The influence of tobacco smoke on indoor atmospheres

PREVENTIVE

4, 66-82

MEDICINE

The influence

(1975)

of Tobacco

Smoke on Indoor

Atmospheres

I. An Overview IRWIN SCHMELTZ, DIETRICH HOFFMANN, AND ERNST L. WYNDER Naylor Dana Institute for Disease Prevention, American Health Foundation, New York, New York 10021

The adverse health effects of actively inhaled tobacco smoke on the smoker are well known. What is less clear is how the nonsmoker is affected by long-term exposure to and passive inhalation of air contaminated by tobacco smoke. Studies on the chemical composition of tobacco smoke have resulted in the identification of numerous compounds, among which are established animal carcinogens and cocarcinogens, cihostats, irritants, and other noxious substances. These are emitted into the atmosphere whenever cigarettes, cigars or pipes are smoked, especially via the sidestream smoke, that portion of the smoke produced between the puffs while the tobacco smoulders. Concentration levels of constituents such as carbon monoxide, benzo[a]pyrene and nicotine have been measured in public places (i.e., indoors) and in laboratory controlled indoor environments. In a number of instances, carbon monoxide levels, depending upon room size, number of cigarettes or cigars/pipes smoked, ventilation rates, etc., are found to approach (if not exceed) the threshold limit value. In nonsmokers, passive inhalation of tobacco smoke results in slightly elevated carboxyhemoglobin levels and the appearance of nicotine in the urine. Animals chronically exposed to tobacco smoke develop lesions of the respiratory tract. Related human data show that school children from smoking families are more prone to develop respiratory infections as are one-year-old babies of smoking mothers.

INTRODUCTION

Although much has been documented with regard to the health effects of cigarette smoking on the smoker (59-61,47,63), in comparison little has been done to show whether an individual (e.g., a nonsmoker) is adversely affected by exposure to room air contaminated by cigarette smoke. Several authors (5,16-19,25,37,50) have considered the problem, but in our view no definite conclusions have yet been arrived at. The problem has been difficult to deal with since the dose of passively inhaled cigarette smoke from contaminated room air is such that one would expect effects only involving morbidity rather than mortality (60). Specifically, we know of no data suggesting that passive inhalation of cigarette smoke increases the risk of developing lung cancer. Recent studies, demonstrating elevated carboxyhemoglobin (COHb) levels in nonsmokers have, however, been cause for concern among those who consider CO a principal factor in the pathogenesis of atherosclerosis (57). The discomfort experienced by some nonsmokers in the presence of smoking individuals especially in terms of eye irritation is well known and can be attributed to well-defined compounds present in the smoke (59,60). Whether a significant health problem exists for those who spend a great deal of 66 Copyright

@ 1975 by Academic

PrOss, Inc. All rights of reproduction

in any form reserved

TOBACCO SMOKE AND INDOOR ATMOSPHERES

67

time indoors, be it in offices, bus or train terminals, airports, theaters, sports arenas, other public buildings, and particularly submarines where up to 80% of the crew may smoke,’ is a key epidemiological question (4). It is to this question that the present review pertains on the basis of relevant chemical and epidemiological studies. BACKGROUND

TO help understand the biological activity of cigarette smoke, much effort has been expended on determining its chemical composition TABLE I SOMECONSTITUENTSOF THE MAINSTREAM OF CIGARETTESMOKES (&CIGARETTE) Gas phase

co co, NH, HCN C&3 CH,=CH-CHO CH,CHO C,H,-CH, CH,--CN

13,400 50,600 80 240 582 84 770 108 21p

(CH&N-N=O V%W&W---NNH2--NH2 CH,-NO, C,H,-NO, U-M&O W,--NO2 Cd%

0.08 0.03 0.03 0.5 1.1 578 25 67

Particulate phase TPM, wet TPM, dry TPM, FTC” Nicotine Phenol o-Cresol m- and p-Cresol 2,CDimethylphenol p-Ethylphenol P-Naphthylamine N-Nitrosonomicotine Cholesterol Campesterol Stigmasterol /3-Sitosterol

31,500 21,900 26,100 1,800 86.4 20.4 49.5 9.0 18.2 0.028 0.14

Carbazole N-Methylcarbazole Indole N-Methylindole Benz[a]anthracene Benzo[a]pyrene Fluorene Fluoranthene Chrysene DDD DDT 4,4’- DCSd HCN

1.0 0.23 14 0.42 0.044 0.025 0.42 0.26 0.04 1.75 0.77 1.73 74

14.2e 24.5’ 53” 37”

a Dataobtained on 85 mm nonfilter blended cigarettes by Hoffmann et al. (27,33) except where noted. * W. R. Johnson et al., on Kentucky Ref. Cigarette (36). c Federal Trade Commission, TPM = Total particulate matter; (H. C. Pillsbury et al., J. Assoc. Off. Anal. Chem. 52, 458, 1%9). d Dichlorostilbene. e I. Schmeltz, A. DePaolis, and D. Hoffmann, unpublished. 1 Personal communication from Dr. Karl E. Schaefer, Submarine Medical Research Laboratory, Groton, CT.

