Document QkROkGa8xB13ZDdO0qMJV8K88

Carcinogenicity... and it has now become clear that there are ast differences among various respirable bores presently used in industry. At the 1992 WHO/IARC (Lyon) Symposium on Biopersistence of Respirable Synthetic Fibres and Minerals, there was a strong consensus mat there appears to be a continuum of val ues for biopersistence ranging from ver\ snort persistence (low durability) to practi cally indefinite persistence (very high dura bility) among the various respirable materi als tested. tbroKen aov-n'. .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 ver- ntiie 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 regulatory 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 (Diological fluid simulation) research have ceen conducted to evaluate the bioperststence of different inhalable fibres. It has been demonstrated that for asbestosl'ibres. 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 halt-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 i Ait 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 glass to RCFs) and natural fibres for m vivo durability Half times for fibre elimination trom the lung ranged from 10 to 500 davs .Another study on durability from the L.S reported that inhaled RCFs showed no cnemical alterations two years following end of exposure, whereas glass fibres snowed that some components had leached CROCIOOUTE ASBESTOS REFRACTORY CERAMIC FtBRES (HIGH A) OXIDE S (LOW Al OXDE %) AMOSrTE ASBESTOS VERY HIGH DURABILITY 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 Simnariy. fibres which are less than 5um m length can be easily eliminated by the bodv s natural defense mechanisms. Fibres of 10. 20 or 30um and longer are increasingly likelv to escape macrophage elimination ana remain in the lungs In addition to the scientific ramifications of this avenue or study, there can be practical and regulator.' implications as well increasingly, regulations will have to focus on nore cnaracteristics and descriptions ratner man , r. mineral or trade names. .As CHBYSOHLg ASBESTOS (HIGH AJ V GLASS flOWAJ*) SLAG ROCK ' rff * tug? r:,-. References Churg. A.. Lung. Asbestos Content in Long term Residents of a Chrysotile Mining Town. Amer. Rev. Resp. Dis . 1986. 13-4(1)' 125-12" Davis. IMG et al. The Pathogenicity ofLong Vi Short Fibre Samples ofAmosite Asbestos Administered to Rats by inhalation and Intrapentoneal Injection. Bnt. l. Exp. Pathol . 1986. 6" -i 15-430 Moali. P A.. Macdonald. I.L . and Kane. A.B (198"). Acute injury and regeneration of the mesothelium m response to asbestos fibres. Amer..I of Path 128 (3): -426-445. .Newhouse. M.L. & Sullivan. K.R.. A Mortality Study of Workers Manufacturing Friction Materials 1941-1980. Bnt. 1. Ind. Med.. 1989. -i6(3). 1~6-1 "9. Ohlson. C G. and Hogstedt. C.. Lung Cancer Among Asbestos Cement Workers: A Swedish Cohort Study and Review. Bnt .1. Ind Med 1985.-i2(6) 397-)02. Thomas. H F.. Beniamin. I.T.. Elwood. P C. & Sweetman P M Further Follow-up Study of U orkers rrom an Asbestos Cement Factory Bnt. I. Ind Med . 1982. 39(3). 2~3-2"6 Wright. G W. & Kuschnen M. 1he Influence of \ drying Lengths of Class and Asbestos Fibres on Tissue Response in Guinea Pigs. Proceedings of the International Symposium ot the Bntish Occ Hvg. Society. Edinburgh September. 19"5 a55~i" i HWBUI0012674 MMMF Research Update A Case-Control Study of Malignant and Non-Malignant Respiratory Disease Among Employees of a Fibreglass Manufacturing Facility Chiazze. L. et a!. British journal of Industrial Medicine, eh. 1992. A case-control study conducted on workers of a fibreglass plant nas concluded to a sta tistically sigmticar.t increase in respiratory cancer. The result or this study have been reevaluated to include non-workplace fac tors. such as cigarette smoking. Results of the interview portion of the case-control study cleariy indicate that smoking is the most important non-workplace factor for risk of lung cancer in mis group of workers. Lung Function in Insulation Workers Clausen. ].. Xetterstrdm. B. & Wolff. C.. British Journal of Industrial Medicine. 