Document N2XerGvjQmggV6kEnnbyEo1DQ

Occupational Exposure to Chrysotile \y Asbestos and Cancer Risk: A Review of the Amphibole Hypothesis ABSTRACT Objectives. This article examines the credibility and policy implica tions of the "amphibole hypothesis," which postulates that (1) the meso theliomas observed among workers exposed to chiysotile asbestos may be explained by confounding expo sures to amphiboles, and (2) chrysotile -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 chiysotile is associated with an increased risk of lung cancer and mesdSielioma. Chrysotile may be less potent thansome amphiboles for inducing mesotheliomas, but there is iluie evidence to indicate lower Jung canccr.-risk. 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 fihers. we conclude that it is prudent to treat chrysotile with virtuallvTHe samelevel of concern as the ampHIbolg^Jorms^-of_asbestos. (Am JlPuSScHealth. 1996;86:179186) Leslie T. Stayner, PhD, DavidA. Dankovic, PhD, and Richard A. Lemen, PhD Introduction Chrysotile 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.' 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 Chiysotile 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 chrysotile asbestos may be explained by the relatively low con centrations (<1%) of tremolite fibers in commercial chrysotile asbestos fibers and (2) that chrysotile asbestos may be less potent than amphiboles in the induction of asbcstosis and lung cancer. This has been dubbed the amphi bole hypothesis.1 It has even been suggested that exposure to chrysotile asbestos in the absence of tremolite N may present little or no carcinogenic hazard.4 The arguments advanced to support the amphibole hypothesis have been pri1 marily based on pathologic studies of burdens of asbestos fibers in human lungs and on toxicologic, mechanistic, and epidci miologic studies. This article presents a critical review of these arguments and of the literature on the carcinogenic hazards associated with exposure to chiysotile 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 chrysotile asbestos revealed an unexpect edly high proportion of amphibole (pri marily tremolite) fibers, considering the relatively low percentage of amphibole fibers in commercial chrysotile asbestos.6 In one of the earliest studies, Pooley observed a greater number of amphibole fibers than chrysotile fibers in 7 of 22 patients with asbestosis who had worked in the Canadian chrysotile mining industry.7 Rowlands et al. also reported a nearly equal concentration of tremolite fibers and chiysotile fibers in the lungs of 47 workers employed as miners or millers in Quebec.6 Similarly, in populationbased studies the percentage of chiysotile fibers found in the lungs has been surpris ingly low considering the fact that chryso tile is the major source of exposure for the general population 6 Most case-control studies that evalu ated the potential relationship between r 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 CIS, Cincinnati, OH 45226. This paper was accepted August 16,1995. Editor's Note. See related annotation by Cullen (p 158) in this issue. February 1996, Vol. 86, No. 2 American Journal of Public Health 179 TABLE 1--Summary of Epidemiological Cohort Studies of Workers Exposed to Predominantly ChrytotUe Asbestos Study Industry Lung Cancer Deaths Mesothelioma Cases Observed Expected Observed Deaths. % Acheson et al.27 Gas masks Cheng and Kong28 Textiles, friction mate rials, and cement Dement et al.29 Textiles Finkelstein30 Electrical conduit pipe Finkelstein31 Automotive Hughes et al.M*c Cement manufacturing Huilan and Zhiming33 8 asbestos factories McDonald et al.34 Friction products McDonald et al.35*38,11 Mining and milling Piolatto et al.37 Mining Shiqu etal.38 Mining Weiss39 Paper and millboard Total 6 21 126 6 11 70 65 73 518 22 6 4 922* 4.8a 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 1-2b 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 s the standardized mortality ratio, which is the ratio between the observed and expected. The expected number is for cancer of the lung and pleura combined. tone or two cases of mesothelioma were reported. Only one was inducted in the totals. Results are for workers exposed only to chrysolite 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 eta), study was not included in the total number of lung cancer cases because expected numbers were not reported.97 ^Significantly different from the observed number, P < .05 (two tailed). mesothelioma risk and lung concentra j 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 