rubentito/OCR-IDL huggingface dataset:
The authors next rely on the unproven assumption that MS or its individual constituents cause lung cancer in humans. Chemists, toxicologists, and epidemiologists agree that it is not possible to identify any particular MS constituent(s) as the alleged cause of disease. [Understanding [of the] components which may act on the cardiovascular and respiratory system is embarrassingly lacking, if not outright contradictory. Uncertainty about the specific attribution of risk to individual smoke components may be greater than ever now, [Gori, 1980, p. 355]. Even vocal anti-tobacco researchers concede that no particular constituent of mainstream smoke has been shown to cause any specific disease in smokers [Hoffmann, 1982]. Tests conducted on individual constituents of smoke, at concentrations far greater than their concentrations in smoke, do not alter these conclusions. Pinpointing specific "causative agents" in a mixture as complex as cigarette smoke is of questionable use in predicting the mixture's biological properties: Cigarette smoke contains over 3,800 chemicals The biologic effects of this galaxy of compounds are virtually impossible to predict from a knowledge of the individual constituents, not only because of their huge number, but also because transient chemicals generated through the processes of pyrolysis, oxidation, and free-radical formation might dissipate or change with time and temperature [NRC, 1988, p. 28]. One simply cannot predict the biological effects of a mixture based on knowledge of individual constituents within the mixture, or based on knowledge of another mixture, even when the mixtures are similar and well characterized. 13
MS and ETS, however, are not similar. The Surgeon General's 1986 Report concluded that knowledge of cigarette smoke composition is of limited utility in predicting ETS-exposure effects. Comparison of the relative concentrations of various components of SS and MS smoke provides limited insights concerning the toxicological potential of ETS in comparison with active smoking. As described above, SS characteristics, as measured in a chamber, do not represent those of ETS, as inhaled by the non-smoker under nonexperimental conditions. Further, the dose-response relationships between specific tobacco smoke components and specific diseases are not sufficiently established for the necessary extrapolations from active smoking to environmental tobacco smoke exposure for individual agents [USPHS, 1986, p. 24]. Nonetheless, the Policy Guide attempts to bolster its arguments by focusing on a number of biologically active compounds that have been reported in MS. The Guide describes health hazards associated with these individual compounds, then completely ignores at least three critical considerations: (i) some of these compounds have never been detected in realistic concentrations of ETS; (ii) the species' minute concentration (dose) in ETS (as well as in MS); and, (iii) interactions with other species in the smoke mixture (e.g., chemical reaction or solution effects). As the NRC concluded: Because the physicochemical nature of ETS, MS, and SS differ, the extrapolation of health effects from studies of MS or of active smokers to nonsmokers exposed to ETS may not be appropriate Laboratory studies in conjunction with epidemiologic investigations are needed to clarify possible health effects of exposure to ETS in nonsmokers [NRC, 1986, p. 8]. The fact is that ETS has never been shown to be carcinogenic in any animal species. Furthermore, ETS has not been shown to be mutagenic in any animal or cell culture system 14
when tested at or near ambient concentrations. Also, none of the individual chemicals in ETS has ever been shown to be carcinogenic or mutagenic when tested at its concentrations in ETS. Following are examples of the document's misleading characterization of supposed hazards associated with ETS constituents. a. Carbon Monoxide The Guide states that carbon monoxide (CO) "is a gas that interferes with the ability of the blood to carry oxygen," and that increased levels of CO in the presence of smokers add to "the body burden of carbon monoxide from other environmental sources" [The Guide, p. 9]. These statements misrepresent the impact of ETS CO on humans or the environment. The American Conference of Governmental Industrial Hygienists (ACGIH) has established a threshold limit value (TLV) of 50 ppm for CO [ACGIH, 1987]. OSHA has established a TLV of 35 ppm for CO, measured as a time-weighted average over an 8-hour period [Federal Register, 1989]. The EPA itself has. established an outdoor CO standard of 9 ppm. In comparison, ETS CO concentrations are trivial. The maximum CO concentration attributed to ETS in a major survey of 31 offices, where smoking was occurring, was 6.6 ppm [Carson, 1988]. Arithmetic mean concentration for ETS CO in this study was 0.2 ppm. The maximum indoor CO concentration, including all sources, was 8.7 ppm, which was still below the EPA's standard. Outdoor CO concentrations were reported for 23 of the 31 offices. Of these, 13 indoor locations 15
possessed lower CO levels than outdoors. Straightforward statistical analysis of these data confirms that CO concentrations in offices where smoking occurs are not significantly different from outdoor levels. Fischer reported results from measurements of CO in three restaurants [Fischer, 1978]. He also measured CO in the air outside the restaurants to account for the outdoor contribution to indoor CO concentrations. He estimated CO associated with ETS by subtracting results of outdoor measurements from results of indoor measurements; the author reported these concentration results in terms of dCO ("delta carbon monoxide"). Average dCO's for two of the restaurants were 0.1 and 1.1 ppm; average dCO's in the smoking and nonsmoking sections of the third restaurant were 0.6 and 0.0 ppm, respectively. The average outdoor CO concentrations were 4.8, 1.5, and 0.4 parts per million. Biological effects associated with exposure to high concentrations of CO are not germane to the low CO concentrations found in ETS. Blood carboxyhemoglobin (COHb) concentrations resulting from normal human metabolism are comparable to those found in the blood of nonsmokers exposed to ETS [Jarvis, 1984]. Furthermore, COHb concentrations associated with exposure to as much as 9 ppm CO do not alter cardiovascular function, as measured by maximal aerobic capacity testing [Horvath, 1989]. In an EPA-funded study in which subjects' COHb concentrations were five times higher than those in Horvath, Sheps concluded that there was no change in the "time to onset" or duration of angina [Sheps, 1987]. Electrocardio-physiologic parameters were also unchanged. Thus, ETS does not make a significant contribution to indoor air CO concentrations 8 The term dCO is the indoor CO concentration minus the outdoor CO concentration. 16
