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B Case Studies Establishing Active Agents armor Interactions In Complex Mixtures SULFUR DIOXIDE AND SUSPENDED PARTICULATE MATTER The case of sulfur dioxide (SO2) and particulate matter (PM) in ambient air and their effects on mortality and respiratory disease morbidity is a classic case of exposure to complex mixtures in which identification of causal factors has proved extremely difficult. Epidemiologic research has been critical in deter- mining the relative roles of SO2 and PM, whereas laboratory inhalation studies have been critical in identifying active components in the PM. An important caveat is that the critical experimental inhalation studies were done on humans and animals not normally used in standardized bioassays (i.e., dogs, rabbits, and guinea pigs). Also, some of the effects assays particle clearance rates, detailed airway morphometry, and CO-diffusing capacity are not used in conventional rodent bioassay tests. Unconventional animal models and non- routine effects measures were needed because available animal models for the human health effects of interest, such as chronic bronchitis and exacerbations of asthma, have not been widely accepted as relevant to human disease. Air pollution health effects have been associated with coal smoke in London in a qualitative sense at least since the thirteenth century, when Edward I banned the use of coal during sessions of Parliament. However, sustained ef- forts to control coal-smoke pollution did not begin until the London "killer fog" of December 1952 (Great Britain, 19541. Because the effluent from coal combustion contains both SO2 and PM, scientists long debated whether SO2 or PM was the causal agent or whether the effects were due to their combined actions, or synergism. In the absence of clear evidence in the 1950s and 1960s, various authorities responsible for air pollution control made different judg- 133
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134 APPENDIX B meets. In the United Kingdom, authorities made efforts to reduce PM, espe- cially the black-smoke component, which was cut by about a factor of 2 be- tween 1952 and 1962. The reduction in SO2 over the same period was substantially smaller. Later reviews of the changes in mortality and morbidity indexes during this period tended to implicate PM as a more important health stressor than SO2. Time-series analyses of daily mortality in New York City (Schimmel, 1978; Schimme] and Murawski, 1975, 1976; Buechley et al., 1973) indicated that mortality increased with increasing SO2 concentrations for both the periods 1963-1966 and 1970-1972. Because the absolute SO2 concentrations dropped by about a factor of 3 over this period, it is highly unlikely that SO2 was the causal factor for the similar association with mortality in the different periods. Rather, the daily fluctuations in SO2 appeared similar to daily fluctuations in other pollutants from the same or similar sources, and other pollutants in the pollutant mixture were probably more directly related to the observed effect. This leads to the conclusion that PM or PM components are better indexes of exposure. The active agents in PM have not yet been clearly identified. Ozkaynak and Spengler (1985) performed regression analyses between daily mortality and four different components of PM: total suspended particulate matter (TSP), inhalable particulate matter (IP), fine particulate matter (FP), and SO42- . TSP has an upper cut-size of ~ 40-60 Am aerodynamic diameter, depending on wind speed and direction. IP has an upper cut-size of 15,um, which is relatively independent of wind speed and direction. FP has an upper cut-size of 2.5 ~m. SO42- is almost all within the FP fraction and varies from less than 10% to more than 50% of FP. All four showed positive regression with daily mortality, with correlation coefficients increasing in the order of TSP < IP < FP < SO42-. Only FP and SO42- had statistically significant coefficients. Although SO42- might be the best predictor of health effects among the commonly measured indexes of PM, it is probably not the active agent. Several physiologic effects of sulfate aerosols have been shown to depend on their H + content. These include specific airway conductance (Utell, 1985) and bron- chial mucocilia~y particle clearance (Schlesinger, 19851. Thus, SO42- might be acting as a surrogate for the strong acid associated with it. Unfortunately, correlation studies between H+ and health effects cannot be performed, be- cause there are too few data available on ambient H+ concentrations (Lipp- mann, 19851. Experimental inhalation studies with SO2 and PM have not played any major role in elucidating the role of these pollutants in population mortality and mor- bidity experience. The only documented human health effect of SO2 exposures at concentrations near those occurring in ambient air are transient changes in airway resistance and compliance. Amdur's guinea pig model (Amdur and Mead, 1958) is much more responsive to SO2 than is any other animal tested
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APPENDIX B 135 (U.S. EPA, 19821. In this respect, it is similar in response to asthmatic hu- mans, who, in controlled chamber exposure studies, are about 10 times more responsive (Sheppard et al., 1980) than healthy humans. However, the tran- sient bronchoconstrictive responses seen in these human and guinea pig studies are qualitatively different from those reported for human populations exposed to polluted ambient air. Amdur's guinea pig model also has been used to demonstrate synergism between SO2 and PM. The bronchoconstrictive effects of SO2 are potentiated by coexposure to hydroscopic and catalytic aerosols (McJilton et al., 1976; Amdur and Underhill, 19681. However, both the end point used transient bronchoconstriction and the vein high ~ > 5 mg/m3) concentrations of parti- cles needed to cause the potentiated response make the relevance of these re- sponses to the effects associated with ambient pollutant exposures somewhat questionable. Experimental PM inhalation studies with concentrations and compositions similar to those encountered in ambient air have generally been unproductive (U.S. EPA, 19821. The only constructive interpretation that one can make of the data from such studies is that insoluble materials such as fixed carbon, resuspended soil, and fly ash could not by themselves account for the effects observed. The only experimental inhalation studies producing effects of possible rele- vance to the human experience have been those involving acidic aerosols, either alone or in complex mixtures. Some recent animal inhalation studies by Amdur (1985) demonstrated that effects produced by single exposures at very low acid concentrations can be persistent. She exposed guinea pigs by inhala- tion for 3 hours to the diluted effluent from a furnace that simulates a model coal combuster. The amount of H2SO4 on the surface of the ZnO particles was less than 40 ,ug/m3. These aerosol studies produced significant decrements of total lung capacity (TLC), vital capacity (VC), functional residual capacity (FRC), and CO-diffusing capacity (DLCo). At 12 hours after exposure, there were distension of the perivascular and peribronchial connective tissues and an increase in lung weight. The alveolar interstitium also appeared distended. At 1 hour, there was an increase in lung permeability. At 72 hours, TLC, VC, and FRC had returned to baseline values, but DLCo was still significantly de- pressed. Based on her experience with pure SO2 and pure H2SO4 exposures in the guinea pig model, Amdur concluded that the furnace effluent produced an acid aerosol effect because of its persistence. The persistent changes in func- tion and morphological changes after exposure to acidic aerosol at vein low concentrations suggested that repetitive exposures could lead to chronic lung disease. Another animal inhalation study with implications for human chronic lung disease involved a group of beagle dogs exposed to 16 hours daily for 68 months to a mixture of SO2 at 1,100 ,ug/m3 and H2SO4 at 90 ,ug/m3, either with
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136 APPENDIX B
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APPENDIX B 137 ther periods of daily exposures needs to be determined. We can expect these issues to be clarified as the results from longer exposure periods become available. The significance of the changes in particle clearance rate in the lungs from repetitive daily exposures to acidic aerosols, in terms of the pathogenesis of chronic respiratory disease, is not yet clear. But the close correspondence be- tween the effects of cigarette smoke and H2SO4 aerosol on mucocilia~y clear- ance after both short-term and long-term exposures, the similarities between the epithelial changes after repetitive H2SO4 inhalation in rabbits and those seen in the lungs of young smokers in postmortem examinations, and the well- established role of smoking in the etiology of chronic bronchitis combine to suggest that chronic bronchitis could result from long-term repetitive expo- sures to H2SO4 (Lippmann et al., 1982~. The fact that the incidence of chronic bronchitis among nonsmokers was higher in the United Kingdom when ambi- ent acidic aerosol concentrations were high lends further plausibility to a causal- relationship. Much more evidence is needed to demonstrate a clear causal rela- tionship, however. Conventional inhalation studies with rodents have not been useful in unrav- eling the effects associated with human exposures to the ambient complex mixtures of sulfur oxides and particles. Research studies with less commonly used experimental animals (e.g., guinea pigs, dogs, and rabbits) have been very useful, but not yet definitive. Perhaps the major lesson is that studies focused on mechanisms of the pathogenesis of chronic lung disease need to be designed with care, with constant attention to the suitability of the animal model and of the relationship to the real-world question. In summary, the excess mortality and morbidity that have been demon- strated in populations exposed to atmospheres containing mixtures of fossil- fuel combustion products might well have been due to a specific component of the mixture for example, the strong acid component of the aerosol or to the combined or synergistic effects of two or more of the many components in the mixture. A more definitive summary is not yet possible, although current labo- rato~y and epidemiologic research might permit one in the near future. LEAD AND NUTRITIONAL FACTORS EFFECTS ON BLOOD PRESSURE Hypertension has long been recognized as a risk factor for cardiovascular disease, and several environmental and nutritional factors have been shown to affect blood pressure in experimental and epidemiologic studies (U.S. EPA, 19841. Among environmental factors that have been associated with blood pressures are lead (Pb) and noise. Among dietary factors associated with blood pressure are calcium (Ca), zinc (Zn), phosphorus (P), alcohol consumption, and vitamins A and C. Although Pb is a single substance, it is always found in
