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Carcinogenicity... and it has now become clear that there are vast differences among various respirable tfbres presently used in industry. At the 1992 WHO/IARC (Lyon) Symposium on Biopersistence of Respirable Synthetic Fibres and Minerals, there was a strong consensus that there appears to be a continuum of val ues for biopersistence ranging from very short persistence (low durability) to practi cally indefinite persistence (very high dura bility) among the various respirable materi als tested. (broken down'. .Animal studies from the Institute o: Occupational Medicine in Edinburgh snowed that chrysotile asbestos and me glass fibres tested were cleared at approximate!'.' the same rate, whereas there was very i;:tie clearance of crocidolite asbestos. with the various forms of asbestos, different man-made mineral fibres vary greatly in each of the three D parameters discussed. A sound regulator}' policy must recognize the existence of a continuum of pathological potential for all respirable fibres, natural and man-made and establish exposure standards predicated on this continuum. Current research points to a continuum in the durability of both natural and man made mineral fibres Both in vivo (animal studies) and in vitro ibiological fluid simulation) research have been conducted to evaluate the biopersistence of different inhalable fibres. It has been demonstrated that for asbestos fibres, chrysotile has low durability' and short per sistence. while amphiboles are highly durable and persistent. While chrysotile is Cleared within weeks or a few months, it is recognized that amphiboles. in particular crocidolite and amosite have clearance half-times in the range of decades. For man-made mineral fibres (MMMF). cata has shown wide variability in the biopersistence and solubility' of different fibres, depending on their respective manufactur ing process and chemical composition. For example, glass fibres with high aluminum (Ai) content were shown to be more durable than those with low Al content. A major German study undertaken by scien tists at the Fraunhofer Institute in Hanover compared a whole series of MMMFs (from giass to RCFs) and natural fibres for in vivo durability. Half times for fibre elimination from the lung ranged from 10 to 500 days, .mother study on durability from the U.S. reported that inhaled RCFs showed no cnemical alterations two years following end of exposure, whereas glass fibres snowed that some components had leached CROCtOOUTE ASBESTOS REFRACTORY CERAMIC FIBRES IHK5H Al OXIOE % :LOW Al OXIDE I AMOSfTE ASBESTOS All fibres are not created equal Today scientists view the three P's (dose, dimension and durability) as interactive and interdependent. Moreover, as with durability, the parameters of dose and dimension exist on a continuum of patho genic potential. At low doses, many fibres produce no detectable health effects. All other things being equal, as the dose increases so too will the potential health risks. Similarly fibres which are less than 5um in length can be easily eliminated by the body's natural defense mechanisms. Fibres of 10. 20 or 30,urn and longer are increasingly likely to escape macrophage elimination ana remain in the lungs. In addition to the scientific ramifications of this avenue of study, there can be practical and regulator}' implications as well. increasingly regulations will have to focus on tiore characteristics and descriptions ratner mars or. mineral or trade names. As CHRYSOTILE ASBESTOS (HIGH A) GLASS (LOW Al %) SLAG HOCK mmm References: Churg. A.. Lung. Asbestos Content in Long term Residents of a Chrysotile Mining Town. Amer. Rev. Resp. Dis.. 1986. 134(1) : 125-12" Davis. IMG et al. Tire Pathogenicity of Long Its Short Fibre Samples ofAmosite Asbestos Administered to Rdts by Inhalation and Intraperitoneal injection. Brit. .1. Exp. Pathol. . 1986. 6":415-430. Moali. P.A.. Macdonald. t.L.. and Kane. A.B. (198"). Acute injury and regeneration of the mesotheiium in response to asbestos fibres. Amer. .1. of Path. 128 (3): 426-495. Newhouse. M.L. & Sullivan. K.R.. A Mortality' Study of Workers Manufacturing Friction Materials: I94I-I986. Brit. I. Ind. Med.. 1989. 46(3) : 1~6-1"9. Ohlson. C.G. and Hogstedt. C.. Lung Cancer Among Asbestos Cement Workers: A Swedish Cohort Study and Review. Brit. I. Ind. Med.. 1985. 