concern for mesothelioma, which has failed to find a relationship with lung been estimated to have~3~fatcncyperiodof' chrysotile concentrations.10-14 McDonald | 'TirfeasTTOyeariT21 For example, assuming et al. reported an association between a 90-day h^f-liTelmdlirst-order kinetics, mesothelioma and lung concentrations of only approximately 1/(8 x 1022) of the long ( 8 pm) chiysotile fibers in univari dose received 20 years earlier^would be ate analyses but not in multivariate analy predictedtoBeprcsent in theTun^atlhe sis, which controlled for the other fiber time^oTtHeaiiitopsy. Hence, lung burdens types.15 Rogers et al. reported a significant \ of chrvsotile mav be a poor measure of the associatioiPBefween mesothelioma risk integrated exposures to chiysotile. aricTTung concentratTonTof short chiyso^ ~ ' The high degree of correlation be- tflejjbers ( <10 iiml--in-Zmultivanai^" ~ tween the lung concentrations of the models and a significant trend for lung different fiber types, which has been concentrations among mesotheljQma case noted by several investigators, further and control^subjects who had only chryso- complicates the interpretation of the lung tile ^etectedinjheixiungsj6 burden analyses.15-16-23 Churg reported ~The' interpretation of the results that the correlation coefficient between from the studies of lung burden is compli the numbers of chiysotile and crocidolite cated by differences in the respiratory fibers in lungs of asbestosis patients was clearance rates of the different forms of ' asbestos. Experimental studies demon strated that chiysotile fibers are cleared far more rapidly from the lungs than are amphibole fibers.17-19 The retention half . life of chiysotile in human lungs is I unknown, but a half-life of 90 days has been reported in experimental studies of baboons.20 If the half-life for chiysotile is similar for humans and baboons, then clearly the vast majority of the dose time chiysotile exposure in these studies. As Churg et al. suggested, `TtjsajUjyrue that the tremolite serves as* a better measure of past chiysotile than thechrvso- tilejtadf^ . =- Finally, studies pf 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 fisStie when amphiboles were the, predominant fiber found in the lung.22*24-26 These rdSOtts'suggest thaT chiysotile may be preferentially translocated to the pleura and that the fiber epunts foundin theTung- may not accurately reflect the concentra tions found at the site for mesothelioma induction. -- Epidemiologic Studies Lung Cancer There have been 12 retrospective cohort mortality studies of workers who were predominantly exposed to chiysotile 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 expected in neariy_alL-of the studies,- Combining 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.28*33-35*36*40*41 Collectively^jhese studies provide strong evjdgiu&ihalfix^^ tosis i 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- 180 American Journal of Public Health Februaiy 1996, Vol. 86, Nc. 2 Asbestos and Cancer industry type appear to be far more remarkable than variations according to fiber type. The potencies for 1 TABLE 2--Estimates of Asbestos Potency tor Lung Cancer from Studies with Individual Exposure Estimates, by Industry and Fiber Type risk are similar among the cohorts. pure chrvsoflIe~~and mixed exposures in the textile industry and are generally --highertharrtfie potencies observed among Study Industry Fiber Type Excess Relative Risk per Fiber/cc x Yr WorkgfsTin 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 etal.12 Petoetal.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.38 Mining Tremolite Mining and milling Crocidolite Mining and milling Chrysotile 0.013 0.010 0.0006*c 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 Enterline45 Hughes et al.32 Berry and Newhouse et al.46 McDonald et a!.34 Asbestos products Cement products Friction products Friction products Chrysotile, amosite, crocidolite Chrysotile* chrysotile,b and crocidolite Chrysotile Chrysotile 0.002* 0.0071 ,* 0.00766 0.00058 0.00053* chrysotile ores than among crocidolite or tremolite miners. It has been suggested that the high lung cancer mortality observed among *A conversion factor of three fibers per cubic centimeter being equivalent to i million panicles per cubic foot was assumed. *Data are based on results for workers employed after 1951. cSlope was estimated by fitting a linear relative risk Poisson regression model to the standardized mortality ratio results reported by McDonald et al* 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 