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138 APPENDIX B
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APPENDIX B 139 An ideal opportunity to separate the role of Pb from a wide range of poten- tially confounding nutritional factors was presented by the large data set from the second National Health and Nutrition Examination Survey of 1976-1980 (NHANES II), based on a random stratified sample of the U.S. population. Pirkle et al. (1985) described the results of their date analyses of 40- to 59-year- old white men from the survey population. After adjustment for age, body- mass index, all measured nutritional factors, and blood biochemistry factors were adjusted for a multiple linear regression model, the relations of both systolic and diastolic blood pressures to blood Pb were statistically significant (p < 0.011. In an examination of the NHANES II population in the age range from 12-74, Harlan et al. (1985) also found a direct relation between blood Pb and systolic and diastolic blood pressures. In the Pirkle et al. (1985) analyses, the authors incorporated additional van- ables, with particular attention directed to the stability and significance of the Pb coefficient in the presence of nutritional factors and blood biochemistry. Their objective was to estimate conservatively the strength and independence of the relationship between blood pressure and blood Pb. Therefore, to provide an unusually rigorous test of the independent significance of blood Pb, 87 nutritional and biochemical variables in NHANES II were included in the stepwise regression. In addition, to account for possible curvilinear relations, squared and natural logarithmic transformations of almost all these variables were also included (see Table B-11. TABLE B- 1 Vanables Included in the Stepwise Regression Analysis, White Males Aged 40-59 years, NHANES II, 1976-1980a Age b Age-squared b Body mass index Dietary sodium C Salt-shaker sodium Dietary sodium x salt-shaker sodium Dietary potassium C Dietary sodium-potassium ratio Dietary calcium C Dietary phosphorus c Dietary protein c Dietary fat C Dietary carbohydrate c Dietary cholesterol c Dietary saturated fatty acids c Dietary oleic acid C Dietary linoleic acid C Dietary iron c a Reprinted with permission from Pirkle et al., 1985. b This variable was forced into each regression to remove any possible age effect on blood pressure. c The natural log and squared transformation of these variables were also included in the stepwise regression. Dietary vitamin A c Dietary vitamin C c Dietary thiamine c Dietary riboflavin C Dietary niacin Serum cholesterol c Serum vitamin C c Serum iron C Serum transferrin saturation Serum zinc Serum copper C Serum albumin C Hemoglobin C Red blood cell count Ethanol consumption per week C Cigarettes smoked per day Total dietary grams c Total dietary calories c
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140 APPENDIX B When they included the nutritional variables, the blood analyses, and their curvilinear transformations, Pb remained significantly associated (p < 0.01) with both systolic and diastolic blood pressures. Furthermore, segmented re- gression analyses indicated that there was not a threshold blood Pb content below which Pb was not significantly related to blood pressure. Between 1976 and 1980, the mean blood Pb levels in the NHANES II popu- lation dropped by 37% owing to reductions in the amount of Pb used in gaso- line. This much reduction in blood Pb in this population would be expected to result in a 17.5% decrease in diastolic blood pressure of at least 90 mm Hg, a value used to define hypertension. Considering the relatively unusual nature of the blood Pb-blood-pressure relation (i.e., characterized by large initial increments in blood pressure at relatively low blood Pb concentrations, followed by leveling off of blood- pressure increments at high blood Pb concentrations), it is not surprising that it was not anticipated by results of animal studies. Many animal studies empha- size results from exposures at higher doses, where results tend to be more definitive. Yet, in retrospect, the human results were consistent with biphasic blood-pressure increases observed in response to blood Pb increases in the rat (Victery et al., 1982a,b). The unusual exposure-response relation might also account for the failure of earlier human studies to find consistent relations between blood pressure and blood Pb in study groups with mild to moderate increases in blood lead. In summary, the use of a very large set of high-quality data covering a wide range of possibly confounding variables allowed a clear-cut determination of the effects of blood Pb on blood pressure for a relatively low range of blood Pb concentrations (5-35 ,ug/dl). The studies also demonstrated the utility of com- prehensive data sets from representative populations for determining the ef- fects of specific components in environmental exposures. RADON DAUGHTERS AND CIGARETTE SMOKE This case study illustrates the interaction of two pulmonary carcinogens, cigarette smoke and radon daughters, to produce an increase in the total inci- dence of bronchogenic carcinoma in humans. Both of these agents are inhaled as gaseous suspensions and are delivered to the epithelium. The result of com- bined exposures is to increase the number of carcinomas, and this increase is interpreted as additive by several investigators, whereas others consider the effect as multiplicative. Exposure to radon daughters and cigarette smoke also appears to decrease the latency induction period for lung cancer. Animal stud- ies in general have supported the human epidemiologic and pathologic findings that the combined exposure to radon daughters and cigarette- smoke yields a greater number of malignancies than that observed for either carcinogen alone. Several of the cigarette-smoke-radon-daughter studies required the transla-
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APPENDIX B 14 lion of the natural circumstances and organ systems to demonstrate the in- creased incidence of tumors. For example, McGregor (1976) used cigarette smoke condensate rather than native smoke. In addition, whereas alpha parti- cles are generated by radon-daughter decay, this study used beta particles. Finally, the test organ was not the lung, but rat skin. These changes in the nature of the carcinogenic agents, in the concentration and manner in which they were applied, and in the target organ itself make this example questionable as an analogue of the human events. The studies of Cross et al. (1982), in our opinion, have been incorrectly interpreted and are also of questionable utility. These investigators found more lung cancers in nonsmoking radon-daughter-exposed dogs than in a group ex- posed to cigarette smoke. These findings were interpreted as "protective" ef- fect. Such conclusions are unwarranted, because dogs do not inhale cigarette smoke in a manner or quantity analogous to those of humans. In fact, a major problem in virtually all animal studies in which inhalation of cigarette smoke is a requisite part of the design is the delivery of the smoke to the target organ in concentrations, temperature, age, and quantity identical to that inhaled by people. For one thing, there is a difference in inhalation path- way (i.e., nasal versus oral). In addition, most mammals find the inhalation of cigarette smoke so irritating that they must be forced to inhale. The volume of diluent air, the quantity of the cigarette smoke received, and the depth and frequency of inhalation are nonuniform and unlike the breathing pattern exhib- ited by human smokers. Furthermore, human lung diseases associated with cigarette smoke inhalation require heavy exposures (one or more packs per day) for periods of 20 or more years. Such exposures for such a duration are not feasible in animal studies. Thus, exposures of animals to cigarette smoke by inhalation are not adequate to initiate the disease states associated with human smoking. Radon is an inert gas that results from the radioactive decay of radium-226; it has a half-life of 3.8 days. Other decay products resulting from the sequence of radioactive decay are polonium-218, lead-214, bismuth-214, and polonium- 210. These elements are known collectively as radon daughters and have a collective half-life of 30 minutes. Small amounts of radon are ubiquitous, can be found in all rocks and soil, and are constantly emanating from ground level and diffusing into the atmosphere. Radon concentrations are increased wher- ever closed spaces exist around rock or soil and where phosphates or uranium ores or ore tailings are deposited. When radon decays, its daughter atoms, being heavy metals and ionized, attach to adjacent objects, surfaces, or dust. When inhaled into the respiratory tract, radon decays rapidly. In so doing, it produces irradiation of the adjacent cells before it can be removed by normal clearance mechanisms. Of the radiation dose, 95 % is delivered to the epithe- lium as alpha radiation; the beta and gamma energies are generally insignifi- cant and diffusely distributed. Exposure is measured in working levels (WL).