42(6): 39~'-402. Thomas. H.F.. Benjamin. I.T.. Elwood. P.C. & Sweetman. P.M. Further Follow-up Study of Workers from an Asbestos Cement Factory. Brit. I. Ind. Med.. 1982. 39(3) : 2"3-2"6. Wright. G.W. & Kuschnen. M. Tise Influence of Varying Lengths of Glass and Asbestos Fibres on Tissue Response in Guinea Figs. Proceedings of the International Symposium of the British Occ. Hyg. Society. Edinburgh. septemDcr. 19" 455-4"-!. 9 HWBUI0003883 MMMF Research Update A Case-Control Study of Malignant and Non-Malignant Respiratory7 Disease Among Employees of a Fibreglass Manufacturing Facility7 Chiazze. L. et a!. British journal of Industrial Medicine. -A 1992. A case-control study conducted on workers of a fibregiass piar.t nas concluded to a sta tistically sianincar.t increase in respiratory cancer. The results or this study have been reevaluated to inciuae non-workplace fac tors. such as cigarette smoking. Results of the interview portion of the case-control study clearly indicate that smoking is the most important non-workplace factor for risk of lung cancer in tnis group of workers. Lung Function in Insulation Workers Clausen. J.. Netterstrdm. B. & Wolff, C.. British loumai of industrial Medicine. 1993: 50: 252-250. To evaluate the effects of working with modern insulation materials (rock and glass wooii ttte members of the Copenhagen Union of insulation Workers were invited to Damcipate in a study based on a health examination that included lung function tests such as forced vital capacity (FVC) ana forced expiratory vol ume in one second (FEY;). No differences in FVC were observed between the experi mental and control groups, but insulation workers were found to have significantly lower FEYi values, independent of smoking. In addition, a foiiow-up of workers who had participated in a similar study six years ear lier found tnat the decline in FVC for insu lation workers wno smoiteo was significant ly greater than for smokers from th^control group. In me present study, the decline in FEY] was sianiiicantiv higher for insulation workers, independent o: smoking habits. Reading ListSelf-assessed former exposure to asbestos i was not associated with iung function in insulation workers. Health Risks from Exposure to 1 Mineral Fibres: An The study concludes that working with 1 International Perspective modern insulation matenais is associated : Edited by G.Gibbs. j. burn:: cam M. Kido & T. Higashi, Captus University Press. 1993 with increased risk of developing obstructive : lung disease. j A timely contribution from international | experts in the field of heaim-reiated effects Environment of mineral fibres: Papers presented at the International Symposium on the Health Canada and Health and Welfare Canada Effects of Low Exposure to Fibrous Materials (Kitakvushu. Japan: Nov.1991) 1 represent an updated overview of the cur rent assessment of health effects of miner Conduct a Study on j al fibres in both the occuoational and general environment. The report of the the Potential Adverse workshop on bioioeicai indicators repre sents an in depth evaluation of modern Effects of Man-Made practices in health monitonnz. The satel lite symposium introduces tne reader to Mineral Fibres current studies on mineral fibres in Japan and other Asian countries Mineral fibres are on Canada's Environmental Protection Act's priority list. All substances mat appear on this list must be assessed to determine whether they are toxic, as defined in Section 11 of the Act The Effects of an Environmental Controversy on Industry: The Asbestos Experience ECODECISION. March 1^5 (i.e. whether exposure to tnese substances j Each year, growing dud::: awareness of causes harm to human neaith or die envi- ; the environment create- scientitic contro ronment). I versies that can have ma t : impacts on i the business activities o: man;, industries. The first par; of this Federal Government j The analysis presented snows that the effects on business depend much more on study will evaluate exposure to these sub- ; stances in Canada, in order to develop a j the fierceness of the controversy than on the regulations that are ultimately imple profile of MMMF use. Environment Canada ; mented. The experience tne asbestos has commissioned an industry survey to j industry is cited as an example of how an obtain information on the amounts of these ; environmental controversv can open the