1993:50- 252-25c To evaluate the enects of working with modern msulatrer. materials (rock and glass wooh ir.r members of the Copenhagen l men oi insulation Workers were invited to participate in a study based on a health examination that included lung function tests such as forced vital capacity (FYC) ana torced expiratory' vol ume in one second <FE\,). No differences in FVC were ooser.ed between the experi mental and control groups, but insulation workers were found to have significantly lower FEN i \aiues. independent of smoking. In addition, a foimw-up of workers who had participated m a similar study six vears ear lier found mat me decline m FVC for insu lation workers vno smoited was significant ly greater than ior smokers from th^control group in the present studv. the decline in FE\] was sistniticar.:.'. msner tor insulation workers, independent ot smoking habits. i Reading ListSelf-assessed termer exposure to asbestos was not associated with tung function in insulation worker ! Health Risks from Exposure to I Mineral Fibres: An The study concludes tnat working with j International Perspective j Edited by G.Gibbs. 1 Dunne.:::. M Kido& modem insulation materials is associated j T. Higashi. Captus I'niverstr. Press. 1993 with increased risk of developing obstructive lung disease. | A timely contribution trom international Environment Canada and Health and Welfare Canada Conduct a Study on the Potential Adverse Effects of Man-Made Mineral Fibres experts in the field of heaitr.-related effects of mineral fibres. Papers presented at the International Symposium on the Health Effects of Low Exposure to Fibrous Materials (Kitakvushu. Japan Nov..l99D i represent an updated overview of the curi rent assessment ot itealtn etrects of miner al fibres in both the occupational and general environment Tr.e report of the i workshop on biological indicators repre! sents an in depth evaluation or modern practices in health monitoring. The satel lite symposium introduces tne reader to current studies on mineral nores 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 EC0DEC1S10N. March I<^ (i.e. whether exDOSure to these substances j Each year, growing dup:.; awareness of causes harm to numan neanh or the envi I the environment create> sctenuiic contro- ronment). I versies that can have mmor impacts on I the business activities o: mam. industries. The first par; or this Federal Government The analysis presented snows that the study will evaluate exposure to these sub effects on business deper.c much more on the fierceness of the controversy than on stances in Canaca. in order to develop a j the regulations that are Ultimately imple- profile of MMMF use. Environment Canada I mented. The experience :: the asbestos has commissioned an industry survey to | industry is cited as an example of how an obtain information on the amounts of these i environmental controvert can open the materials, whicn are produced in. imported I door to scientific inexactitude and arouse to and exported trom Canada. Source' Thermal Insulation Association of Canada. TIAC Times. March 199? j strong public opinion ircrtt tne outset. A i frequent consequence is mat too much I attention is given to some problems to the i detriment of others, ieactttc to a wasteful . use of resources Fma.r -nvironmental We have moved... Our newoinccs re located r. 1002 Sherbrooke ! St. West. Suite ;"0 Montreal. Quebec. Canada. H3A 3L6. uur onone and tax numbers have remained me same controversv raises socie: - implicit eco logical standards" For industries, prevent: mg such controversies, c ensuring that their products meet me- standards has 1 become a necessn ]Dl roohe- s:;rr: Wi.' Telephone- 6 THE ASBESTOS buite Mom:?i Ouencc < Telex iiNSTAV INSTITUTE t.ara -- Telecopier fM-o X-i-i-l HWBUI0012675 FEBRUARY/MAY 1993 THE ASBESTOS INSTITUTE :ihs$jiesn s iwimvn*t x> f'-rta-- term*l 77rtey*e:; 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 nose, dimension and durability or bio-persistence. The dose makes the poison In the 16th century, tr.e Swiss physician Paracelsius wrote that an substances can be toxic. The difference oerween the remedy (see Carcinogenicity 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 matenals. 