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(27,29,31,33,44,53,64). Thus as seen in Table 1, smoke has been shown to contain polynuclear aromatic hydrocarbons (PAH) (32), phenols (62), carbon monoxide (7), oxides of nitrogen (60), hydrogen cyanide (59), acrolein (59), acetaldehyde (59), arylamines (45), N-nitrosamines (28), nicotine (51), ammonia (6), and others (61,63). As for possible health effects, PAH, N-nitrosamines, and arylamines are established animal carcinogens (60,63); phenols have been shown to be cocarcinogens in experimental studies (63); carbon monoxide and possibly nicotine have been implicated in atherosclerosis and cardiovascular disease in man (59,60); and oxides of nitrogen in the development of experimental emphysema (60); hydrogen cyanide, acrolein, and acetaldehyde are cilia-toxins under laboratory conditions (59,63). The smoker, as he inhales, is exposed to these substances, the extent of his exposure determined primarily by the degree of smoke inhalation and smoking frequency as well as number of cigarettes smoked per day, number of puffs per cigarette, butt length, filters vs nonfilters, etc. These same constituents enter the atmosphere when cigarettes are smoked, for the most part via the sidestream smoke (the smoke emitted between puffs while the cigarette smoulders). The effect of these constituents, as they pollute atmospheres, would be greatest in enclosed rooms or chambers where individuals would be passively inhaling them. On the basis of available data the sidestream smoke, as opposed to the mainstream smoke (i.e., that portion emerging from the butt end of a cigarette during puffing), is the major contributor to indoor pollution as produced by cigarettes because the sidestream smoke generally contains TABLE II CONSTITUENTSOFCIGARETTESMOKE: RATIOSOFSIDESTREAM(SS) MAINSTREAM (MS) CONCENTRATION LEVELS (SSIMS)

SSIMS Nicotineb Phenol Benzo[ualpyrene (mg)b Benzo[a]pyrene @pm)* Dry Condensate* 3-Vinylpyridinec Waterd Ammonia Methane Acetylene Propane-propene Methylchloride Hydrazinef

2.7 2.6 3.4 2.1 1.7 43.0 24 106 3.1 0.81 4.1 2.1 3

TO

SSIMS Methylfuran Propionaldehyde 2-Butanone Butanedione Pyridine Carbon monoxide Carbon dioxide Toluene Hydrogen cyanide Acetonitrile Acetone CholesteroP CampesteroP Stigmasterol” @Sitosterol

3.4 2.4 2.9 1.0 20.3 2.5 8.1 5.6 0.66 3.9 2.5 0.8 0.9 0.8 0.8

n Data from W. R. Johnson et al., (36) except where noted. * G. Neurath and H. Ehmke, Beitr. Tabakforsch. 3, 117-121 (1964). c G. Neurath, H. Ehmke, and H. Schneemann, Beitr. Tabakforsch. 3, 351-357 (1966). d F. Seehofer, D. Hanssen, H. Rabitz, and R. Schriider, Beitr. TabalCforsch., 3, 491-503 (1966). e I. Schmeltz, A. DePaolis, and D. Hoffmann, unpublished. f Y. Y. Liu, I. Schmeltz, and D. Hoffmann (44).

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ATMOSPHERES

TABLE III CIGARETTE PHYSICAL CHARACTERISTICS RELATED TO FORMATION OF SIDESTREAM AND MAINSTREAM SMOKE (36) Tobacco consumption (mg/cigarette) Cigarette type Burley Bright Turkish Kentucky (IRU

Paper porosity (set)

Smoulder rate (mm/min)

Puff count

ss

MS

21 21 21

6.0 3.84 3.69

6 11 13

320 580 680

290 280 190

40

4.31

10

490

230

Ref.