cancer observed in this cohort is unrelated compelling, the critical issue is whether to mineral oil exposure.29'48 In addition, this excess may be attributable to trace studies of workers exposed to mineral oils have generally not demonstrated an ex cess of lung cancer.47 There is evidence that asbestos fibers in the textile industry . were considerably longer than the fibers measured in chrysotile mining and milling and other industries.50 Thus, differences (in fiber dimensions would appear to be a more likely explanation than mineral oil exposures for the higher lung cancer rates observed in textile workers. contamination by tremolite. All of the asbestos workers studied (Table 1) are likely to have potential exposures to tremolite, although in minute concentra tions compared with their chrysotile expo sures. In a few studies the percentage of tremolite is known and varies. Contrasting the results from these studies provides some information on the plausibility of the amphibole hypothesis. Two cases of mesothelioma have been reported among Mesothelioma A total of 45 cases of mesothelioma chrysotile asbestos miners and millers in Zimbabwe, where the chrysotile ores are believed to be free of tremolite contamina (primarily pleural) were reported in the epidemiologic studies of workers who were predominantly exposed to chrysotile asbestos (Table 1). Although it has gener tion.52 Begin et al. noted that although exposure to tremolite may be as much as 7.5 times higher in Thetford than in Asbestos, the incidence of mesothelioma ally not been possible to estimate ex in these two Quebec mining towns was pected numbers of mesothelioma deaths, j proportional to the size of their work the percentage of deaths due to mesothe I forces.53 He suggested that this fact may lioma may be estimated and compared I 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 different exposure-response relationship for mesothelioma. On the other hand, McDonald and McDonald54 recently re 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 In contrast, the percentage of deaths due to pleural malignancies (most of which of the study of Quebec miners and millers, McDonald et al.36 presented separate known to increase exponentially with follow-up time,55 and 72% of the Quebec are mesotheliomas) was only 0.02% in the United States in 1988.51' exposure-response analyses for workers at the Thetford and Asbestos mines and miners and millers had died,36 compared with 42% of the workers in the South Although the evidence of excess mortality of mesothelioma among work mills. There is no indication in their findings that these two facilities exhibit a 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 80 - Control AmosHe A Anthophyilite r C. Chrysotile R. Chrysotile Crocidolite 20 - 3 Months 6 Months 12 Months Duration of Exposure 24 Months Note. Data are from Wagner et al.,T: approximate 95% confidence intervals for a binomial outcome have been added. C = Canadian; R x Rhodesian. FIGURE 1--Lung tumors In rats exposed to 10 mg/m5 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 crocidolite, which is substantially greater than the percentage of deaths due to mesothe lioma oL^erved 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 pchrysotile- and amphibole (primarily cro- ; jcidolite)-exposed workers are so striking j (that alternative explanations for these '' I differences appear unlikely. Toxicologic Studies Lung Cancer Toxicologic studies demonstrated that all forms of asbestos can induce Jung 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, anthophyilite, Canadian chrysotile, Rhodesian chrysotile, and crocidolite is shown in Figure l.17 The overlapping 95% confidence intervals suggestJhat there is no significant difference in potency among the five types of asbestos. (Le.. the am phiboles are not systematically more or less potent than the chrvsotiiesl. Davis and co-workcrs 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 producedmoirrtgfiglumors than the other forms of asbestos.56 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 length vs 0.5% of the fibers for the amosite and crocidolite exposures 58 Other studies by Davis et al. showed that long-fiber samples ofamosite59 and chryso tile60 are considerably more active than short-fiber samples in inducing lung tumors. Davis et al. also showed that tremo lite,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 pm 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 18.3% of the animals testeclvs 4.6% for crocidolite.62 . Overall