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Asbestos and other natural mineral fibres (EHC 53, 1986) rvcii Gil INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY ENVIRONMENTAL HEALTH CRITERIA 53 ASBESTOS AND OTHER NATURAL MINERAL FIBRES Page 1 of 129 This report contains the collective views of an international group of experts and does not necessarily represent the decisions or the stated policy of the United Nations Environment Programme, the International Labour Organisation, or the World Health Organization. Published under the joint sponsorship of the United Nations Environment Programme, the International Labour Organisation, and the World Health Organization World Health Orgnization Geneva, 1986 The International Programme on Chemical Safety (IPCS) is a joint venture of the United Nations Environment Programme, the International Labour Organisation, and the World Health Organization. The main objective of the IPCS is to carry out and disseminate evaluations of the effects of chemicals on human health and the quality of the environment. Supporting activities include the development of epidemiological, experimental laboratory, and risk-assessment methods that could produce internationally comparable results, and the development of manpower in the field of toxicology, other activities carried out by the IPCS include the development of know-how for coping with chemical accidents, coordination of laboratory testing and epidemiological studies, and promotion of research on the mechanisms of the biological action of chemicals. PLAINTIFFS EXHIBIT ISBN 92 4 154193 8 The World Health Organization welcomes requests for permission to reproduce or translate its publications, in part or in full. Applications and enquiries should be addressed to the Office of Publications, World Health Organization, Geneva, Switzerland, which will be glad to provide the latest information on any changes made to the text, plans for new editions, and reprints and translations PLAINTIFFS EXHIBIT 32QOQ.VO http ://\v\v\v. inchem.org/docurnents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 2 of 129 already available. 7 World Health Organization 1986 Publications of the World Health Organization enjoy copyright protection in accordance with the provisions of Protocol 2 of the Universal Copyright Convention. All rights reserved. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. The mention of specific companies or of certain manufacturers' products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. CONTENTS ENVIRONMENTAL HEALTH CRITERIA FOR ASBESTOS AND OTHER NATURAL MINERAL FIBRES 1. SUMMARY AND RECOMMENDATIONS FOR FURTHER RESEARCH 1.1 1.2 Summary 1.1.1 Identity; physical and chemical properties, methods of sampling and analysis 1.1.2 Sources of occupational and environmental exposure 1.1.3 Environmental levels and exposures 1.1.4 Toxicological effects on animals 1.1.5 Effects on man 1.1.6 Evaluation of health risks Recommendations for further research 2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, SAMPLING AND ANALYSIS 2.2 1.3 Identity; physical and chemical properties of asbestos minerals 2.1 Serpentine group minerals chrysotile 2.1 Amphibole group minerals 2.1.2.1 Crocidolite (Riebeckite asbestos) 2.1.2.2 Amosite (Grunerite asbestos) 2.1.2.3 Anthophyllite asbestos 2.1.2.4 Tremolite and actinolite asbestos Identity; physical and chemical properties of other natural mineral fibres 2.2.1 Fibrous zeolites 2.2.2 Other fibrous silicates (attapulgite, sepiolite, and wollastonite) Sampling and analytical methods 2.3.1 Collection and preparation of samples 2 . 3 . 1 . 1 Air 2.3 . 1.2 Water 2.3.1.3 Biological tissues 2.3.1.4 Geological samples 2.3.2 Analysis http://\v\vw. incheni.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 3 of 129 2.3.3 2.3.4 2.3.2.1 Light microscopy 2.3.2.2 Electron microscopy 2.3.2.3 Gravimetric determination Other methods Relationships between fibre, particle, concentration and mass 3. SOURCES OF OCCUPATIONAL AND ENVIRONMENTAL EXPOSURE 3.1 3.2 Natural occurrence Man-made sources 3.2.1 Asbestos 3.2.1.1 Production 3.2.1.2 Mining and milling 3.2.1.3 Uses 3.2.2 3.2.3 3.2.4 Other natural mineral fibres Manufacture of products containing asbestos 3.2.3.1 Asbestos - cement products 3.2.3.2 Vinyl asbestos floor tiles 3.2.3.3 Asbestos paper and felt 3.2.3.4 Friction materials (brake linings and clutch facings) 3.2.3.5 Asbestos textiles Use of products containing asbestos 4. TRANSPORT AND ENVIRONMENTAL FATE 4.1 4.2 Transport and distribution 4.1.1 Transport and distribution