materials, which are produced in. imported j door to scientific inexactitude and arouse to and exported from Canada. i strong public opinion trom tne outset. A Source: Thermal Insulation Association of Canada. TIAC Times. March 199? frequent consequence is mat too much [ attention is given to some problems to the detriment of others, ieacm.c to a wasteful use of resources. Final?. environmental We have moved... Our new offices are iocatea a: 1002 Sherbrooke St. West. Suite !"9. Montreal. Quebec. Canada, H3A Alb. Our onone and tax numbers have remained tne same. controversy raises socie- s implicit eco logical standards". For industries, prevent ing such controversies r ensuring that their products meet these standards has become a necessm. 6 THE ASBESTOS lov. -.".rrrronKt We-' buitc :_i Montreal Quebec Telephone: i Mm ! Telex: (INSTA.V INSTITUTE CariaJ.. H-a Telecopier (Mms S44-I-- HWBUI0003884 FEBRUARYA1AY 1993 THE ASBESTOS INSTITUTE %s$e:rn s inawi tasgtewnmvn o f 'r-?a-- -/ Towards an Understanding of the Carcinogenicity of Fibrous Materials The last decade has seen great advances in scientific understanding of the carcino genic potential of some fibres. Recent studies of fibre dimensions, durability and dose-response relationships are helping to explain why some fibres, such as chrysotile asbestos are considered safe at low levels of exposure. Twenty years ago. scientists had no clear understanding of the mechanisms of the carcinogenicity of fibrous materials. The principal parameter studied was fibre dimension, and the nature of the correla tion between the iength and width of a fibre and its carcinogenicity. It became clear from research programs of this nature that, although dimensions could explain some of the variations in the carcinogenic potential of different fibres, other factors were also involved. With increased sophistication in analytical methods, scientists discovered that in addi tion to vast differences in fibre dimensions, there were also large variations in the dura bility of different fibres. The structure of some fibres were such that they could be cleared by the body's natural defense mech anisms more quickly than others. Over the last 10 to 15 years, the concept of durability or biopersistence has plaved an increasingly important role in our under- standing of the carcinogenicity of fibrous materials. Today, scientists are evaluating carcinogenicity of fibrous materials as an interaction between dose, dimension and durability7 or bio-persistence. The dose makes the poison In the 16th century, the Swiss physician Paracelsius wrote that aii substances can be toxic. The difference between the remedy (see Carcumemcity on page 4) Inside Asbestos Fibres in the General Environment Health Effects of Low Levels of Chrysotile Exposure Changes Required to Fibre Research Methodology MMMF Research Update Environment Canada Study Reading List Studies find extremely low concentrations of mostly short asbestos fibres in the general environment. A number of studies have been conducted in recent years to respond to concerns over what health risks, if any. arise from asbestos emis sions in the general environment. Air sam pling was conducted in various rural and urban environments as well as in the vicinity of asbestos-containing materials. Three major conclusions have emerged from this avenue of study. Asbestos occurs naturally in the environment The vast majority of asbestos fibres in the envi ronment (air. soil, water, etc.) are the result of natural phenomena suer, as erosion. In fact, asbestos was present in :.n.e environment in similar quantities io.rw it was mined and used commercially. isee i-nr.ivnment on page 2) 1 HWBUI0003885 Environment... Asbestos-containing materials contribute little to environmental fibre levels The Health Effects of Several studies have examined the effects of weathering on asbestos-cement products. Low Levels of Meyer (1986) concluded that tire increase in Chrysotileasbestos fibre concentrations in the near vicini- : ty of asbestos-cement cladding and roofing ; material caused by weathering is so small that : Exposureit moves into the range below the limit of ; detection of SEM. In a similar study of emis sion measurements. Borneman and ' Hildebrandt (1986) round that airborne ; asbestos levels were significantly lower than ; The October 1992/January 1993 edition 0.001 f/cc. In 