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 (ait soil, water, e:; i are the result of natural phenomena suer, as erosion. In fact, asbestos was present m me environment in similar quantities ion1: it was mined and used commercial! tsee tnnmiment on page 2) / HWBUI0012676 Environment... The Health Asbestos-containing materials : contribute little to environmental . Effects offibre levels Several studies have examined the effects of ; Low Levels ofweathering on asbestos-cement products. Meyer (1986) concluded that the increase in Chrysotileasbestos fibre concentrations in the near vicini- I ty of asbestos-cement cladding and roofing ; material caused by weathering is so small that 1 Exposureit moves into the range below the limit of i detection of SEM. In a similar study of emis sion measurements. Borneman and '. Hildebrandt (1986) found that airborne j The October 1992/January 1993 edition asbestos levels were significantly lower than ; of The Asbestos Institute Newsletter 0.001 f/cc. In 1991. the Western Australia ! 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 ' environmental asbestos. The final report was of a landmark studv 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 | workers born 1891-1920 who had sur- report found, based on air monitoring data i vived into 1976. It was conducted by gathered around schools with asbestos-cement roofs, that concentrations are unlikely to ' Drs. F.D.K. Liddell, A.D. McDonald and I J.C. McDonald who found that "In each exceed 0.002 f/cc and are more likely to be less than 0.0002 f/cc. | of six classes of exposure up to 300 i mpcf x years, the lung cancer SMR Most particles released into the environment are innocuous short tibres ; [Standard Mortality Ratio = observed mortalitv/expected mortality] was close to 1.3 (a total of 25-r 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 found to be exceedingly trend." (Abstract presented at the 9th low. other data shows those fibres detected are International Svmposium of likely to be short. Chattield (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 5pim. The 1984 Report of the The authors have expressed concern to us Royal Commission on Matters ofHeath and that the article's subtitle "Important study Safety Arising From the Use ofAsbestos m 1 finds that at exposure levels below a Ontario published similar findings. In its threshold of 50 f/cc. chrysotile asbestos review of environmental asbestos, it noted the is not linked to any increased incidence prevalence of very short fibres and low counts of lung cancer" could lead to misun (a maximum of 0.008-r t/cc of all lengths). derstanding. The notion of a threshold References available from the Asbestos Institute. was entirely our interpretation and not a direct quote of am of the authors or the studv's abstract, which made no mention of such a concept. We wish to add that our use of the mreshold con cept was not meant to reier 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 of 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 ot the prelimi nary report. The Asbestos Institute is in no wav 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 otnervvise would clearly be a distortion of 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 any other study is an invitation to reiax standards, but ratr.er that it supports our view that current exposure limits are realistic ana accentable. E HWBUI0012677 Changes Required to Fibre A workshop on fibre toxicology conducted by the .National Institute of Environmental Health Sciences (NIEHS) came to a similar conclusion. Its summary indicated that "A major failing 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. Research A) THE EXPERIMENTS AS CARRIED OUT 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 vary 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. Dosage used Mass Fibre number Observations following 24 months exposure 5 hrs/day; 5 days/week MMVF10* MMVF11' 30mg/M3 30 mg/M^ 232 f/cc 246 f/cc Wagner PGS*: 2.5 to 3 Wagner PGS: 2.5 to 3 RCF* 30mg/M3 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* lOmg/M3 10 600 t/cc Wagner PGS: 4 Lung tumours: 13 (18%) Mesothelioma: 1 (1.4%) B) THE EXPERIMENT WHICH WAS NEVER CARRIED OUT Chrysotile O.IBmg/M3 200 f/cc ? * Hesterberg, T.W. et aJ (1993), Fund Apol Toxicol, (in the press) ** Lee. K.P. etal. (1988), Fund. Appl. Toxicol 11.1-20 PGS: Wagner Pathology Gracing Scale Cellular changes Fibrosis 