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142 APPENDIX B One WL is the concentration of any combination of short-lived radon daugh- ters in air whose complete decay produces 1.3 x 105 MeV of alpha energy per liter. Exposure at this level for 1 working month, about 170 hours, constitutes an exposure of 1 working level month (WLM). The maximal permissible ex- posure for underground miners is 4 WLM/year, an equivalent of 0.3 WL/ month. Levels in mines have cumulatively reached as high as 10,000 WLM. Average levels in homes appear to be about 0.004 WL in the United States, although some homes have been found to have levels as high as 10 WL. When the first bronchogenic carcinoma was observed in a nonsmoking ura- nium miner in 1965 (described by Archer, 1985), there had already been 80 lung-cancer deaths in cigarette-smoking U.S. uranium miners. Because of the increased expectancy of lung neoplasms in cigarette smokers, it was quite natural to assume that the cause of all lung cancers in this group of miners was cigarette-smoking. In 1969, a second primary bronchogenic carcinoma was observed in a nonsmoking uranium miner (Archer, 19851. This case repre- sented a significant excess of lung cancers from what might be expected in this nonsmoking population. As the mortality study of uranium miners continued, Archer (1985) noted that nonsmoking uranium miners experienced 7 times the incidence of lung cancer observed in nonsmoking persons who were not miners, and smoking uranium miners had 9.5 times the incidence of lung cancers found in non- miners with similar smoking histories. Despite the fact that uranium miners smoked more than the comparably aged nonminer U.S. males, the excess ex- posure to cigarette smoke explained only a small part of the observed increase in lung cancer. This unexplained increase in cancer incidence suggested an interaction between cigarette-smoking and radiation exposure in the miners. Archer (1985) described additional studies which showed that the lung- cancer rate among smoking uranium miners declined after age 65. The expla- nation suggested was that the latency induction period had been shortened in smoking miners. Interpretation of this finding was that cigarette smoke might act as a promoter, whereas radiation acted as the initiator. Axelson and Sundell (1978) suggested that the increased incidence of lung cancer reflected an additive effect between smoking and radon-daughter expo- sure. Damber and Larsson (1985) interpreted their findings as a multiplicative effect. The studies of Hornung et al. (1981), Edling (1982), and Radford and St. Clair Renard (1984) all supported an additive effect, rather than a multipli- cative one. The early studies of the cell type of bronchogenic carcinoma seen in uranium miners suggested that there were greater numbers of undifferentiated small- cell carcinomas in this group than in the lung cancers of nonminers. The in- creased proportion of small-cell or differentiated lung cancers which appeared to be the same in smoking and nonsmoking uranium miners, suggests that mining exposure and radiation were responsible for any difference in the num-
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APPENDIX B 143 her of undifferentiated carcinomas. Recent pathologic studies have not con- firmed this increase in undifferentiated small-cell cancers in miners. All cell types—the squamous carcinoma, the adenocarcinoma, and the small-cell un- differentiated carcinoma have been observed in cigarette-smoking uranium miners in numbers similar to that present in cigarette smokers who are not miners. Factors that might influence the cell type and progression of lung cancers in U.S. uranium miners are age at the start of mining, high radiation exposure rates, and cigarette-smoking. The risk of lung cancer appears to decline in miners who have reached age 65 and have had 25 or more years of latency. Several animal studies have addressed the interaction of cigarette smoke, cigarette-smoke condensate (CSC), and ionizing radiation. McGregor (1976) studied the interaction of CSC and beta particles on rat skin and observed an increase in skin tumors 3 times greater than the increase produced by radiation alone. CSC alone did not produce tumors. Treatment with both agents caused tumors to appear earlier than in the radiation-only group. Nenot (1977) used cigarette-smoke inhalation and americium-241 applied to the lungs in rats. The animals receiving the combination of smoke and radiation had an increased yield of lung cancers, which appeared earlier than with radiation alone. In summary, epidemiologic studies of exposure to radon daughters and ciga- rette smoke have demonstrated two effects. The first is an additive effect of the two agents on the number of cancers induced. The second is the decrease in induction latency period, which produces a different time distribution of tu- mors in smokers and nonsmokers: the tumors in smokers appear earlier. We have seen comparable results in animals exposed to components of cigarette smoke at high concentrations, but not when the animals were exposed to fresh smoke by inhalation. The discordance in the latter case is most likely due to technical limitations in our ability to produce conditions that match human smoking. ASBESTOS EXPOSURE AND CIGA1lETTE-SMOKING This case study is one of the most current and well-recognized examples of how two distinct agents administered together can produce an increased inci- dence of lung cancer that is greater than that predicted from the administration of either agent alone. The increase in lung-cancer incidence in cigarette-smok- ing asbestos workers is considered multiplicative by most investigators who have studied the problem. That is in contrast with the increased incidence of lung cancer in uranium miners, in whom it has been observed that the increase in lung-cancer incidence from the combined exposure is additive. This case study also differs from that of the radon-daughter-cigarette-smoke example, in that asbestos, unlike radon gas, is a fibrous mineral particulate material that enters the lung via the airways and remains in the lung for long
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APPENDIX B 157 cisely which experiments to do to determine specific human health effects of complex mixtures. Given the imperfect nature of animal data, can they be used to make decisions concerning health threats posed by complex mixtures? Judg- ing from our experience with coke-oven emissions, the answer is clearly yes. Although there are substantial differences between the human and animal data, we conclude that the adverse effects of coal tar seen in animals are echoed by the effects of coke-oven emissions in humans. The above discussion of coke-oven emissions demonstrates that data gener- ated by animal toxicity testing of complex mixtures can be a reasonable predic- torofhuman disease, if the mixture being tested in the laboratory is representa- tive of mixtures in the human environment, if studies are properly designed to detect diseases, and if we are aware that the specific diseases and target organs in test animals can vale from those in humans. COAL-MINE DUST The studies of lung disease in coal miners have focused principally on chest x-ray alterations, pulmonary function deficits, chronic bronchitis, and patho- logic alterations of lung tissue. Attempts have been made to relate those to each other, as well as to an exposure index (e.g., years spent underground in coal mines) and dose (mass of respirable coal dust per cubic meter of air times total hours exposed). An immense