the toxicologic data suggest that ctirysotile asbestos is at least as potent, if not more so, as the amphibole forms in the induction of lunglumors oh a per-mllfigTam basis. The data shown in Figure 2 furthersuggest 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.17 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%; anthophyllite, 1.4%; crocidolite, 2.8%; and Canadian chtysotile, 2.9%. No mesothelio mas were observed in control animals or animals exposed to chrysotile from Zim babwe.17 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 chrysotile.58-60 The highest mesothelioma incidence in these studies, 7.5%, was produced by exposure to long-fiber chryso tile.60 Although the low incidence rates land 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, anthophyllite, crocidolite, Canadian chiysotile, and Zimbabwe chrysotile all produced mesotheIiomas~nr~rats_ after intrapleural inocujaiion.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 sions have much more influence on mesothelioma yield than any differences that may exist between types of asbestos.65 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 chiysotile asbestos" does have the potent7aPtd~n1riuce~ mesotneiioma^ but ou - - 50 n A ao HE3 40 - Oc3) 30 - C' 2 Q0-) 20 - A 10 - A n -i > 0 ... . 1000 2000 3000 Control Amosite A Chrysotile T Crocidolite Tremolite 4000 5000 6000 Fibers per ml Note. Data are from Davis et al. and Davis and Jones.9*-4' Controls are the pooled control animals from all four studies. FIGURE 2--Lung tumors In rats exposed to 10 mg/m3 concentrations o? crocidolite, amostte, chrysotile, ortremollte for 1 year. these studies do not resolve the question trfwhetherryr norchrysofiic is less potent in this regard than the amphibole forms. Coffin et al. recently reported that both chiysotile 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 greatermesothelioma- inducing potential than crocidolite on a per-milljgrain 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 fxm in length, it appears that crocidolite produced nearly 12 times more mesotheliomas per fiber than chrysotile. 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 p,m for both chrysotile and crocidolite. If short fibers do in fact have some mesothelioma- inducing potential, the attribution of all mesotheliomas to the small fraction of the fibers that were greater than 5 p.m in length may lead to an exaggerated esti- mati th(` difference in potency of crociu.. me chrysotile. 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 that this process may be catalyzed by iron on the fiber surface. Furthermore, it has . been suggested that the needle-iike con figuration, durability, and increased iron , content of crocidolite render it more pathogenic than cither amosite or chryso tile 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 tumoricidal defense mecha nisms, and a nutrient for unrestricted tumor cell replication.67 However, com parison of the carcinogenic potencies of v fibers in the rat in vivo does not support ithe 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 chiysotile, 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 J tween iron content and carcinogenicity is apparent in the rat. Summary Our review of both the toxicologic and epidemiologic literature strongly sup ports the view that occupationa[exposure -to chiysotile asbestos is associated.with.an increased risk of both lung cancer and mesothelioma. 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 chiysotile 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 J samples,6 and it has been suggested that chrysotile from Zimbabwe70 and other countries may be free ofcontamination by amphiboles. Hence, the amphibole hy 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 mesothefioma excesses observecTmthe 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 facnbatchrysotilc lungjturdens areit and the fact that chrysotile exposure is highly correlated with lung burden-of the amjphiboles^e.g., tremolite). In addition, the patfeffTof 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 byl. the lack of correlation between iron V content and carcinogenic potency ob- 1 served in experimental studies. * Whether chiysotile asbestos is less potent than the amphibole forms of asbestos is a question that has not yet been fully resolved. There is currently very 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 eviderice-To- support-the'-ar^umenL-that chrysotile asbestos is anyjess potent than other forms of asbestosTSrTnducing 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 p-m. 