1991. the Western Australia : of The Asbestos Institute Newsletter Department of Occupational Health. Safety published as its lead story, a summary and analysis of the preliminary results and Welfare conducted an extensive review of 1 environmental asbestos. The final report was of a landmark study of the health comprised of school surveys, measurement ! effects of exposure to chrysotile. The studies and a literature review of the topic. The ; study was of 5,351 Quebec asbestos report found, based on air monitoring data i workers born 1891-1920 who had sur gathered around schools with asbestos-cement vived into 1976. It was conducted by roofs, that concentrations are unlikely to Drs. F.D.K. Liddell. A.D. McDonald and exceed 0.002 f/cc and are more likely to be less than 0.0002 1/cc. J.C. McDonald who found that "In each of six classes of exposure up to 300 mpcf x years, the lung cancer SMR Most particles released into the environment are innocuous short fibres [Standard Mortality Ratio = observed mortality/expected mortality] was close to 1.3 (a total of 254 cases of lung can cer among 4,384 men. against 190.6 In addition to the fact that environmental con expected); there was no evidence of a centrations have been iound to be exceedingly trend." (Abstract presented at the 9th low. other data shows those fibres detected are International Svmposium of likely to be short. Chatfield (1983) reported to Epidemiology in Occupational Health, a Government of Sweden Symposium, that Cincinnati, 1992). between 95 to 98 of fibres observed were shorter than 5|um. The 1984 Report of the Royal Commission on Matters ofHealth and Safety Arising From me Use ofAsbestos in Ontario published similar findings. In its review of environmental asbestos, it noted the prevalence of very short fibres and low counts (a maximum of 0.008-t f/cc of all lengths). The authors have expressed concern to us that the article's subtitle "Important study finds that at exposure levels beiow a threshold of 50 f/cc. chrysotile asbestos is not linked to any increased incidence of lung cancer" could lead to misunaerstanding. The notion of a threshold References available from The Asbestos Institute. was entirely our interpretation and not a direct quote of anv of the authors or the study's abstract, which made no mention of such a concept. We wish to add that our use of the threshold con cept was not meant to refer to a level below which the exposure risk is zero, since this cannot be proven with absolute certainty. However, it did refer to a level of exposure beiow which excess risk is not statistically signifi cant. At the conclusion of the presentation of the study's preliminary report. Dr. J.C. McDonald noted that 300 mpcf x years could be regarded as approximately equivalent to 1,000 fibre years, which could have been accumulated over 20 years at about 50 f/cc. He concluded that "The significance or this study is that any deaths from asbestosis or lung cancer arising from current occupa tional exposure levels are most unlike ly." In publicizing Dr. McDonald's com ments and the findings of the prelimi nary report, The Asbestos Institute is in no way endorsing relaxed chrysotile occupational exposure limits. The group of experts convened by the WHO in 1989 recommended mat chrysotile exposures should not exceed 1 f/cc. This has been and continues to be the level which we urge producers and users to meet. To believe otherwise would clearly be a distortion or the Institute's position. In fact, since its inception. The .Asbestos Institute has been dedicat ed to actively promoting, through close to one hundred training seminars and information sessions in more than 60 countries, the application of interna tionally accepted safe exposure limits and work place practices. The Asbestos Institute has never suggested that this, or anv other study is an invitation to reiax standards, but rather that it supports our view that current exposure limits are realistic ana acceptable. E HWBUI0003886 Changes Required to Fibre Research Methodology The practice of using fibre mass rather than number does not allow for accurate compar isons of the health effects of different fibres It is widely known that different fibre types have different masses. A similar mass of two different fibrous materials can van significantly in fibre number (see table). David L. Coffin, of the U.S. Center