amount of data has been generated. The purpose of this example is to document the correlations, point out the difficulties in- volved, and explain how animal experiments have or have not assisted in ex- plaining some of the biologic response variables. Coal workers' pneumoconiosis (COOP) was originally described in terms of descriptive pathology (Gough, 1947; Heppleston, 19471. The characteristic lesion is a focal collection of coal-dust-laden macrophages at the division of respiratory bronchioles that can exist within alveoli and extend into the peri- bronchiolar interstitium with associated reticulin deposits and focal emphy- sema (Kleinerman et al., 19791. The black lesions have been termed macules; they are 1 - mm in diameter. Other lesions can occur in lungs of coal miners, including micronodules ~ 7 mm in diameter), silicotic nodules, progressive massive fibrosis (PMF), Caplan's le- sions, and infective granulomas (e.g., in histoplasmosis and tuberculosis). The nodular lesions are palpable and gray to black, and they contain collagen, silica, and silicates, as well as black particles. The silicotic nodules are com- posed of whorled or laminated collagen and silica and can also contain some black particles. The lesions in PMF are black and rubbery to hard, and they can contain inlay fluid. One of the criteria for defining PMF lesions is a minimal size, 1-3 cm (Kleinerman et al., 19791. One of the major subjects of controversy in CWP is whether coal-mine dust causes emphysema and, if it does, whether it is clinically significant. In early
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158 APPENDIX B reports, two British pathologists considered focal emphysema around the coal macules to "constitute the characteristic feature ofthe disease" (Gough, 1947) or to represent "the most important feature of the larger lesions," macules 2 - mm in diameter (Heppleston, 19471. The researchers did not try to relate the extent of the emphysema to clinical signs and symptoms. Heppleston (1947) did note, however, that "focal emphysema is occasionally so extensive as to leave but little of the parenchyma unaffected." It was not until recently that controlled studies were performed in an attempt to determine whether coal miners exhibited more emphysema than other work- ers. Cockcroft et al. (1982), in an autopsy series on 39 coal workers and 48 other workers, found that coal workers who smoked exhibited much more centrilobular emphysema than controls who smoked. There were too few non- smoking coal workers in the sample to determine whether work in coal mines by itself could produce significant emphysema. Ruckley et al. (1984) were able to show, in a series of 450 miners, that centriacinar emphysema was signifi- cantly more prevalent in smoking (72%) than in nonsmoking (42%) miners. They also showed that increasing concentrations of lung dust correlated with a higher incidence of centriacinar emphysema (p < 0.051. Although there were no nonsmoking, nonminer controls, the fact that a high percentage (75 %) of the nonsmoking miners with PMF had emphysema strongly suggests that non- smoking miners with PMF have a much higher risk of developing emphysema than do nonsmoking nonminers. Ryder et al. (1970), in a study of 247 coal miners, were able to show a highly significant correlation between extent of emphysema and a decrease in LEVI. It seems clear that coal miners have a higher risk of emphysema than do other workers; however, this trend has been clearly demonstrated only for smokers and possibly for nonsmoking coal miners with PMF. A small but statistically significant decrease in LEVI in active coal miners has also been demonstrated. Rogan et al. (1973) reported a statistically signifi- cant (p < 0.001) progressive reduction in LEVI with increasing cumulative exposure to coal-mine dust in a prospective study on 3,581 coal-face workers. In men without PMF, the reduction in LEVI was calculated to be 120-150 ml over 35 years at mean respirable-dust concentrations of 4 mg/m3. The authors equated that with the loss one might expect from smoking 20 cigarettes/day for the same period. The decrements in LEVI were seen in nonsmokers, as well as in smokers. They found no interaction (synergism) between cigarette-smoking and dust exposure. However, the greatest decrement in LEVI was found in workers with chronic bronchitis, and it could not be explained solely on the basis of dust exposure and cigarette-smoking. In a longitudinal study of 1,677 active coal miners without PMF, Love and Miller (1982) found that the loss of LEVI over approximately 11 years increased with cumulative dust exposure, when the effects of age, height, and smoking were allowed for. They estimated that exposure to dust at the average concentration (117 g x hours/m3) recorded
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APPENDIX B 159 for the 1,677 men studied was associated with about a 40-ml loss in LEVI over an 11-year period. Lloyd (1971) was able to show a significant difference in pulmonary function between active miners and a nonmining control group. Of current miners, 20% had an LEVI less than 80% of predicted, compared with 10% of active telecommunication workers. Hankinson et al. (1977) demonstrated a statistically significant correlation between decrements in flow rates at high lung volumes and years of under- ground exposure. The decrement was more noticeable among the nonsmokers. They suggested that a dust-induced bronchitis was responsible. Those studies, as well as others, have shown that the pulmonary function deficits are rather small (except in workers with PMF). Most of the studies focused on active miners and therefore might have analyzed a self-selected group of people who can tolerate dust exposures without significant effects on pulmonary function. Some support for that idea was recently published by Hurley and Soutar (19861. In a study of 199 men without PMF who had left the coal industry before normal retirement age, a much greater loss of LEVI than expected was found (average loss, 600 ml in those who had experienced moderately high exposures). A higher incidence of chronic bronchitis also has been shown to occur in coal miners than in nonminers (Lloyd, 19711. Because the sample contained so few nonsmokers, however, the comparison was statistically significant only in the smoking group. Rae et al. (1971), in a study of 4,122 face workers from 20 collieries, found a statistically significant association between increasing ex- posure to coal dust and increasing prevalence of bronchitis in the 25-34 and 35 44 age groups. That was true in both nonsmokers and smokers. Coal-mine dust exposure was also found to be significantly related to maximal ratio of mucous-gland thickness to bronchial-wall thickness, an anatomic index of chronic bronchitis (Douglas et al., 19821. The most common method for evaluating CWP in the living is with diagnos- tic chest x rays. A rather elaborate system has been adopted internationally for the grading of x-ray changes in coal workers. CWP is divided into simple CWP and complicated COOP, or PMF. Simple CWP includes all cases in which the x-ray opacities (rounded or irregular) are less than 1 cm in diameter and is sub- divided into several categories that depend on the abundance ("profusion") of these opacities. Jacobsen et al. (1971), in a prospective study of 4,122 coal workers over a 10-year period, found a linear correlation between the progres- sion of chest x-ray category and exposure, measured as the concentration of respirable coal-mine dust per cubic meter. They estimated that exposures to coal-mine dust at 2 mg/m3 for 35 years would lead to fewer than 1 % of miners progressing from category 0/0 (no COOP) to category 2 or higher. On the basis of the studies noted here, it is clear that coal miners exhibit a higher incidence of bronchitis, pulmonary function deficits, and emphysema than nonminers. It is not clear to what extent the changes are caused by coal-
