmann et al. 1983). These deviations from machin~moking patterns cause a greater ammt of tobacco to be consumed during MS generation. Conse quently, the quantity of tobacco burned between puffs is diminished, and lower amounts of combustion products are released as SS. Because of the proximity to the burning tobacco product, the active smoker usually inhales more of the SS and ETS than a nonsmoker. It is not known to what extent the different constituents of inhaled ETS aerosols can be retained in the respiratory tract of nonsmokers. Studies with MS have shown that more than 90 percent of the volatile, hydrophilic components are retained by the smoker @al- hamn et al. 1968a) and that less than 50 percent of the volatile, hydrophobic MS components are retained by the smoker (Dalhamn et al. 196813). On the basis of these data, it may be assumed that the 126 passive smoker retains a high percentage of the vapor phase components of ETS and significantly less of its hydrophobic volatiles. Sidestream Smoke Formation7 and Physicochemical Nature When nonfilter cigarettes are being smoked under standardized conditions, approximately 45 percent of the tobacco column is consumed during the generation of MS (puff-drawing), whereas the remainder is burned between puffs and under conditions of a strongly reducing atmosphere. In addition, MS and SS is generated at distinctly higher temperatures than SS (Wynder and Hoffmann 1967). Thus, undiluted SS contains more tobaccoderived combustion products than does MS, and contains especially greater quantities of those combustion products that are formed by nitrosation or amination. Consequently, the composition of SS differs from that of MS. The SS of a smoldering cigarette enters the surrounding atmo- sphere about 3 mm in front of the paper burn line, at about 350" C (Baker 1984). In Table 1, the MS and the SS from nonfilter cigarettes are compared. Under standardized conditions, the formation of the MS of a nonfilter cigarette (80 mm, 1,230 mg) is completed during 10 puffs, requires 20 seconds, and consumes 347 mg of tobacco. The formation of SS from the same cigarette during smoldering requires 550 seconds and consumes 411 mg of tobacco (Neurath and Horst- mann 1963). The pH of the MS of a blended U.S. cigarette ranges from 6.0 to 6.2 and the pH of SS, from 6.7 to 7.5. Above pH 6, the proportion of unprotonated nicotine in undiluted smoke rises; at pH 7.9, about 50 percent is unprotonated. Therefore, SS contains more free nicotine in the vapor phase than MS. The reported measurements of the pH of cigars were 6.5 to 8.5 for MS and 7.5 to 8.7 for SS; measurements for the pH of SS from pipes have not been published (Brunnemann and Hoffmann 1974). Chemical Analysis In order to establish reproducible chemical-analytical data, ciga- rette SS is generated in a special chamber. This assures that the cigarettes burn evenly during puff intervals when an air-stream at a velocity of 25 mL per second is drawn through the chamber. At this flow rate in the chamber, MS generation is quantitatively similar to that measured without the SS chamber (Neurath and Ehmke 1964; Brunnemann and Hoffmann 1974; Dube and Green 1982). Through- out this chapter the data refer primarily to MS, SS, and ETS deriving from cigarettes and not from cigars or pipes, because 127 TAEJLE l.-Comparison of mainstream smoke (MS) and sidestream smoke (SS) of a nonfilter cigarette: Some physicochemical data Study Parameter3 MS ss Neurnth and Horstmarm Duration of emoke production (see) 20 660 `1963) Tobaccn burned (m& 347 411 ynder end Hofhann Peak temperature dm formation ("`3 a900 a600 367) Brunnemann and HoEman (1974) pHoft&alaemi3ol a-6.2 6.7-75 sceSaellati-SfOlZOlhli and Savino WE6) Number of partiolen per ckareW1 10.6 x 10" 36 x 10" Carter and Haqawa (1975); Hiller et al. m82) Particle s&a cnm)' Particle meau diameter (rut91 0.1-1.0 0.01-0.8 0.4 0.32 Wynder and Hoffinann Smoke dilution (~01 %I' (I967); K&b and Derrick wo); carbon momxide 3-S 2-3 B&or (1964); Hoffmann, Bnmnemann carbon dioxide 6-11 4-6 et al. w34) 1!&16 1.6-2 cigarette smoke is the major source of EYE3 in public places. Few data are available on the SS and ETS from cigars and pipes. About 300 to 400 of the several thousand individual compounds identified in tobacco smoke have been quantitatively determined in both mainstream and, sidestream smoke. A listing of selected agents iu the MS of nonfilter cigarettes with their reported range of concentration and their relative ratio of distribution in SS compared &ith MS is presented in Table 2. Values greater than 1.0 reflect the greater release of a given compound into SS than intO MS. The grouping of the compounds in Table 2 into vapor phase components and particulate phase constituents refers to the makeup of MS, but does not represent the physicochemical distribution of these corn- pounds in SS. Some of the volatile compounds in MS and SS are compared. On the basis of the amount of tobacco burned in the MS and SS of a nonfilter cigarette (see Table 11, the ratio of SS to MS should be 1.2 to 1.5 if the combustion conditions during both phases of smoke generation were comparable. However, this is not the case, 128 as is indicated by the higher SS to MS ratios for carbon monoxide (2.5-4.7), carbon dioxide W-11), acrolein (3-15), benzene (IO), and other smoke constituents. The high yield of carbon monoxide and carbon dioxide in SS indicates that more carbon monoxide is generated during smoldering than during puff-drawing. After passing very briefly through the hot cone, most of the carbon monoxide gas in both MS and SS is oxidised to carbon dioxide, most likely owing to the high temperature gradient and the sudden exposure to environmental oxygen upon emission., The higher yields of volatile pyridines in SS compared with MS are probably caused by the preferred formation of these compounds from the alkaloids during