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 Tire current Occupational Safety and Health Administration (OSHA) method counts asbestos fibers that are longer than 5 ftm and that have a length-to-diameter ratio of at least 3 to 1. This method implicitly assumes that fibers less than 5 jim 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 the experimental data and most likely result iiL 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 chiysotile, 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 appearsJo- he-just -as potent lung._eargiiu^en_as--the--other-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 clearly 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 chrysotile asbestos with virtually the same level ofconcern 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 past National Institute for Occupational Safety and Health Administration recom mendation and the recently revised OSHA standard to limit occupational exposures for alJ forms of asbestos to 0.1 fiber/cc. References 1. Pigg BJ. The uses of chrysotile./Inn Occup Hyg. 1994:38:453-458. 2. Lemen RA Bingham E. A case study in avoiding a deadly legacy in developing countries. Toxicol ind Health. 1994; 10(1 /2): 59-87. 3. Mossman BT. Bignon J, Com M, Seaton A, Gee JBL. Asbestos: scientific develop ments and implications for public policy. Science. 1990;24:294-301. 4. Dunnigan, J. Linking chrysotile asbestos with mesothelioma./bn J Irtd Med. 1988;14: 205-209. 5. Pooley FD, Clark NJ. Quantitative assess ment of inorganic fibrous particulates in dust samples with an analytical transmis sion electron microscope. Ann Occup Hyg. 1979;22:253-271. 6. Addison J, Davies LST. Analysis of amphibole asbestos in chrysotile and other minerals. Ann Occup Hyg. 1990;34:159175. 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. 8. Rowlands N, Gibbs GW, McDonald AD. Asbestos fibres in the lungs of chrysotile miners and millers--a preliminary report. Ann Occup Hyg. 1982;26:411-415, 9. Churg A, Wamock ML. Asbestos fibers in the general population. Am Rev Respir Dis. 1980;122:669-678. 10. Jones JSP, Roberts GS, Pooley FD, et al. The pathology and mineral content of lungs in cases of mesothelioma in the United Kingdom in 1976. In: Wagner JC, ed. Biological Effects of Mineral Fibers. Lyon. France: International Agency for Research on Cancer; 1980:188-199. Scien tific Publication No. 30. 11. Wagner JC, Pooley FD, Berry G, et al. A pathological and mineralogical study of asbestos-related deaths in the United King' domin \911. Ann Occup Hyg. 1982;26:423431. 12. McDonald AD, McDonald JC, Pooley FD. Mineral fibre content of lung in mesothelial tumours in North America. Ann Occup Hyg. 1982;26:417-422. 13. Gaudichet A, Janson X, Monchaux G, et al. Assessment by analytical microscopy of the total lung fibre burden in mesothe lioma patients matched with four other pathological series. Ann Occup Hyg. 1988; 32(suppM):213-223. 14. Wagner JC, Berry G, Pooley FD. Mesothe liomas and asbestos type in asbestos textile 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 concentration and relative risk of mesothe lioma. Cancer. 1991;67:1912-1920. 17. Wagner JC, Berry G, Skidmore JW, Timbrell V. The effects of the inhalation of asbestos in rats. BrJ Cancer. 1974;29:252~ 269. 18. Middleton AP, Beckett ST, Davis JMG* A study of the short-term retention and clearance of inhaled asbestos by rats, using U.I.C.C. standard reference samples. In: Walton WH, ed. Inhaled Panicles I\'. Edinburgh, Scotland: Institute of Occupa tional Medicine; 1975:247-258. 19. Churg A, Wright JL, Vedel S. Fiberburden and patterns of asbestos-related disease in chtysotile miners and millers. Am Rev RespirDis. 1993;48:25-31. 20. Rendall RE. Retention and Clearance of Glass Fibers and Different Varieties of Asbestos by the Lung. Johannesburg, South Africa: University of Witwatemand; 1988. Dissertation. 21. Selikoff IJ, Hammond EC Seidman H. Mortality experience of insulation workers in the United States and Canada, 1943 1916.Ann N YAcad ScL 1979;330:91-116. 22. Sebastien P, Janson X, Gaudichet A. Hirsch A Bigon J. Asbestos retention in human respiratory tissues: comparative measurements in lung parenchyma and in parietal pleura. In: Wagner JC, ed. Biologi 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 airways disease. Am Re\> Respir Dis, 1983; 127:470-473. 24. LeBouffant L, Martin JC, Duyif S, Daniel H. Structure and composition of pleural plaque. In; Bogovski P, Gilson JC, Timbrell V, Wagner JC, eds. Biological Effects of Asbestos. Lyon, France: International Agency for Research on Cancer; 1973:249 257. Scientific Publication No. 8. 