Formation ss MS

temperatures

(“C)

180 850

greater concentrations of smoke constituents (Table II, 36,52) inasmuch as it represents a greater portion of tobacco consumed during burning (Table III; 36). Temperature effects and smoking product design may also play a role in the establishment of sidestream to mainstream concentration ratios (3 6). In addition to contributing comparatively less than sidestream smoke to indoor pollution, the mainstream smoke, as it finally enters the atmosphere, after being exhaled, may be chemically modified depending on the duration of its inhalation by the smoker. The exhalant should differ between cigar/pipe and cigarette smokers because of differences in depth of inhalation (65). Moreover, the sidestream smoke emanating from cigars differs quite markedly from that of cigarettes, especially in quantities of ammonia. For example, the sidestream smoke of a large cigar (6.8 g) was shown to contain up to 100 mg of ammonia (8). This is quite significant in terms of discomfort and possibly irritation to a nonsmoker being exposed to and passively inhaling such smoke. Studies along these lines need to be considered. As a first approximation, concentrations of smoke constituents in the sidestream may serve as an indication of the extent and nature of tobacco-generated indoor pollution, and for this purpose, values in Tables I and II may serve as a guide. There have been objections, however, to such an approach because the reactivity and sedimentation rates of the various smoke constituents differ, and these factors would influence their concentration levels, at given times in room atmospheres (16,17). For example, the reactivity of CO and nicotine are not the same, and CO being the less reactive, would persist in closed atmospheres for a longer time, thus prolonging its potential health hazard. Therefore, it may be more realistic, when establishing the extent of indoor pollution generated by smoking products, to determine the actual concentrations of smoke constituents in a given space over a given interval of time. Such measurements and their results will be discussed. In addition to the extent of tobacco-generated indoor pollution, an important

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aspect of the problem is the degree of uptake of smoke constituents by the nonsmoker. In this regard most recent studies have concentrated primarily on carbon monoxide. Uptake of other smoke constituents (i.e., NO, NO,) by the exposed nonsmoker and their possible implications on his health have not yet been studied. By and large, current concern centers around carbon monoxide and its effects on health, especially its relation to cardiovascular diseases. CURRENT

STATUS

The objectives of studies, undertaken in recent years, on the effect of cigarette smoke on indoor pollution have been: (1) to measure the concentration levels of selected smoke constituents in indoor atmospheres, and to determine the factors affecting such levels; (2) to measure the extent of “absorption” of smoke constituents by nonsmokers and; (3) to determine whether adverse health effects are related to passive inhalation of smoke constituents. Measurement of Smoke Constituents in Indoor Pollution Several different approaches to the study of smoke-contaminated room air have been taken. Measurements have been made of smoke constituents in the air of various public places, such as theaters (15), vehicles (54), ferryboats (1% aircraft (58), “party rooms” (5), and submarines (10). These data are given in Table IV. Among the points to be noted from Table IV is that only three smoke constituents, carbon monoxide (CO), benzo[a]pyrene (BaP) and nicotine, have generally been considered in the indoor atmospheres investigated. CO is, of course, a major smoke constituent (Table I), being a predominant product of limited combustion and is, moreover, relatively easy to measure. In addition, it may be important from the point of view of health. Note from the data (Table IV) that in several cases the values obtained for indoor CO (as generated by tobacco) approach or exceed the threshold limit value (TLV: 50 ppm) as set by the American Conference of Governmental Industrial Hygienists for time-weighted concentrations for a 7- or 8-hour workday and 40-hour workweek (1). Note for example the level of CO measured in submarines to which crew members may be exposed for extended periods of time (10). Some of the CO measured may of course be derived from sources other than tobacco (e.g., cooking, outdoor air, faulty furnaces). However, the data comparing smoking and nonsmoking areas in a ferryboat (15) and in a theater (15) clearly demonstrate differences in CO levels that can be attributed only to the combustion of tobacco (60). The data, moreover, indicate the importance of adequate ventilation in keeping indoor CO levels down even when a considerable number of cigarettes are smoked (e.g., in a “party room”). This point will be made more evident from the data obtained in controlled experiments (Table V, vide in&). Nicotine, which could be expected to arise only from burning tobacco, is found to be present in the instances cited below its TLV (0.5 mg/m3). Of course, this value would depend on the number and type of cigarettes and/or cigars/pipes smoked. The only BaP data given pertain to levels present in the air of a smoky restaurant (14), and in Kenyan huts

TOBACCO

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ATMOSPHERES

TABLE IV LEVELSOFSMOKECONSTITUENTSIN~~PUBLICPLACES" Chamber volume (ma)

Place

car

2.09

No. cigarettes smoked 10 in 1 hr (2 smokers)

Train “Public

co (pw)

90 40

houses”

30-80

157in 1 day (6 smokers) 94-103/day for 4 days

Submarines Submarines

"Party room" "Party room" Ferryboat Smoking compartment: Nonsmoking colnpartnlent: Theater Foyer Auditorium Aircraft