for Environmental Medicine and Lung Biology and his former EPA colleagues P.M. Cook and J.P. Creason have warned for many years against inappropriate compar ison of pathological potential of different fibre preparations when only gravimetric (measurements of weight) units were used to report biological effects. A workshop on fibre toxicology conducted by the National Institute of Environmental Health Sciences (NTEHS) came to a similar conclusion. Its summary indicated that "A major tailing of past experimental studies has been the use of mass as the main dose its. It is only logical that research pro grams devised to better understand the nature of the health effects of fibrous materials provide data in a manner that is meaningful and useful to those concerned with protecting worker safety. A) THE EXPERIMENTS AS CARRIED OUT Dosage used Mass Fibre number Observations following 24 months exposure 5 hrs/day; 5 days/week MMVF10" MMVFir 30 mg/M3 30 mg/M^ 232 f/cc 246 f/cc Wagner PGS+: 2.5 to 3 Wagner PGS; 2.5 to 3 RCP 30 mg/M** 187 f/cc Wagner PGS: 4 Lung tumours: 16(13.0%) Mesotheiioma: 2(1.6%) Aramid** Not stated 100 f/cc Fibrosis and cystic keratinizing squamous tumours Chrysotile* 10 mg/M^ 10 600 f/cc Wagner PGS: 4 Lung tumours: 13(18%) Mesotheiioma: 1 (1.4%) B) THE EXPERIMENT WHICH WAS NEVER CARRIED OUT Chrysotile O.ISmg/M3 200 f/cc ? * Hesterberg, T.W. et al. (1993), Fund. Apoi. Toxicol, (in the press) '* Lee, K.P. et al. (1988), Fund. Appl. Toxicol. 11:1-20 + PGS: Wagner Pathology Gracing Scale Cellular change* Flbroait 1. Normal 4. Minimal: Minimal fibrosis 2. Minimal: Macrophage response 5. Mild: Linking fibrosis 3. Mild: Inflammation, broochiolizabon 6. Moderate: Consolidation 7. Severe: Marked fibrosis and consolidation 8. Severe: Complete obstruction of most airways Dose-response research using mass rather thanfibre counts has resulted in overestimations ofthe health effects ofchrysotile asbestos. The need for a meaningful common mea surement unit is underscored by a recent study by Hesterberg et al. (in press) of the health effects of man-made vitreous fibres (MMVF). For the purposes of comparison, the authors included the results of concur rent studies on the effects of refractory ceramic fibres (RCF) and chrvsotile asbestos. Close scrutiny of the experimen tal design reveals that the results reported are from animals exposed 6 hrs/day x ' days/wk for 24 months to -250 f/ml for MMVFs. -180 f/ml for RCF and 10.000 f/ml for chrvsotile asbestos! parameter. Data are needed on fibre com parisons by fibre number... Most studies using fibres in vitro have in the past expressed dosage on the basis of fibre mass as opposed to number of fibres per cell, which now appears to be a more valid means of comparison of fibre effects in relation to their potential to cause human disease." In addition, the results of air monitoring are expressed in f/cc. as are exposure iim- References: Coffin. D.L.. Cook, P.M. & Creason, J.P. Relative Mesothelioma Induction in Rats by Mineral Fibres: Comparison with Residual Pulmonary Mineral Fiber Number and Epidemiology. Inhal Toxicol. 1992:4:2"3-300. Dement. J.M. Overview: Workshop on Fiber Toxicology-Research Needs. Environ Health Perspect 1990;88:261-268. Dunnigan. I. Comparing Biological Effects of Mineral Fibres. Brit. 1. Ind. Med.. 1989. 46:681-682. Hesterburg et al. Chronic inhalation toxic ity of size-separated glass fibers in Fischer .>44 rats. Fund Appl Toxicol, (in press) 1 HWBUI0003887 Carcinogenicity... and the poison lies in the amount; thus tr.-c often-cited expression "the dose makes the poison . A tew centuries iater. the issue w iow-dose risk remains a hotly debated topic in the scientific communin'. Although the techniques, models and jargon ha\c changed, the controversy essentially revolves around the same basic question: "Is some thing that is toxic at high doses necessarily toxic at much lower doses!'" Elegant theo retical models of toxicity and carcinogenici ty are presented in response to this question, and vet in some respects we are no closer a conclusive answer. The principal point o: contention centers around the possibility that even though no health effects mav br observed, it is possible that these effects exist, but are undetectable using current data and methodology. Some scientists maintain that for the pur poses of regulatory policy, the weight of ani mal and human epidemiological evidence is more important than theoretical postula tions. in the case of chrvsotile asbestos. there is a large bodv ot evidence that demonstrates that at low levels of exposure, the carcinogenicity' is zero or undetectable low. The research ot Churg. 