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16;0 APPENDIX B mine dust, cigarette-smoking, a combination of coal-mine dust and cigarette- smoking, or other factors. The composition of coal dust and coal-mine dust might vary considerably, depending on the type of coal and the geologic area of the coal seams. Typical constituents in coal in the United States (Schtick end Fannick, 1971) are shown carbon (29.5-81%), volatile matter (5.1-36.8%), moisture (4.3-36.8%), ash (4.3-9.6%), and sulfur (0.5-0.9%~. The ash can contain quartz, aluminum silicates (e.g., mica and kaolin), and iron oxides in substantial concentrations. Coal-mine dusts might contain a variety of other minerals, depending on how much and what kind of rock dust is generated in the process of roof-bolting and cutting the coal seams. In addition, miners are occasionally exposed to fumes from cable fires and explosives. Faced with this wide range of variables and limited resources, most investi- gators studied what they considered to be the most active ingredient in coal- mine dust quartz. The pulmonary effects of coal dusts that have various con- centrations of mineral matter and of quartz have been studied sporadically in animal systems for more than 50 years. The principal end points in the investi- gations were the development of macules and fibrotic nodules in the lungs of the experimental animals. The results of inhalation studies in animals have generally shown that coal dust containing less than 10% quartz has not produced substantial pulmonary fibrosis. Ross et al. (1962) exposed rats to a mixed dust of anthracite coal with a low ash content and quartz added in various concentrations. Exposure was to respirable dust at about 60 mg/m3 for about 3,200 hours over 10-17 months. Rats exposed to mixtures of coal dust with 5% and 10% quartz showed little or no pulmonary fibrosis, whereas those exposed to coal dust with 20% quartz showed grade 2 fibrosis, and those exposed to coal dust with 40% quartz showed graded fibrosis (maximal grade, 51. Weller and Ulmer (1972) exposed animals to coal dust at 45 mg/m3 containing 30-35 % added quartz for 1,800- 2,200 hours over 18 months (rats) and 3 years (monkeys). The rats developed grade 2 fibrosis, and the monkeys developed grade 2-3 fibrosis. The monkeys developed macules thatlooked similar to those seen in coal miners' lungs. Rats did not develop macules with the same appearance as those in coal miners, probably because the anatomy of the rat lung is considerably different from that of the human lung. Gross and Nau (1967) exposed monkeys, rats, guinea pigs, and mice to lignite coal dust at 7. 8 mg/m3 containing 2 % quartz and carbon dust at 8.1 mg/m3 containing 6.5% quartz for 1,820 hours over 1 year. They observed no fibrosis and little or no reticulin in the dust aggregates in either experiment. They observed that the lungs of mice contained less dust than the lungs of rats, which contained less dust than the lungs of monkeys. Martin et al. (1977) exposed rats to coal dust at 200 mg/m3 or with logo quartz for up to 1,300 hours over 2 years. They observed small amounts of reticulin (but no fibrosis) in the dust masses in the lungs of rats exposed to coal dust and massive
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APPENDIX B 161 nodular lesions with collagen fibers in the lungs of rats exposed to coal dust Mat contained 10% quartz. The nodules looked similar to fibrotic nodules seen in the lungs of coal miners with COOP, but did not look like the classical silicotic nodules composed of laminated or whorled collagen. The effects of the minerals in coal dust on the f~brogenicity of quartz have also been studied. In relatively short-term studies, Martin et al. (1972) have shown that mineral matter from coal dust can partially inhibit the fibrogenicity of quartz. They also found that quartz treated with a dialysate from coal min- eral matter has a significantly reduced solubility and induced much less colla- gen in the lungs of rats in 3-month expenments. That raises the possibility that quartz in different coal-mine dusts might have different capacities to induce fibrotic changes in the lungs of miners and that the capacity might vale with the composition of the mineral matter that is inhaled with it. Lungs of coal miners might contain quartz at relatively high concentrations (Davis et al., 19831. Lungs with macules but no fibrotic nodules contained quartz at a mean concen- tration of 800 mg per lung the same mean concentration seen in the lungs of workers with slight silicosis (Nagelschmidt, 1965.) The lungs also contained 3,300 mg of kaolin and mica, however. The high concentration of those miner- als might have modified the fibrogenic effect of the quartz. Few pulmonary function studies in animals have been reported. Moorrnan et al. (1977) exposed germ-free and conventional rats to coal dust at 10 mg/m3 for 960 hours. They showed small but statistically significant reductions in flow maximums at 10% of vital capacity in the exposed rats, compared with the controls. Weller and Ulmer (1972) performed pulmonary function tests on rats exposed to coal dust at 45 mg/m3 (with 30-35% quartz) for 18 months. They found small but statistically significant differences only in the values for compliance. No experimental models have been developed to study chronic bronchitis and centnlobular emphysema as they occur in humans. REFERENCES Alavanja, M., I. Goldstein, and M. Susser. 1978. A case control study of gastrointestinal and urinary tract cancer mortality and drinking water chlorination, pp. 395-409. In R. L. Jolley, H. Gorchev, and D. H. Hamilton, Jr. (eds.). Water Chlorination: Environmental Impact and Health Effects. Vol. 2. Ann Arbor Science, Ann Arbor, Mich. Amdur, M. O. 1985. When one plus zero is more than one. Am. Ind. Hyg Assoc. J. 46:467-475. Amdur, M. O., and J. Mead. 1958. Mechanics of respiration in unanesthetized guinea pigs. Am. J. Physiol. 192:364-368. Amdur, M. O., and D. Underhill. 1968. The effect of various aerosols on the response of guinea pigs to sulfur dioxide. Arch. Environ. Health 16:460-468. Archer, V. E. 1985. Enhancement of lung cancer by cigarette smoking in uranium and other miners, pp. 23-37. In M. J. Mass (ed.). Carcinogenesis. Vol. 8. Raven Press, New York. Axelson, O., and L. Sundell. 1978. Mining, lung cancer and smoking. Scand. J. Work Environ. Health 4:46-52.
OCR for page 162