and it does not, as the Guide implies, starve nonsmokers of oxygen [The Guide, p. 9]. b. Hydrogen Cyanide The Guide's discussion of hydrogen cyanide (HCN) is oversimplified and inappropriate [The Guide, p. 9]. Again, concentration is ignored. High levels of HCN have indeed been reported in in vitro studies to impair ciliary function, produce lung irritation, and inhibit oxygen uptake [USEPA, 1981]. However, HCN produces none of these effects at levels found in ETS. In fact, all reported HCN levels in ETS [Ball, 1986; Hoffmann, 1984; Klus, 1986] fall below or just within the "no effect" range [Ball, 1986]. Reported ETS HCN levels range from 0.009 ppm [Klus, 1986] to 0.11 ppm [Ball, 1986]. The "no effect" range is 0.1 to 0.9 ppm [Ball, 1986]. Despite these facts, the authors elected to juxtapose a toxicologically accurate characterization of HCN (as "more potent than carbon monoxide in its ability to starve one of oxygen)" [The Guide, p. 9] next to scientifically unsubstantiated and inflammatory statements about ETS CO exposure. In short, the toxicity of undiluted HCN is unquestioned, but the authors' comments in the context of ETS are deceptive. c. Ammonia The Guide characterizes ammonia (NH) as "a powerful eye and respiratory irritant" [The Guide, p. 9]. By ignoring concentration, the Guide implies that ETS will irritate the eyes and respiratory system because it contains ammonia. The irritation threshold for ammonia has been reported to be 104 ppm [Ruth, 1986]. According to the 1986 Surgeon General's Report, NH, concentrations in ETS range from 1 to 4.6 ppm [USPHS, 1986, p. 230]. A more recent study reported concentrations ranging from "not detectable" to 9.5 ppm, with the median reported as "not detectable" [Sterling, E.M., 1988]. Even at the 17
maximum reported value (9.5 ppm), ammonia concentrations in ETS are an order of magnitude less than the irritation threshold [Ruth, 1986]. Given levels found in typical real- world environments and irritation threshold levels, ETS ammonia cannot be characterized as an irritant. d. Nicotine The Policy Guide states "Nicotine, a poison, is also the addictive agent in tobacco smoke" [The Guide, p. 9]. This statement is pejorative, unsubstantiated and misleading. There is absolutely no evidence that ETS nicotine is toxic. Consequently, characterizing nicotine as a poison (in this context) is emotional rhetoric, not scientific fact. Similarly there is no evidence that ETS nicotine is addictive. Relevant data ignored by the Policy Guide demonstrate that nicotine, at ETS concentrations, is not a poison. OSHA has established permissible exposure limits (PEL) and short term exposure limits (STEL) for nicotine at 500 g/m³ [Federal Register, 1989]. One 1984 study reported a 13.2 g/m³ mean nicotine concentration in public buildings occupied by one to five smokers [USPHS, 1986, p. 156] -- less than 3% of the OSHA standards. A more recent survey of offices containing smokers reported average nicotine levels of 4.8 g/m³ [Oldaker, 1990a] -- 100 times less than OSHA standards. Moreover, nicotine concentrations in ETS frequently are not detected by sensitive analytical methods -- even when smoking is occurring [Carson, 1988; Oldaker, 1986; Oldaker, 1990a; Oldaker, 1990b]. Characterizing nicotine as "the addictive agent in tobacco smoke," is inflammatory and is irrelevant to ETS. This gratuitous comment must have been included for propaganda 18
purposes because no one remotely suggests that exposure to ETS causes anyone to be addicted to cigarettes. e. Summary Without explanation, the authors ignore the central, inescapable conclusion reached by researchers at the EPA in 1989: "Data are lacking, however, on the presence and concentration of potentially toxic and carcinogenic components in tobacco-smoke polluted indoor environments" [Lofroth, 1989]. The Agency emphasized this conclusion in its 1990 Report to Congress on Indoor Air Quality: Information on exposure in homes and buildings is limited to a very few pollutants and groups of pollutants. In addition, virtually nothing is known about cancer and noncancer health effects due to low level respiratory exposures to multiple chemical contaminants [USEPA, 1989a, p. 1]. In light of pertinent data and the Agency's recent statements, the Guide's simplistic, misleading and inflammatory discussion of ETS constituents can only be viewed as a clear abuse of the EPA's statutory authority. 3. The Policy Guide Trivializes The Complexities Of Exposure Assessment An accurate measurement of exposure is critical to assess the potential impact of ETS on human health. Current technology for measuring ETS concentrations in the air provides only upper bound estimates for some ETS components. Current biomarker technology for measuring ETS dose in the body is inadequate. The EPA recently stated that "air quality problems are pervasive in a wide spectrum of buildings, but the prevalence of such problems, the nature of their sources and the amount of human exposure attributable to these sources remains virtually unknown" [USEPA, 1990a, p. 3]. 19