in air 4.1.2 Transport and distribution in water Environmental transformation, interaction, and degradation processes 5. ENVIRONMENTAL EXPOSURE LEVELS 5.1 Air 5.1.1 Occupational exposure 5.1.2 Para-occupational exposure 5.1.3 Ambient air 5.2 Levels in other media 6. DEPOSITION, TRANSLOCATION, AND CLEARANCE 6.1 6.2 Inhalation 6.1.1 Asbestos 6.1.1.1 Fibre deposition 6.1.1.2 Fibre clearance, retention,and translocation 6.1.2 Ferruginous bodies 6.1.3 Content of fibres in the respiratory tract Ingestion 7. EFFECTS ON ANIMALS AND CELLS 7.1 Asbestos 7.1.1 Fibrogenicity 7.1.1.1 Inhalation 7.1.1.2 Intrapleural and intraperitoneal injection 7.1.1.3 Ingestion 7.1.2 Carcinogenicity 7.1.2.1 Inhalation 7.1.2.2 Intratracheal instillation 7. 1.2.3 Direct administration into body cavities 7.1.2.4 Ingestion http://www.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 4 of 129 7.1.3 In vitro studies 7.1 . 3 . 1 Haemolysis 7 . 1 . 3 . 2 Macrophages 7.1.3.3 Fibroblasts 7.1.3.4 Cell-lines and interaction with DNA 7.1.3 . 5 Mechanisms of fibrogenic and carcinogenic action of asbestos Other 7.2.1 7.2.2 7.2.3 7.2.4 7 . 1.3 . 6 Factors modifying carcinogenicity natural imineral fibres Fibrous clays 7.2 .1.1 Palygorskite (Attapulgite) 7.2 . 1 . 2 Sepiolite Wollastonite Fibrous zeolites - erionite Assessment EFFECTS ON MAN 8.1 Asbestos 8.1.1 Occupational exposure 8.1.1.1 Asbestosis 8.1.1.2 Pleural thickening, visceral, and parietal 8.1.1.3 Bronchial cancer 8.1.1.4 Mesothelioma 8.1.1.5 Other cancers 8.1.1.6 Effects on the immune system 8.1.2 Para-occupational exposure 8.1.2.1 Neighbourhood exposure 8.1.2.2 Household exposure 8.1.3 General population exposure 8 . 2 Other natural mineral fibres 8.2.1 Fibrous clays 8.2.1.1 Palygorskite (Attapulgite) 8.2 . 1.2 Sepiolite 8.2.2 Wollastonite 8.2.3 Fibrous zeolites - erionite 9. EVALUATION OF HEALTH RISKS FOR MAN FROM EXPOSURE TO ASBESTOS AND OTHER NATURAL MINERAL FIBRES 9.1 9.2 9.3 Asbestos 9.1.1 General considerations 9.1.2 Qualitative approach 9.1.2.1 Occupational 9.1.2.2 Para-occupational exposure 9.1.2. 3 General population exposure 9.1.3 Quantitative approach 9.1.3.1 Bronchial cancer 9.1.3.2 Mesothelioma 9.1.3.3 Risk assessment based on mesothelioma incidence in women 9.1.4 Estimating the risk of gastrointestinal cancer Other natural mineral fibres Conclusions 9.3.1 Asbestos 9.3.1.1 Occupational risks 9.3.1.2 Para-occupational risks 9.3.1.3 General population risks 9.3.2 Other mineral fibres 10. PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES 10.1 IARC http:,Vwww. inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) 10.2 CEC REFERENCES WHO TASK GROUP ON ASBESTOS AND OTHER NATURAL MINERAL FIBRES Members Dr I.M. Ferreira, Department of Preventive and Social Medicine, Unicamp, Campinas, Brazil Dr J.C. Gilson, Hembury Hill Farm, Honiton, Devon, United Kingdom (Chairman) Professor M. Ikeda, Department of Environmental Health, Tohoku University School of Medicine, Sendai, Japan Dr V. Kodat, Department of Hygiene and Epidemiology, Ministry of Health of the Czech Socialist Republic, Prague, Vinohrady, Czechoslovakia Dr A.M. Langer, Environmental Sciences Laboratory, Mount Sinai School of Medicine, New York, New York, USA Dr F. Mansour, Amiantit, Saudi Arabia and Middle East, Damman, Saudi Arabia Ms M.E. Meek, Health and Welfare Canada, Health Protection Branch, Environmental Health Centre, Tunney's Pasture, Ottawa, Ontario, Canada (Rapporteur) Ms C. Sonich-Mullin, US Environmental Protection Agency, ECAO, Cincinnati, Ohio, USA Dr U.G. Oleru, College of Medicine, University of Lagos, Lagos, Nigeria (Vice-Chairman) Professor K. Robock, Institute for Applied Fibrous Dust Research, Neuss, Federal Republic of Germany Members from Other Organizations Dr A. Berlin, Commission of the European Communities, Luxembourg Dr A.R. Kolff van Oosterwijk, Commission of European Communities, Luxembourg Observers Dr K. Browne, Asbestos International Association, London, United Kingdom Dr E. Costa, Asbestos International Association (London), Genoa, Italv Dr J. Dunnigan, L'Institut de l'Amiante, Sherbrooke, Canada Dr Fischer, Federal Health Office, Berlin (West) Dr R. Konstanty, German Trade Union Congress, Diisseldorf, Federal Republic of Germany Mr L. Mazzuckelli, National Institute for Occupational Safety and http://\vww. inchem.org/documents/ehc/ehc/ehc53.htm Page 5 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 6 of 129 Health, Cincinnati, Ohio, USA Dr E. Meyer, Federal Health Office, Institute for Hygiene of Water, Soil, and Air, Berlin (West) Dr H.