smoldering (S&melts et al. 1979). In contrast, hydrogen cyanide (HO is primarily formed from protein at temperatures above 700" C (Johnson and Kang 1971), and the smoldering of tobacco at about 690" C does not yield the pyrosynthe- sis of HCN to the extent that it occurs at the higher temperature present during MS generation. The very high levels of ammonia, nitrogen oxide, and the volatile N-nitrosamines in SS compared with the levels in MS is striking. Studies with `6N-nitrate have under- scored that the burning of tobacco results in the reduction of nitrate to ammonia, and that the latter is released to a greater extent during SS formation than during puff-drawing (Johnson et al. 1973). In a blended cigarette, this higher level of ammonia in SS causes its elevated pH to reach levels of 6.7 to 7.5, while the pH of MS is about 6 (Brunnemann and Hoffmann 1974). The increased release of the highly carcinogenic volatile N-nitrosa- mines into SS (20 to 100 times greater than into MS) has been well established (Brunnemann et al. 1977). The carcinogenic potential of SS may also be affected by the levels of the oxides of nitrogen (NO=). Four to ten times more nitrogen oxide (NO) is released into the environment in sidestream smoke than is inhaled with the main- stream smoke. The smoker inhales more than 95 percent of the NO, in the form of NO, and only a small portion is oxidized to the powerful nitrosating agent nitrogen dioxide (NOa). Only a fraction of NO is expected to be retained in the respiratory system of smokers by being bound to hemoglobin. The NO, gases released into the environment are partially oxidized to NO, (Vilcins and Lephardt 1975). Therefore, sidestream smoke-polluted environments are ex- pected to contain the hydrophilic nitrosating agent NO,. Data for particulate matter and some of its constituents in MS and SS are also listed in Table 2. The release of tobacco-specific N- nitrosamines into SS is up to four times higher than that into MS. Whether the distribution of these agents in the vapor phase and the particulate phase of SS is of major consequence with respect to the carcinogenic potential of SS needs to be determined. It is equally 129 t; 0 TABLE `lo-Distribution of constituents in mainstream smoke (MS) and the ratio of sidestream smoke @X3) to MS of noufilter cigarettes Vapor phase constituents ' MS SS/MS range ratio Particulate phase constituents' MS range SSIMS ratio Carbon monoxide Carbon dioxide Carbonyl sulfide Benzene ' Toluene Formaldehyde Acroiein Acetone Pyridine SMethylpyridine S-Vinylpyridine Hydrogen cyanide Hydrazine ' Ammonia Methylamine Dimethylamine Nitrogen oxide 10-23 mg 2.5-4.7 20-40 mg a11 16-42 pg 0.03-0.13 12-46 pg 10 160 PET 6 70-100 Ilg o.k&O 6&m I% 8-16 1w250 pg 2-6 16-40 PB 6.5-20 12-36 p.g 3-13 11-30 w CD-40 4-w 0.1-0.25 32 ng 3 50-130 pg 40-170 11.5-28.7 pg 4.2-6.4 7.610 pg 3.7-5.1 1-W 4-10 Particulate matter * Nicotine Anatabine Phenol C&echo1 Hydroquinone Aniline 2-Toluidine 2-Naphthylamine* 4-Aminobiphenyl * Benz[a]anthracene' Benzo[a]pyrene s Cholesterol y-Butyrolactone' Quinoline I Harman N!-Nitrcsonornicotine' 15-4a mg 1.3-1.9 l-Z.5 mg 2.6-3.3 2-%l% <0.1-0.6 60-140 pg 1.6-3.0 1-w 0.60.9 110-300 pg 0.749 3130 w 30 160 ng 19 1.7 ng 30 4.6 ng 31 2C-70 ng 2-i 20-W 2.5-3.6 22 w 0.9 10-22 pg 3.k5.0 0.5-2 pg a11 1.7-3.1 w 0.7-1.7 200-3,~ ng 0.6-3 TABLE 2.-Continued MS -&SIMS MS Vapor phase constituents' SSIMS range ratio Particulate phase constituents' range ratio N-Nitrusodimethylamine' 1040 ng 20-1cQ NNK' 100-1,006 ng 14 N-Nitrosopyrrolidine' 630 ng 6-30 N-Nitrosudienthanolamine' 20-70 ng 1.2 Formic acid 216-490 ug 1.4-1.6 Cadmium 100 ng 7.2 Acetic acid 33O-SlO l(g 1.9-3.6 Nickel a 20-80 ni3 13-30 ZiiC 624 w 6.7 Polonium-210' 0.64-0.1 pCi 1.0-4.0 Hensoic acid 14-28 pg 0.67-0.95 Lactic acid 63-174 Iig 0.3-0.7 Glycolic acid 37-126 pg 0.6-0.96 Succinic acid 110-140 pg 0.43-0.62 ' Values are given far fresh and undiluted MS and SS. *Human carcinogen (IARC 1936). 3Suspxted human carcinogen (IARC 19%). `Animal carcinogen (IARC 1966). SOURCE: Elliott and Rowe (1975); Hoffmann et al. (1983); Klw and Kuhn (1982); Sakuma et al. Nfl3); Sakuma, Kusama, Ysmaguchi. Mabuki et al. (1984); Sakuma. K-ma, Yamaguchi, Sugawara (1994); Schmeltz et al. (1976). important to examine the significance of the abundant release of amines into SS (levels are up to 30 times higher than in MS), indicated by the data for aniline, Ztoluidine, and the alkaloids. This is of concern because certain amines are readily nitrosated to N- nitrosamines. However, analytical data on secondary reactions of amines in polluted environments are lacking. For a meaningful interpretation of the data on the distribution of the compounds in cigarette smoke presented in Table 2, certain aspects of the methodology should be emphasized. First, the data are baaed on analyses of nonfilter cigarettes that were smoked under standardized laboratory conditions. Second, the standardized ma- chine-smoking conditions were established according to human smoking patterns observed three decades ago and do not reflect the smoking behavior of contemporary smokers. This caveat applies particularly to smoking patterns observed with filter cigarettes designed for low smoke yields. Most consumers of these cigarettes inhale the smoke more intensely than smokers of nonftiter cigarettes (Herning et al. 1981; Hill et al. 1983). This change in smoking intensity affects the delivery of the side&ream smoke. The conven- tional filter tips of cigarettes influence primarily the yield of MS and have little impact on SS yield. However, in the case of cigarettes with specially designed filter tips such as perforations, the yield of SS is also affected (Table 3) (Adams et al. 1985). Radioactlvity of Tobacco Smoke Naturally occurring decay products of radon are found in tobacco and, therefore, also in tobacco smoke. These include the isotopes of lead (Pb-2101, bismuth (Bi-210), polonium (Po210), and radon, which originates from the decay of uranium through radium (Radford and Hunt 1984; Max-tell 1975). Radon and its short-lived daughters (Po- 218, Pb214, Bi-214, Po214), which precede long-lived daughters in the decay chain, are ubiquitous in indoor air and are largely derived from sources other than tobacco smoke. Most of the radon daughters are attached to particles in the air, but a small proportion, referred to as the unattached fraction, is not (Raabe 1989; Kruger and Nijthling 1979; Bergman and Axelson 1983). It has been suggested that the presence of Pb-210 and subsequent decay products in tobacco is dependent upon an absorption of short- lived radon daughters on the leaves of the tobacco plant, especially where phosphate fertilizers that are rich in radium have been used and have caused increased leakage of radon from the ground. These attached short-lived radon daughters then decay to long-lived Pb-210 and subsequent nuclides found in the tobacco (Fleischer and Parungo 1974; Martell 1975). However, the origin of these decay products may 132 TABLE 3.-Distribution of selected components in the sidestream smoke (SS) and the ratio of SS to mainstream smoke (MS) of four U.S. commercial cigarettes components Cigarette A Cigarette B Cigarette ( Cigarette D 85 mm NF 85 mm F 85 mm F 85 mm PF ss SWMS ss SSiMS ss SS/MS ss SSIMS Tar imglgl 22.6 1.1 24.4 1.6 20.0 2.9 14.1 15.6 Nicotine lmgigl 4.6 2.2 4.0 2.7 3.4 4.2 3.0 20.0 C'arbon monoxide cmg/g) 28.3 2.1 36.6 2.7 33.2 3.5 26.8 14.9 Ammonia ImyJgl 524 7.0 8Y3 46 213.1 6.3 236 5.8 (`atecho (pgtgl 58.2 1.4 89.8 1.9 69.5 2.6 117 12.9 Benzolalpyrenv Ingig 67 2.6 45.7 2.6 51.7 42 448 20.4 N~N~trosodlmethyumine tng/gl 735 236 597 139 611 50.4 685 167 N-Nitrosopyrrolidtne cng/g~ 177 2.7 13Y 13.6 233 71 234 11.7 N -Niirosonornlcotme (ng/yi 857 0.85 307 0.63 1x5 0.68 338 5.1 also depend on the general occurrence of radon in the atmosphere and not on the local emanation of radon (Hill 1982). In recent years, it has been shown that relatively high levels of radon and short-lived radon daughters may occur in indoor air, and consistent observations in this regard have been made in several countries (Nero et al. 1985). In the air with a very low concentration of particles, the proportion of unattached radon daughters is increased beyond that found with a higher concentration of particles. The unattached daughters are removed more rapidly than those that are attached by plating out on walls and fixtures. The addition of an aerosol, such as tobacco smoke, increases the attached fraction, elevates the concentration of radon daughters, and reduces the rate of removal of radon daughters (Bergman and Axelson 1983). The dose of a radiation received by the airway epithelium depends not only on the concentration of radon daughters but also on the unattached fraction and on the size distribution of the inhaled particles. The interpIay among these factors as they are modified by KTS has not yet been fully examined. Environmental Tobacco Smoke The air dilution of side&ream smoke, and of other contributors to ETS, causes several physicochemical changes in the aerosol. The concentration of particles in ET'S depends on the degree of air dilution and may range from 300 to 500 mg/mg to a few p&ma. At the same time, the median diameter of particles may decrease as undiluted SS is diluted to form ETS (Keith and Derrick 1960, Wynder and Hoffmann 1967; Ingebrethsen and Sears 1936). Further- more, nicotine volatilizes during air dilution of SS, so that in ET'S it occurs almost exclusively in the vapor phase (Eudy et al. 1985). This is reflected in the fairly rapid occurrence of relatively high concen- trations of nicotine in the saliva of people entering a smokepolluted room (Hoffmann, Haley et al. 1984). Most likely there are also redistributions between the vapor phase and the particulate phase of other constituents in SS due to air dilution, which may account for the presence of other semivolatiles in the vapor phase of KTS. However, evidence of such effects needs to be established. Comparison of Toxic and Carcinogenic Agents in Mainstream Smoke and in Environmental Tobacco Smoke The combustion products of cigarettes are the source of both environmental tobacco smoke and mainstream smoke. Therefore, comparisons of the levels of specific toxins and carcinogens in KTS with the corresponding levels in the mainstream smoke are relevant to an estimation of the risk of E'I'S exposure. Although KTS is a far 134 less concentrated aerosol than undiluted MS, both inhalants contain the same volatile and nonvolatile toxic agents and carcinogens. This fact and the current knowledge about the quantitative relationships between dose and effect that are commonly observed from exposure to carcinogens have led to the conclusion that the inhalation of ET'S gives rise to some risk of cancer (IARC 1986). However, comparisons of MS and ETS should include the consider- ation of the differences between the two aerosols with regard to their chemical composition, including pH levels, and their physicochemi- cal nature (particle size, air dilution factors, and distribution of agents between vapor phase and particulate phase). Another impor- tant consideration pertains to the differences between inhaling ambient air and inhaling a concentrated smoke aerosol during puff- drawing. Finally, chemical and physicochemical data established by the analysis of smoke generated by machine-smoking are certainly not fully comparable to the levels and characteristics of compounds generated when a smoker inhales cigarette smoke. This caveat applies particularly to the smoking of low-yield cigarettes, for which the yields of smoke constituents in machine-generated smoking and human smoking activities may be most divergent (Heming et al. 1981). The levels of certain smoke constituents in the