After acknowledging the uncertainties inherent to ETS exposure measurement [The Guide, pp. 11-14], the authors rationalize the use of several problematic measures. The Guide wrongly implies that ETS exposure has been "measured" and promotes several inappropriate surrogate "markers." The authors never discuss the severe limitations of these markers and never acknowledge the absence of an accepted quantitative method for them. a. Air Monitoring -- RSP The Guide recognizes that several surrogates, or tracers, are necessary to estimate ETS exposure, but relies primarily on respirable suspended particles (RSP) as a marker in its discussion of air monitoring with respect to ETS. As Ogden and Maiolo have noted: "RSP, although a necessary indicator of indoor air quality in general, is an inappropriate tracer of ETS [Ogden, 1990, p. 420]. The National Research Council's Committee on Passive Smoking has established four criteria to assess the reliability of a proposed ETS tracer: unique or nearly unique to the tobacco smoke so that other sources are minor in comparison, a constituent of the tobacco smoke present in sufficient quantity such that concentrations of it can be detected in air, even at low smoking rates, similar in emission rates for a variety of tobacco products, and in a fairly consistent ratio to the individual contaminant of interest or category of contaminants of interest (e.g., suspended particulates) under a range of environmental conditions encountered and for a variety of tobacco products [NRC, 1986, p. 70]. Respirable suspended particles fail to meet two of these criteria. First, RSP is not "uniquely attributable to tobacco" and RSP measurements overestimate ETS exposure. 20
Although total RSP concentration can be reliably determined, it too is not specific to tobacco smoke As a result, total RSP can overestimate exposure to ETS, although the magnitude of this bias can be reduced by determining a quantity identified as ultraviolet- particulate matter (UV-PM). Based on an empirical relationship between RSP and its UV absorption established on particulate matter collected in an environmental chamber containing only ETS, the contribution of ETS to RSP in indoor environments can be estimated. Since this procedure relies on measuring the total absorbance at 325 nm of the methanol extract of filters used to collect RSP, the tendency is still toward overestimating the ETS contribution to RSP [Ogden, 1988, pp. 77-78] (Emphasis added). Many sources contribute to RSP in indoor environments -- clothing, furniture, office equipment, paper, carpet, and dust. Humans themselves are a major source of particles. "Virtually everything we use in buildings sheds particulate matter and/or produce gases" [Robertson, 1990, p. 334]. Consequently, according to DiNardi, "the measured increase in RSP due to ETS can only be reported if the occupied and nonsmoking RSP background is determined and compared to the occupied and smoking level of RSP" [DiNardi, 1986, p. 94]. Second, RSP is not in constant ratio to other constituents of ETS "under a range of environmental conditions encountered." As the Guide correctly notes, ETS is a two-phase mixture, consisting of particulate and gaseous phases [The Guide, p.7]. However, the Guide fails to note that both phases are in a continuous and complex state of flux. At any given moment, constituents of either phase are evolving chemically, thermodynamically and mechanically according to laws of aerosol physics and chemistry. One important aspect of this disequilibrium is decay. Constituents within each phase of ETS deplete at different 21
decay rates (e.g., by condensation, evaporation, nucleation, sedimentation, sorption, chemical reaction, selective filtration) [Kay, 1990; Nelson, 1990a; Nelson, 1990b]. The relative concentrations are never static. Consequently, no single component, including RSP, can be in constant ratio with all other components in a dynamic two-phase mixture. Measurement of RSP does not produce an accurate estimate of ETS exposure. The Guide's virtually exclusive reliance upon RSP as a marker is therefore unwarranted and arbitrary. Even if RSP were a reliable ETS surrogate, the Guide incorrectly implies that ETS levels in the workplace are high. The authors ignore pertinent workplace data and manipulate other, irrelevant data to exaggerate the contribution of ETS to indoor air quality. The Guide relies exclusively on studies of home, as opposed to workplace, environments. Workplace environments differ dramatically from home environments in terms of smoking behavior, ventilation, RSP sources and other important parameters. Workplace exposure levels are generally very low [Oldaker, 1990a]. Inexplicably the Guide never acknowledges these important differences. The authors contend both that ETS is "the major contributor to RSP in indoor air," and that "each smoker generates 25 to 35 micrograms of RSP per cubic meter of air (ug/m³)" [The Guide, p. 12].9 Neither contention is supported by the data. The Guide describes a The Guide also claims that "[h]omes with two or more heavy smokers frequently exceed the federal 24-hour outdoor particle standard of 260 g/m3" [The Guide, p. 12]. This statement contains an egregious error, because there is no such federal standard. EPA abandoned that standard in 1986, replacing it with a standard for particulate matter known as PM-10. The authors of the Guide should at least be held to modest accuracy in such assertions. 22