25. Dodson RF, Williams MG, Corn CJ, Brolio A, Bianchi C. Asbestos content of lung tissue, lymph nodes, and pleural plaques from former shipyard workers. Am Rev Respir Dis. 1990;142:843-847. 26. Kohyama N, Suzuki Y. Analysis of asbestos fibers in lung parenchyma, pleural plaques, and mesothelioma tissues of North Ameri can insulation workers. Ann N Y Acad Sci. 1991;643:27-52. 27. Acheson ED, Gardner MJ, Pippard EC, Grime LP. Mortality of two groups of women who manufactured gas masks from chrysotile and crocidolite asbestos: a 40year follow-up. BrJ Ind Med. 1982;39:344348. 2JJ. Cheng W, Kong J. A retrospective mortal ity cohort study of chrysotile asbestos products workers in Tianjin 1972-1987. Environ Res. 1992;59:271-278. 29. Dement JM, Brown DP, Okun A. Mortal ity among chrysotile asbestos textile work ers: Cohort mortality and case-control 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 Ind Med. 1989;16:281-287. 31. Finkelstein MM. Mortality rates among employees potentially exposed to chryso tile asbestos at two automotive parts factories. Can Med Assoc J. 1989:141:327 330. 32. Hughes JM, Weill H, Hammad YY. Mortal ity of workers employed in two asbestos cement manufacturing plants. Br J Ind Med. 1987;44:161-174. 33. Huilan Z, Zhiming W. Study of occupa tional lung cancer in asbestos factories in China. BrJ Ind Med. 1993;50:1039-1042. 34. McDonald AD, Fry JS, Woolley AJ. McDonald JC. Dust exposure and mortal ity in an American chrysotile asbestos friction products plant. Br J lrtd Med. 1984;41:151-157. 35. McDonald JC. Liddell FDK, Gibbs GW, Eyssen GE. McDonald AD, Dust exposure and mortality in chrvsotile mining, 1910 1975. BrJ Ind Med. 1980;37:11-24. 36. McDonald JC, Liddell FDK, Dufresne A. McDonald AD. The 1891-1920 birth co hort of Quebec chrysotile miners and millers: mortality 1976-88. Br J Ind Med. 1993;50:1073-1081. 37. Piolatto G, Negri E, LaVecchia C, Pira E, Decarli A, Peto J. An update of cancer mortality among chrysotile asbestos miners in Balangero, Northern Italy. BrJ Ind Med. 1990;47:810-814. 38. Shiqu Z, Yongxian W, Fusheng M, Hong- shuen M, Wenzht S, Zhenhuan J. Retro spective mortality study of asbestos work ers in Laiyuan. In: Proceedings of the VH International Pneumoconioses Conference, Part II; August 23-26,1988; Pittsburgh, Pa. National Institute for Occupational Safety and Health; 1990:1242-1244. DHHS publi cation 90-109, part II. 39. Weiss W. Mortality of a cohort exposed to chrysotile asbestos. J Occup Med. I977;19: 737-740. . 40. Dement JM, Harris RL, Symons MJ, Shy CM. Exposures and mortality among chrysotile asbestos workers, part I: expo sure estimates. Am J Ind Med. 1983;4:399~ 419. . 41. Dement JM, Harris RL, Symons MJ, Shy CM. Exposures and mortality among chrysotile asbestos workers, part 11: mortal ity. Am J IndMed. 1983;4:421-433. 42. Peto J, Doll R, Hermon C. Binns W, Clayton R, Goffe T. Relationship of mortal ity to measures of environmental asbestos pollution in an asbestos textile istcxory.Ann Occup Hyg. 1985;29:305-355. 43. McDonald JC. McDonald AD, Armstrong B, Sebastien P. Cohort study of mortality of vermiculite miners exposed to tremolite. Br J Ind Med. 1986;43:436-444. 44. de Klerk NH, Armstrong BK, Musk AW, Hobbs MST. Cancer mortality in relation to measures of occupational exposure to crocidolite at Wittenoom Gorge in West ern Australia. Br J Ind Med. 1989;46;529- 536. 45. Henderson VL, Enterline PE. Asbestos exposure: Factors associated with excess cancer and respiratory disease mortality. AnnNYAcadSci 1979;117-126. 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 worlcers. CellBiol ToxicoL 1991;7:59-65. 49. Tolbert P, Eisen E, Pothier LJ, Monson RR, Hallock MF, Smith TJ. Mortality studies of machining-fluid exposure in the automobile industry, II: risks associated with specific fluid types. Scand J Work Environ Health. 1992;18:353-360. . 50. Dement JM and Wallingford KM. Com parison of phase contrast and electron microscopic methods for evaluation of occupational asbestos exposures. Appl Oc- cup Environ Hyg. 1990*^:242-247. 51. Vital Statistics ofthe United States, 1989, Vol II--Mortality, Part B. Hyattsville, Md: National Center for Health Statistics; 1992. DHHS publication PHS 92-1102. 52. Cullen MR and Baloyi RS. Chiysotile asbestos and health in Zimbabwe, 1: analy sis of miners and millers compensated for asbestos-related diseases since indepen dence {\9W).AmJlndMe<L 199l;29:161- 169. 53. Begin R, Gauthier J, Desmeules M, Os* tiguy G. Work-related mesothelioma in Quebec, 1967-1990.