mainstream smoke of one cigarette compared with the amounts of such compounds inhaled as constituents of ETS in 1 hour at a respiratory rate of 10 L per minute are presented in Table 4. Unaged MS does not contain nitrogen dioxide (NO* < 5 &cigarette) because the nitrogen oxides generated during tobacco combustion in the reducing atmosphere of the burning cone are transported in the smoke stream (a10 vol % 0,) to the exit of the cigarette mouthpiece in less than 0.2 seconds, and it takes 500 seconds for half of the nitrogen oxide in MS to oxidize to nitrogen dioxide (Neurath 1972). The relatively low values for nicotine reported in ETS may be explained, in part, by the inefficiency of the trapping devices for collecting all of the available nicotine; the alkaloid is predominantly in the vapor phase, which escapes retention by the filters of such devices. The assignment of benzene as a "human carcinogen," benzo- [alpyrene as a "suspected human carcinogen," and N-nitrosodi- methylamine and N-nitrosodiethylamine as "animal carcinogens" is based on definitions by the International Agency for Research on Cancer (1986). Accordingly, a human carcinogen is an agent for which "sufficient evidence of carcinogenicity indicates that there is a causal relationship between exposure and human cancer." A SUS- petted human carcinogen is an agent for which "limited evidence of carcinogenicity indicates that a causal interpretation is credible, but that alternate explanations, such as chance, bias, or confounding, could not adequately be excluded." An animal carcinogen is an agent 135 E TAFHJZ 4-Concentrations of toxic and carcinogetic agents in notilbr cigarette mainstream smoke and in environmental tobacco smoke (EiTS) in indoor environments Agent . Inhaled ae ETS constituents during 1 hour Mainstream Smoke Range Episodic high values' Weight Concentration Weight Concentration Weight Concentration Carbon monoxide lo-23 mg Nitrogen oxide 100-600M Nitrogen dioxide <5 w Acrolein 60-100 pg Acetone KNJ-260 pg Benzene 1248 pg N-Nitrosodimethylamine' 10-40 ng N-NitrosodiethylemineJ 4-25 ng Nicotine v.3=2,500 Pl? Be@alpyre"e' 20-40 ng 2WXQ-5~,300 rm 23O,ooo-1,400,ooO ppb <7&Q ppb 75,CG+125,000 ppb 120.~,~ ppb 11$00-43,000 ppb s-36 ppb 3-17 ppb 434I,OGC-1,080,000 ppb 5-11 ppb 1.2-22 mg 7-90 pg 24-S7Irg S-72 M 210-720 pg u-190 pg 6-140 ng (6120 ng 0.630 pg 1.7-460 ng l-18.5 ppm 9-120 ppb 21-76 ppb 6-50 ppb 160-500 wb 6-9~ wb 0.003-0.072 ppb <0.00%0.05 ppb 0.15-7.5 ppb 0.0002-0.04 ppb 37 mg 146 w 120 l4z 110 pg 3,500 I% 190 l% 140 ng 120 ng 3cQws 460 ng 32 PP~ 196 ppb 106 wb 8~ wb 2,400 wb 98 wb 0.072 ppb 0.05 ppb 76 wb 0.04 ppb NOTE: Values for inhaled mainstream smoke components were calculated from values in Table 2 and on a respiratory rate of 10 L per minute. Valuea for carbon monoxide and nicotine represent the range in mainstream smoke of U.S. nonfilter cigarettes 88 reported by the U.S. Federal Trade Commission (19%). Data under EIS are derived from Tables 8 through 16, with data fmm the unventilated interior compartmenta of automobiles excluded (Badre et al. 1978). `The designation "episodic high values" was chosen to classify those data in the literature that require confirmation. *Human carcinogen according to the IARC (Vainio et al. 1986) and suspected carcinogen according to the ACGIH (198%. `Animal carcinogen according to the IARC (V&do et al. 1995). 4 Suep&.ed human carcinogen, according to the IARC (Vainio et al. 1985) snd according to the ACGIH (1986). "for which there is sufficient evidence of carcinogenicity in animals but for which no data on humans are available." Polonium-210 is not listed in Table 4 because there are no data on the concentration of this isotope in ETS, although it is a component of both MS and SS. Whereas in clean air the short-lived radon daughters tend to plate out on room surfaces, in the presence of an aerosol such as El's, some of the short&& radon daughters become attached to particles and consequently remain available for inhala- tion. Radon daughter background concentration may more than double in the presence of EYI'S (Bergman and Axelson 1989). Number and Size Distribution of Particles in EnvIronmentsI Tobacco Smoke Environmental tobacco smoke consists of the combined products of both fresh and aged sidestream smoke and exhaled Ilaainstream smoke. Coagulation, evaporation, and particle removal on surfaces occur simultaneously to modify the physical characteristica of the ETS particles; as a result, the "typical" particle size and chemical composition of ETS may vary with the age of the smoke and the characteristics of the environment. Other factors such as relative humidity, particle concentration, and temperature may also tiect the characteristics of EYE. The rapid dilution of SS smoke as it is emitted into a room leads to a number of physical and chemical changes. For example, the evaporation of volatile species as the ETS ages reduces the median diameter of the smoke particles. Several studies have measured the particle distribution of SS under controlled conditions (Table 5), and indicate that the mass median diameter (MMD) of ETS is between approximately 0.2 w and 0.4 v. The differences among the studies reflect the varying analytical methods. EYE3 particles are in the diffusioncontrolled regime for particle removal and therefore will tend to follow stream lines, remain airborne for long periods of time, and rapidly disperse through open volumes. As indicated, a number of factors can produce variation in the mean size of the particles in EYl'S, however, in considering transport, deposition, and removal in the human lung, it is useful to assume that the particle sizes of aged ETS will generally be between 0.1 and 0.4 pm. Although the results presented in Table 5 do not permit the assignment of a single value for the diameter of side&ream smoke particles, the difference in deposition efficiency in the human respiratory tract of 0.2 pm particles and 0.4 w particles is negligible (C&an and Lippmann 1980). Particles in this size range are not efficiently removed by sedimentation or impaction. Although diffu- sion is the major removal mechanism for particles of this size, it is . . mmnnally efficient in the 0.2 to 0.4 v range. The relatively low 137 iii TABLE li.