study by Spengler which reports mean indoor RSP concentrations of 24.4 g/m³ for 35 homes with no smokers, and 36.5 g/m³ for 15 homes with one smoker [Spengler, 1981, Table 2]. If one assumes conservatively that tobacco smoke particulate matter accounts for the entire observed difference, then a simple calculation shows that ETS contributes at most 12.1 g/m³ to the RSP concentration in homes with one smoker. At least twice as much RSP comes from other sources. Other studies not cited in the Guide confirm that ETS does not constitute the bulk of RSP in indoor air. For example, Proctor demonstrated in a field study that ETS contributed <6% to 40% of the total RSP of one modern, air-conditioned office building in England. The bulk of particulate matter in the offices surveyed came from non-ETS sources [Proctor, 1989]. Similarly, Oldaker reported that, based on UV-PM10 and RSP measurements taken in a survey of indoor air quality in four major cities, ETS contributed at most 21% and 30% to the total RSP in offices and restaurants, respectively [Oldaker, 1990a]. b. Air Monitoring -- Nicotine The most commonly used surrogate for ETS monitoring is nicotine. But nicotine, a vapor-phase component [Eudy, 1986] also fails to meet a critical NRC criterion. Like RSP it is not present in a constant ratio to other ETS constituents, even within a single controlled environment -- much less, among a wide variety of environments as mandated by the NRC 10 UV-PM is an estimate of ETS respirable suspended particles. "Based on an empirical relationship between RSP and its UV absorption established on particulate matter in an environmental chamber containing only ETS, the contribution of ETS to RSP in indoor environments can be estimated" [Ogden, 1990, p. 415]. Ogden reports that UV-PM overestimates the contribution of ETS to RSP by 26%. 23
[Kay, 1990; Nelson, 1990a; Nelson, 1990b; Oldaker, 1990a]. In fact, nicotine is particularly elusive as a marker: The peculiar decay behavior of nicotine, which is believed to be caused by its ready adsorption onto and desorption from surfaces, causes the ratio of nicotine concentrations to the concentrations of other ETS constituents such as CO, volatile organic compounds, and particulate matter to be highly variable. By itself, the large variation in nicotine/constituent ratios can lead to large errors in the estimation of exposure to ETS. If nicotine concentrations are measured for a long time following smoking, the concentration of ETS components other than nicotine may decay to background levels before nicotine. Under these circumstances, if nicotine is used to predict exposure to other ETS constituents or to calculate an "equivalent number of cigarettes smoked" the numbers obtained can greatly overestimate actual exposures [Nelson, 1990a, p. 371]. Plausible ETS exposure estimation must integrate all the NRC tracer acceptability criteria. Additionally, it must include accurate quantification of several ETS-specific constituents -- i.e., representative cross-sections of each phase. Few studies to date have measured more than one surrogate [Carson, 1988; Crouse, 1990; Oldaker, 1990a; Oldaker, 1990b]. Inexcusably, the Guide ignores these complications. The measurements of ETS nicotine and particulate matter have no proven relationship to health effects. The best measurement techniques in use merely indicate an upper bound for the contribution of ETS to the concentrations of certain components found in indoor air. 24 este
c. Air Monitoring -- Dynamics The Guide states that "ETS diffuses rapidly through buildings [The Guide, pp. 3, 12]. This statement reveals a technical misunderstanding of the term "diffuse" and perpetuates a false, pernicious notion of ETS dynamics. First, the Guide's authors confuse the term "diffuse," which has a specific physical/mathematical meaning, with the generic terms "disperse" or "dissipate" throughout the document. ETS disperses in buildings by convective and diffusive mechanisms. ETS is removed by the simultaneous mechanisms of deposition, impaction, filtration, sorption, and ventilation. For the particulate phase, convective forces dominate; for the gaseous phase, diffusion may be equally important. Diffusion coefficients may differ by orders of magnitude among particulate- and vapor-phase species [Reist, 1984]. Second, the authors falsely imply that ETS rapidly pervades all confines of a building at like concentration, regardless of distance from the source. In reality, concentration depends critically on location and time. Sterling examined the influence of ventilation and smoking-rate parameters on ETS concentrations in indoor environments [Sterling, T., 1989]. His data indicated minimal recirculation of ETS between smoking and nonsmoking areas -- areas on different floors or within different sections of a single large room. In his study, smoking and nonsmoking areas of a cafeteria (which were neither separately ventilated nor physically separated) could be distinguished by nicotine or RSP measurements. In this case, different concentrations of ETS components were measured within the same room. Concentrations were lower in areas further from the cafeteria, even though served by the same ventilation system [Sterling, T., 1989]. Sterling's work supports Kim's conclusions 25
regarding concentration gradients within the same room [Kim, 1990]. Sterling also found that nicotine concentrations were below the detection limit in nonsmoking offices -- offices that shared recirculated air from the cafeteria. RSP concentrations were also low and apparently unaffected by ETS [Sterling, T., 1989]. Hedge measured ETS constituent concentrations in smoking and nonsmoking areas of a smoking restricted 40-story office building [Hedge, 1990]. Both nicotine and UV-PM were monitored. Results are Table 1: Nicotine and UV-PM Concentrations presented in Table 1. From CONCENTRATION (ug/m³ morning to afternoon, UV-PM SMOKING NONSMOKING a.m. p.m. a.m. p.m. levels in nonsmoking areas Nicotine 27.2 41.2 0.0 0.0 remained constant (or decreased UV-PM 120 185 9.0 7.0 slightly), while increasing in smoking areas. Clearly, concentrations of both species depend upon time and location. This result, coupled with the absence of detectable nicotine in nonsmoking areas, refutes the Guide's implication that concentration gradients are transitory or nonexistent. The data also suggest that ETS has a negligible impact in the nonsmoking areas of properly ventilated buildings. The Guide's statement that ETS "persists for long periods after smoking ends " [The Guide, pp. 3, 12] is misleading. In fact, most ETS constituents are removed rapidly from building interiors by dilution with fresh air introduced by the ventilation system [Arfi, 1989; Kim, 1990]. Several studies have demonstrated that removal of most ETS constituents (for which measurements exist) from room environments is proportional to the air exchange 26