^my/miAfed. 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 V. Mesothe lioma mortality in asbestos workers: impli cations for models of carcinogenesis and risk assessment. BrJ Cancer. 1982;45:124-- 135. 56. Hughes JM, Weil! H. Asbestos Exposure- Quantitative Assessment of Risk. Am Rev RespirDis. 1986;133:5-13. 57. Sluis-Cremer GK, Liddell FDK, Logan WPD, Bczuidenhout BN. The mortality of amphibole miners in South Africa, 1946BO.BrJInd Med, 1992:49:566-575. 58. Davis JMG, Beckett ST, Bolton RE, Collins P, Middleton AP. Mass and num ber of fibres in the pathogenesisofasbestosrelated lung disease in rats. Br J Cancer. 1978^37:673-688. 59. DavisJMG, 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 intraperitoneal injection. Br JExp Pathol 1986;67:415-430. 60. Davis JMG, Jones AD. Comparisons ofthe pathogenicity of long and short fibres of chrysotile asbestos in rats. BrJ Exp Pathol. 1988;69:717-737. 61. Davis JMG, Addison J, Bolton RE, Donald . son fC 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, CreasonJP. Relative mesothelioma induction in rats by mineral fibers: comparison with residua! pulmo nary mineral fiber number and epidemiol ogy. Inhal Toxicol. 1992;4:273-300. 63. Timbrell V, Gibson JC, Webster I. UICC standard reference samples of asbestos. Int J Cancer. 1968;3:406-408. 64. WagnerJC, Berry G, Timbrell V.Mesotheliomata 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 Cancer fnst. 1981:67; 965-975. 66. Mossman BT., Mechanisms of asbestos carcinogenesis and toxicity: the amphibole hypothesis revisited. BrJ Ind Med. 1993;50: 673-676. Letter. 67. Weinberg ED. Association of iron with respiratory tract neoplasia. J Trace Elan Exp Med 1993;6:117-123. 68. Kdk-OthmerEncyclopedia ofChemical Tech nology. 3rd ed. Vol 15. New York, NY: John Wiley & Sons; 1981:639. 69. Davis JMG. Mineral fibre carcinogenesis: experimenta! 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 Mine Resi dents and Asbestosis 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 Amotatkms, andTopics affaetUlAmJPubcHeaUi 1996,86253 256. 2. Escobedo LG, Peddicord JP. Smoking prevalence in US birth cohorts: the influ ence of gender and education. AmJ Public Health. 1996;86:231-236. 3. DiFranza JR, Savageau JA, Aisquith BF. Youth access to tobacco: the effects of age, gender, vending machine lodes, 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. Crowing 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 folly 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 moots.JAMA. 1991;266:3159-3161. 11. DiFranza JR, Carlson RR, Caisse REJ. Reducingyouth access to tobacco. Tobacco Control 1992:138. 1Z Hinds MW. Impact of a local ordinance banning tobacco sales to minors. Pubkc 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-November Z1995; San Diego, Calif. Session 2277. 14. Skolnick A. Court orders governor to restore anti-smoking mediacampaign ftmding.JAMA. 1992367:2721-2723. 15. Begay ME, Traynor MP, Glantz SA. The tobacco industry, state politics, and to bacco education in California. AmJPubSc Health. 1993;83:1214-1221. 16. Begay ME, Traynor MP, Glantz SA. The TMBght of Proposition 99: Reauthorizotian of Tobacco Education Programs mid To bacco Industry Political Expenditures in 1993. San Francisco, Calif: Institute tor Health PolicyStudies, UniversityofCalifor nia, San Francisco; 1994. 17. Skolnick A Antitobacco advocates fight `illegal' diversion oftobacco control enooey. JAMA. 1994;271:1387-1390. 18. Aguinaga S, Macdonald H, Traynor M, Begay M, Glantz S. Undermining Popular Government Tobacco Industry Political Ex penditures in California, 1993-1994. San Francisco, Calif: University of California Institute for Health Policy Studies; 1995. 19. Skolnick A. Judge rules diversion of anti smoking money illegal. JAMA. 1995:273: 610-611. 20. Glantz S. Removing the incentive to aefi kids tobacco.X4AL4. 1993;269:793-794. 21. US Occupational Safetyand HealthAdmin istration. Indoor Air Quality (Proposed Rule). Federal Register. 1994;59(April 5): - 15968-16039. 2Z Pierce JP, Evans N, Farkas AJ, et al. Tobacco Use in California:An Evaluation of dir Tobacco Control Program, 1989-1993. San Diego, Calif: University of'California, StnDiegp; 1994. 21 Stillman F, Becker D, Swank R, et al. Ending smoking at the Johns Hopkins Medical Institutions: an evaluation of - Hacking prevalence and indoor pollution. JAMA. 1990264:1565-1569. 24. WoodruffT, Rosebrook B, Pierce J, Glantz S. Lower levels of cigarette consumption found in smoke-free workplaces in Califortern. Arch Intern Med. 1993;153:1485-1493. 