-Summary of sidestream smoke size distribution studies Study Cigarette Method Chamber concentration (pg/m sJ count median diameter Ma.% median diameter Geometric standard deviation Number per cm' Keith and Derrick IlW-ll Blended "Conifuge" Not reported 0.15 Not reported Not reported 38 x 10" PorstendGrfer and Schraub (19721 Not reported CNUdiffusion tube Not reported 0.24 Not reported Not reported 3.3 x 10" Hiller et al. (1982J Not reported SPART analyzer 5@100 0.32 0.41 1.5 Not reported Leaderer et al. (1984) Commercial EAA mcl Not reported 0.225 21 Not reported lngebrethsen and sears (1986) MCICNC 0.2 1.5 particle deposition efficiency for SS particles in human volunteers observed by Hiller and colleagues (1982) is consistent with particles in this size range. Several investigators have measured the size distribution of MS smoke (Table 6). As is the case with SS smoke, the different instruments and methodologies employed yielded differing results. For purposes of comparison, only two sets of studies utilizing similar instruments are discussed. McCusker and colleagues (19831, using a single particle aerodynamic relaxation time @PART) analyz- er to study highly diluted MS smoke particles, found a mass median diameter of 0.42 pm with a geometric standard deviation (GSD) of 1.38. Hiller and colleagues (1982) used the SPART analyzer on SS smoke particles and found a mass median diameter of 0.41 pm and GSD of 1.5. Chang and colleagues (1985) used an electrical aerosol analyzer (EAA) to measure MS for various dilution ratios and reported a MMD of 0.27 pm (GSD 1.26) for the highest dilution. Leaderer and colleagues (1984) used an EAA to determine the size distribution for SS smoke particles in an environmental chamber and determined an MMD of 0.23 urn (GSD 2.08). These results also show that studies utilizing similar instruments provide similar results for the size distribution of both SS and MS particles. As discussed in an earlier section, however, the chemical composition of the MS and ETS particles can be quite different because of the very different conditions of their generation and the subsequent dilution and aging ETS undergoes before inhalation. Estimating Human Exposure to Environmental Tobacco Smoke Human exposure to ETS can be estimated using approaches similar to those used for other airborne pollutants. The concentra- tion of ETS to which an individual is exposed depends on factors such as the type and number of cigarettes burned, the volume of the room, the ventilation rate, and the proximity to the source. These factors, along with the duration of exposure and individual characteristics such as ventilatory rate and breathing pattern, dictate the dosage received by an individual. Ideally, the health effects of exposures to ETS might be assessed by quantifying the timedependent exposure dose for each of the several thousand compounds in cigarette smoke and defining the dose- response relationships for these compounds in producing disease, both as isolated compounds and in various combinations. The magnitude of this task, given the number of compounds in smoke, and the limited knowledge of the precise mechanisms by which these compounds cause disease have led to a simpler approach, one that attempts to use measures of exposure to individual smoke constitu- ents as estimates of whole smoke exposure. The accuracy with which 139 8' TABLE 6.-s ummary of niainstream smoke size distribution studies count MaSa median median Geometric Dilution diameter diameter etadad concentration Study cigarem Method rati0 k-1 (run) deviation (number/cm') Keith and Derrick ma3 Blended "ConIf~" 298 0.23 Not reported 1.6 6.9 I 10 Pomtmdllrfer and Sehraub (1972) Not reported CNC/diffueion tube Not reported 0.22 Not reported Not reported Not regmted Okada and Matmnama (1974) Blended Light e&t.ering Hinds ww Commercial Caecade impactor cascade impactor Cascade @iactor Aerosol certifuge Aeroeol certifuge Aerosol certifuee Aemol CeltitilKe 10 60 100 100 320 Ka 700 0.18 Not reported 0.62 Not reported 0.44 Not reported 0.39 Not reported 0.38 Not reported 0.98 Not reported 0.36 Not reported 0.37 0.29 1.5 1.36 Not reported 1.44 Not reportad 1.43 Not reported 1.33 Not reported 1.37 Not mported 1.35 Not rqmrted 1.31 Not revorkd 3 a 10'" Mdxlsker et al. 2Rl SPAm analmr 1.2611~ 0.36 0.42 1.38 4.2 x t cbang et al. 2Rl EAA 6 0.25 0.30 127 4.2 I 10' mm 10 0.24 0.26 1.18 3.6 x 10' 18 0.22 0.96 1.26 7 a 1w measurements of a single compound reflect exposure to whole smoke is limited by the changes in the composition of M`s with time and the conditions of exposure. For this reason, exposures to E'l'S are often afessed using several measures as markers, including mark- ers of the vapor phase and the particulate phase as well as reactive and nonreactive constituents. Although biological markers show promise as measures of exposure because they measure the absorp tion of smoke constituents, they too have limitations (diecussed ' Chapter 4). An individual's exposure is a dynamic integration of &: concentration in various environments and the time that the individual spends in those environments. In specifying an individual's exposure to specific components of EITS, consideration must be given tc the time scale of exposure appropriate for the response of interest. Immediate exposures of seconds or hours would be most relevant for irritant and acute allergic responses. Time-averaged exposures, of hours or days, may be important for acute contemporary effects such as upper and lowe respiratory