rate [Baker, 1990; Nelson, 1990a; Nelson, 1990b]. Other studies have shown that ETS concentrations decrease so rapidly that it is often difficult to determine whether, or where, smoking has occurred [Carson, 1988; Oldaker, 1990a; Oldaker, 1986]. The Guide therefore oversimplifies the science of air monitoring and ignores important relevant data. A more comprehensive review of the literature compels the following conclusions: 1. Because of dilution and decay, ETS is generally present in extremely low levels in the workplace; often ETS constituents are not detectable by current scientific methods; 2. Removal of ETS from an interior environment is strongly dependent on air exchange rate; 3. If a building is properly ventilated, the dilution process is both rapid and efficient; and 4. Under proper ventilation conditions, ETS recirculates to a very small extent between smoking and nonsmoking areas. d. Biomarkers -- Cotinine The Guide's section on "Biomarker Studies" [The Guide, p. 13] creates an impression of manifest scientific verity by oversimplification, false assumptions and mischaracterizations. This section fails to acknowledge the complexities of biomarker science and the scarcity of hard data regarding ETS biomarkers. It assumes incorrectly that cotinine levels in body fluids are reliable indicators of ETS exposure. Quantitative measures of ETS exposure are necessary to evaluate whether health effects may be attributed to ETS exposure. To be useful, biomarkers must indicate whether exposure to a specific chemical or mixture of chemicals has occurred, and be related to health. Ideally, a biomarker should (i) be specific to the agent being studied; (ii) serve as 27 0110
an index of exposure; (iii) give an indication of the health risks, if any, of exposure; and (iv) be measurable at low levels [Reasor, 1990]. Several ETS species (individual chemical compounds, as well as RSP) have been proposed as biomarker candidates, but none meets these criteria [Reasor, 1990]. Biomarkers can sometimes provide accurate estimates of exposure to individual chemical species. Nicotine and cotinine in body fluids, for example, indicate exposure to nicotine. Neither can serve as surrogates for exposure to other ETS constituents [Kay, 1990; Nelson, 1990a; Nelson, 1990b]. Consequently, the Guide's statement that observation of a single biomarker (cotinine) indicates that subjects "have inhaled and retained ETS" is an oversimplification [The Guide, p. 13]. i. Dietary Nicotine The Guide contends that cotinine, a nicotine metabolite, is "totally unique to tobacco" and therefore "is a reliable indicator of ETS exposure" [The Guide, p. 13]. The assumption follows that anyone with cotinine in their blood has been exposed to ETS. Positive cotinine concentrations in three out of four nonsmokers, including persons reporting no exposure to tobacco smoke in the measuring period (up to a few days, depending on the body fluid tested) demonstrate the ubiquity of ETS exposure in nonsmokers [The Guide, p. 13]. This conclusion and the assumptions on which it is based are speculative and probably false. Nicotine is present in a variety of foods (solanaceous vegetables including green peppers, tomatoes and eggplants). As a result, the observation of cotinine in body fluids does not confirm exposure to ETS [Castro, 1986; Idle, 1990; Sheen, 1988]. It only indicates 28 15119
exposure to nicotine -- which may or may not have come from tobacco. Cotinine, therefore, is not always a reliable indicator of ETS exposure. Significantly, Castro have concluded: The data we have obtained thus far suggests that the amount of nicotine ingested from dietary sources closely parallels or may exceed that ingested directly or indirectly from the smoke of nationally advertised 'low-yield' cigarettes [Castro, 1986, p. 94]. The Guide's statement that "[c]otinine has also been measured in the urine of people who were unaware they had been exposed" [The Guide, p. 13] is entirely consistent with ingestion of nicotine through dietary sources. Dietary nicotine, particularly the presence of nicotine in tea [Sheen, 1988] might explain why, as the Guide notes, "in several British studies, nearly all nonsmokers had measurable cotinine levels, regardless of reported exposure" [The Guide, p. 13]. Moreover, as a consequence of nicotine's unique environmental "decay" behavior, the presence of cotinine in nonsmokers exposed to tobacco-smoke nicotine may be of little relevance to overall ETS exposure. Because nicotine tends "to linger in the environment longer than other ETS constituents" [Nelson, 1990a], it is not possible to correlate cotinine levels with direct exposure to ETS. It may, for example, have originated from the clothing of a smoker or interior surfaces of the room [Nelson, 1990a; Nelson, 1990b]. In addition, a vapor-phase marker cannot be used to estimate particulate-phase exposure. ii. Cotinine Measurement Errors The low concentrations found in nonsmokers' body fluids seriously diminish its viability as a biomarker. Contrary to the Guide's claim [The Guide, p. 13], cotinine is very difficult to measure in any biological fluid. In fact, cotinine levels in nonsmokers' body fluids are near the detection limits of most reported analytical methodologies [Watts, 1990]. 29