-J. Nantke, Umweltbundesamt, Berlin (West) Secretariat Professor F. Valic, IPCS Consultant, World Health Organization, Geneva, Switzerland (Secretary)a Dr A. David, International Labour Office, Geneva, Switzerland Mr A. Fletcher, International Agency for Research on Cancer, Lyons, France1 Ms B. Goelzer, Office of Occupational Health, World Health Organization, Geneva, Switzerland Dr H. Muhle, Fraunhofer Institute for Toxicology and Aerosol Research, Hanover, Federal Republic of Germany (Temporary Adviser) a Department of Public Health, Andrija Stampar School of Public Health, University of Zagreb, Zagreb, Yugoslavia D Present for only part of meeting. NOTE TO READERS OF THE CRITERIA DOCUMENTS Every effort has been made to present information in the criteria documents as accurately as possible without unduly delaying their publication. In the interest of all users of the environmental health criteria documents, readers are kindly requested to communicate any errors that may have occurred to the Manager of the International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland, in order that they may be included in corrigenda, which will appear in subsequent volumes. ENVIRONMENTAL HEALTH CRITERIA FOR ASBESTOS AND OTHER NATURAL MINERAL FIBRES Following the recommendations of the United Nations Conference on the Human Environment held in Stockholm in 1972, and in response to a number of resolutions of the World Health Assembly and a recommendation of the Governing Council of the United Nations Environment Programme, a programme on the integrated assessment of the health effects of environmental pollution was initiated in 1973. The programme, known as the WHO Environmental Health Criteria Programme, has been implemented with the support of the Environment Fund of the United Nations Environment Programme. In 1980, the Environmental Health Criteria Programme was incorporated into the International Programme on Chemical Safety (IPCS), a joint hup:/7w\v\v. inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 7 of 129 venture of the United Nations Environment Programme, the International Labour Organisation, and the World Health Organization. The Programme is responsible for the publication of a series of criteria documents. A WHO Task Group on Environmental Health Criteria for Asbestos and Other Natural Mineral Fibres was held at the Fraunhofer Institute for Toxicology and Aerosol Research, Hanover, Federal Republic of Germany from 15-22 July 1985. Professor W. Stober opened the meeting and greeted the members on behalf of the host institution, and Dr U. Schlottmann spoke on behalf of the Government. Professor F. Valic addressed the meeting on behalf of the three co-sponsoring organizations of the IPCS (WHO/ILO/UNEP). The Task Group reviewed and revised the draft criteria document and made an evaluation of the risks for human health from exposure to asbestos and other natural mineral fibres. The first draft of the document was a combination of texts prepared by DR H. MUHLE and DR K. SPURNY of the Fraunhofer Institute for Toxicology and Aerosol Research, Hanover, Federal Republic of Germany, PROFESSOR F. POTT of the Medical Institute for Environmental Hygiene, Diisseldorf, Federal Republic of Germany, PROFESSOR J. PETO, of the Institute of Cancer, University of London, London, United Kingdom, PROFESSOR M. LIPPMANN, of the Institute of Environmental Medicine, New York University Medical Center, New York, USA, MS M.E. MEEK, Department of National Health and Welfare, Ottawa, Canada, and DR J.F. STARA and MS C. SONICHMULLIN, of the US Environmental Protection Agency, Cincinnati, Ohio, USA. A Working Group consisting of PROFESSOR C. MCDONALD, MS M.E. MEEK, DR H. MUHLE, MS J. HUGHES, and PROFESSOR F. VALIC reviewed the first, and developed the second, draft. The efforts of all who helped in the preparation and finalization of the document are gratefully acknowledged. 