tract symptoms or infections; chronic exposures occur ring over a year or a lifetime might be associated with increases prevalence of chronic diseases and risk of cancer. The spatial dimensions or the proximity of the individual to the source of smoke is important in assessing that individual's exposure to ETS. E!lTS is a complex, dynamic system that changes rapidly once emitted from a cigarette. Physical processes such as evaporation and dilution of the particles, scavenging of vapors on surfaces, and chemical reactions of reactive compounds are continuously occurring and modify the mixture referred to as ETS. An individual located a few centimeters or a meter from a burning cigarette may be exposed to a high concentration of ETS, ranging from 200 to 300 mg/m*, and may inhale components of the mostly undiluted smoke plume and of the exhaled mainstream smoke. Ayer and Yeager (1982) reported cigarette plume concentrations of formaldehyde and acrolein in the core smoke stream emitted from the cigarette of up to 190 times higher than known irritation levels. Hirayama, as reported by Lehnert (1984), cites the importance of this "proximity effect" in assewing exposure. llist.anw on the order of a meter tc tens of meters from a burning cigarette are relevant for exposures in offices, restaurants, a room in a how, a car, or the cabin of a commercial aircraft. At these distances, the mixing of ETS throughout the airspace and the factors that affect concentration are of importance in determinin g exposure for people in the space. In many rooms, mixing is not completely uniform throughout the volume, and significant concentration gradients can be demonstrated Wizu 1930). These concentration gradients wilI affect an individual's exposure by modifying the effectiveness of ventilation in diluting or removing pollutants. The airborne mass concentration may vary by 141 a fa&r of 10 or more within a room. Short-term measurements in rooms with smokers can yield respirable particulate concentrations of 100 to 1,000 CLg/mS (Repace and Lowrey 1980). Multihour measurements average out variations in smoking, mixing, and ventilation and yield concentrations in the range of 20 to 200 CLg/mS (Spengler et al. 1981,1985,1986). Finally, on a systems scale, as in a house or building, concentrations are influenced by dispersion and dilution through the volume. Most timeintegrated samples are taken on tbis larger scale. Using a piexobalance, Lebret (1985) found significant variation in respirable suspended particulate (R.SP) levels between the living room, kitchen, and bedroom in homes in the Netherlands during smoking or within onehalf hour of smoking. Ju and Spengler (1981) studied the room-toroom variation in 24-hour average concentra- tions of respirable particles in various residences. Although differ- ences between some rooms were statistically sign&ant, absolute differences were relatively small, with a maximum difference of a factor of 2. Moscbandreas and colleagues (1978) released sulfur hexafluoride, a tracer gas, in the living rooms of several residences and observed uniform concentrations in adjacent rooms within 30 to 90 minutes, RSP, which is slightly reactive, and nonreactive gases would be expected to rapidly migrate through adjacent rooms. Therefore, in a setting such as the work environment, where the duration of exposure is several hours or more, HTS would be expected to disseminate throughout the airspace in which smoking is occurring. Smoke dissemination may be reduced when air exchange rates are low, as may occur when internal doors are closed. Time-Activity Patterns Individual time-activity patterns are a major determinant of exposure to ETS. The population of the United States is mobile, spending variable amounts of time in different microenvironments. Individual activity patterns depend on age, occupation, season, social class, and sex. For example, Letz and colleagues (1984) surveyed the time-activity patterns of 332 residents of Roane County, Tennessee, and found that 75 percent of the person-hours were spent at home, 10.8 percent at work, 8.5 percent in public places, 2.9 percent in travel, and 2.8 percent in various other places. As expected, occupation and age were strong determinants of time-activity patterns. Housewives and unemployed or retired individuals spent 84.9 percent of their time at home, and occupational groups worked 21 to 24 percent of the hours. Students tended to spend the largest percentage of their time in public places, presumably schools, ranging from 14.7 percent for the youngest group to 19.17 percent for the oldest group of students. 142 TABLJZ `I.-Mean percent and standard deviation of time allocation iu various locations by work or school classification subgroup outdoor ofiice/ Indwtrial/ Thl,aU Location HOlIlemaLer student worker ssrvice c4luhuction perticipant.9 Home 84.34 60.91 49.97 63.74 57.23 64.21 (2.02l' (13.92) (12.24) (8.72) c7.05) (13.99) outside 5.52 8.62 19.81 2.47 -10.69 (3-m 6.53 K4.55) (2491 (10.74) (Fi Motor vehicle 4.28 5.11 8.67 (3.19) (3.74) (6.15) 0 (7% 5.51 (4.m other incLmn 6.01 23.61 21.56 24.99 24.80 21.68 (3.27) (10.61) (5.32) (10.241 a28a (11.37) cooking 4.69 0.52 1.24 u.fm (lit (iii (:: @.W cw Near mnokem 2.34 5.!20 275 11.73 (4.32) c1.88) (3.38) (15.19) (12: (!z: Number 8 32 4 12 8 66' `Numbershparentheemarethe~darddeviation. ' `ho unemployed partioipanta - inchded in the total. but not given a mparate catqmy. SOURCE: Data f-mm Quaokerlb et al. (1982). The time allocations for various population subgroups in Portage, Wisconsin, are summarized in Table 7 (Quackenboss et al. 1982). The data are consistent with the findings of Letz and colleagues (1984) and show that the variability of individual nonsmokers' exposure to smokers can be quite marked between the various occupational subgroups. Infants have unique time-activity patterns; their mobility is limited and