At present, no standardized, validated method exists to quantify such low concentrations. Researchers have developed several different methods. Reproducibility of results is a problem. In a comparative study, Biber found that nonsmoker cotinine levels varied significantly among laboratories [Biber, 1987]. He also found that several laboratories were unable to detect cotinine in serum from exposed nonsmokers. Concentrations reported by some laboratories bore no relationship to estimated ETS exposure, or were unrealistically high. In two separate studies, Haley and Schepers reported a problem in immunoassays of cotinine due to cross-reactivity between the commonly-used anticotinine antibodies and trans-3-hydroxycotinine [Haley, 1990; Schepers, 1988]. In addition, cotinine measurement in urine can be subject to error because of caffeine interference. Cummings [the Guide's reference 37] used an HPLC method [Machacek, 1986] to screen the urine of 663 never-smokers and exsmokers for nicotine and cotinine [Cummings, 1990]. The reported mean urinary cotinine concentrations appear unusually high (9.5 ng/ml) for people who claimed they had not been exposed to ETS. These levels of cotinine may be explained by the caffeine interference inherent in this HPLC method. Thuan found that caffeine eluted between cotinine and the phenylimidazole internal standard, causing interference with the cotinine determinations [Thuan, 1989]. In contrast, Matsunga offered a better estimate of nonsmoker exposure to environmental nicotine, using gas chromatography to determine nicotine and cotinine [Matsunga, 1989]. He reported mean urinary cotinine concentrations of 0.4 + 0.2 ng/ml in nonsmokers claiming no ETS exposure, and 3.5 + 2.1 ng/ml in nonsmokers with confirmed ETS exposure. Finally, the measurement of urinary cotinine concentrations is complicated further 30 5318
because cotinine is present in smokers' urine in two chemically distinct forms: the free base and as a conjugate [Curvall, 1989]. Either form can predominate and there are considerable intra- and inter-individual differences. Current methods for the quantification of cotinine only determine the free-base form, therefore providing an incomplete measure of the cotinine present. For these reasons, the Guide's ETS exposure estimates based on cotinine concentrations are arbitrary and misleading. Because of potential dietary sources of nicotine, the inability of nicotine or its metabolite, cotinine, to predict exposure to other ETS constituents, and the potential for error in measuring cotinine, ETS exposure estimates based upon cotinine have serious limitations. e. Other Surrogates The Guide's discussion of "Other Surrogates" [The Guide, p. 13] perpetuates the errors of preceding sections. Specifically, it reinforces the false impression that RSP, nicotine, or other individual constituents when measured independently, are reliable indicators of ETS exposure. It also reinforces the unproven assertion that ETS presents a major health threat to nonsmokers. The Guide states: "Air monitor studies have shown nicotine levels considerably greater in homes with smokers than in homes without" [The Guide, p. 13]. This is another example of the authors' reliance on data from non-workplace environments to build a case for workplace smoking bans. Moreover, as previously discussed, several studies have shown that nicotine overestimates ETS exposure, because of its unique decay behavior and other properties [Baker, 1990; Nelson, 1990a; Nelson, 1990b]. 31
The discussion of benzene [The Guide, p. 13] is particularly inaccurate and misleading. By juxtaposing such statements as: "[Benzene] causes leukemia in humans at occupational levels," with "ETS is a significant source of benzene exposure" [The Guide, p. 13], the Guide leaves a strong, but totally false, impression that nonsmokers develop leukemia from ETS exposure. Benzene exposure from ETS is negligible. Automotive fuel is, by far, the largest, most pervasive source of benzene exposure. In 1989, the U.S. Department of Health and Human Services estimated that 1 billion pounds of benzene were released into the atmosphere from the refueling and operation of approximately 130 million motor vehicles in 1976 [NIEHS, 1989]. This translates into 7.8 pounds of benzene per vehicle per year. In contrast, a pack-per-day smoker would generate approximately 0.008 pounds of benzene per year, assuming that, at most, 0.5 mg of benzene is generated from one cigarette (MS plus SS) [Hoffmann, 1990]. Based on these estimates, an average person is potentially exposed to 1,000 times more ambient benzene from one automobile than from a smoker in a given year. The Guide's characterization of ETS as "a significant source of benzene exposure" is plainly wrong. This mischaracterization, coupled with the false implication that ETS benzene is a proven cause of leukemia, is yet another example of the Guide's distortion of data in its campaign to persuade the reader that ETS presents a major health threat to nonsmokers -- an implication that has not been proven and that is not supported by scientific data. 32 5110
f. Questionnaires The Guide's "Questionnaires" section [The Guide, p. 14] identifies some limitations of using questionnaires to quantify ETS exposure: First, questionnaires usually only can address short term exposure and do not provide an indication of dose over a lifetime. Second, most questionnaires have limited the discussion of ETS exposure to the home, while a large amount of the exposure may take place away from the home (at work or in public places). Third, it is often difficult to measure and quantify ETS exposure at work [The Guide, p. 14]. These limitations are by no means all the shortcomings of questionnaires. In fact, the Guide ignores many important provisos to their use in developing statistical data -- including respondent bias and subsequent misclassification [Jarvis, 1984]. Experts repeatedly question the reliance on questionnaires to assess ETS exposure [e.g., Coultas, 1989]. The Surgeon General identified several additional problems with questionnaires: In studies of the effect of ETS exposure, two types of misclassification are of concern: misclassification of current or former smokers as never smokers and misclassification of the extent of ETS exposure. [USPHS, 1986, p. 35]. Because of the many drawbacks to questionnaires, RJRT disagrees with the Guide's statement that "questionnaires have proved to be an effective tool to distinguish between populations that receive a high level of exposure and those that receive a smaller level" [The Guide, p. 14]. Questionnaire responses do not reliably predict ETS exposure levels. Questionnaires may be of some value as supplements to other exposure indicators (such as appropriate biomarkers), but they cannot be used blindly or alone. g. Mathematical Models The Guide's extremely brief discussion of mathematical modeling -- and its conclusion 33