Aircraft

lU(ventilationrate = 20.4 m%r/penon) 101 (ventilation rate = 15 mvbr/penon)

Nicotine: 5.2 pglrn” Nicotine: 0.7-3.1 fig/m3

Harmsen

and Effenberger

(21) Hannsen

and Effenberger

(21)

Cam et al. (10) Nicotine: 15-35 &In” B&J Inside: 2.82-14.4 mg/100 ma Outside: 0.28-0.46 mg/l@l ma

can0 et al. (10) GaluSkinovl(14)

7

Bridge

and Corn (9

9

Bridge

and Corn (5)

18.4 r 8.7

Godin er al. (15)

3.0 k 2.4

(18 O”erseas Bights, 100% passenger density) (8 domestic Bights, 66% passenger density)

small conference room Kenyanhut

10

Mountain region coastal region

93.4m9 93.4ma

n Indoor

due to cooking.

pollutants

50 cigarettes 1 cigar in 1 hr 63 cigarettes/hr 10 cigar butts

Srch (54)

40

Restaurant

Reference

Others

3.4 k 0.8 1.4 ” 0.8 2-5

Godin

et al. (15)

2(“w.)

U.S. Department of Health, Education and Welfare (58)

U.S. Department ofHealth, Education and Welfare (58)

20

Cobum BaP? 166&1000m* BaP? 24 ILB/lOGilms

Hoffmann

et al. (I 1) and Wynder

(30)

(30). However, the authors of the first report indicate that some of the BaP they measured may have originated from the cooking of foods. This is apparently the case in the second report in which, in addition to levels of BaP, levels of particulate matter and benz(a)anthracene were also measured (30). It is clear that the preceding data do not firmly establish the extent of indoor pollution generated by tobacco smoke, nor do they define clearly all the factors influential in this regard. One thing, however, that seems clear is that tobacco smoke in indoor environments without adequate ventilation (and perhaps in spite of it) may be a source of significant levels of carbon monoxide (and possibly other materials) to exposed nonsmokers. Additional studies of the extent of tobacco smoke contamination in indoor atmospheres have been undertaken under “controlled” conditions insofar as room volume, number of cigarettes, smoking conditions, ventilation and other

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TABLE

AND

WYNDER

V

LEVELSOFSMOKECONSTITUENTSINROOMATMOSPHERESUNDERCONTROLLEDCONDITIONS

Room WI

No. of cigarettes

57

42 by 21 smokers in 16-18 min 105 by 11 smokers in 2 hr 101 5” 10 15 30 150 in 32-34 min by machine

170

38.2

170

Ventilation rate (m%r/person)

co @pm) 50

0.57

33.4 none none none none

5 11.56 21 32 64 53

28

98

none

80

15

7 in 1 hr

Ventilated

20d

25

4 8 16 24

none none none none

12.3 24.6 46.7 69.8

Reference Harke (16)

Harke (16)

30

102 in 120 min by machine 62 in 2 hr

170

Nicotine (mshf?

0.06b 0.14 0.27 0.51 0.69” 0.54 0.21 0.03 0.18 0.19

Harke er al. (17)

Harke et al. (17)

Harke et nl. (17)

Harmsen and Effenberger (21) Lawther and Commins (39) Hoegg (25)

a Machine smoked. b Maximum values, obtained 11-75 min after beginning of smoking. c In order of increasing time from beginning of smoking, O-264 min. d Maximum 90 ppm passed across face of person next to smoker.

factors are concerned. Such studies by Harke and others (5,16-19,25) have resulted in the data summarized in Table V. Several important variables are seen to influence concentration levels of smoke constituents determined in room air. These factors are ventilation as noted above, number of cigarettes smoked and elapsed time (from beginning of smoking) in a chamber of given volume. The effect of ventilation on CO levels is striking, although it appears not so marked in the case of nicotine. On the other hand, over a period of time nicotine levels also seem to decrease significantly (by means of sedimentation on room fixtures). In the example shown (Table V), nicotine levels decreased to less than one-twentieth of the initial amount in nearly four and one-half hours. The effect of the number of cigarettes smoked on levels of smoke constituents in room air may be obvious; nevertheless the relevant data are summarized in Table V for both CO and nicotine. As shown, Hoegg’s results (25) are similar to those of Harke (17), i.e., CO levels increase with increasing numbers of ciga-