1. Normal 4. Minimal: Minimal fibrosis 2. Minimal' Macrophage response 5 Mid: Unking fibrosis 3. Mild: Inflammation, broochioii2atoon 6 Moderate: Consolidation 7 Severe: Marked fibrosis and consolidation 6 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 chrysotile asbestos. Close scrutiny of the experimen tal design reveals that the results reported are from animals exposed 6 hrs/day x 4 davs/wk for 24 months to -250 f/ml for MMVFs. -180 f/ml for RCF and 10.000 [/ml for chrysotile asbestos1 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, I.P Relative Mesothelioma Induction in Rats by Mineral Fibres: Comparison with Residual Pulmonary Mineral Fiber Sumber and Epidemiology. Inhal Toxicol. 1992:4:2"3-300 Dement. J..\l. Overview Workshop on Fiber Toxicology-Research Needs. Environ Health Perspect 1990:88:261-268. Dunnipan. J. Comparing Biological Effects ofMineral Fibres. Brit I. lnd Med.. 1989. 46:681-682. Hesterburg et al. Chronic inhalation toxic ity of siie-separated glass fibers in Fischer .144 rats. Fund Appl Toxicol, (in press) J HWBUI0012678 Carcinogenicity... and the poison lies in the amount: thus the otten-cited expression "the dose makes the poison A tew centuries later, the issue >: low-dose risk remains a hotly debated top:: in the scientific communin' Although the techniques, models and jargon have changed, the controversy essentially revolve? around the same basic question: "Is some thing that is toxic at high doses necessaniv toxic at much lower doses''" Elegant theo retical models of toxicity and carcinogenici ty are presented in response to this question, and yet in some respects we are no closer to a conclusive answer. The principal point o: contention centers around the possibility that even though no health effects may hr obsened. 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 postuiations. In the case of chrvsotile asbestos, there is a targe bodv of evidence that demonstrates that at low levels ot exDOsure. the carcinogenicity is zero or undetectanh evaluating carcinogenic potential. Fibre dimensions are important in that the;, determine whether a fibre is "respirable . borne 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 pom! 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 all Several factors seem to come into play. trom exnerimental studies which demonstrates that while long, thin fibres are assn- Newhouse & Sullivan. 1989: Ohison & animats, no such association is found with Hogstedt. 1985: Thomas et al, 1982: Liddell tibres shorter than Spun long. et al. 1992 and others detected no signm- 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 In 1989. world-renowned epidemiologist Sir Richard Doll, indicated that "there is increasing evidence that short fibres -- properly described as elongated particles -- than current occupational exposure limits are much less carcinogenic, if they are car cinogenic at all. We should base our esti Fibre Dimensions Mediate "Respirability" and Carcinogenicity7 mate of potential nsk on both the chemicai * constitution of the tibres and their size counting onlv those fibres that are res pirable and more than Sum long" (IARC Progress m the study of asbestos and other bcientihc Publication No. 90. Lyon) fibres made during the last 15 years has confirmed that fibre length and diameter are important parameters to consider ::: in attempting to explain this phenomenon researeners have discovered that short fibre? can be cleared hv the body's natural defens es without provoking inflammation or mesothehai miur- However, long fibres appear to induce the secretion of inflamma tory substances bv macrophage ceiis. A recent report by scientists at the Institute of 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 oi health effects, researchers have focussed on the extent to which the durability' of a sub stance determines its "bionersistence". or the length ot time which inhaled fibres per sist in the lung betore they are eventual iv dissolved ana/or cleared. In general, the longer an inhaled particle persists in th_iung. the more likely it is to adversely affect surrounding tissues. biopersistence studies have been carried out on a nuremer of different respirable fibre?. isee Caranopenicitv on pane '' HWBUI0012679