19SP: Newhouse & Sullivan. 1989: Ohlson & Hogstedt. 1985: Thomas et al. 1982: Liddell et al. 1992 and others detected no signifi cant excess mortality amongst workers exposed to low levels of chrvsotile. Moreover, the low levels of exposure, as defined in some of these studies, are still much higher than current occupational exposure limits. Fibre Dimensions Mediate "Resoirahilitv" and Carcinogenicity Progress in the study of asbestos and other fibres made during the last 15 years has confirmed that fibre length and diameter are important parameters to consider m evaluating carcinogenic potential. Fibre dimensions are important in that they determine whether a fibre is respirable . Some particles or fibres are too large to infiltrate into the lungs. They are blocked by the body's natural filtration system. .Although some larger fibres are able to find their way into the lungs, many are still too iarge to penetrate deep into the alveoli and as such are not a carcinogenic risk. Those fibres, which are capable of bypassing these physical barriers, generally fibres of up to 3um in diameter, have been termed "res pirable". Thus in order for fibres to have carcinogenic potential, they must first be of respirable size. Scientists are clear to point out however that respirability. though nec essary. is not sufficient in explaining car cinogenic potential. Fibres which are res pirable are not necessarily carcinogenic. A significant body of research has examined why some fibres of respirable size are either less carcinogenic or not carcinogenic at ail. Several factors seem to come into play. Generally speaking, there is ample evidence from experimental studies which demon strates that while iong, thin fibres are asso ciated witn pathological manifestations in animais. no such association is found witn fibres snorter than 5|Jm long. In 1989. world-renowned epidemiologist Sir Richard Doll, indicated that "there is increasing evidence that short fibres -- properly described as elongated particles -- are much less carcinogenic, if they are car cinogenic at all. We should base our esti mate of potential risk on both the chemical constitution of the fibres and their size, counting only those fibres that are res pirable and more than Sum long" (IARC bcientiric Publication No. 90. Lyon). In attempting to explain this phenomenon. researchers have discovered that short fibres can be cleared hv the body's natural defens es without provoking inflammation or mesotheliai injury. However, long fibres appear to induce the secretion of inflamma tory substances bv macrophage cells. A recent report by scientists at the Institute ot Occupational Medicine in Edinburgh, has identified such a substance called TNF or Tumor Necrosis Factor, which is released by activated alveolar macrophages. As scientists have continued to unravel the reasons for the pathogenicity of longer, res pirable fibres, they have discovered that fibre length alone cannot explain the wide variance in the carcinogenic potential of different substances. Different fibres of sim ilar dimensions mav vary significantly in tneir health effects. With the evolution of new techniques of chemical and mineral analysis, referred to as tissue burden, an additional parameter of fibrous materials is now recognized as of paramount impor tance to our understanding of the patho genic potential of respirable fibres. Chrvsotile Low on the Continuum of In Vivo Durability Durability varies widely among different respirable fibres. It appears to be related to a substance's chemical composition and crystalline configuration, in terms of health effects, researchers have focussed on the extent to which the durability of a sub stance determines its "bionersistence". or the length of time which inhaled fibres per sist in the lung beiore they are eventually dissolved ano/or cleared. In general, the ionger an inhaled particle persists in th_ iung. the more likely it is to adversely affect surrounding tissues. biopersistence studies have been carried ou: on a number of dinerent respirable fibres. 'see Carcinogenicity on page 5 HWBUI0003888