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rettes smoked, in a fairly straight line relationship. In addition, levels of total particulate matter (TPM) were also shown by Hoegg to be related to numbers of cigarettes smoked and inversely proportional to time elapsed after igniting of cigarettes. In Hoegg’s study, the levels of TPM generated in a 25m3 chamber frequently exceeded air quality standards. Furthermore, under various experimental conditions, as evidenced by the data in Table V, CO levels often exceeded the threshold limit values. Harke also measured chamber levels of acetaldehyde and acrolein as generated by burning tobacco ( 17,19). Although these levels were lower than those of CO, they were influenced by the same factors: ventilation, number of cigarettes smoked, and elapsed time from beginning of smoking. Thus far we have reviewed individual studies pertaining to the extent to which cigarette smoke constituents contaminate room air under various conditions. It would be desirable to normalize the data from the different studies on the basis of number of cigarettes smoked per unit volume per unit time. Harke (17,19) has attempted this, and has shown some relationship between “relative load,” i.e., number of cigarettes smoked per cubic meter per hour, and ppm CO generated. As a result, he concludes that only under extreme conditions of indoor smoking is the TLV of CO exceeded. The difficulties inherent in trying to compare and normalize data obtained by different workers are obvious: type of cigarettes, smoking conditions, room volumes and fixtures may vary, as well as ventilation rates, and of course, exhaled smoke from persons smoking in the room. However, the experiments described do permit the identification of those factors, notably ventilation, that influence room concentrations of smoke constituents, and show how such concentrations can be reduced or minimized. In the future, it may be preferable to measure levels of smoke pollutants in actual situations where smokers and nonsmokers congregate such as theaters, elevators, bus or train terminals and airports, and to determine the actual extent of public exposure to smoke polluted air. Levels of nicotine might be used to estimate the contribution of burning tobacco to indoor pollution. Recently, odd numbered pa&ins have been suggested as indicators of the degree of smoke pollution in indoor atmospheres (22). An approximation of the extent of such indoor pollution could be obtained also by measuring levels of smoke constituents (e.g., CO) in indoor environments where smokers are found and comparing these levels to those in “nonsmoking” indoor environments. In considering the effects of smoke-polluted indoor atmospheres, however, one must not only examine exposure levels, but in the long run must determine the extent to which the noxious smoke pollutants are “absorbed” or taken up by the nonsmoker and thereby possibly atfect his health. It is to this question that we will now turn. Uptake

of Toxic Smoke Constituents by Nonsmokers

Carbon monoxide. Numerous epidemiological studies have demonstrated an association between cigarette smoking and coronary heart disease (CHD), particularly in younger individuals. In addition to cigarette smoke, other CHDrelated factors include high blood pressure and particularly high serum cholesterol levels (3,24,59,60). Chronically high carboxyhemoglobin (COHb) levels

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TABLE

CARBOXYHEMOGLOBINLEVELS(%)

AND

WYNDER

VI

INVARIOUSGROUPS(~)

Carboxyhemoglobin level (%)

Group

OS-l.0 1.o-3.0 1.4-3.0

Normal individuals Hemolytic conditions Nonsmoking taxi drivers in London Smokers CO poisoning

l-20 20-80

are suggested to play a role in the pathogenesis of atherosclerosis, and tobacco smoke is cited as the major source of elevated COHb levels in man. Table VI illustrates the point (3). The question here, however, is whether long-term exposure to smoke-contaminated air adversely affects the nonsmoker as well, as measured primarily by levels of blood COHb. Work along these lines has been carried out by a number of investigators, the results summarized in Table VII. The data here show that smokers generally have much higher levels of COHb than do nonsmokers, and in a smoke contaminated environment achieve even greater increases in COHb levels. Russell et al. (49) showed that in a room containing 38 ppm CO (generated by burning tobacco) both smokers and nonsmokers exhibited elevated COHb. In the nonsmokers, COHb levels increased from 1.6 to 2.6%, while in the smokers, the increase was from 5.9 to 9.6%.

TABLE VII CARBOXYHEMOGLOBIN (COHb) LEVELSIN SMOKERSANDNONSMOKERS

Environmental conditions

Chamber Closed car Nonventilated room Ventilated room Nonventilated room Submarine

Vol (m”)

No. cigarettes smoked

co @pm)

Exposure time (min)

COHb (%) Smoker

Nonsmoker

Reference

2.09

5

90

62

5 lo”

2 5a

170

>lOO

30

90

3.3 -+ 7.5”

0.9 + 2. la

Harke (16)

170

>lOO

90

2.7 -+ 5.0”

1.1 -+ 1.6”

Harke (16)

78

5.9 -+ 9.6”

1.6 -+ 2.6”

8,18b

1.1”

Russell et al. (49) Lightfoot (42)

43

38 8-10

a Initial and maximum values prior to and after exposure period, respectively. * Average values for two groups of smokers (moderate vs heavy). c Average value.