that "[m]athematical models have proved to be a reasonable way to estimate ETS exposure" [The Guide, p. 14] -- leave the reader with the impression that accurate and reliable mathematical models have been developed to predict ETS exposure. The Guide fails to describe any specific model used to estimate ETS exposure, the many factors that must be considered in any such model, and the relative significance of these various factors. By failing to discuss the many assumptions, approximations and unknowns inherent in the model-building process, the Guide exaggerates the ability of mathematical models to predict ETS exposure. The Guide should include a full and fair assessment of model types, their applicability and their many limitations. A typical, drastic assumption which afflicts many ETS models in the literature is that of instantaneous, perfect mixing [Repace, 1982; Ryan, 1988]. Yamamoto identified several problems with models which assume rapid diffusion and good mixing in indoor air spaces: Numerous models have been developed to calculate airflow distribution and concentration profiles, many of these being supplied by the clean room research community. However, these models do not adequately account for various parameters such as supply/return air duct location and source location. Especially, the contaminant concentration in the occupants' breathing zones (1.0 to 1.5 m from the floor) will be an important consideration for evaluating the indoor air quality and the ventilation effectiveness [Yamamoto, 1990, p. 243]. Kim has addressed some of these concerns in a more rigorous aerodynamic model [Kim, 1990]. His work indicates that ETS is rapidly removed from an office space once smoking has stopped. Many experts question the utility of mathematical models to predict ETS exposure. The accuracy of ETS models is limited both by the precision of data that are used in the 34
model and by the sophistication of the model itself. Several types of mathematical models have been used to estimate ETS exposure. Each type is characterized both by its own level of physicochemical and mathematical sophistication and by its utility in predicting ETS exposure. Some models in the literature are suitable only for very restricted, unrealistic environments (e.g., environments at thermodynamic, chemical or mechanical equilibrium) [Repace, 1982; Ryan, 1988]. Others can be applied more generally, but are severely limited by computational requirements [Horstman, 1988]. None, however, can be applied universally. The Guide ignores this important qualification. Contrary to the impression created by the Guide, accurate prediction of ETS exposure in workplace environments by mathematical modeling has never been achieved. 4. The Purported Relationship Between ETS And Certain Health Effects Is Dubious Throughout Chapter 3, "Health Effects of ETS" [The Guide, pp. 15-18], the Guide makes sweeping assertions regarding purported health effects relative to ETS. These assertions are based in part on the biased and inaccurate Health Assessment. The Guide's discussion of alleged health effects is selective; when contrary data are acknowledged, they are minimized. In addition, the Guide reviews data that are largely irrelevant to the workplace. a. Irritation Many statements in the Guide's section "Irritation" [The Guide, p. 15] are unsubstantiated. The authors do not discuss workers' responses to ETS in the workplace. For instance, there are undocumented statements such as: "[f]or many people the effect is annoying; for some it can be incapacitating" and the "result [of ETS irritation] is generally 35
a sore throat or cough" [The Guide, p. 15]. In poorly ventilated areas, occupants may consider high levels of ETS to be annoying. These complaints are most frequently associated with inadequate ventilation [Oldaker, 1989] or to indoor air contaminants other than ETS [Robertson, 1990]. There are no studies of "incapacitation" due to ETS exposure. Subjective perceptions of urge to cough and sensations of sore throat have been studied. Winneke found that subjects' responses to ballot terms: "urge to cough," "sore throat," "breathing is impaired" or "my eyes are burning" were not significantly different from control responses at or below 5 ppm dCO [Winneke, 1984]. Subjects' responses were significantly different from control responses at 15 ppm dCO. To put these data in perspective, dCO values above 5.0 ppm were found in only one out of 23 offices in a survey of smoker-occupied offices [Carson, 1988]. The mean dCO for the 23 offices was 0.2 ppm; the range was -4.3 to 6.6 ppm. Even ignoring the likely potential irrelevance of CO measurements to ETS concentrations, these data indicate that workplace ETS levels are below the threshold levels at which subjects experience discomfort. There are no data to support the suggestion that irritation results from ETS levels found in the workplace. Researchers typically expose subjects to levels of ETS much greater than those encountered in real environments in order to elicit significant responses. Kay found that high levels of ETS were required to produce subjective complaints. Exorbitantly high ETS levels, 13 to 65 times greater than the approximately 5 to 12 g/m³ nicotine levels found in field studies, were selected for this study so that quantifiable and significant differences in subject responses could be obtained [Kay, 1990, p. 275]. 36