the locations where they spend their time depend primarily on their caretakers. The time-location patterns for 46 infants is illustrated in half-hour segments in E'igure 1 (Harlos et al. in press). Although infants spend most of their time in their bedrooms, they are in contact with a caretaker while traveling or in the living room or the kitchen for approximately half of the day. These infant time-activity patterns presumably correspond to the family patterns and may significantly influence the infants' poten- tial exposure. Although most people spend approximately 90 percent of their time in just two microenvironments (home and work) (&alai 1972), important exposures can be encountered in other environments. For instance, commuting or being Yn transit" accounts for about 0.5 to 1.5 hours per day for most people. Therefore, additional information 143 -L --M -3 ,aD -a r -9 -Lx -0 FIGURE I.-Time location patterns for 46 infants SOURCE: HarIm et al. (in prem). on the time spent and the EZS concentration in various microenvi- ronments may be useful in defining exposure. This exposure information can be obtained by questionnaire and validated by personal monitoring programs. The characterization of concentra- 144 tions or exposures or both in microenvironments should use time scales appropriate for the health effect of interest. These variations in location -and time-activity patterns can make the reconstruction of detailed ETS exposure difficult in studies of long-term health effects. The limitations in utilizing this timeactivity approach in charac- terizing exposures to other environmental pollutants also apply for ETS exposures. They include the following: the extent to which overall population estimates can be generalized to individual pat terns is poorly understood; concentrations in various microenviron- ments are only partially characterized, the variation in time and activity patterns and their effects on concentration levels are not established; extrapolation to longer time scales either prospectively or retrospectively has not been validated; the differences within structures, i.e., room to room ~variations, are not well established. Temporal and Spatial Distribution of Smokers Exposure to ETS can occur in a wide variety of public and private locations. Approximately 30 percent of the U.S. adult population currently are cigarette smokers. Nationwide, 46 percent of homes have one or more smokers (Bureau of the Census 1985). In a survey of more than 10,000 children in six U.S. cities, the percentage of children living with one or more smoking adults varied from a low of 60 percent to a high of 75 percent (Ferris et al. 1979). Lebowitx and Burrows (1976) reported that 54 percent of children in a study in Tucson had at least one smoker in the home; Schilling and colleagues (1977) reported that 63 percent of homes in a Connecticut study had a smoker in the home. These data indicate that the population potentially exposed to ETS in the home is greater than might be inferred from aggregated national statistics on the prevalence of smoking. A variation in the percentage of homes with smokers may be observed among different regions. Furthermore, within house holds, smoking does not take place uniformly in time or space. Smoking patterns may change with activity, location, and time of day. These variables all serve to modify a nonsmoker's exposure to ETS. Exposure to ETS at home may also correlate with ETS exposures outside the home, possibly because nonsmokers married to smokers may have a greater tolerance for ETS-polluted environments or may be in the company of more smokers because of the spouses' tendency to associate with other smokers. Wald and Ritchie (1984) used a biological marker and questionnaires to show that nonsmokers married to smokers reported a duration of exposure to ETS greater outside the home than was reported by nonsmokers married to nonsmokers (10.7 hours and 6.0 hours, respectively). Smoking prevalence varies widely among different groups (e.g., teenage girls, nonworking adults, and adults employed in VICIOUS 145 occupations); this variation modifies the exposure of nonsmokers to EEL Smokers are present in nearly all environments, including most workplaces, restaurants, and transit vehicles, making it almost impossible for a nonsmoker to avoid some exposure to ETS. The number of cigarettes consumed per hour by the smoker may vary at different times in the day, and the rate and density of smoking will also differ by the type of indoor environment and activity in such hales as schools, autos, planes, offices, shops, and bars. Although there have been numerous measurements of ETS concentrations in various indoor settings, these data do not repre- sent a comprehensive description of the actual distribution of ETS exposures in the U.S. population. Spengler and colleagues (1995) and Sexton and colleagues (1984) demonstrated by the personal monitor- ing of respirable particles and the use of time-activity questionnaires that exposures to EZS both at home and at work are significant contributors to personal exposures. However, additional data on the distribution of smokers in the nonsmokers' environment, as well as the distribution of ETS levels in that environment, are needed in order to characterize the actual E!CS exposure of the U.S. population. Determinations of Concentration of Environmental Tobacco Smoke Environmental tobacco smoke is a complex mixture of chemical compmmds that individually may be in the particulate phase, the vapor phase, or both. ETS concentration varies with the generation rate of its tobacco-derived constituents, usually given as micrometer per hour. The generation rate for ETS has been approximated by the number of cigarettes smoked or the number of people present in a room who are actively smoking. Room-specific characteristics such as ventilation rate, decay rate, mixing