162 APPENDIX B Balster, R. L., and J. F. Borzelleca. 1982. Behavioral toxicity of trihalomethane contaminants of drinking water in mice. Environ. Health Perspect. 46: 127-136. Batuman, V., E. Landy, J. K. Maesaka, and R. P Wedeen. 1983. Contribution of lead to hypertension with renal impairment. N. Engl. J. Med. 309: 17-21. Begin, R., A. Cantin, Y. Berthiaume, R. Boileau, S. Peloquin, and S. Masse. 1983. Airway function in lifetime-nonsmoking older asbestos workers. Am. J. Med. 75:631-638. Bellar, T. A., J. J. Lichtenberg, and R. C. Kroner. 1974. The occurrence of organohalides in chlori- nated drinking waters. J. Am. Water Works Assoc. 66:703-706. Berry, G., M. L. Newhouse, and M. Turok. 1972. Combined effect of asbestos exposure and smoking on mortality from lung cancer in factory workers. Lancet 2:476-478. Brenniman, G. R., J. Vasilomanolakis-Lagos, J. Amsel, T. Namekata, and A. H. Wolff. 1980. Case- control study of cancer deaths in Illinois communities served by chlorinated or nonchlorinated water, pp. 1043-1057. In R. L. Jolley, W. A. Brungs, R. B. Cumming, and V. A. Jacobs (eds.). Water Chlorination: Environmental Impact and Health Effects. Vol. 3. Ann Arbor Science, Ann Arbor, Mich. Buechley, R. W., W. B. Riggan, V. Hasselblad, and J. B. VanBruggen. 1973. SO2 levels and perturba- tions in mortality: A study in the New York-New Jersey metropolis. Arch. Environ. Health 27: 134-137. Burke, T. A., J. Amsel, and K. P. Cantor. 1983. Trihalomethane variation in public drinking water supplies, pp. 1343-1351. In R. L. Jolley, W. A. Brungs, J. A. Cotruvo, R. B. Cumming, J. S. Mattice, and V. A. Jacobs (eds.). Water Chlorination: Environmental Impact and Health Effects. Vol. 4, Book 2: Environment, Health, and Risk. Ann Arbor Science, Ann Arbor, Mich. Cantor, K. P., R. Hoover, P. Hartge, T. J. Mason, D. T. Silverman, and L. I. Levin. 1985. Drinking water source and risk of bladder cancer: A case-control study, pp. 145-152. In R. L. Jolley, R. J. Bull, W. P. Davis, S. Katz, M. H. Roberts, Jr., and V. A. Jacobs (eds.). Water Chlorination: Chemis- try, Environmental Impact and Health Effects. Vol. 5. Lewis Publishers, Chelsea, Mich. Cockcroft, A., R. M. E. Seal, J. C. Wagner, J. P. Lyons, R. Ryder, and N. Andersson. 1982. Post- mortem study of emphysema in coalworkers and non-coalworkers. Lancet 2(8298):600-603. Cragle, D. L., C. M. Shy, R. J. Struba, and E. J. Siff. 1985. A case-control study of colon cancer and wafer chlorination in North Carolina, pp. 153-159. In R. L. Jolley, R. J. Bull, W. P. Davis, S. Katz, M. H. Roberts, Jr., and V. A. Jacobs (eds.). Water Chlorination: Chemistry, Environmental Impact and Health Effects. Vol. 5. Lewis Publishers, Chelsea, Mich. Craun, G. F. 1985. Epidemiologic considerations for evaluating associations between the disinfection of drinking water and cancer in humans, pp. 133-143. In R. L. Jolley, R. J. Bull, W. P. Davis, S. Katz, M. H. Roberts, Jr., and V. A. Jacobs (eds.). Water Chlorination: Chemistry, Environmental Impact and Health Effects. Vol. 5. Lewis Publishers, Chelsea, Mich. Cross, F. T., R. F. Palmer, R. E. Filipy, G. E. Dagle, and B. O. Stuart. 1982. Carcinogenic effects of radon daughters, uranium ore dust and cigarette smoke in beagle dogs. Health Phys. 42:33-52. Damber, L. and L. G. Larsson. 1985. Underground mining, smoking, and lung cancer: A case-control study in the iron ore municipalities in northern Sweden. J. Natl. Cancer Inst. 74: 1207-1213. Davis, J. M. G., S. T. Beckett, R. E. Bolton, and K. Donaldson. 1980. A comparison of the pathologi- cal effects in rats of the UICC reference samples of amosite and chrysotile with those of amosite and chrysotile collected from the factory environment, pp. 285-292. In J. C. Wagner (ed.). Biological Effects of Mineral Fibers. Vol. 1. IARC Scientific Pub. No. 30. International Agency for Research on Cancer, Lyon, France. Davis, J. M. G., J. Chapman, P. Collings, A. N. Douglas, J. Fernie, D. Lamb, and V. A. Ruckley. 1983. Variations in the histological patterns of the lesions of coal workers' pneumoconiosis in Britain and their relationship to lung dust content. Am. Rev. Respir. Dis. 128: 118-124. DeRouen, T. A., and J. E. Diem. 1977. Relationships between cancer mortality in Louisiana drinking- water source and other possible causative agents, pp. 331-356. In H. H. Hiatt, J. D. Watson, and
OCR for page 163
APPENDIX B I63 J. A. Winsten (eds.). Origins of Human Cancer. Book A: Incidence of Cancer in Humans. Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. DeShazo, R. D., D. J. Hendrick, J. E. Diem, J. A. Nordberg, Y. Baser, D. Brevier, R. N. Jones, H. W. Barkman, J. E. Salvaggio, and H. Weill. 1983. Immunologic aberrations in asbestos cement work- ers: Dissociation from asbestosis. J. Allergy Clin. Immunol. 72:454~61. Doll, R. 1955. Mortality from lung cancer in asbestos workers. Br. J. Ind. Med. 12:81-86. Douglas, A. N., D. Lamb, and V. A. Ruckley. 1982. Bronchial gland dimensions in coalminers: Influence of smoking and dust exposure. Thorax 37:760-764. Edling, C. 1982. Lung cancer and smokingina group ofiron ore miners. Am. J. Ind. Med.3:191-199. Gottlieb, M. S ., and J. K. Carr. 1982. Case-control cancer mortality study and chlorination of drinking water in Louisiana. Environ. Health Perspect. 46: 169-177. Gough, J. 1947. Pneumoconiosis in coal workers in Wales. Occup. Med. 4:86-97. Great Britain, Committee on Air Pollution. 1954. Report. Cmd 9322. Her Majesty's Stationery Of lice, London. Gross, P. and C. A. Nau. 1967. Lignite and the derived steam-activated carbon: The pulmonary re- sponse to their dusts. Arch. Environ. Health 14:450~60. Hammond, E. C., I. J. Selikoff, and H. Seidman. 1979. Asbestos exposure, cigarette smoking and death rates. Ann. N.Y. Acad. Sci. 330:473-490. Hankinson, J. L., R. B. Reger. R. P. Fairman, N. L. Lapp, and W. K. C. Morgan. 1977. Factors influencing expiratory flow rates in coal miners, pp. 737-755. In W. H. Walton (ed.). Inhaled Particles IV. Part 2. Pergamon, New York. Harlan, W. R., J. R. Landis, R. L. Schmouder, N. G. Goldstein, and L. C. Harlan. 1985. Blood lead and blood pressure: Relationship in the adolescent and adult U.S. population. J. Am. Med. Assoc. 253 :530-534. Harries, R. G., F. A. F. MacKenzie, G. Sheers, J. H. Kemp, T. P. Oliver, and D. S. Wright. 1972. Radiological survey of men exposed to asbestos in naval dockyards. Br. J. Ind. Med. 29:274-279. Heppleston, A. G. 1947. The essential lesion of pneumoconiosis in Welsh coal workers. J. Pathol. Bacteriol. 59:453-460. Hornung, R. W., and S. Samuels. 1981. Survivorship models for lung cancer mortality in uranium miners: Is cumulative dose an appropriate measure of exposure?, pp. 363-368. In M. Gomez (ed.). International Conference—Radiation Hazards in Mining: Control, Measurement, and Medical As- pects, Golden, Colo., October 4-9, 1981. Society of Mining Engineers of the AIME, New York. Hurley, J. F., and C. A. Soutar. 1986. Can exposure to coalmine dust cause a severe impairment of lung function? Br. J. Ind. Med. 43: 150-157. International Agency for Research on Cancer (IARC). 1985. IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Volume 35: Polynuclear Aromatic Compounds. Part 4: Bitumens, Coal-Tars and Derived Products, Shale-Oils and Soots. International Agency for Research on Cancer, Lyon, France. Jacobsen, M., S. Rae, W. H. Walton, and J. M. Rogan. 1971. The relation between pneumoconiosis and dust-exposure in British coal mines, pp. 903-919. In W. H. Walton (ed.). Inhaled Particles III, Vol. II. Unwin Brothers, Surrey, England. Johnson, G. A. 1911. Hypochlorite treatment of public wafer supplies: Its adaptability and limitations. J. Am. Public Health Assoc. 1 :562-574. Kanarek, M. S., and T. B. Young. 1982. Drinking water treatment and risk of cancer death in Wiscon- sin. Environ. Health Perspect. 46:179-186. Keller A. Z., and M. Terris. 1965. The association of alcohol and tobacco with cancer of the mouth and pharynx. Am. J. Public Health 55: 1578-1585. Kennaway, N. M., and E. L. Kennaway. 1936. Study of the incidence of cancer of the lung and larynx. J. Hyg. 36:236-267. Khera, A. K., D. G. Wibberley, K. W. Edwards, and H. A. Waldron. 1980. Cadmium and lead levels
OCR for page 164