Srch (54)

TOBACCO SMOKE AND INDOOR ATMOSPHERES

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Harke (16) showed similar results, with smokers having higher levels of COHb both before and after exposure to smoke-contaminated atmospheres. Ventilation of the atmosphere resulted in somewhat lowered COHb levels after exposure, but smokers’ COHb was still rather high at the 5% level compared to the 1.6% level of nonsmokers. Following the exposure, individuals experience a lowering of COHb levels. In the case of a smoker, the blood COHb drops back to the level prior to smoking. However, the fall in COHb is relatively slow, and in one study it took two and one-half hours for the COHb level of the cigarette smokers to drop the 1.6% gained in only six and one-half minutes of smoking (48). COHb has a half-life of at least 3-4 hours in the body, and in one case (56,60), 2 hours after cessation of a 3-hour exposure to 50 ppm CO, the COHb level fell only to 2.7% (from 3.7%). This lengthy half-life extends the period of effect of exposure to CO and provides for a build-up of COHb concentration from fresh exposures. As for the nonsmoker, it is clear that exposure to smoke contamination results in higher than normal levels of COHb. It remains to be shown to what extent there may be long-term negative health consequences related to such levels. There is some evidence (60) that at blood COHb levels as low as 3%, subtle perceptual abilities (e.g., visual acuity, brightness threshold, and time/interval discrimination) may be temporarily impaired. The levels of CO found to be present in “smoked rooms” (20-80 ppm) are similar to levels felt to be associated with some adverse health effects (Table VIII). As one can see by the data, long-term exposure to CO can have an effect on health, and certainly nonsmokers, especially in the frequent presence of smokers, may experience such exposure. The health effect would depend on degree and duration of exposure and obviously on individual susceptibilities. Further studies are dictated, perhaps in natural settings of nonsmokers who in their daily lives are in contact with smokers in enclosed environments. Monitoring of the COHb levels of such individuals in conjunction with room CO levels would be informative. In fact, a recent study (57) has shown that many nonsmokers do indeed have abnormally high COHb levels though not as high as smokers. However, the source of such high levels may not be entirely related to exposure to tobacco smoke, but also to exposure to a highly urbanized (gasoline-cornbusting)

TABLE VIII HEALTH EFFECTSOF ELEVATED CARBOXYHEMOGLOBIN LEVELS (60) Room CO” @pm)

Exposure (hr)

Nonsmokers’ blood COHb (%)

lo-15 30

8 8

2.0-2.5 5 >5

Health effects Impaired time-interval discrimination Impaired performance on certain other psychomotor tests Physiological stress in patients with heart disease

a TLV for CO = 50 ppm; EPA safe level = 9 ppm (8 hr); 35 ppm (1 hr).

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environment (2). It is obvious that further work along these lines is needed. Nicotine. There have been a number of reports of nicotine present in the urine of nonsmokers, ostensibly transferred via room air from the burning cone of a smoking product to the respiratory tract of the nonsmoker and subsequently to the urine. Harke (16) measured the levels of nicotine and its metabolite, cotinine, in the urine of both smokers and nonsmokers in a room (170 m3) in which 98 and 108 cigarettes were smoked, with and without ventilation, respectively. In both cases, levels of nicotine and cotinine in the urine of nonsmokers were strikingly lower than they were in smokers. For example, nicotine levels in smokers’ urine averaged 622 pg” and 1526 rug3without ventilation, and 1160 pg2 and 2198 pg3 with ventilation; on the other hand, in the urine of nonsmokers they averaged 10 ,ug and 18 pug,respectively. Cotinine values in smokers’ urine were 577 ,ug2 and 1199 pg3 without ventilation, and 906 pg2 and 1.583pg3 with ventilation. Corresponding values for nonsmokers were 34 ,ug and 19 pg. Room ventilation seems to play an important role here with higher values of urine nicotine and cotinine seemingly occurring under conditions of ventilation. This has been rationalized by suggesting that inhalation is less likely when the atmosphere is heavily contaminated with smoke pollutants as in nonventilated rooms (50) Another factor affecting nicotine (and cotinine) levels in urine is the type of cigarette smoked (i.e., filter vs nonfilter). In the values cited above for smokers, the lower values were found when filter cigarettes were used. In addition, urine volume and pH should also be considered. In another interesting study, 5% of the level of nicotine found in smokers’ urine was observed to be present in nonsmokers’ urine. These nonsmokers shared the same area as the smokers, and were inadvertently exposed to cigarette smoke, the route of transfer of nicotine being the room air. The water supply was found to be nicotine-free (35). There is no doubt as to the extreme toxicity of the alkaloid nicotine and its physiological effects on the cardiovascular and central nervous systems (5 l), but its significance in tobacco-related diseases is still open to question. However, nicotine, by causing a release of catecholamines may adversely affect cardiovascular disease by increasing the likelihood of ventricular arrhythmia, and/or by affecting blood clotting on the arterial walls (24). Nicotine does not seem to have a synergistic effect on the CO-enhanced accumulation of lipids in arterial walls (3). Nevertheless, we are faced with the question of whether low levels of chronic nicotine exposure affect the nonsmoker. This question needs to be answered by future epidemiological studies. Other smoke constituents. Other smoke constituents that adversely affect health, and that in the long run may be of serious concern to the nonsmoker chronically exposed to them have been alluded to. Nitrogen dioxide, for example, has been shown in experimental studies to destroy cellular membranes and subcellular structures (60). Moreover, continuous administration of low concentrations of NO, to rats has produced an emphysemalike disease (55) and 2 Filter cigarette. 3 Nonfilter cigarette.

