Document 5Lxqq8QMmLNoMVoonxw9xaMKJ

as ji proierstand the :s of fibrous lanner that is ise concerned FEBRUARYALVY 1993 ! THE ASBESTOS INSTT f f.s%e;rn s -i tt--r-'ci- Miesa-ft-sursrru -l- Dose-response research using mass rather thanfibre counts has resulted in overestimations ofthe health effects t rysotile asbestos. .*ason. l.P. :tion in Rats on with l Fiber inhat Toxicol. "ksbop on ?ecls. Environ 268. 'logical Effects i. Med.. 1989. hr' *ion to.xici )fiscbcr . v. r>ress > Towards an Understanding of the Carcinogenicity of Fibrous Materi: The last decade has seen great advances in scientific understanding of genic potential of some fibres. Recent studies of fibre dimensions, dura dose-response relationships are helping to explain why some fibres, sue 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 care materials. Today, sc carcinogenicity of fi: interaction between durability' or bio-pers The dose makes In the l6th centun Paracelsius wrote th: toxic. The differenc {see Card, Inside Health Effects of Low Levels of Chrysotile Exposure Changes Required to Fibre Research Methodology' MMMF Research Update Environment Canada Study Reading List Asbestos Fibres in the General Environment Studies find extremely low concentrations short asbestos fibres in the general envirt A number of studies have been conducted in recent years to respond to concerns over what health risks, it 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 environment The vast majority of: ronment (air. soil, w natural phenomena asbestos was oresen similar quantities j and used commerce tseet HWBUI0012235 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 grams devised to better understand nature of the health effects of fibi materials provide data in a manner th meaningful and useful to those conce 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 daysAveek MMVF10* MMVF11RCP 30 mg/M^ 30 mg/M^ 232 f/cc 246 t/ce 30 mg/M^ 1B7 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* lOmg/M^ 10 600 f/cc Wagner PGS: 4 Lung tumours: 13(18%) Mesothelioma: 1 (1.4%) B) THE ElXPERIMENIT WHICH WJkS NEVER CARRIED OUT Chrysotile O.IBmg/M3 200 l/ee ? Hesterberg, T.W. et al. (1993). Fund. Apol. Toxicol, (in the 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: MnimaJ fibrosis 2. Minimal: Macrophage response 5. Mild: Unking fibrosis 3. Mild: Inflammation, broochiofeabon 6. Moderate: ConsoJidafon 7. Severe: Mamed fibrosis and consolidation 8. Severe: Complete obstruction of most airways Dose-ri researc rather. counts in over ofchry asbesti 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 ; davs/wk for 2a months to -250 f/ml for MMVFs. - ISO f/ml for RCF and lO.OOu f/ml for chrvsotiie 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.l Relative Mesothelioma Induction in by Mineral Fibres: Comparison with Residual Pulmonary Mineral Fiber Number and Epidemiology, lnhal To 1992:-S:2'?-M)0. Dement. I.M. Overview: Workshop o Fiber Toxicology-Research Needs. En' Health Perspect 1990:88:261-268. Durtnigan. I. Comparing Biological i ofMineral Fibres. Brit..I. Ind. Med.. -(6:681-682. Hesierburg et al. Chronic inhalation try of size-separated glass fibers in F f-te rats Fund Appl Toxicol, tin pre HWBUI0012236 Carcinogenicity... :-nd it has now become clear that there are vast differences among various respirable fibres presently used in industry. At the 1992 WHO/1ARC (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. ibroken down'. .Animal studies from the institute or 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 ibiological fluid simulation) research have been conducted to evaluate the biopersis tence of different inhalable fibres. It has oeen demonstrated that for asbestos fibres. chrysotile has low durability' and short per sistence, while amphiboles are highly durable and persistent. While chrvsotiie 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 bioperststence and solubility of different fibres, depending on their respective manufactur ing process and chemical composition. For example, glass fibres with high aluminum i 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 rrom the lung ranged from 10 to 500 dais. .Another study on durability from the 1.5. renorted that inhaled RCFs showed no chemical alterations two years following end of exposure, whereas glass fibres snowed that some comnonents had leached CROCIDOLITE ASBESTOS REFRACTORY CERAMIC FIBRES (HIGH Al OXIDE** . '.LOW Al OXIDE hhhhhmhi bi AMOSITE ASBESTOS BBS MHBHH BBB 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. Similarly, fibres which are less than 5um in length can be easily eliminated by the bodv s natural defense mechanisms. Fibres of 10. 20 or 30,11m and longer are increasingly liKelv to escape macrophage elimination and remain in the lungs. in addition to the scientific ramifications of this avenue o: study, there can be practical and regulator.4 implications as well. increasing;-.', regulations will have to focus on imre cnaracteristics and descriptions ratner 'man ::: mineral or trade names. As CHRYSOTHE ASBESTOS (HIGH A! V GLASS (LOW AIM) BBB BBB SLAG ROCK BBB References: Churg. A.. Lung. Asbestos Content in Long term Residents of a Chrysotile Mining Toil'll. Amer. Rev. Resp. Dis.. 1986. 154(1): 125-12- Davis. .IMG et al. The Pathogenicity of Long l-s Short Fibre Samples ofAmosite Asbestos Administered to Rats by Inhalation and intrapentoneal Injection. Brit. I. Exp. Pathol. . 1986. 6":415-430. Moali. P.A.. Macdonald. I.L.. and Kane. A.B. (198~). Acute injury and regeneration of the mesorbelium in response to asbestos fibres. Amer. .1. of Path. 128 (5): 426-445. Newhouse. M.L.& Sullivan. K.R.. A Mortality Study of Workers Manufacturing Friction Materials: 1941-1086. Brit. I. Ind. Med.. 1989. *6(5): l-6-l"9. Ohlson. C.G. and Hogstedt. C.. Lung Cancer Among Asbestos Cement Workers: A Swedish Cohort Study and Review. Brit. I. Ind. Med.. 1985. ^2(6): 59--J02. Thomas. H.F.. Benjamin. I.T.. Elwood. P.C. & Su-eetman. P.M. Further Follow-up Study of W orkers from an Asbestos Cement Facton: Brit. .1. ind. Med.. 1982. 59(5): W right. G XV. & Kuschnen. M. The Influence of Varying Lengths of Glass and Asbestos Fibres on Tissue Response in Guinea Figs. Proceedings of the International Symposium ot the British Occ. Hyg. Sociery. Edinburgh, sememner slS-r , j HWBUI0012237