164 APPENDIX B in blood and urine in a series of cardiovascular and normotensive patients. Int. J. Environ. Stud. 14:309-312. Kleinerman, J., F. Green, R. A. Harley, N. L. Lapp, W. Laqueur, R. Naeye, P. Pratt, G. Taylor, J. Wiot, and J. Wyatt. 1979. Pathology standards for coal workers' pneumoconiosis. Arch. Pathol. Lab. Med. 103:375-432. Kromhout, D., and C. de Lezenne Coulander. 1984. Trace metals and CHD risk indicators in 152 elderly men (the Zutphen study). Eur. Heart J. 5 (Abstr. Suppl. 1): 101. Kromhout, D., A. A. E. Wibowo, R. F. M. Herber, L. M. Dalderup, H. Heerdink, C. de Lezenne Coulander, and R. L. Zielhuis. 1985. Trace metals and coronary heart disease risk indicators in 152 elderly men (the Zutphen study). Am. J. Epidemiol. 122:378-385. Kuzma, R. J., C. M. Kuzma, and C. R. Buncher. 1977. Ohio drinking water source and cancer rates. Am. J. Public Health 67:725-729. Lange, A. 1980. An epidemiological survey of immunological abnormalities in asbestos workers. II. Serum immunoglobulin levels. Environ. Res. 176-183. Liddell, F. D. K., G. W. Gibbs, and J. C. McDonald. 1982. Radiological changes and fibre exposure in chrysotile workers aged 60-69 years at Thetford Mines. Ann. Occup. Hyg. 26:889-898. Lippmann, M. 1985. Airborne acidity: Estimates of exposure and human health effects. Environ. Health Perspect. 63:63-70. Lippmann, M., R. B. Schlesinger, G. Leikauf, D. Spektor, and R. E. Albert. 1982. Effects of sulphu- ric acid aerosols on respiratory tract airways. Ann. Occup. Hyg. 26:677-690. Lloyd, I. W. 1971. Long-term mortality study of steelworkers. V. Respiratory cancer in coke plant workers. J. Occup. Med. 13:53-68. Love, R. G., and B. G. Miller. 1982. Longitudinal study of lung function in coal-miners. Thorax 37: 193-197. Lynch, K. M., and W. A. Smith. 1935. Pulmonary asbestosis III: Carcinoma of lung in asbesto- silicosis. Am. J. Cancer. 24:56-64. Martin, J. C., H. Daniel-Moussard, L. Le Bouffant, and A. Policard. 1972. The role of quartz in the development of coal workers' pneumoconiosis. Ann. N.Y. Acad. Sci. 200: 127-141. Martin, J. C., H. Daniel, and L. Le Bouffant. 1977. Short- and long-term experimental study of the toxicity of coal-mine dust and some of its constituents, pp. 361-371. In W. H. Walton (ed.). Inhaled Particles IV. Part 1. Pergamon, New York. McDonald, J. C., F. D. K. Liddell, G. W. Gibbs, G. E. Eyssen, and A. D. McDonald. 1980. Dust exposure and mortality in chrysotile mining, 1910-75. Br. J. Ind. Med. 37: 11-24. McGregor, J. F. 1976. Tumor-promoting activity of cigarette tar in rat skin exposed to irradiation. J. Natl. CancerInst. 56:429-430. McJilton, C. E., R. Frank, and R. J. Charlson. 1976. Influence of relative humidity on functional effects of an inhaled SO2-aerosol mixture. Am. Rev. Respir. Dis. 113: 163-169. Meier, J. R., H. P. Ringhand, W. E. Coleman, J. W. Munch, R. P. Streicher, W. H. Kaylor, and K. M. Schenck. 1985. Identification of mutagenic compounds formed during chlorination of humic acid. Mutat. Res. 157:111-122. Meurman, L. O., R. Kiviluoto, and M. Hamaka. 1974. Mortality and morbidity among the working population of anthophyllite asbestos miners in Finland. Br. J. Ind. Med. 31: 105-112. Moorman, W. J., R. W. Hornung, and W. D. Wagner. 1977. Ventilatory functions in germfree and conventional rats exposed to coal dusts. Proc. Soc. Exp. Biol. Med. 155:424-428. Moreau, T., G. Orssaud, B. Juguet, and G. Busquet. 1982. Blood lead levels and arterial pressure: Initial results of a cross sectional study of 431 male subjects. Rev. Epidemol. Sante Publique 30:395-397. (In French.) Mossman, B. T., and J. E. Craighead. 1982. Comparative cocarcinogenic effects of crocidolite asbes- tos, hematite, kaolin and carbon in implanted tracheal organ cultures. Ann. Occup. Hyg. 26: 553-567. Nagelschmidt, G. 1965. The study of lung dust in pneumoconiosis. Am. Ind. Hyg. Assoc. J. 26: 1-7.
OCR for page 165
APPENDIX B 165 Nenot, J. C. 1977. In IAEA. Proceedings of the IAEA Symposium. International Atomic Energy Agency, Chicago., Newhouse, M. L., G. Berry, J. C. Wagner, and M. E. Turok. 1972. A study of the mortality of female asbestos workers. Br. J. Ind. Med. 29: 134-141. Ozkaynak, H., and J. D. Spengler. 1985. Analysis of health effects resulting from population expo- sures to acid precipitation precursors. Environ. Health Perspect. 63:45-55. Page, N. P., and U. Saff~otti. 1976. Report on Carcinogenesis Bioassay of Chloroform. National Cancer Institute, Division of Cancer Cause and Prevention, Bethesda, Md. (60 pp.) Pirkle, J. L., J. Schwartz, J. R. Landis, and W. R. Harlan. 1985. The relationship between blood lead levels and blood pressure and its cardiovascular risk implications. Am. J. Epidemiol. 121 :246-258. Pocock, S. J., A. G. Shaper, D. Ashby, T. Delves, and T. P. Whitehead. 1984. Blood lead concentra- tion, blood pressure, and renal function. Br. Med. J. 289:872-874. Pocock, S. J., A. G. Shaper, D. Ashby, and T. Delves. 1985. Blood lead and blood pressure in middle- aged men, pp. 303-305. In T. D. Lekkas (ed.). International Conference: Heavy Metals in the Environment. Vol. 1. September; Athens, Greece. CEP Consultants, Edinburgh, United Kingdom. Pott, P. 1775. Cancer scroti, pp. 63-68. In Chirurgical Observations Relative to the Cataract, the Polypus of the Nose, the Cancer of the Scrotum, the Different Kinds of Ruptures, and the Mortifica- tion of the Toes and Feet. Printed by T. J. Carnegy for L. Hawes, W. Clarke, and R. Collins, London. Radford, E. P., and R. G. St. Clair Renard. 1984. Lung cancer in Swedish iron miners exposed to low doses of radon daughters. New Engl. J. Med. 310: 1485-1494. Rae, S., D. D. Walker, and M. D. Attfield. 1971. Chronic bronchitis and dust exposure in British coalminers, pp. 883-896. In W. H. Walton (ed.). Inhaled Particles III. Volume II. Unwin Brothers, Surrey, England. Regan, G. M., B. Tagg. J. Walford, and M. L. Thomson. 1971. The relative importance of clinical, radiological and pulmonary function variables in evaluating asbestosis and chronic obstructive air- way disease in asbestos workers. Clin. Sci. 41:569-582. Rogan, J. M., M. D. Attfield, M. Jacobsen, S. Rae, D. D. Walker, and W. H. Walton. 1973. Role of dust in the working environment in development of chronic bronchitis in British coal miners. Br. J. Ind. Med. 30:217-226. Rook, J. J. 1974. Formation of haloforms during chlorination of natural waters. Water Treat. Exam. 23:234-243. Ross, H. F., E. J. King, M. Yoganathan, and G. Nagelschmidt. 1962. Inhalation experiments with coal dust containing 5 per cent, 10 per cent, 20 per cent and 40 per cent quartz: Tissue reactions in the lungs of rats. Ann. Occup. Hyg. 5: 149-161. Rothman K., and A. Keller. 1972. The effect of joint exposure to alcohol and tobacco on risk of cancer of the mouth and pharynx. J. Chron. Dis. 25:711-716. Ruckley, V. A., S. J. Gauld, J. S. Chapman, J. M. G. Davis, A. N. Douglas, J. M. Fernie, M. Jacobsen, and D. Lamb. 1984. Emphysema and dust exposure in a group of coal workers. Am. Rev. Respir. Dis. 129:528-532. Ryder, R., Lynons, J. P., H. Campbell, and J. Gough, . 1970. Emphysema in coal workers' pneumoco- niosis. Br. Med. J. 3:481-487. Salg, J. 1977. Cancer Mortality Rates and Drinking Water Quality in the Ohio River Valley Basin. Ph.D. dissertation, University of North Carolina at Chapel Hill. (144 pp.) Saracci, R. 1977. Asbestos and lung cancer: An analysis of the epidemiological evidence on the asbestos-smoking interaction. Int. J. Cancer20:323-331. Schimmel, H. 1978. Evidence for possible acute health effects of ambient air pollution from time series analysis: Methodological questions and some new results based on New York City daily mortality, 1963-1976. Bull. N.Y. Acad. Med. 54:1052-1108. Schimmel, H., and T. J. Murawski. 1975. SO2—Harmful pollutant or air quality indicator? J. Air Pollut. Control Assoc. 25:739-740.