rate, and room volume also modify the concentration. Because ETS particles have MMDs in the 0.2 to 0.4 Frn range, convective flows dominate their movement in air, they remain airborne for long periods of time, and they are rapidly distributed through a room by advection and a variety of mixing forces. Under many conditions, the ventilation rate of a space will dominate chemical or physical removal mechanisms in deter- mining the levels of ETS particles. Nonreactive ETS components distribute rapidly through an air- space volume, and their elimination depends almost solely on the ventilation rate. For example, Wade and colleagues (1976) simulta- neously measured carbon monoxide, a nonreactive gas, and nitrogen &oxide, a reactive gas, in a house and determined their half-lives to be 2.1 and 0.6 hours, respectively. This study demonstrates the need for caution in extrapolating from one vapor phase compound to another. Reactive gases and vapors may be rapidly lost to surfaces or 146 may react with other chemical species. Their removal may be dotted by their reactiOn Or absorption rates. Furthermore, the decay of ETsderived Substances can be a function of the chemical as well as the physical characteristics of room surfaces. For example, Walsh and colleagues (1977) found that sulfur dioxide removal was greater for rooms with neutral and alkaline carpets than for rooms bving carpets with acidic PH. Reactions with furnishings and other materials may occur for some M`s components as well. ~tx-c-tenvjronmental Measurementa of Conce&r&ion As was discussed earlier, the complex chemical tieup of ETS makes the measurements of individual levels for each compound present in JWS impossible with existing resources; thus, some individual constituents have been measured as markers of overall smoke exposure. Because many of these constituents are also emitted from other sources in the environment, the contribution of El% to the levels of these constituents is quantified by determining &e enrichment of specific compounds found in smoke-polluted environments relative to the concentration measured in nonsmoking areas. Various ETS components have been measured for this purpose, including acrolein, aldehydes, aromatic hydrocarbm, carbon monoxide, nicotine, nitrogen oxides, nitrosamines, phenols, and respirable particulate matter. A summary of the levels found and the conditions of measurement are presented in Tables 8 through 15. The major limitation of using most of these gases, vapors, and particles is their lack of specificity for ETS. The presence of sources, other than tobacco smoke, of these compounds may limit their utility for determining the absolute contribution made by EITS to room concentrations. Levels of nicotine and tobacco-specific nitrosamines, however, are specific for ETS exposure. Obviously, no single measurement can completely characterize the nonsmoker's exposure to ETS, and many studies have measured several of these components in order to characterize the exposure. Markers should be chosen both because of their accuracy in estimating exposure and because of their relevance for the health outcome of interest. One widely reported marker of ETS is respirable suspended particulate (RSP) matter. Although lacking specificity for tobacco smoke, the prevalence and number of smokers correlates well with RSP levels in homes and other enclosed areas. A study of the RSP levels in 80 homes in six cities (Figure 2) (Spengler et al. 1981) showed that indoor concentrations were higher on average and had a greater range than the outdoor concentrations. From these data, it is evident that even one smoker can SigllifiCiUltig elevate indoor R+SP levels. 147 TABLE EL-Acrolein measured under realistic conditions Study Badre et al. wm c%fee &Ken Hospital lobby 2 train compartment9 car F&her et al. (1978) and Weher et al. (1979) lleataurant Rataurant Bar Cafeteria Varied Not &em 18 smokers Not given 12 to a0 amokem Not given 2to3mokera Not given 3 smokers Natural, open 2 mnokem Natural, cloned F&80/470 m' 6@-m/440 m* 30 -40/&l ma NJ-l&Y674 ma Mechanid Natural Natnral, open 11 changeanu loo n&L. sampled 100 mL eamplen loo mL mmpla 100 mL .mulplea loo mL m.mpled 1OOmLsampla 27 x 30 mic samplea 29X3Odlumpla 28 x 30 min analplea 24 x 30 min 8anlpla 0.03-0.10 m&n' 0.195 m&n* 0.02 mglm' 0.0!&0.12 &In' 0.03 tag/m* 0.20 mg/m' 7PPh 8 Ppb 10 ppb 6 ppb (5 Ppb non8moking eecticad TABLE 9.-Aromatic hydrocarbons measured under realistic conditions Study Type of premises Levele Ncmemcha aatde Monitwing Ventilation mnditiona Mean Ranec-w Badre et al. (1978) cafes Room Train compartmente car cf&a Varied Not given loo mL sampled Room 18 amokem Not @en loo mL Eamplee Train wmpartmente 2 to 3 emokem Not &en loo mL namplw car 2 maokern Natural, clcued loo mL samples FXllott and Rowe (1976) Arena Galuakinova ww Ileetaurant Varied Not given 100 mL Blrmplen 18 smokera Not given loo mL Mmples 2 ta 3 amokere Not given loo mL amnples 3 nmokera Natural, open loo mL Bamph 2 amokere Natural, clod loo mL samples s,647-10,7S9 people 12,00&4S44 people 13,ooO-l4Xl7 people Not given Not @en Not given Not given Not &en Separate non- =Ktif,Y dsJrs 7.1 9.9 21.7 ~dweineummer 6.2 18 daya in the fall 2aHU Benzene b&m*) 0.102 0.04 0.16 O.W.16 0.oM.10 Toulene (mg/ms) 0.04-1.04 0.216 1.87 0.60 Beinclabymae (M/m*) 0.69 TABLE 9.-Continued Study Just et al. (1972) Coffee houses Not given Not given 6 hr wntinuoue 02610.1 4.0-9.3 (outdoola) Jhzde~yrone (ng/m") 3.3-23.4 3.0-5.1 (outdoola~ Benmkhihmrylene (ng/m*) W-10.6 6.9-13.6 (outdoors) Perylene bglm*) o-7-1.3 0.1-1.7 (outdoola) F%mne (s&m') 4.1-9.4 2%?.O (outdoom) Anthanthrene (&ma) 0.61.9 0.5-1.8 knltdooE3) Coronene (rig/d 05-1.2 1.0-2.8 Phenols b/m') 7.4-11.6 Beruda$yreae (r&m') Peny (1973) ' 14 public placea Nat piven Not given samples, 6 outdoor IoCatiOllE < 20460 (20-43 ' The correctn~ of the data ia doubtful (Grimmer et al. 1977).