Document pm0VX62q6DQJmOQxnpORykQv7

Occupational Exposure to Chrysotiie y Asbestos and Cancer Risk: A Review of the Amphibole Hypothesis PLAINTIFF'S EXHIBIT SA-472 ABSTRACT Objectives. This article examines the credibility and polity implica tions of the "amphibole hypothesis," which postulates that (1) the meso theliomas observed among workers exposed to chrysotiie asbestos may be explained by confounding expo sures to amphiboles, and (2) chryso tiie -may have lower carcinogenic potency than amphiboles. Methods. A critical review was conducted of the lung burden, epide miologic, toxicologic, and mechanis tic studies that provide the basis for the amphibole hypothesis. Results. Mechanistic and lung burden studies do not provide con vincing evidence for the amphibole hypothesis. Toxicologic and epide miologic studies provide strong evi dence that chrysotiie is associated with an increased risk of lung cancer and mesothelioma. Chrysotiie may be less potent than some amphiboles for inducing mesotheliomas, but there is little.. evidence to indicate lower lungcancerjrisk* Conclusions. Given the evidence of a significant lung cancer risk, the lack of conclusive evidence for the amphibole hypothesis, and the fact that workers are generally exposed to a mixture of fibers, wgjanclude4hat it is prudent to treat chrysotiie with virtuallvtfie same level of concern as the ~ampHibolg^fhnns--of--ashggtos. (Am J~FubScHealth. 1996;86:179-- 186) February 1996, Vol. 86, No. 2 Leslie T. Stayner, PhD, DavidA. Dankovic, PhD, and Richard A. Lemen, PhD Introduction Chrysotiie is the predominant type of asbestos produced and consumed in the world today, and it accounted for over 98.5% of US asbestos consumption in 1992.1 Although asbestos consumption has declined in North America and Europe, sales in other countries (e.g.. Southeast Asia, South America, and East ern Europe) have increased primarily due to the use of asbestos-based construction materials.2 . . Chrysotiie is a serpentine (curly) form of asbestos that is distinguished from other amphibole forms of asbestos (i.e., crocidolite, amosite, tremolite). It has been hypothesized that (1) the mesothelioma risk observed among work ers exposed to chrysotiie asbestos may be explained by the relatively low con centrations (<1%) of tremolite fibers in commercial chrysotiie asbestos fibers and (2) that chrysotiie asbestos may be less potent than amphiboles in the induction of asbcstosis and lung cancer. This has been dubbed the amphi bole hypothesis.3 It has even been suggested that exposure to chrysotiie asbestos in the absence of tremolite may present little or no carcinogenic hazard.4 The arguments advanced to support the amphibole hypothesis have been pri marily based on pathologic studies of burdens of asbestos fibers in human lungs and on toxicologic, mechanistic, and epide miologic studies. This article presents a critical review of these arguments and of the literature on the carcinogenic hazards associated with exposure to chrysotiie asbestos and considers the implications of these findings for the development of occupational health policies. Lung Burden Studies The development of methods that involve electron diffraction and energy dispersive analysis of x-rays (EDAX)5 has made possible the measurement of the amounts of different fiber types in the lung. The results from lung burden studies have provided the primary basis for the advancement of the amphibole hypothesis. Case studies of individuals who have worked in industries using or producing chrysotiie asbestos revealed an unexpect edly high proportion of amphibole (pri marily tremolite) fibers, considering the relatively low percentage of amphibole fibers in commercial chrysotiie asbestos." In one of the earliest studies, Pooley observed a greater number of amphibole fibers than chrysotiie fibers in 7 of 22 patients with asbestosis who had worked in the Canadian chrysotiie mining indus try.7 Rowlands et al. also reported a nearly equal concentration of tremolite fibers and chrysotiie fibers in the lungs of 47 workers employed as miners or millers in Quebec.8 Similarly, in populationbased studies the percentage of chrysotiie fibers found in the lungs has been surpris ingly low considering the fact that chryso tiie is the major source of exposure for the general population.9 Most case-control studies that evalu ated the potential relationship between The authors are with the Risk Assessment Program and Office of the Director, National Institute for Occupational Safety and Health, Cincinnati, Ohio. Requests for reprints should be sent to Leslie T. Stayner, PhD, National Institute for Occupational Safety and Health, Robert A. Taft Laboratories, 4676 Columbia Parkway, Mail Stop C15, Cincinnati, OH 45226. This paper was accepted August 16,1995. Editor's Note. See related annotation by Cullen (p 158) in this issue. American Journal of Public Health 179 TABLE 1--Summary of Epidemiological Cohort Studios of Workers Exposed to Predominantly Chrysotlle Asbestos Study Industry Lung Cancer Deaths Mesothelioma Cases Observed Expected Observed Deaths, % Acheson et al.27 Gasmasks Cheng and Kong28 Textiles, friction mate rials. and cement Dement et al.29 Textiles Finkelstein30 Electrical conduit pipe Finkelstein31 Automotive Hughes et a).32-' Cement manufacturing Huilan and Zhiming33 8 asbestos factories McDonald etal.34 Friction products McDonald et al.35-30-8 Mining and milling Piolatto et al37 Mining Shiqu et al.38 Mining Weiss39 Paper and millboard Total 6 21 126 6 11 70 65 73 518 22 6 4 922* 4.8* 6.7* 64.0* 3.7 7.9 53.2 15.6** 49.1* 389.7* 19.9 4.3 618.9 1 0 2 1 1-2 1 2 0 28 2 3 0 41.0 0.6 0 0.2 1.0 1.0-1.9 0.4 0 0.4 0.5 4.5 0 0.3 Note. SMR = the standardized mortality ratio, which is the ratio between the observed and expected. The expected number is tor cancer of the lung and pleura combined. "One or two cases of mesothelioma were reported. Only one was included in the totals. 'Results are for workers exposed only to chrysotile from one of two plants studied. The total number of deaths was not reported; thus, the percentage of mesothelioma deaths could not be estimated. ''Observed and expected numbers exclude observations from the asbestos factory. The Shiqu et al. study was not included in the total number of lung cancer cases because expected numbers were not reported.*7 Significantly different from the observed number, P < .05 (two tailed). mesothelioma risk and lung concentra \ received in early years would not be tions of the different fiber types of reflected in the lung burdens measured at asbestos demonstrated a clear relation the time of autopsy. This is of particular ship with amphibole lung burdens but l concern for mesothelioma, which has failed to find a relationship with lung 1 been estimated to tTavgaiateiffi period ot chrysotile concentrations.10-14 McDonald `Trt'feasTZO years.21 For example, assuming et al. reported an association between a 90-day fialPIife and first-order kinetics, mesothelioma and lung concentrations of only, approximately 1/(8 x 1022) of the long (s 8 p.m) chrysotile fibers in univari dose received 20 years earlier would be ate analyses but not in multivariate analy predicted to be present m the lungs at the sis, which controlled for the other fiber timeoTthe autopsy. Hence, lung burdens types.15 Rogers et al. reported a significant \ ofchrysotile may be a poor measure nf rhp associatioiPbetween mesothelioma risk- integrated exposures to chrysotile. and lung concentrations of short chryso-' The high degree of correlation be tile jibers l<10 nml in multivariate tween the lung concentrations of the models and a significant trend for lune different fiber types, which has been concentrations among mesothelioma case noted by several investigators, further and control subjects who had only chrvso- complicates the interpretation of the lung tile detected in their lungsj6 burden analyses.1515-20 Churg reported "The interpretation of the results that the correlation coefficient between from the studies of lung burden is compli the numbers of chrysotile and crocidolite cated by differences in the respiratory fibers in lungs of asbestosis patients was clearance rates of the different forms of .88 (P < .05).23 Rowlands et al. reported asbestos. Experimental studies demon a stronger correlation between cumula strated that chrysotile fibers are cleared tive asbestos exposure and lung fiber far more rapidly from the lungs than are counts for tremolite than between cumula amphibole fibers.17-19 The retention half tive asbestos exposure and lung burdens life of chrysotile in human lungs is of chrysotile in their study of Quebec : unknown, but a half-life of 90 days has miners and millers.8 The high degreejrf been reported in experimental studies of correlation might explain the negative baboons.70 If the half-life for chrysotile is findings in some of the case-control similar for humans and baboons, then studies if amphibole exposures are simply clearly the vast majority of the dose actinjfara'surrogate for integrated life time chrysotile exposure in these studies. As Churg et al. suggested, "Jhjnayi>ejrue that the tremolite serves as a better measureofpast chrysntilp than the chrvsotile itself."19 Finally, studies of fiber counts in extrapulmonary sites raise serious ques tions about the validity of using lung burden studies for assessing mesothe lioma risk. Several investigators reported cases in which short chrysotile fibers were the predominant fiber found in the pleura, pleural plaques, or pleural fibrotic tissue when amphiboles were the predominant fiber found in the lung.22-24-25 These results suggest tnat chrysotile may be preferentially translocated to the pleura and that the fiber counts fniinriiiUhe-lwngmav not accurately reflect the concentra tions found at thejsite for mesothelioma induction. Epidemiologic Studies Lung Cancer There have been 12 retrospective cohort mortality studies of workers who were predominantly exposed to chrysotile asbestos fibers. Results for mortality from lung cancer (and mesothelioma) from the most recent updates of these cohorts are summarized in Table 1. Mortality from lung cancer was greater than experteri in nparly gll nf thp ctiidipc_ rnmhi^iqg the results from these studies, there were 928 observed and 618.9 expected lung cancer deaths, resulting in a pooled standardized mortality ratio for lung cancer of 1.50 (95% confidence interval [Cl] = 1.40, 1.60). The observed excesses of lung cancer mortality did not appear to be explained by differences in cigarette smok ing habits in the studies that had informa tion on tobacco consumption.2823-35-36-40-41 Collectively, these studies provide strong evidence that exposure tnrhrysntile.ashestQS is associated with an excess risk of lung cancer. There is little, if any, evidence to suggest that the excess in lung cancer mortality observed in these cohorts may be attributable to tremolite contamina tion. In fact, this hypothesis is strongly contradicted by the fact that the-lung nfierrgsprmse in the cturiii-c pf popula rity with relatively nnre chrysotile expoures is similar to that in studies ofcohorts Kvith amphibole nr_in""*d erpfrii!r??~Fstimates of the increase in excess relative risk per unit ofexposure (i.e., potency) for lung cancer based on cohort studies by industry and fiber type are presented in Table 2. Variations in risk according to 180 American Journal of Public Health February 1996, Vol. 86. No. 2 Asoesios and Cancer industry type appear to be far more remarkable than variations according to fiber type. The potencies for lung cancer TABLE 2--Estimates of Asbestos Potency for Lung Cancer from Studies with Individual Exposure Estimates, by Industry and Fiber Type risk are similar among the cohorts with pure Chrysotile and mixed exposures in' the textile maustiy and are generally --higher than the potencies observed among Study Industry Fiber Type Excess Relative Risk per Fiber/cc x Yr workgfsTn the mining or asbestos prod ucts industries. The studies of asbestos products industry workers all show very low potencies, with the lowest unit risks Dement et al.29 McDonald etai.12 Peto et al.42 Textiles Mainly textiles Textiles Chrysotile Chrysotile, amosite, crocidolite Chrysotile, crocidolite 0.031 0.017* 0.0156 observed among friction product workers. One study of cement workers, which provided separate analyses for workers exposed to chrysotile asbestos and work McDonald et al.43 de Klerk et al.44 McDonald et al.36 Mining Tremolite Mining and milling Crocidolite Mining and milling Chrysotile 0.013 0.010 0.0006*-6 ers exposed to a mix of chrysotile and crocidolite fibers, produced remarkably similar potency estimates for these two groups.32 Among the studies of miners, lung cancer potency was substantially lower among workers in the Quebec mining industry who were exposed to Henderson and Asbestos products Chrysotile, amosite. 0.002* Enterline45 crocidolite Hughes et al.32 Cement products Chrysotile,* chrysotile,6 0.0071 *0.0076 and crocidolite ,, Berry and Newhouse Friction products Chrysotile 0.00058 etal.46 McDonald et al.34 Friction products Chrysotile 0.00053* chrysotile ores than among crocidolite or tremolite miners. It has been suggested that the high lung cancer mortality observed among A conversion (actor of three fibers per cubic centimeter being equivalent to 1 million particles per cubic foot was assumed. Data are based on results for workers employed after 1951. Slope was estimated by fitting a linear relative risk Poisson regression model to the standardized mortality ratio results repotted by McDonald et al.56 South Carolina textile workers might be explained by exposure to mineral oils.47 However, Dement et al. demonstrated in case-control analyses that the risk of lung ers exposed to commercial chrysotile is different exposure-response relationship cancer observed in this cohort is unrelated compelling, the critical issue is whether for mesothelioma. On the. other hand, to mineral oil exposure.29-48 In addition, this excess may be attributable to trace McDonald and McDonald54 recently re studies of workers exposed to mineral oils ,{contamination by tremolite. All of the have generally not demonstrated an ex 11 asbestos workers studied (Table 1) are cess of lung cancer.49 There is evidence 1 likely to have potential exposures to I* that asbestos fibers in the textile industry. j tremolite, although in minute concentra- were considerably longer than the fibers , tions compared with their chrysotile expo measured in chrysotile mining and milling sures. and other industries.50 Thus, differences In a few studies the percentage of in fiber dimensions.would appear to be a tremolite is known and varies. Contrasting more likely explanation than mineral oil the results from these studies provides exposures for the higher lung cancer rates some information on the plausibility of observed in textile workers. the amphibole hypothesis. Two cases of mesothelioma have been reported among Mesothelioma chrysotile asbestos miners and millers in Zimbabwe, where the chrysotile ores are A total of 45 cases of mesothelioma believed to be free of tremolite contamina (primarily pleural) were reported in the tion.52 Begin et al. noted that although epidemiologic studies of workers who exposure to tremolite may be as much as were predominantly exposed to chrysotile asbestos (Table 1). Although it has gener ally not been possible to estimate ex 7.5 times higher in Thetford than in Asbestos, the incidence of mesothelioma in these two Quebec mining towns was pected numbers of mesothelioma deaths, ! proportional to the size of their work the percentage of deaths due to mesothe / forces.53 He suggested that this fact may lioma may be estimated and compared indicate that tremolite contamination may with background percentages. This per , not be a determinant of mesothelioma centage is 0.3% for all studies combined. 1 risk in Quebec. In the most recent update In contrast, the percentage of deaths due of the study of Quebec miners and millers, to pleural malignancies (most of which McDonald et al.34 presented separate are mesotheliomas) was only 0.02% in the exposure-response analyses for workers United States in 1988.51' at the Thetford and Asbestos mines and Although the evidence of excess mills. There is no indication in their mortality of mesothelioma among work- findings that these two facilities exhibit a ported that the average concentration of tremolite fibers in the lungs of miners was higher in one area of the Thetford mine, which also demonstrated a stronger asso ciation with mesothelioma risk than an other area of the mine. Informative comparisons may also be made between the proportion of deaths from mesothelioma observed in the South Carolina textile workers study and that observed in the Quebec miners and millers study. Based on lung burden studies, Sebastien et al. estimated that the proportion of tremolite in dust was prob ably 2.5 times higher in the Thetford mines of Quebec than in the Charleston textile facility.47 The percentage of deaths due to mesothelioma in the most recent reports was one half as high in the South Carolina textile workers (0.2%) as it was among Quebec miners and millers (0.4%) (Table 1). However, in making this com parison one needs to consider the fact that the incidence of mesothelioma is known to increase exponentially with follow-up time,55 and 72% of the Quebec miners and millers had died,36 compared with 42% of the workers in the South Carolina study,29 in the most recent updates of these cohorts. In the previous February 1996. Vol. 86. No. 2 American Journal of Public Health 181 100 eo e 60 4 Control Amosite Anthophyilite C. Chrysotile R. Chrysotile Crocidolite 40 4 a Cl 20 4 3 Months 6 Months 12 Months Duration of Exposure 24 Months Nate. Data are from Wagnar at al.'7; approximate 95% confidence intervals for a binomial outcome have been added. C = Canadian; R = Rhodesian. FIGURE 1--Lung tumors In rats exposed to 10 mg/m3 concentrations of asbestos for 3,6,12, or 24 months. update of the Quebec miners and millers study, the percentage that had died was 41% and the percentage of deaths due to mesothelioma was 0.2%, which is nearly identical to the percentage of deaths from mesothelioma in the most recent update of the South Carolina textile workers.35 The fact that these percentages are so similar is even more remarkable when it is recognized that the fiber exposure levels were approximately ten times higher in the Quebec miners and millers than in the South Carolina textile workers.47 Thus, comparison of the mesothelioma results from the study of Quebec miners and millers with those from the study of South Carolina textile workers does not provide support for the hypothesis that tremolite exposure explains the mesothelioma ex cess observed in these studies. In contrast to the evidence for lung cancer, there is epidemiologic evidence indicating that exposure to chrysotile may be less potent than exposure to some amphiboles with regards to the induction of mesothelioma. Hughes and Weill esti mated that the risk of mesothelioma was approximately five times lower among workers exposed to chrysotile fibers than among workers with mixed fiber expo sure.56 The percentage of deaths due to mesothelioma among South African asbes tos miners was recently reported to be 4.7% among those exposed to croddolite, which is substantially greater than the percentage of deaths due to mesothe lioma observed in either the Quebec miners (0.4%) or the South Carolina textile workers (0.2%) exposed to pre dominantly chrysotile fibers.57 The per centage of deaths due to mesothelioma was only slightly higher among South African miners exposed to amosite (0.6%) than among the chrysotile-exposed co horts.57 McDonald et al.43 reported that the percentage of deaths due to mesothe lioma was 2.4% among vermiculite miners who were predominantly exposed to tremolite fibers, which is approximately six times higher than the percentage (0.4%) reported in the study of Quebec miners and millers.36 It must be recog nized that the usefulness of these compari sons is limited by our inability to control for potential differences in exposure con centrations, fiber size distributions, and length of observation and are thus difficult to interpret. Nonetheless, the differences in mesothelioma response observed among ^chrysotile- and amphibole (primarily croiridoIite)-exposed workers are so striking ' 'that alternative explanations for these < differences appear unlikely. Toxicologic Studies Lung Cancer Toxicologic studies demonstrated that all_ forms of asbestos can induce lung cancers in experimental animals. For example, the lung tumor response to 3- to 24-month exposures to Union Interna tional Contre le Cancer reference amos ite, anthophyllite. Canadian chrysotile, Rhodesian chrysotile, and crocidolite is shown in Figure l.17 The overlapping 95% confidence intervals suggest that there is no significant differencein potency among the five types of..asbestos .(le., the am phiboles are not systematically more or Davis and co-workers also compared the carcinogenic potencies of chrysotile and amphibole asbestos by exposing rats to 10 mg of amosite, crocidolite, and Zimbabwe chrysotile per m3 for 1 year. These investigators found that chrysotile actually produced mortrlung tumors'than the other fomts of asbestos.5* These results obviously differ from those of Wagner et al.17 and may point to the need to consider differences in fiber length when comparing the potencies of differ ent types of asbestos. Davis et al. noted that 5% of the chrysotile in their study consisted of fibers greater than 20 pm in I length vs 0.5% of the fibers for the j amosite and crocidolite exposures.58 Other ' studies by Davis et al. showed that long-fiber samples of amosite5' and chrysotile60 are considerably more active than j short-fiber samples in inducing lung < tumors. Davis et al. also showed that tremolite,61 crocidolite,58 and long-fiber chryso tile60 produce similar numbers of lung tumors. Figure 2 represents lung tumors due to amosite, crocidolite, chrysotile, or tremolite from the 1-year inhalation stud ies of Davis et al. and Davis and Jones, plotted against the exposure concentra tion in units of fiber count.58-61 Inspection of Figure 2 suggests that the tumor incidence is strongly related to the concen tration of fibers 5 p.m or greater in length, regardless of which type of asbestos is involved. More recently. Coffin et al.62 re ported the results from studies of rats exposed via intratracheal instillation of chrysotile or crocidolite. Although these investigators focused primarily on meso theliomas, it is worth noting that (summed across all dose groups) intratracheal instil lation of chrysotile asbestos produced 182 American Journal of Public Health February 1996. Vol. 86, No. 2 Asbestos and Cancer lung carcinomas in 183% of the animals teste? vs~4~6% for crocidolite.62 Overall, the toxicologic. data_silggest that. chrysotile asbestos is at least as potent, if not more so, as the amphibole forms in the induction oflung tumors on a per-milligram basis. The data shown in Figure 2 further 'suggest that the carcino genic potencies of the various types are similar when the dosage is measured in terms of the number of fibers greater than 5 pm in length, as is customary in epidemiologic studies. Mesothelioma Rats exposed to asbestos by inhala tion also develop mesotheliomas, albeit at a low incidence. Wagner et al.'7 exposed rats to 10 mg/m3 of Union International Contre le Cancer reference asbestos63 for periods of 1 day to 2 years; the mesothe lioma yields were amosite, 0.7%; antho- phyliite, 1.4%; crocidolite, 2.8%; and Canadian chiysotile, 2.9%. No mesothelio mas were observed in control animals or animals exposed to chiysotile from Zim babwe.11 Similarly, Davis et al. and Davis and Jones reported small numbers of mesotheliomas in response to 1-year inhalation exposures to amosite, crocidol ite, Canadian chrysotile, and Zimbabwe chiysotile.5-60 The highest mesothelioma ^ incidence in these studies, 7.5%, was produced by exposure to long-fiber chiyso tile.60 Although the low incidence rates and small numbers of animals make quantitative comparisons uncertain, it cannot be said that these studies provide convincing support for the amphibole hypothesis. ` The mesothelioma-inducing poten tial of asbestos fibers that reach pleural surfaces has also been examined via implantation studies. Union International Contre le Cancer reference amosite, anthophylli'te, crocidolite, Canadian chiysotile, and Zimbabwe chiysotile all produced mesotheliomas' in rats after intrapleural inoculaiion.64 Extensive stud ies by Stanton and co-workers suggest that all long, thin, durable fibers have the potential to induce mesotheliomas after surgical implantation and that fiber dimen- j sions have much more influence on ; mesothelioma yield than any differences that may exist between types of asbestos.65 I However, it is certainly possible that different types of asbestos fibers may have differing probabilities of reaching pleural surfaces when inhaled into the lungs. Overall, the implantation studies suggest that chrysotile asbestos does have the potential ~to induce mesothelioma, but 60 50 A | 40 3 I- cn 30 l. L 10 A A A 0 ........ 0 1000 2000 3000 Control Amosite A Chrysotile Crocidolite Tremolite 4000 5000 6000 Fibers per ml Note. Data are from Davis at al. and Davis and Jones.5*-*' Controls are the pooled control animals from all four studies.- ' FIGURE 2--Lung tumors in rats exposed to 10 mg/m1 concentrations of crocldollte, amoalte, chrysolite, or tremollte for 1 year. these studies do not resolve the question 'ofwhether'ornaTchrysotile is less potent in this regard than the amphibole forms. Coffin et al. recently reported that both chrysotile and crocidolite produce mesotheliomas when administered intratracheally.62 No consistent dose-response relationship was observed in these experi ments, but (summing across all dose groups) chiysotile asbestos produced me sotheliomas in 9.5% of the animals vs 5.1% for crocidolite. This suggests that chrysotile may have greatermesotheliomainducine potential than crocidolite on a per-milligram basis. However, the chiyso tile preparation used in this experiment contained more fibers per milligram than the crocidolite preparation, as well as a larger proportion of long fibers. If the experimental exposures are expressed on the basis of the number of fibers greater than 5 pm in length, it appears that crocidolite produced nearly 12 times more mesotheliomas per fiber than chiysotile. It should be noted that the fiber prepara tions in the Coffin et al. experiments consisted primarily of short fibers, with median fiber lengths on the order of 1 |im for both chrysotile and crocidolite. If short fibers do in fact have some mesotheliomainducing potential, the attribution of all mesotheliomas to the small fraction of the fibers that were greater than 5 pm in length may lead to an exaggerated estimati the difference in potency of crocHi. me chiysotile. In addition, reli ance on the quantitative responses in this study should probably be limited due to the lack of dose-response. Nevertheless, these data do provide some support for the hypothesis that chrysotile may have lower mesothelioma-inducing potential than the amphibole forms of asbestos. Mechanistic Studies It has been hypothesized that the cytotoxic, genotoxic, and proliferative ef fects of asbestos are in part mediated by the production of reactive oxygen species released by alveolar macrophages in re sponse to engulfment of long fibers and February 1996, Vol. 86, No. 2 American Journal of Public Health 183 mat this process may be catalyzed by iron on the fiber surface. Furthermore, it has ( been suggested that the needle-like con figuration, durability, and increased iron . content of crocidolite render it more ' pathogenic than either amosite or chryso- I tiie.66 Experimental support for this hy pothesis is primarily derived from in vitro studies, which suggest that iron could potentially act as a source of free radicals, an inhibitor of tumoriridal defense mecha nisms, and a nutrient for unrestricted tumor cell replication.67 However, com parison of the carcinogenic potencies of ' fibers in the rat in vivo does not support the hypothesis that carcinogenic potency is related to iron content. As discussed above, Wagner et al.n observed similar numbers of tumors in rats with crocidol ite, amosite, and chrysotile, even though these fibers have an elemental iron con tent of 40%, 28%, and less than 1%, respectively.67 The nonasbestos mineral erionite does not include iron as a constituent68 but is nonetheless a potent mesothelioma inducer in rats.69 Silicon carbide "whiskers," with an iron content of essentially zero, induce pleural tumors , in rats after intrapleural implantation.65 | Therefore, no obvious correlation be ] tween iron content and carcinogenicity is < apparent in the rat. I Summary Our review of both the toxicologic and epidemiologic literature strongly sup ports the view that occupational exposure to chrysotile asbestos is associated.with.an increased risk of both lung cancer and mesotheliomi. The hypothesis that these observations may be attributable to trace amounts (< 1%) of tremolite contamina tion may seem to be primarily of academic interest, because chrysotile exposures in workers and the public are also contami nated with tremolite. However, the per centage of tremolite has been reported to range from 0.5% to 6.9% in one analysis of eight commercial chrysotile asbestos i samples.6 and it has been suggested that chrysotile from Zimbabwe70 and other countries may be free of contamination by amphiboles. Hence, the amphibole hy1 pothesis may be of some public health relevance. In our view, the currently available scientific literature does not provide per suasive evidence for the hypothesis that tremolite contamination explains the mesothelioma~excesses observed in the stud ies of chrysotile-exposed workers. The primary evidence for this hypothesis comes from pathologic studies in which lung burdens were measured. However, inter pretation of these studies is hampered by the fart that-chiymtile lung burdens are a poor reflection of integrated exposures and the fact that chrysotile exposure is highly correlated with lung burden_of4he amphiboles (e.g., tremolite). In addition, the patlenrof asbestos fiber deposition in the lung does not appear to be consistent with the pattern of deposition in the target tissue (i.e., pleura). The previously reviewed empirical data from toxicologic studies and comparisons of mesothelioma mortality and lung cancer mortality be tween epidemiologic studies with differ ing levels of tremolite contamination do not provide support for this hypothesis. Mechanistic arguments that have been made to support the amphibole hypoth esis, which are based on in vitro studies of | iron content, appear to be contradicted by the lack of correlation between iron content and carcinogenic potency ob served in experimental studies. Whether chrysotile asbestos is less potent than the amphibole forms of asbestos is a question that has not yet been fully resolved. There is currently vety little toxicologic evidence to support this hypothesis. There is evidence from epidemiologic studies that chrysotile may be less potent for mesothelioma induction than crocidolite. The proportion of deaths due to mesothelioma are strikingly lower in chrysotile-exposed miners and millers than in crocidolite miners. There is absolutely no epidemiologic or toxicologic evidence-to-support the- argumenL-that chrysotile asbestos is any less potent than other forms of asbestosforinducing lung cancer. It should be recognized that compari sons of the potency of the different forms of asbestos are severely limited by uncon trolled differences in the bivariate distribu tion of fiber length and diameter (i.e., fiber dimensions). Experimental studies clearly demonstrated that fiber dimen sions are a critical component of the carcinogenic potency of fibers.65 This concern applies to most of the toxicologic studies in which exposure is determined on an equal mass basis and is particularly pertinent to the epidemiologic investiga tions. Historic exposures in most of the epidemiologic investigations were based on impinger samples that assessed the number of fibers, and conversion factors were applied to estimate the number of fibers longer than 5 pm. Concerns have been raised about the accuracy of these conversion factors and the potential im pact of associated errors on the assess ment of risk.71 The current Occupational Safety and Health Administration (OSHA) method counts asbestos fibers that are longer than 5 pm and that have a length-to-diameter ratio of at least 3 to 1. This method implicitly assumes that fibers less than 5 pm in length are not carcino genic and that all fibers greater than 5 pm in length are of equal carcinogenic po tency. These assumptions are clearly inconsistent with thF experimehfal data and most likely result in substantial misclassification of exposure in the epide miologic studies. Policy Implications The American Conference of Gov ernmental Industrial Hygienists and sev eral countries (e.g., the United Kingdom) have adopted less restrictive standards for chrysotile asbestos than for the other forms of asbestos.72 In our view, the currently available scientific evidence does not provide sufficient support for develop ing separate standards for the different forms of asbestos. As this article docu ments, the scientific evidence for the amphibole hypothesis is still tenuous. Furthermore, the fact remains that in practice workers in this country and other countries are not exposed to pure chryso tile, but rather to a mixture of chrysotile, tremolite, and other forms of asbestos. Thus, it is highly impractical to consider setting separate standards for the differ ent forms of asbestos. Finally, even if one accepts the argument that chrysotile asbes tos does not induce mesothelioma (which we do not), the risk of lung cancer (and asbestosis) can not be dismissed, and chrysotile appgarsJo-be-jusi-as-potent a lungj^rcinogen-js-the-otheF-forms of asbestos. It is noteworthy that the risk of lung cancer'is of greater concern than the risk of mesothelioma because in most studies there are at least two excess lung cancers for every mesothelioma observed (see Table 1). There is also the additional concern of asbestosis risk, which was not considered in this article but dearly adds to the risk associated with chrysotile exposure. Therefore, given the clear evidence of a lung cancer risk, the lack of compel ling evidence for the amphibole hypoth esis, and the fact that workers are gener ally exposed to mixture of fiber types, we believe that it is prudent policy to treat chiysotile asbestos with virtually the same level of concern as the amphibole forms of asbestos. This view is consistent with the 184 American Journal of Public Health February 1996, Vol. 86, No. 2 Asbestos and Cancer ss- past National Institute for Occupational concentration and relative risk of mesothe factories. Can Med Assoc J. 1989:141:327 iaJ Safety and Health Administration recom lioma. Cancer. 1991;67:1912-1920. 330. on mendation and the recently revised OSHA 17. Wagner JC, Berry G, Skidmore JW, Tim brel! V. The effects of the inhalation of 32. Hughes JM, Weill H. Hammad YY. Mortal ity of workers employed m two asbestos ;rs standard to limit occupational exposures asbestos in rats. BrJ Cancer. 1974:29:252 cement manufacturing plants. Br J Ind for all forms of asbestos to 0.1 fiber/cc. 269. Med. 1987:44:161-174. 18. Middleton AP, Beckett ST, Davis JMG. A 33. Huilan Z, Zhiming W. Study of occupa study of the short-term retention and tional lung cancer in asbestos factories in References clearance of inhaled asbestos by rats, using China. BrJ Ind Med 199350:1039-1042. m 1. Pigg BJ. The uses of chrysotile. Ann Occup Hyg. 1994:38:453-458. U.I.C.C. standard reference samples. In: Walton WH, ed. Inhaled Particles IV. 34. McDonald AD. Fry JS. Woolley AJ. McDonald JC. Dust exposure and mortal O- 2. Lemen RA. Bingham E. A case study in Edinburgh, Scotland: Institute of Occupa ity in an American chrysotile asbestos iy ta al avoiding a deadly legacy in developing countries. Toxicol lnd Health. 1994:10(1/2): 59-87. 3. Mossman BT. Bignon J, Com M, Seaton tional Medicine; 1975:247-258. 19. Churg A Wright JL, Vedel S. Fiber burden and patterns of asbestos-related disease in chrysotile miners and millers. Am Rev friction products plant. Br J Ind Med. 1984;41:151-157. 35. McDonald JC. Liddell FDR. Gibbs GW, Eyssen GE. McDonald AD. Dust exposure A, Gee JBL. Asbestos: scientific develop RespirDis. 1993;48:25-31. and mortality in chrysotile mining. 1910-- ments and implications for public policy. 20. Rendall RE. Retention and Clearance of 1975. BrJ lnd Med. 1980:37:11-24. Science. 1990:24:294-301. Glass Fibers and Different Varieties of 36. McDonald JC, Liddell FDK, Dufresne A. 4. Dunnigan. J. Unking chrysotile asbestos Asbestos by the Lung. Johannesburg. South McDonald AD. The 1891-1920 birth co with mesothelioma. Am .//ndMed 1988; 14: Africa: University of Witwatersrand; 1988. hort of Quebec chrysotile miners and 205-209. Dissertation. millets: mortality 1976-88. Br J lnd Med. 5. Pooley FD. Clark NJ. Quantitative assess 21. Seiikoff IJ, Hammond EC, Seidman H. 1993:50:1073-1081. ) r ment of inorganic fibrous particulates in dust samples with an analytical transmis sion electron microscope. Ann Occup Hyg. 1979;22:253-271. Mortality experience of insulation workers in the United States and Canada, 1943 1976. Ann N YAcad Set 1979;330:91-116. 22. Sebastien P, Janson X, Gaudichet A, 37. Piolatto G, Negri E, LaVecchia C. Pira E, Decarli A, Peto J. An update of cancer mortality among chrysotile asbestos miners in Baiangero. Northern Italy. BrJ lnd Med. r 6. Addison J, Davies LST. Analysis of am- Hirsch A, Bigon J. Asbestos retention in 1990:47:810-814. phibole asbestos in chrysotile and other minerals. Ann Occup Hyg. 1990:34:159 human respiratory tissues: comparative measurements in lung parenchyma and in parietal pleura. In: Wagner JC, ed. Biologi 38. Shiqu Z, Yongxian W, Fusheng M, Hongshuen M, Wenzhi S, Zhenhuan J. Retro spective mortality study of asbestos work ( 175. 7. Pooley FD. An examination of the fibrous mineral content of asbestos lung tissue form the Canadian chrysotile mining indus try. Environ Res. 1976;12:281-298. cal Effects ofMineral Fibers. Lyon, France: International Agency for Research on Cancer; 1980:237-246. 23. Churg A. Asbestos fiber content of the lungs in patients with and without asbestos ers in Laiyuan. In: Proceedings of the VII International Pneumoconioses Conference, Part II; August 23-26,1988: Pittsburgh, Pa. National Institute for Occupational Safety and Health: 1990:1242-1244. DHHS publi 8. Rowlands N, Gibbs GW, McDonald AD. airways disease. Am Rev Respir Dis. 1983; cation 90-109, part II. Asbestos fibres in the lungs of chrysotile miners and millers--a preliminary report. 127:470-473. . ... 24. LeBouffant L, Martin JC, Duyif S, Daniel 39. Weiss W. Mortality of a cohort exposed to chrysotile asbestos. J Occup Med. 1977;19: Ann Occup Hyg. 1982;26:411-415. H. Structure and composition of pleural 737-740. 9. Churg A. Wamock ML. Asbestos fibers in plaque. In: Bogovski P, Gilson JC, Timbrell 40. Dement JM. Harris RL Symons MJ. Shy the general population. Am Rev RespirDis. V, Wagner JC, eds. Biological Effects of CM. Exposures and mortality among 1980:122:669-678. Asbestos. Lyon, France: International chrysotile asbestos workers, part I: expo 10. Jones JSP, Roberts GS. Pooley FD, et al. Agency for Research on Cancer; 1973:249 sure estimates. Am J Ind Med. 1983:4:399 The pathology and mineral content of 257. Scientific Publication No. 8. 419. lungs in cases of mesothelioma in the 25. Dodson RF, Williams MG, Corn CJ, 41. Dement JM, Harris RL Symons MJ, Shy United Kingdom in 1976. In: Wagner JC, Brollo A. Bianchi C. Asbestos content of CM. Exposures and mortality among ed. Biological Effects of Mineral Fibers. lung tissue, lymph nodes, and pleural chrysotile asbestos workers, part 11: mortal Lyon. France: International Agency for plaques from former shipyard workers. Am ity. Am J Ind Med. 1983;4:421-433. Research on Cancer; 1980:188-199. Scien Rev Respir Dis. 1990;142:843-847. 42. Peto J, Doll R. Hermon C. Binns W, tific Publication No. 30. 11. Wagner JC. Pooley FD. Berry G, et al. A 26. Kohyama N, Suzuki Y. Analysis of asbestos fibers in lung parenchyma, pleural plaques, Clayton R, Goffe T. Relationship of mortal ity to measures of environmental asbestos pathological and mineralogical study of and mesothelioma tissues of North Ameri pollution in an asbestos textile factory. Ann asbestos-related deaths in the United King can insulation workers. Ann NY Acad Sci. Occup Hyg 1985;29:305-355. dom in 1977. Ann Occup Hyg. 1982:26:423 1991;643:27-52. 43. McDonald JC, McDonald AD, Armstrong 431. - 27. Acheson ED, Gardner MJ, Pippard EC, B, Sebastien P. Cohort study of mortality of 12. McDonald AD. McDonald JC. Pooley FD. Grime LP. Mortality of two groups of vermiculite miners exposed to tremolite. Br Mineral fibre content of lung in mesothe- women who manufactured gas masks from J Ind Med. 1986:43:436-444. lial tumours in North America. Ann Occup chrysotile and crocidolite asbestos: a 40- 44. de Klerk NH. Armstrong BK, Musk AW, Hyg. 1982:26:417-422. year follow-up. BrJ Ind Med. 1982:39:344 Hobbs MST. Cancer mortality in relation 13. Gaudichet A, Janson X. Monchaux G. et 348. ' to measures of occupational exposure to al. Assessment by analytical microscopy of 21j. Cheng W, Kong J. A retrospective mortal crocidolite at Wittenoom Gorge in West the total lung fibre burden in mesothe ity cohort study of chrysotile asbestos ern Australia. BrJ lnd Med. 1989;46:529- lioma patients matched with four other products workers in Tianjin 1972-1987. 536. pathological series. Ann Occup Hyg. 1988; Environ Res 1992;59:271-278. 45. Henderson VL, Enterline PE. Asbestos 32(suppl 1 ):2I3--223. 29. Dement JM. Brown DP. Okun A. Mortal exposure: Factors associated with excess 14. Wagner JC. Berry G. Pooley FD. Mesothe ity among chrysotile asbestos textile work cancer and respiratory disease mortality. liomas and asbestos type in asbestos textile ers: Cohort mortality and case-control Ann N YAcad Sci. 1979:117-126. workers: a study of lung contents. BrMedJ. 1982:285:603-606. 15. McDonald JC. Armstrong B. Case B, et al. Mesothelioma and asbestos fiber type: evidence from lung tissue analyses. Cancer. 1989:63:1544-1547. 16. Rogers AJ. Leigh J, Berry G, Ferguson DA, Mulder HB, Ackad M. Relationship between lung asbestos fiber type and analyses. Ann Occup Hyg. 1994;38:525-532. 30. Finkelstein MM. Mortality among employ ees of an Ontario factory that manufac tured construction materials using chryso tile asbestos and coal tar pitch. Am J lnd Med. 1989;16:281-287. 31. Finkelstein MM. Mortality rates among employees potentially exposed to chryso tile asbestos at two automotive parts 46. Berry G, Newhouse ML. Mortality of workers manufacturing friction materials using asbestos. BrJ Ind Med. 1983:40:1-7. 47. Sebastien P. McDonald JC, McDonald AD, Case B, Harley R. Respiratory cancer in chrysotile textile and mining industries: exposure inferences from lung analysis. Br J Ind Med. 1989:46:180-187. 48. Dement JM. Carcinogenicity of chrysotile February 1996. Vol. 86, No. 2 American Journal of Public Health 185 asbestos: a case control study of textile workers. CellBiol TaxicoL 1991;7:59-65. 49. Tolbert P, Eisen E, Pothier LJ, Mooson RR, Hallock MF, Smith TJ. Mortality studies of machining-fluid exposure in the automobile industiy, II: risks associated with specific fluid types. Scand J Work Environ Health. 1992;18:351-360. 50. Dement JM and Wallingford KM. Com parison of phase contrast and electron microscopic methods for evaluation of occupational asbestos exposures. Appi Occup Environ Hyg. 1990^^42-247. 51. Vital Statistics ofthe UnitedStates, 1989, Vol II--Mortality, Part B. Hyattsville, Md: National Center for Health Statistics; 1992. DHHS publication PHS 92-1102. 52. Cullen MR and Balpyi RS. Chrysotile asbestos and health in Zimbabwe, I: analy sis of miners and millers compensated for asbestos-related diseases since indepen dence (1980). Am J Ind Med. 1991;29:161- 169. 53. Begin R, Gauthier J, Desmeules M, Os- tiguy G. Work-related mesothelioma in Quebec, l967-l990.AmJlndMcd 1992;22: 531-542. 54. McDonald JC, McDonald AD. Chrysotile, tremolite and mesothelioma. Science. Feb ruary 10,1995;267:775-776. 55. Peto J, Seidman H, Selikoff U. Mesothe lioma mortality in asbestos workers: impli cations for models of carcinogenesis and risk assessment. BrJ Cancer. 1982;45:124- 135. 56. Hughes JM, Weill H. Asbestos Exposure- Quantitative Assessment of Risk. Am Rev RespirDis. 1986;133:5-13. 57. Sluis-Cremer GK, Liddell FDK, Logan WPD, Bezuidenhout BN. The mortality of amphibole miners in South Africa, 1946 m. BrJ lnd Med. 1992:49:566-575. 58. Davis JMG, Beckett ST, Bolton RE, Collins P, Middleton AP. Mass and num ber offibres in the pathogenesis of asbestos- related lung disease in rats. Br J Cancer. 1978;37:673-688. 59. Davis JMG, Addison J, Bolton RE, Donald son K, Jones AD, Smith T. The pathogenic ity of long versus short fibre samples of amosite asbestos administered to rats by inhalation and intraperitonea! injection. Br JExp Pathol 1986;67:415-430. 60. Davis JMG, Jones AD. Comparisons of the pathogenicity of long and short fibres of chrysotile asbestos in rats. BrJ Exp Pathol. 1988;69:717-737. 61. DavisJMG, Addison J, Bolton RE, Donald son K, Jones AD, Miller BG. Inhalation studies on the effects of tremolite and brucite dust in rats. Carcinogenesis. 1985;6: 667-674. 62. Coffin DL, Cook PM, Creason JP. Relative mesothelioma induction in rats by mineral fibers: comparison with residual pulmo nary mineral fiber number and epidemiol ogy. InhalTadcoL 1992;4:273-300. 63. Timbrel! V, Gibson JC, Webster I. UICC standard reference samples of asbestos. Ini J Cancer. 1968;3:406-408. 64. WagnerJC, Berry G.TimbrellV. Mesothe- liomata in rats after inoculation with asbestos and other materials. BrJ Cancer. 1973;28:173-185. 65. Stanton MF, Layard M, Tegeris A, et al. Relation of particle dimension to carcino genicity in amphibole asbestoses and other . fibrous minerals.JNatl CancerInst. 1981:67: 965-975. 66. Mossman BT.. Mechanisms of asbestos carcinogenesis and toxicity: the amphibole hypothesis revisited. BrJ ind Med. 1993:50 673-676. Utter. 67. Weinberg ED. Association of iron with respiratory tract neoplasia. J Trace Elem Exp Med 1993;6:117-123. 68. fSrk-OlhmerEncyclopedia ofChemical Tech nology-. 3rd ed. Vol 15. New York, NY: John Wiley & Sons: 1981:639. 69. Davis JMG. Mineral fibre carcinogenesis: experimental data relating to the impor tance offibre type, size, deposition, dissolu tion, and migration. In: Bignon J, Peto J, Saracci R, eds. Non-occupational Exposure to Mineral Fibers. Lyon. France: Interna tional Agency for Research on Cancer; 1989:33-45. 70. Baloyi R. Exposure to Asbestos among Chrysotile Miners. Millers and Mme Resi dents andAsbestosis in Zimbabwe. Helsinki, Finland: University of Kuopio; 1989. Disser tation. 71. Peto J. Fibre carcinogenesis and environ mental hazards. In: Bignon J, Peto J, Saracci R, eds. Non-occupational Exposure to Mineral Fibres. Lyon, France: Interna tional Agency for Research on Cancer, 1989:457-470. 72. Threshold Limit Values for Chemical Sub stances and Physical Agents and Biological Exposure Indices. Cincinnati, Ohio: Ameri can Conference of Governmental Indus trial Hygienists; 1994-1995. 186 American Journal of Public Health February 1996, Vol. 86, No. 2 agpxtSOn'tAmJPubic Heath. 1996;86253- 256. 2. Escobedo LG, Peddioord JP. Smoking prevalence in US birth cohorts: the influ ence of gender and education. Am J Public Health. 1996;86:231-236. 3. DiFranza JR, Savageau JA, Aisquhh BF. Youth access to tobacco: the effects of age, gender, vending machine locks, and "It's the Law" programs. Am J Public Health. 1996;86:221-224. ' 4. Food and Drug Administration. Regula tions restricting the sale and distribution of cigarettes and smokeless tobacco products to protect children and adolescents. Fed eral Register. 1995;60(August 11):41313- 41375. 5. Food and Drug Administration. Proposed rule analysis regarding FDA's jurisdiction over nicotine-containing cigarettes and smokeless tobacco products. Federal Regis ter. 1995;60(August 11):41454-41787. 6. Staff Report of the Cigarette Advertising Investigation. Washington, DC US Federal Trade Commission; 1981. 7. Institute of Medicine. Growing Up Tobacco Free; Preventing Nicotine Addiction in Chil dren and Youths. Washington, DC Na tional Academy Press; 1994. 8. Carol J. It's a good idea to criminalise purchase and possession of tobacco by minors--NOT!*. Tobacco Control 1992;1: 296-297. 9. Cismoski J. Blinded by the light: The foQy of tobacco possession laws against minors. WisMedJ. 1994;93:591-597. 10. Jason LA, Ji PY, Anes MD, Birkhead SH. Active enforcement of cigarette control laws in the prevention of cigarette sales to minors.JAMA. 1991;266:3159-3161. 11. DiFranza JR, Carlson RR, Caisse REJ. Reducingyouth access to tobaoook Tobacco Control 1992:1:58. 12. Hinds MW. Impact of a local ordinance banning tobacco sales to minors. Pubic Health Rep. 1992;107:356-358. 13. Lopez R, Tucker B, Childs R, et aL Reducing tobacco access to teens: Arizona pilot projects. In: Abstracts, 123rd Annual Meeting of the American Public Health Association; October29-Novembcr2,1995; San Diego, Calif. Sesskm 2277. 14. Skolnick A. Court orders governor to restoreanti-nnoking media campaign fund ing.JAMA. 1992267:2721-2723. 15. Begay ME, Traynor MP, Glantz SA. The tobacco industry, state politics, and to bacco education in California.AmJPubic Health. 1993;83:1214-1221. 16. Begay ME, Traynor MP, Glantz SA. The Twilight of Proposition 99: Rcautkoriemkm of Tobacco Education Programs and To bacco Industry Political Expenditures In 1993. San Francisco, Calif: Institute for Health PolicyStudies, Universityof Califor nia, San Francisco; 1994. 17. Skolnick A. Antitobacco advocates light Illegal' diversion oftobacco control money. JAMA. 1994;271:1387-1390. 18. Aguinaga S, Macdonald H, Traynor M. Begay M, Glantz S. Undermining Papular Government Tobacco Industry Pobtical Ex penditures in California, 1993-1994. San Francisco, Calif: University of CilHhnda Institute for Health Policy Studies; 1995. 19. Skolnick A. Judge rules diversion at anti smoking money illegal. JAMA. 1995273: 610-611. 20. Glantz S. Removing the incentive to sefl kids tobacco.JAMA.. 1993;269:793-794. 21. US Occupational Safety and Health'Admin' istration. Indoor Air Quality (Proposed ' Rale). Federal Register. 1994;59(April 5): . 15966-16039. 22. Fierce JP, Evans N, Farkas AJ, et al. Tobacco Use in California:An Evaluation of ' the Tobacco Control Program, 1989-1993. San Diego, Calif: University of California, San Diego; 1994. 23. Stillman F, Becker D, Swank R, et al. Eliding smoking at the Johns Hopkins Medical Institutions: an evaluation of ` n*inc prevalence and indoor pollution. JAMA. 1990264:1565-1569. 24. WoodruffT.RosebrookB, Pierce J, Glantz S. Lower levels of cigarette consumption found in smoke-free workplaces in Califor aia. Arch Intern Med 1993;153:1485-1493. 25. Khme S, Krista] AR, White E, Hunt J. Work-site smoking policies: their popula tion impact in Washington State. Am J PubBc Health. 1993;83:1031-1033. 26 Brenner H, Fleischle B. Smoking regula tions at the workplace and smoking behav ior a study from southern Germany. Prev Med. 199423230-234. 27. Brigham J, Gross J, Stitzer ML, Felch LJ. Effects of a restricted work-site smoking . policy on employees who smoke. Am J Pubic Health. 1994;84:773-778. 28. Jeffery RW, Kelder SH, Forster JL, et al. Restrictive smoking policies in the work place: effects on smoking prevalence and cigarette consumption. Prev Med. 199423: 78-82. 29. Borland R, Owen N. Need to smoke in the context of workplace smoking bans. Prev Med. 19952456-60. 30. Patten CA, Gilpin E, Cavin S, Pierce JP. Workplace smoking policy and changes in smoking behavior in California: a sug gested association. Tobacco Control 1995:4: 36-41. Annotation: The Amphibole Hypothesis ofAsbestos-Related Cancer-- Gone but Not Forgotten It would hardly come as a revelation on these pages that legal agendas have often and somewhat unpredictably inter posed their vagaries on environmental health practice. The effort to control the staggering asbestos hazard provides one of the dearest examples. On the positive side, manufacturers' recognition of the potential for direct product liability led, in the 1970s, to the explosive growth of occupational medicine clinks, enhanced interest in environmental health among worker groups, and rapid substitution of alternative products for most asbestos uses. Less valuable may have been some of the intense public and private efforts to remove all remaining asbestos, paradoxi cally risking further exposure and involv ing costs that were larger than the gross domestic product of some asbestos exporting countries and that could have possibly been put to better public health use. However, there has been no mote perverse consequence of this frenzied litigation than the incursions of liability issues into sdentific research and betiefo. The matter ofdifferential pathogenicityof differing sources of asbestos, eloquently discussed by Stayner and his colleagues1 in this issue of the Journal, serves as a disturbing case in point The underlying idea for the "am phibole hypothesis"--the theory that only amphibole fibers (e.g., croccidolite, tmosite, and trcmolite), and not serpentine (mainly chrysotile) asbestos can cause cancer--arose because of two important observations in the 1970s: (1) serpentine fibers are cleared much foster than amphiboles in the human lung; and (2) several cohorts ofchrysotile-cxpoKdwofkers were reported to have lower (albeit still elevated) rates of hmg cancer and mesothelioma- than groups with am phibole or mixed exposures previously studied. Because many naturally occur ring chrysotile deposits were known to be contaminated by the amphibole trcmolite (which might explain the modest eleva tions of risk among those exposed to dnyiotiie), the scientific concept ap peared initially attractive. The ramifica tions for future scientific inquiry rcgardfav fiber carcinogenesis and the public health ramifications were obvious and important. No sooner had this theory been articulated, however, than evidence emerged to undermine it. The elegant ride-by-side studies of McDonald and colleagues23 confirmed by Dement4 dem onstrating astronomical rates of lung caaoer among textile workers exposed Ufort Kale. See related article by Stayner et aL(p 179) ia this issue. 158 Americas Journal ofPublic Health February 1996, Vol. 86, No. 2 Editorials, AMoCatMc,aad14tfcs only to (contaminated) chiysotile prod ucts, with far lower rates among friction products workers (workers making brake linings, clutch plates, and other friction products) exposed to asbestos from the same source, overshadowed the most important observation on which the amphibole hypothesis had been based. What doubt could there be that some other exposure characteristic, such as fiber length, formed the basis for differentia] lung cancer risk? The idea that all of the health consequences associated with chiysotile could be attributed to trace tremoiite fiber contamination proved in consistent with the veiy modest health risks demonstrated in other groups more heavily exposed to tremoiite.5 Nor did animal studies of the different fiber types offer even a shred of support for the amphibole hypothesis, the fibers having largely similar effects in experimental animal models.6'7 By the mid 1980s, what was left to lend scientific support to the amphibole hypothesis? There remained the interest ing and as yet unexplained observation that workers and others exposed to chiysotile materials experience lower rates of mesothelioma than those who had been exposed to various amphiboles. Although, as summarized by Stayner et al.,1 reason able observers have disagreed regarding the extent of this difference, most have concluded that there likely is some differ ence that fiber type alone may explain. Since we still know so little about the mechanisms of carcinogenesis in lung epithelium and mesothelial tissues, this observation may yet prove scientifically very important. Beyond this, there re mained only the curious observation, now confirmed in yet additional studies,8 that chiysotile fibers are underrepresented in the lungs of chrysotile-exposed workers dying of asbestos-related diseases. For those who remained unwilling or unable to accept the most obvious inter pretations, new hypotheses and explica tions were necessary.9 To explain the spectacular excess risk of lung cancer among chiysotile textile workers, it was theorized that the mineral oil coating of fibers, not the asbestos per se, was the cause, a concept without empiric evidence or even theoretical appeal, given the lew level of carcinogenicity of these oils. To obviate the animal evidence of chiysotile carcinogenicity, it was argued that these experiments are irrelevant to humans because of the proven more rapid clear ance of chiysotile and the obviously much longer latent interval in humans between exposure and disease. While these plau sible alternative interpretations may hold certain scientific interest, they hardly seem adequate pillars for the "amphibole hypothesis," officially introduced in 1990lQ already several years after scientifically it had all but died.11 Without addressing the more cynical question regarding how this hypothesis was proffered so prominently and so late in the scientific day, we cannot ignore the impact As documented by Stayner et al.,1 several countries have adopted differen tial standards for asbestos based on fiber type, including decisions to continue im portation and use of "safe" asbestos by some. Many ptheiwise well-informed phy sicians and scientists worldwide continue to believe that chiysotile is a "good" form of asbestos, if only it could be separated from contamination. And judging from personal observations, many victims of this "good" form have had compensation claims controverted or denied because they were exposed to "only" chiysotile. To be sure, the amphibole hypothesis has raised many crucial issues and served well to focus research on the still partially unanswered question of why different exposed papulations have experienced such different rates of the major asbestos diseases. But with the now overwhelming evidence that fiber type poorly explains most of that difference, at least in regards to lung cancer, continued reference to the hypothesis serves only to distort debate and confuse the audience. To paraphrase Shakespeare's Julius Caesar, "The evil that theories do lives after them; the good is oft interred with their banes." Mark R. Cullen Yale Universitj School cfMediant New Haven, Conn References 1. Stayner LT, Dankovic DA Lemen RA Occupational exposure to chiysotile asbes tos and cancer risk: a review of the amphibole hypothesis. Am J Public Health. 1996;86:179-186; Z McDonald AD; Fty JS, Woolley AJ, McDonald JC Dust exposure and mortal ity in an American chiysotile asbestos friction products plant. Br J Ind Med. 1984;41:151-157. 3. McDonald AD, Fry JS, Woolley AJ, McDonald JC Dust exposure and mortal ity in an American chiysotile textile plant BrllndMcd. 1983;37:11-17. 4. Dement JM, Harris RL, Symons MJ, Shy C Estimates of dose response for respira tory cancer among chiysotile asbestos textile workers. Ann Occun Hyg 196226: 869-887. 5. McDonald JC McDonald AD, Armstrong B, Scbastien P. Cohort study ofmortality of vermiculite minets exposed to tremoiite. fir JIndMed. 1986;43:436-444. 6. Wagner JC Bcny G, Skidmore JW, Timbrel] V. The effects of the inhalation of asbestos in rats. BrJ Cancer. 197429-.252 269. 7. Davis JMG, Beckett ST, Bolton RE, Collins P, Middleton AP. Miss and num berof fibres in the pathogenesis ofasbestos- related lung disease in rats. Br 1 Cancer. 1978;37:673-688. 8. ChutgA WrightJL, VedelS. Fiberburden and patterns of asbestos-related disease in chiysotile miners and millers. Am Rev RespirDis. 1993;48:25-31. 9. Sebastian P, McDonald JC McDonald AD, Case B, Harley R. Respiratory cancer in chiysotile textile and mining industries: exposure inferences from lung analysis. Br J Ind MetL 1989;46:180-187. 10. Mossman BT, Bignon J, Corn M, Seaton A Gee JBL. Asbestos: scientific develop ments and implications for public policy. Science. 199024:294-301. 11. Cullen MR. Controversies in aUwirv, related lung cancer. Occup Med State An Rev. 1987*259-272. Topics for Our Times: Don't Inhale--Reflections on Garbage! For more than a centuiy, garbage removal has been central to the contro versy of how best to organize public health services. Throughout the 19th centuiy in New York City, Tammany Hall politi cians, generally turning to private contrac tors, found in garbage removal a fertile field for kick-back and graft. Because of the failure, in part, of private contractors to clean the city's streets effectively, sanitation was made an activity of munici pal government. Beginning in the early 1970s, however, academics and policy makers have called for the dismantling of public sanitation departments and the provision of "market incentives" to pri vate haulers. . A recent exhibition at the New York Public Library, Garbage: The History and Politics of Trash in New York City, should cause public health practitioners and February 1996, Vol. 86, No. 2 American Journal of Public Health 159 - '>' ,.' vj'i," , -.' *V"( 111^ >, ' , a> / * t <? * 'y.v-i ,''/k',' >/ * ft > 'k *';V t'v, : iS- t t( t i's'(yx^` ** <. jt h/ <* V<t *t f > i 1 fr fS v ,t ,' i \* . ., y .' fM i /fVc-l->rV'y^ -! * ft r'if-'A-'-I'-y *t f ........>- <" ' / ^" ::r.- `t< ' ''n ` >' c :>.?;.*/yt.' > ' T/ ft 4} ^ l r~ > ^7 yv,t' ............?....>.- 3-0 ' V V ) f fC t5 * > I*ff^ ., jA*, Y r1 `j l..,.':..., ,<(.v. ,. 1 * * ^ *f $*V .":...... ,* X / <v i ^ - } ,> >.. 4; *\^v v_ > ^ i 1 ' 1 ' '' </<` n %\ ^ j` >t * *J\j , '/ (,''( 3 ^, i *" <, > / ' 4' , >^J 4 i *> ' ,,}fe#i,' <> '* ' 5 5 "V -, I '< < \ ,J X >A ^., ---tyxv-y"' 7 r. ?,fevrT>, , ,`f '*> ' i# *fx) * i l '% >c..^ < i :fl: < *N i / t * ?i 1 j 4t 5 *< x 1 >i . 1 *1' \ / ,4 yM ' . ^ -.,^y - -St .< ' ' . /, , V V/ ^ *? > - ' .........r 4' -i r- 'v;4>>;t*'/-^"' 7'V{5'`?/'\'4--1''Vr- * fils * { i ^n 4* ^ ' '<'w^ '' l *>"'* ' V*r* t / ^A >< '/' J <'t.'/j;j \'vSyTt:b > > i il * < \ xi ^> * 3$W '!?' i< 1 ' M i <i 7*'4t` %-%ii:Vr''^'r0 i* 'x 4 *\ ti i! V > S* ) Tt >f i It *i /. ,.^ !,b ^ r 3 A< <b \ V > V' A/ xv }' A