OCR for page 166
166 APPENDIX B Schimmel, H., and T. J. Murawski. 1976. The relation of air pollution to mortality. J. Occup. Med. 18:316-333. Schlesinger, R. B. 1985. The effects of inhaled acids on respiratory tract defense mechanisms. Envi- ron. Health Perspect. 63:25-38. Schtick, D. P., and N. L. Fannick. 1971. Coal in the United States, pp. 13-26. In M. M. Key, L. E. Kerr, and M. Bundy (eds.). Pulmonary Reactions to Coal Dust: A Review of U.S. Experience. Academic Press, New York. Seidman, H., I. J. Selikoff, and E. C. Hammond. 1979. Short-term asbestos work exposure and long- term observation. Ann. N.Y. Acad. Sci. 330:61-89. Selikoff, I. J., E. C. Hammond, and J. Churg. 1968. Asbestos exposure, smoking, and neoplasia. J. Am. Med. Assoc. 204:106-112. Sheppard, D., W. S. Wong, C. F. Uehara, J. A. Nadel, and H. A. Boushey. 1980. Lower threshold and greater bronchomotor responsiveness of asthmatic subjects to sulfur dioxide. Am. Rev. Respir. Dis. 122:873-878. Stevens, A. A., R. C. Dressman, R. K. Sorrell, and H. J. Brass. 1985. Organic halogen measurements: Current uses and future prospects. J. Am. Water Works Assoc. 77(4):146-154. Topping, D. C., and P. Nettesheim. 1980. Two-stage carcinogenesis studies with asbestos in Fischer 344 rats. J. Natl. Cancer Inst. 65:627-630. U.S. EPA (Environmental Protection Agency), Environmental Criteria and Assessment Office. 1980. Long-Term Effects of Air Pollutants in Canine Species. EPA-600/8-80-014. U.S. EPA, Cincinnati, Ohio. U.S. EPA, Environmental Criteria and Assessment Office. 1982. Air Quality Criteria for Particulate Matter and Sulfur Oxides. Vol. III. EPA-600/8-82-029a. U.S. EPA, Research Triangle Park, N.C. U.S. EPA, Environmental Criteria and Assessment Office. 1984. Air Quality Criteria for Lead, Re- view Draft. EPA-600/8-83-028. U.S. EPA, Research Triangle Park, N.C. (4 vole.) U. S. Public Health Service, Division of Water Supply and Pollution Control. 1964. Inventory of Municipal Water Facilities (1963). Region V. Illinois, Indiana, Michigan, Ohio, and Wisconsin. PHS Publication No. 775. Vol. 5. U. S. Government Printing Off~ce, Washington, D.C. (Available from NTIS as PB-218194.) (152 pp.) Utell, M. J. 1985. Effects of inhaled acid aerosols on lung mechanics: An analysis of human exposure studies. Environ. Health Perspect. 63:39~4. Victery, W., A. J. Vander, H. Markel, L. Katzman, J. M. Shulak, C. Germain. 1982a. Lead exposure, begun in utero, decreases renin and angiotensin II in adult rats (41398). Proc. Soc. Exp. Biol. Med. 170:63-67. Victery, W., A. J. Vander, J. M. Shulak, P. Schoeps, and S. Julius. 1982b. Lead, hypertension, and the renin-angiotensin system in rats. J. Lab. Clin. Med. 99:354-362. Wagner, M. M. F. 1980. Immunology and asbestos, pp. 247-251. In J. C. Wagner (ed.). Biological Effects of Mineral Fibers. Vol. 2. IARC Scientific Pub. No. 30. International Agency for Research on Cancer, Lyon, France. Wagner, J. C., C. A. Sleggs, and P. Marchand. 1960. Diffuse pleural mesothelioma and asbestos exposure in the North Western Cape Province. Br. J. Ind. Med. 17:260-271. Wagner, J. C., G. Ber~y, J. W. Skidmore, and F. D. Pooley. 1980. The comparative effects of three chrysotiles by injection and inhalation in rats, pp. 363-372. In J. C. Wagner (ed.). Biological Effects of Mineral Fibers. Vol. 1. IARC Scientific Pub. No. 30. International Agency for Research on Cancer, Lyon, France. Walker, A. M. 1984. Declining relative risks for lung cancer after cessation of asbestos exposure. J. Occup. Med. 26:422~26. Wehner, A. P., R. H. Busch, R. J. Olson, and D. K. Craig. 1975. Chronic inhalation of asbestos and cigarette smoke by hamsters. Environ. Res. 10:368-383. Weiss, S. T., A. Munoz, A. Stein, D. Sparrow, and F. E. Speizer. 1986. The relationship of blood lead to blood pressure in a longitudinal study of working men. Am. J. Epidemiol. 123:800-808.
OCR for page 167
APPENDIX B 167 Weller, W., and W. T. Ulmer. 1972. Inhalation studies of coal-quartz dust mixture. Ann. N.Y. Acad. Sci. 200:142-154. Wright, J. L., and A. Churg. 1984. Morphology of small-airway lesions in patients with asbestos exposure. Hum. Pathol. 15:68-74. Wynder E. L., I. J. Bross, and R. M. Feldman. 1957. A study of the etiological factors in cancer of the mouth. Cancer 10: 1300-1323. Yamagiwa, K., and K. Ichikawa. 1918. Experimental study of the pathogenesis of carcinoma. J. Cancer Res. 3:1-29. Young, T. B., and M. S. Kanarek. 1983. Matched pair case control study of drinking wafer chlorination and cancer mortality, pp. 1365-1380. In R. L. Jolley, W. A. Brungs, J. A. Cotruvo, R. B. Cumming, J. S. Mattice, and V. A. Jacobs (eds.). Water Chlorination: Environmental Impact and Health Ef- fects. Vol. 4, Book 2: Environment, Health, and Risk. Ann Arbor Science, Ann Arbor, Mich.
Representative terms from entire chapter: