Document wgMEg404a3YzBenkQeJ27yXJ6

FEBRUARY/MAY 1993 THE ASBESTOS INSTITUTE *sre n s i -t o f a `n ya>'t~u *r -u l r c'tsnio ni 'rrcve 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 length 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 durability or bio-persistence. The dose makes the poison In the l6th century, the Swiss physician Paracelsius wrote that all substances can be toxic. The difference between the remedy (see Carcinogenicity on page T) 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 such as erosion. In fact, asbestos was present in the environment in similar quantities long eetore it W3S mine and used commercially. [seekmmnment on page 2) HWBUI0012382 Environment... i The Health Asbestos-containing materials i contribute little to environmental j Effects offibre levels j i Several studies have examined the effects of ! Low Levels ofweathering on asbestos-cement products. Meyer (1986) conduced that the increase in asbestos fibre concentrations in the near vicini ty of asbestos-cement cladding and roofing Chrysotile material caused by weathering is so small that it moves into the range belowythe limit of detection of SEM. In a similar study of emis Exposure sion measurements. Borneman and Hildebrandt (1986 > found that airborne ' asbestos levels were significantly lower than 0.001 f/cc. In 1991- the Western Australia Department of Occupational Health. Safety and Welfare conducted an extensive review of environmental asbestos. The final report was comprised of school surveys, measurement studies and a literature renew of the topic. The report found, based on air monitoring data gathered around schools with asbestos-cement roofs, that concentrations are unlikely to exceed 0.002 f/ec and are more likely to be less than 0.0002 f/cc. The October 1992/lanuary 1993 edition of The Asbestos Institute Newsletter published as its lead story, a summary and analysis of the preliminary results of a landmark stud;.' of the health effects of exposure to chrysotile. The study was of 5.351 Quebec asbestos workers born 1891-1920 who had sur vived into 1976. It was conducted by Drs. F.D.K. Liddell. A.D. McDonald and 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 I mdrtality/expected mortality] was close | to 13 (a total oL254 cases of lung can- j eer "among 4.38a men. against 190.6 In addition to the fact that environmental con centrations have been found to be exceedingly low. other data shows those fibres detected are expected): there was no evidence of a 'trend." (Abstract presented at the 9th International Symposium of likely to be short Chatfield (1983) reported to Epidemiology in Occupational Health, a Government of Sweden Symposium, that between 95 to 98o of fibres observed were Cincinnati, 1992). shorter than 5|um. The 1984 Report of the The authors have expressed concern to us Royal Commission on Matters ofHealth arid | that the article's subtitle "Important study Safety Arising From the Use ofAsbestos in i finds that at exposure levels below a Ontario published similar findings. In its j threshold of 50 f/cc. chrysotile asbestos review of environmental asbestos, it noted the i is not linked to any increased incidence prevalence of very short fibres and low counts i of lung cancer" could lead to misun(a maximum of 0.008-t f/'cc of all lengths). : derstanding. The notion of a threshold References available from The Asbestos Institute. i was entirely our interpretation and not : a direct quote of any 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 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 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 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 ar. invitation to relax standards, but rather that it sup ports our view that current exposure limits are realistic arm acceptable. B ') \ > HWBUI0012383 } 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 toxicology7 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. A) THE EXPERIMENTS AS CARRIED OUT Dosage used Mass Fibre number Observations following 24 montns exposure 5 hrs/day; 5 days/week MMVF10" MMVF11* RCP 30 mg/M^ 30 mg/M^ 30 mg/M^ 232 i/ce 246 f/cc 187 f/cc Wagner PGS+: 2.5 to 3 Wagner PGS: 2.5 to 3 Wagner PGS: 4 Lung tumours: 16(13.0%) Mesothelioma: 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%) Mesothelioma: 1 (1.4%) B) THE EXPERIMENT WHICH WAS NEVER CARRIED OUT Chrysotile O.iamg/M3 200 f/cc ? Hesterberg, T.W. etal. (1993), Fund Appl. Toxicol, (in tne press) Lee, K.P. et al. (1968), Fund Appl. Toxicol. 11:1-20 PGS: Wagner Pathology Gracing Scale Cellular changes Fibrosis 1. Normal 4. Minimal: Mnimal fibrosis Z Minimal: Macrophage response 5. Mild: Unking fiorosis 3. Mild: Inflammation, bronohiohzation 6. Moderate: Consolidation 7. Severe: Mamad fibrosis arc consolidation 6. Severe: Complete obstruction of most airways Dose-response research using mass rather thanfibre counts has resulted in overesimations 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 refractoryceramic 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 ; days/wk for 24 months to -250 f/ml for MMVFs. -180 f/ml for RCF and 10.000 I/ml for chrysotile 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 lim References: Coffin. D.L.. Cook, P.M. & Creason, J.P. Relative Mesothelioma Induction in Rats . by Mineral Fibres: Comparison with Residual Pulmonary Mineral Fiber Sumber and Epidemiology'. Inhal Toxicol. 1992:4:2"J-300. Dementi J.M. Overview: Workshop on Fiber Toxicology-Research Needs. Environ Health Perspect 1990:88:261-268. Dunnigan. j. Comparing Biological Effects ofMineral Fibres. Brit. J. lnd. Med.. 1989. 46 :681-6S2. Hesterburg et al. Chronic inhalation toxic ity ofsize-separated glassfibers in Fischer .144 rats. Fund Appl Toxicol, (in press) HWBUI0012384 Carcinogenicity... and the poison lies in the amount: thus the evaluating carcinogenic potential. Fibre often-cited expression "the dose makes the poison". A few centuries later, the issue .v low-dose risk remains a hotly debated topi: in the scientific community. .Although the techniques, models and jargon have dimensions are important in that they determine whether a fibre is respirabic . Some particles or fibres are too large to infiltrate into the lungs. They are blocked by the body's natural filtration svstem. 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 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 health1 effects may hr observed, it is possible that these effects exist, but are undetectable using current data and methodology. .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 3(Jm 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 essary7, is not sufficient in explaining car cinogenic potential. Fibres which are res pirable are not necessarily carcinogenic. 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. 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. there is a large body of evidence'that "demonstrates that at low levels of exposure, the carcinogenicity is zero or undetectabr. low. The researcli oi Cnurg. 1980: Newhouse & Sullivan, 1989: Ohlson & Hogstedt. 1985: -Thomas et al. 19S2: Liddell et al, 1992 and others detected no signifi Generally speaking, there is ample evidence from experimental studies which demon strates that while long, thin fibres are asso ciated with pathological manifestations in animals, no such association is round with fibres shorter than 5Mm long. cant excess mortality amongst workers exposed to low levels of chrysolite. Moreover, the low levels of exposure, as defined in some of these studies, are still much higher than current occupational exposure limits. 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 Fibre Dimensions Mediate "Resoirabiiitv" and Carcinogenicity7 mate of potential risk on both me chemical * constitution of the fibres and their size, counting only those fibres that are res pirable and more than 5um long" (I.ARC Progress in the study of asbestos and other Scientific Publication No. 90. Lyon 1. fibres made during the last 15.years has confirmed that fibre length and diameter are important parameters to consider m In attempting to explain this phenomenon, researchers have discovered that short fibres can be cleared bv the body's natural defens es without provoking inflammation or mesothelial injury. However, long fibres appear to induce the secretion ot inflamma tory substances bv macrophage cells. A recent report by scientists at the Institute of Occupational Medicine in Edinburgh, has identified such a substance called TXF or Tumor Necrosis Factor, which is released by activated alveolar macrophages. .As scientists have continued to unravel the reasons for the pathogenicity7 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 van7 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 ofIn Vivo Durability7 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 before they are eventually dissolved and/or cleared. In general, the ionger an inhaled particle persists in the lung, the more likely it is to adversely affect surrounding tissues. Biopersistence studies have been carried out on a number of different respirable fibres, (see Carcinogenicity on pasc 5: > HWBUI0012385 Carcinogenicity... :1:1a it has now become clear that there are vast differences among various respirable f ores presently used in industry. At the 1992 V'i'HO/lARC (Lyon) Symposium on Biopersistence of Respirable Synthetic Fibres and Minerals, there was a strong consensus that there appears to be a continuum of val ves for biopersistence ranging from very short persistence (low durability7.) to practi cally indefinite persistence (very high dura bility) among the various respirable materi als tested. (broken down . .Animal studies from the Institute of 'occupational Medicine in Edinburgh showed that chrysotile asbestos and the glass fibres tested were cleared at approximately the same rate, whereas there was very little 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 'biological fluid simulation) research have been conducted to evaluate the biopersis tence 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). data has shown wide variability in the biop ersistence and solubility of different fibres, depending on their respective manufactur ing process and chemical composition. For example, giass fibres with high aluminum (Al) 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. .Another study on durability from the U.S. reported that inhaled RCFs showed no chemical alterations two years following end of exposure, whereas glass fibres snowed that some components had leached CROCIDOUTE ASBESTCS REFRACTORY CERAMIC FIBRES (HIGH Al OXIDE % :LOW Al OXIDE %) AMOSITE ASEESTOS VERY HIGH DURABHJTY CHRYSOTILE ASBESTOS (HIGH Al w GLASS (LOW A) %) SLAG ROCK a m Ail 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 eetectable' health effects. All other things being equal, as the dose increases so 100 will the potential health risks. Similarly, fibres which are less than 5fJm in iengtn can be easily eliminated by the body s natural defense mechanisms. Fibres of 10. 20 or 30pm and longer are increasingly litteiv to escape macrophage elimination ana remain in the lungs. In addition to me scientific ramifications of this avenue or study, there can be practical and regular::;.