TOBACCO

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NO, in cigarette smoke may carry a major responsibility for the high incidence of emphysema in cigarette smokers (13). Oxides of nitrogen may also be related to the pot.entially hazardous N-nitrosamines. One encounters in mainstream cigarette smoke (28): dimethylnitrosamine, 84 nglcigarette; methylethylnitrosamine, 30 nglcigarette; and N-nitrosonornicotine, 137 nglcigarette. The last mentioned compound has been found to be present in unburned tobacco as well in amounts ranging from 2-90 ppm (26). In food and drink, N-nitrosamine levels rarely exceed 0.1 ppm. Whether these agents especially in their concentrations in room air contaminated by cigarette smoke pose a hazard to the nonsmoker who passively inhales such air is not clear. No data are available on levels of Nnitrosamines in sidestream smoke, but even if they are the same as in mainstream smoke, their contribution to smoke-contaminated indoor air may be significant. Other toxic substances such as hydrogen cyanide, acrolein, and acetaldehyde also occur in smoke, in addition to the various animal carcinogens identified, and the chronic effects of these, if any, on exposed nonsmokers are not yet known. Health effects of passive smoking. Relevant animal and other studies: Besides the possible effects of long-term exposure to low levels of CO discussed above, the extent of adverse health effects in humans due to passive smoking has not yet been firmly established. The detrimental effects of the passive inhalation of cigarette smoke in the respiratory tract of animals, however, have been demonstrated by a number of workers (12,38,41,60,63). In this regard, pathologic changes have been noted, including parenchymal disruption (23), bronchitis (40), tracheobronchial epithelial dysplasia and metaplasia (34), and tumors of the larynx (12,38,63). However, the relevance of these observations to the human situation may be questioned, inasmuch as the animals were exposed to extremely high levels of smoke, far in excess of levels encountered in the case of human exposure. Nevertheless, there are human data that may lend credence to the idea that passive smoking may be of some hazard, particularly to susceptible populations. Cameron et al. (9) noted that acute respiratory ailments were more common (and frequent) among children from homes in which the parents smoked than among children of nonsmoking parents. Other investigators have observed that school age children passively exposed to cigarette smoke experienced increased heart rate and blood pressure immediately upon such exposure (43). A recent report from England describes a survey taken of the respiratory infections and family smoking habits of a number of children (46). The survey showed that the percentage of children with adverse effects or symptoms of respiratory infections or both increased as the level of family smoking increased. However, social status may be another factor here, as it is suggested that heavy smoking is more often found in low income families. In another investigation, in Israel, it was noted that maternal smoking may be damaging to a baby, not only in utero, but in the cradle too. In a study of about 10,000 families (20), it was found that the infants of mothers who smoked had a significantly higher rate of admission to the hospital for bronchitis and pneumonia during the first year of life than the infants of nonsmoking mothers ( 13.1 vs 9.5 admissions per 100 infants). The admission rate was found to be positively

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related to the mothers’ cigarette consumption, and the association persisted when social class, birth-weight and birth order were controlled. Finally, there are individuals who are especially sensitive (including eye irritation) and even allergic to tobacco smoke, who develop chronical symptoms such as cough, respiratory tract congestion, wheezing, and respiratory distress after exposure to tobacco smoke (60). CONCLUSION