25. Kinnc S, Kristal AR, White E, Hunt J. Work-site smoking policies: their popula tion impact in Washington State. Am J Public Health. 1993:83:1031-1033. 26. Brenner H, Flcischlc B. Smoking regula tions at the workplace and smoking behav ior: a study from southern Germany. Prev Med. 1994;23:230-234. 27. Brjgham J, Gross J, Stitzer ML, Felch LJ. Effects of a restricted work-site smoking , policy on employees who smoke. Am J Public 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. 1994^23: 78-82. 29. Borland R, Owen N. Need to smoke in the context of workplace smoking bans. Prev Med. 199504:56-60. 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 clearest 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 clinics, 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 mom perverse consequence of this frenzied litigation than the incursions of lifibility issues into scientific research and beliefs. The matter of differential 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, siresite, and tremolite), and not serpentine (mainly chrysotile) asbestos can cause cancer--arose because of two important observations in the 1970s: (1) serpentine fibers are cleared much faster than amphibotes in the human lung; and (2) several cohortsofchrysotile-expoocdvrorkers were reported to have lower (albeit still elevated) rates of hung 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 tremolite (which might explain the modest eleva tions of risk among those exposed to chiyaotile), the scientific concept ap peared initially attractive. The ramifica tion* for future scientific inquiry regard ing 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 side-by-side studies of McDonald and colleagues2-3 confirmed by Dement4 dem onstrating astronomical rates of lung cancer among textile workers exposed MMsriB Nate. See related article by Stayner et ai,(p 119) in this Issue. 758 American Journal ofPublic Health February 1996, Vol. 86, No. 2 Editorials, Aaaotaikww, and Tafia 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 differential lung cancer risk? The idea that all of the health consequences associated with chiysotile could be attributed to trace tremolite fiber contamination proved in consistent with the very modest health risks demonstrated in other groups more heavily exposed to tremolite.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 chiysotile-exposcd 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 sc, was the cause, a conceptwithout empiric evidence or even theoretical appeal, given the low 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 199010 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 otherwise well-informed phy sicians and scientists worldwide continue to believe that chiysotile is a "good" form Oi 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 populations 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 bones." Mark R. Cullen Yak University SchoolofMmtidne New Haven, Conn References 1. Stayner LT, Dankovic DA, Lenten RA. Occupational exposure to chiysotile asbes tos and cancer risk: a review of the amphibole hypothesis. Am J Public Health 1996iS6:119-m. 2. McDonald AD-, Fry 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. BrJlndMedL 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 Occup Hyg. 196236: 869-887. 5. McDonald JC McDonald AD, Armstrong B.Sebastien P. Cohort study ofmortality of vermiculite miners exposed to tremolite. Br JInd Med. 1986;43:436-444. 6. Wagner JC Berry G, Skidmore JW, Timbrell V. The effects of the inhalation of asbestos in rats. Br 1 Cancer. 197439352 269. 7. Davis JMG, Beckett ST, Bolton RE, Collins P, Middleton AP. Mass and num ber of fibres in the pathogenesis ofasbestosrelated lung disease in rats. Br J Cancer, 197837:673-688. 8. Churg A, Wright JL, Vedcl S. Fiber burden and patterns of asbestos-related disease in chiysotile miners and millets. Am Rev ResprrDis. 1993;48:25-31. 9. Sebastian P, McDonald JC McDonald AD, Case B, Harley R. Respiratory cancer in chrysotile textile and mining industries; exposure inferences from lung analysis. Br JInd Med. 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. 199034:294-301. 11. Cullen MR. Controversies in asbestos related lung cancer. Occup Med State Art Rev. 19873:259-272. Topics for Our Times: Don't Inhale--Reflections on Garbage! For more than a century, garbage removal has been central to the contro versy of how best to organize public health services. Throughout the 19th century 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