- implications as well. Increasingly regulations will have to focus on imre characteristics and descriptions ratner man 0 n mineral or trade names. As 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. JMG et al. The Pathogenicity ofLOg Vs Short Fibre Samples ofAmosite Asbestos Administered to Rats by inhalation and Intraperitoneal Injection. Brit. J. Exp. Pathol. . 1986. 6-:4I5-430. Moali. P.A.. Macdonald. I.L.. and Kane. A.B. (1987). Acute injury and regeneration of the mesothelium in 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: 1941-1086. Brit..). Ind. Med.. 1989. 46(31: 1"6-1"9. Ohlson. C.G. and Hogstedt. C.. Lung Cancer Among Asbestos Cement Workers: A Swedish Cohort Study and Revietc. Brit. I. Ind. Med.. 1985. 42(6) : 39"7-402. Thomas. H.F.. Benjamin. I.T.. Elwood. P.C. & Sweetman. P.M. Further Follow-up Study of Workers from an Asbestos Cement Factory. Brit. .1. In'd. Med.. 1982. 39(3) : 27.3-2-6. Wright. G.V. & Kuschnen. M. The Influence of Varying Lengths of Glass and Asbestos Fibres on Tissue Response in Guinea Pigs. Proceedings of the International Symposium of the British Occ. Hyg. Society. Edinburgh. September. 19"5 : 455-1-.;. HWBUI0012386 MMMF Research Update workers, independent of smoking habits. Self-assessed former exposure to asbestos was not associated with lung function in insulation workers. A Case-Control Study of Malignant and Non-Malignant Respiratory Disease Among Employees of a Fibreglass Manufacturing Facility7 Chiazze. L. et al. British Journal of Industrial Medicine. -*9-1992. The study concludes that working with modern insulation materials is associated with increased risk of developing obstructive lung disease. Environment A case-control study conducted on workers of a fibreglass plant has concluded to a sta tistically significant increase in respiratory cancer. The results of 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 clearly indicate that smoking is the most important non-workplace factor for risk of lung cancer in this group of workers. Lung Function in Insulation Workers Clausen, J.. Xetterstrom. B. & Wolff. C.. British Journal of Industrial Medicine. 1993; 50:252-256. To evaluate the effects of working with modern insulation materials (rocffand glass wool) the members of the Copenhagen Union of Insulation Workers were invited to participate in a study based on a health examination that included lung function tests such as forced vital capacity (FTC) and forced expiratory vol ume in one second (FEVj). No differences in FVC were observed between the experi mental and control groups, but insulation workers were found to have significantly lower FEY] values, independent of smoking.' Canada and Health and Welfare Canada Conduct a Study on the Potential Adverse Effects of Man-Made Mineral Fibres Mineral fibres are on Canada's Environmental Protection Act's priority' list. All substances that appear on this list must be assessed to determine whether they are toxic, as defined in Section 11 of the Act fi.e. whether exposure to these substances causes harm to human health or the envi ronment) . The first part of this Federal Government study will .evaluate exposure to these sub stances in Canada. In order to develop a profile of MMMF use. Environment Canada has commissioned an industry1 survey to obtain information on the amounts of these materials, which are produced in. imported to and exported from Canada. L In addition, a follow-up of workers who had' participated in a similar study six years ear lier found that the decline in FYC for insu lation workers who smoked was significant ly greater than for smokers from the control group. In the present study, the decline in FEY] was signiricantiy higher for insulation Source: Thermal Insulation Association of Canada. T1AC Times. March 1993 We have moved... Our new offices are located at 1002 Sherbrooke ' St. West. Suite T50. Montreal. Quebec. Canada. H3A3L6. Our phone and fax numbers have remained the same. Reading List Health Risks from Exposure to Mineral Fibres: An International Perspective Edited by G.Gibbs. 1. Dunnican. M. Kido T. Higashi. Captus University Press. 1993 A timely contribution from international experts in the field of health-related effects of mineral fibres: Papers presented at the International Symposium on the Health Effects of Low Exposure to Fibrous Materials (Kitakvushu. Japan: Nov.,1991) represent an updated overview of the cur rent, assessment of health effects of miner al fibres in both the occupational and general environment. The report of the workshop on biological indicators repre sents an in depth evaluation of modern practices in health monitonng. The satel lite symposium introduces the reader to current studies on mineral fibres in Japan and other Asian countries. The Effects of an Environmental Controversy on Industry: The Asbestos Experience ECODECISION. March 199: Each year, growing public awareness of die environment creates scientific contro versies that can have ma:or impacts on the business activities or many industries. The analysis presented snows that the effects on business depend much more on the fierceness of the controversy than on the regulations that are ultimately imple mented. The experience of the asbestos industry is cited as an example of how an environmental controversy can open the door to scientific inexactitude and arouse strong public opinion'irom the outset. A frequent consequence is that too much attention is given to some problems to the detriment of others, leading to a wasteful use of resources. Finally, environmental controversy raises society's "implicit eco logical standards". For industries, prevent ing such controversies bv ensuring that their products meet these standards has become a necessitv 6 THE ASBESTOS linj >r.rrr>ronKe Mrcet Wc'i iuite Montreal (Quebec. ) Tdconwi'.v 'M-n Telex: (INSTAM INSTITUTE CaiTAJ..-. H;A ' Telecnr:er ^hi S-m-1 a.v. HWBUI0012387