AND FURTHER

DIRECTIONS

The potential health hazards of cigarette smoking are well-documented in the scientific literature. Nonsmokers are also exposed to some of the constituents of cigarette smoke primarily as a result of the emergence of sidestream smoke of tobacco products into the atmosphere. Although carboxyhemoglobin (COHb) levels in smokers may be quite high, similar levels have not been noted in nonsmokers. Passive smoking, however, does result in an elevation of COHb levels in nonsmokers, and chronic exposure to CO may cause some physiological distress in nonsmokers, and may be a risk for individuals with cardiovascular difficulties. Recent studies have shown that many nonsmokers, especially in urban centers, have high COHb levels, which may be related to general urban pollution in addition to exposure to smoke-contaminated indoor atmospheres. The relative contribution of these two sources has yet to be resolved. The effect on nonsmokers of chronic exposure to other tobacco smoke constituents also needs further study. Nonsmokers passively inhale nicotine in the presence of smouldering tobacco inasmuch as nicotine and its major metabolite, cotinine, have been identified in the urine of nonsmokers. The significance of this exposure with regard to health is not known. Some human data indicate that prolonged passive smoking results in an increased incidence in respiratory ailments, especially of children. Additional studies are needed to establish whether passive inhalation of cigarette smoke represents a significant health risk in addition to the obvious discomfort involving eye irritation and the short-term effects of increased respiratory diseases in children. At the moment the primary concern of those involved in tobacco and health research is with the smoker himself. On the basis of available epidemiological evidence, it appears that passive inhalation of tobacco smoke by nonsmokers or smokers does not increase their risk for chronic illnesses such as cancer of the respiratory tract, emphysema, or cardiovascular disease. The absence of such a relationship could have been predicted on the basis of total exposure to smoke constituents compared to the exposure of inhaling cigarette smokers. Yet, it should be considered that individuals with advanced emphysema or advanced coronary artery diseases might aggravate their conditions by passively inhaling certain cigarette smoke constituents, especially in closed environments over a long period of time. Even the short-term effects related to eye irritation that individuals may suffer in smoke filled environments should induce us to pay more attention to adequate ventilation which we know reduces environmental smoke constituents. As the “tar” and nicotine yield of cigarettes decreases, it appears that levels of various smoke constituents in the sidestream smoke may also decrease. Work in the area of the “less harmful cigarette” would thus affect “sidestream smoke.”

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However, while the major research efforts of those concerned with “tar” and nicotine levels and “less harmful cigarettes” must continue, other components of tobacco smoke which pollute the environment, such as carbon monoxide, oxides of nitrogen and other noxious substances should not be neglected. In this regard, it would be meaningful to assess the potential hazard of smokecontaminated atmospheres to selected population groups such as nonsmokers who use public transportation for daily commuting, submarine crews which may remain in enclosed environments for lengthy periods of time, and even smokers, especially cigar and pipe smokers who inhale sidestream smoke directly from the smoking article while the latter remains in the mouth. In the case of the submarine, we have essentially controllable conditions providing an atmosphere to which smokers and nonsmokers are equally exposed. Determining how such an atmosphere, as well as the others alluded to above, affect the health of exposed individuals would go a long way in assessing the potential hazards posed by smoke-contaminated indoor environments. REFERENCES 1. American Conference of Governmental Industrial Hygienists, Threshold limit values for chemical substances in workroom air. Med. Bull (ESSO) 33, 267-296 (1973). 2. Aronow. W. S., Cassidy, J., Vangrow, J. S., March, M., Kern, J. C., Goldsmith, J. R., Khemka, M., Pagano, J., and Vawter, M., Effect of cigarette smoking and breathing carbon monoxide on cardiovascular hemodynamics in angina1patients. Circulation 50,340-347 (1974). 3. As&up, P., and Kjeldsen, K., Carbon monoxide, smoking and atherosclerosis. Med. C/in. N. Amer. 58, 323-350 (1970). 4. Benson, F. B., Henderson, J. J., and Caldwell, D. E., Indoor-outdoor air pollution relationships: A literature review. Environmental Protection Agency, Publication No. AP- I1 2, 1972. 5. Bridge, D. P., and Corn, M., Contribution to the assessment of exposure of nonsmokers to air pollution from cigarette and cigar smoke in occupied spaces. Environ. Rex 5, 192-209 (1972). 6. Brunnemann, K. D., Hoffmann, D., and Wynder, E. L., Studies on the “inhalability” of cigarette and cigar smoke. Abstract, 27th Tobacco Chemists’ Research Conference, Winston-Salem, North Carolina, 1973. 7. Brunnemann, K. D., and Hoffmann, D., Chemical studies on tobacco smoke. XXIV. Quantitative method for carbon monoxide and carbon dioxide in cigarette and cigar smoke. J. Chromatogr. Sci. 12, 70-7.5 (1974).

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(1972).