Conclusions about irritation from ETS as a problem in the workplace are unwarranted. b. Lung Cancer The Guide follows several lines of evidence to conclude that ETS is a proven cause of human lung cancer: epidemiologic studies of lung cancer and spousal smoking, the 1986 reports by the Surgeon General [USPHS, 1986] and the National Research Council [NRC, 1986], and the EPA's draft Health Assessment11. Evaluations of ETS and lung cancer that either reach alternate conclusions [e,g., Layard, 1990; Letzel, 1988; Uberla, 1988; Uberla, 1987], or suggest alternate explanations for the data [Koo, 1989; Lee, 1987] are ignored. Contrary to the discussion presented in the Guide [The Guide, pp. 15, 16, 19], neither the Health Assessment nor any other review has presented a persuasive case that ETS is a risk factor for lung cancer -- let alone that ETS is a proven cause of lung cancer. The flaws in the Guide's conclusion regarding ETS and lung cancer [The Guide, pp. 15, 16, 19] and in the EPA's draft Health Assessment are discussed in detail in RJRT's response to the Health Assessment. Nevertheless, several points are worthy of emphasis here. The epidemiologic studies are primarily of spousal smoking (not ETS) and lung cancer. Over 80% of the studies relied upon by the EPA's Health Assessment found no statistically significant increased incidence of lung cancer for nonsmokers married to a smoker. The observed associations in the few remaining studies are weak. Those studies were conducted in countries where lifestyles, diet and environmental factors are very 11 RJRT has submitted comments on the Health Assessment. Those comments contain a more complete review of ETS and lung cancer studies and discuss the many flaws in the EPA's Health Assessment. 37
different from those in the United States. In contrast to these foreign studies, no U.S. study of spousal smoking and lung cancer, including the largest study performed to date [Varela, 1987], has reported a statistically significant association. Bias and the many confounding factors cannot be excluded in any of the studies. The authors ignore epidemiologic studies which investigated ETS exposure in the workplace. To date, six studies [Garfinkel, 1985; Kabat, 1984; Lee, 1986; Shimizu, 1988; Varela, 1987; Wu, 1985] have examined workplace ETS exposure and lung cancer. None found a statistically significant risk of lung cancer associated with exposure to ETS in the workplace. Results from three of these studies are summarized below. Varela failed to find an association between exposure to ETS in the workplace and lung cancer (OR = 0.99, 95% CI = 0.97, 1.01) [Varela, 1987]. Variations in duration of exposure did not affect the results. Garfinkel examined the odds ratio for lung cancer and workplace ETS exposure for women [Garfinkel, 1985]. No association with workplace exposure was observed (OR = 0.88,95% CI = 0.66, 1.18; OR = 0.93, 95% CI = 0.73, 1.18, for 5 years and 25 years workplace exposure, respectively). Wu found that nonsmokers exposed to ETS in the workplace did not have a statistically significant increased risk of developing lung cancer, compared to nonsmokers not exposed to ETS in the workplace (RR = 1.2, 95% CI = 0.8, 2.2) [Wu, 1985]. In summary, the EPA's conclusions regarding ETS and lung cancer are based on a biased and incorrect interpretation of epidemiologic studies of spousal smoking and lung cancer. The Guide does not adequately address the uncertainty and limitations associated with these studies. 38
c. Spurious Health-Effect Claims The authors buttress their allegations regarding irritation and lung cancer with discussions of other health concerns which are unrelated to the workplace or for which current data do not permit conclusions to be drawn. i. Children Nearly one-third of Chapter 3, "Health Effects of ETS" [The Guide, pp. 15-18], discusses respiratory diseases in children. This section concludes with the following bold- lettered statement: "it is prudent to eliminate ETS exposure from the environments of small children" [The Guide, p. 17]. In the Health Assessment the EPA correctly recognizes that a causal relationship between ETS and respiratory diseases in children has not been established. The Guide fails to acknowledge this point or to describe how tenuous are the observed associations. Most important, a discussion of childhood respiratory disease has no bearing on whether smoking should or should not be allowed in workplaces. Few would seriously argue that workplaces are "the environments of small children" [The Guide, p. 17]. For these reasons, the Guide's discussion of respiratory problems in children is irrelevant and should be eliminated. ii. Asthma, Heart Disease, Allergies And Other Cancers A significant portion of Chapter 3 relates to alleged effects of ETS on asthmatics, people with heart disease and people with allergies [The Guide, pp. 17, 18]. The Guide describes how ETS increases symptoms, aggravates the conditions or brings on allergic reactions and then acknowledges that "data are too limited," [The Guide, pp. 17, 18] or that 39
it "is still too early" [The Guide, p. 18] to draw conclusions. These sections appear designed to establish guilt by association. The reader will be misled by the implication that there are health concerns when, as the Guide acknowledges, no solid evidence for such conclusions exists. The section, "People with Heart Disease," suggests that exposure to CO from ETS results in alterations of cardiovascular function in individuals already compromised with coronary vascular disease [The Guide, p. 17]. CO concentrations in ETS are trivial and are unlikely to affect those with heart disease. This section leaves the reader with the impression that ETS aggravates heart disease. Nonetheless, the authors admit that "[a] complete analysis of the data linking ETS and heart disease has not been conducted by the EPA" [The Guide, p. 17]. The Guide should state clearly that ETS exposure has not been demonstrated to aggravate existing heart disease. Similarly, the authors discuss "Cancer at Other Sites" [The Guide, p. 18] ("brain tumors, nasal sinus cancers, genital, breast and endocrine cancers, and cervical cancer" in "nonsmoking women"). They concede that "the data are too limited to be conclusive," and note that "additional research is needed in this area" [The Guide, p. 18]. They do not, however, state clearly that ETS exposure in the workplace has never been implicated in these chronic diseases. In short, sections on asthma, heart disease, allergies and other cancers are filled with suppositions [The Guide, pp. 17, 18]. The Guide's treatment of these issues appears contrived to mislead the reader. 40