1. SUMMARY AND RECOMMENDATIONS FOR FURTHER RESEARCH 1.1. Summary of sampling and analysis," >1.1.1. Identity; physical and chemical properties, me the The commercial term asbestos refers to a group of fibrous serpentine and amphibole minerals that have extraordinary tensile streng_thj _conduct heat poorly, and are relatively resistant to chemica1 attack. The principal varieties of asbestos used in commerce are chrysotile, a serpentine mineral, and crocidolite and amosite, both of which are amphiboles. Anthophvllite, tremolite. and actinolite asbestos are also amphiboles. but they are rare, and the commercial exploitation of anthophvllite asbestos has been discontinued. Other natural mineral fibres that are considered potentially hazardous because of their physical and chemical properties are erionite, wollastonite, attapulgite, and sepiolite. Chrysotile fibres consist of aggregates of long, thin, flexible fibrils__that resemble scrolls or cylinders. The dimensions of individual chrysotile fibres depend on the extent to which the samp1e has been manipulated. Amphibole fibres generally tend to be straight and splintery. Crocidolite fibrils are shorter with a smaller diameter than other amphibole fibrils, but they are not as narrow as fibrils of chrysotile. Amosite fibrils are larger in diameter than those of both crocidolite and chrysotile. Respirable http: 'wuw.inchem.org/docuirients/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 8 of 129 fractions of asbestos dust vary according to fibre type and manipulation. Several methods involving optical phase contrast microscopy have been developed for determining levels of asbestos fibres in the air of work-places. Only fibres over 5 urn in length with an aspect ratio > 3:1 and a diameter of less than 3 pm are counted. Thus, the resulting fibre count can be regarded only as an index of actual numbers of fibres present in the sample (fibres with diameters 1ess_.than the resolution of the light microscope are not included.in this assay).___Fibres with diameters smaller than approximately 0.25 um cannot be seen by light microscopy, and an electron microscope is necessary for counting and identifying these fibres. Electron microscopes that are equipped with auxiliary eguipment can provide information on both structure and elemental composition. The results of analysis using light microscopy can be compared with those using transmission or scanning electron microscopy, but only if the same counting criteria are used. of sampling and analysis">1.1.2.___ Sources of occupational and environmental exposur Asbestos is widely distributed in the earth's crust. Chrvsotile. which accounts for more than 95% of the world asbestos trade, occurs in virtually all serpentine rocks. The remainder consists of the amphiboles (amosite and crocidolite) . Chrvsotile deposits are currently exploited in more than 40 countries; most of these reserves are found in southern Africa, Canada, China, and the USSR. There are, reportedly, thousands of commercial and iiiaustnai. applications of asbestos. Dissemination of asbestos and other mineral fibres from natural deposits may be a source of exposure for the general population. Unfortunately, few quantitative data are available. Most of the asbestos_present in the atmosphere and ambient water probably results from the mining, milling, and manufacture of asbestos or from the deterioration or breakage of asbestos-containing ma t e rials , 1.1.3. Environmental levels and exposures _____ Asbestos is ubiquitous in the environment because of its extensive^industrial use and the dissemination of fibres from natural sources. Available data using currently-accepted methods of sampling and analysis indicate that fibre levels (fibres > 5 um in 1ength) at remote rural locations are generally below the detection limit (less than 1 fibre/litre), while those in urban air range from < 1 to 10 fibres/litre or occasionally hiqher. Airborne levels in residential areas in the vicinity of industrial sources have been found to be within the range of those in urban areas or occasionally slightly higher. Non-occupational indoor levels are generally within the range found in the ambient air. Occupational .exposure levels vary depending on the effectiveness of dust -control measures; they may be up to several hundred fibres/ml in industry or mines without or with poor dust control, but are generally well below 2 fibres/ml in modern industry. Reported concentrations in drinking-water range up to 200 x 10fibres,'litre (all fibre lengths), 1.1.4. Toxicological effects on animals http://\v\v\v.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 9 of 129 Fibiosis in many animal species,_and bronchial carcinomas and pleural mesotheliomas in the rat, have been observed following inhalation of both chrysotile and amphibole asbestos.___In these studies, there were no consistent increases in tumour incidence at other sites, and there is no convincing evidence that ingested asbest.os_is carcinogenic in animals__ Data from the inhalation studies have shown that shorter asbestos fibres are less fibrogenic and carcinogenic. Few data are available concerning the pathogenicity of the other natural mineral fibres. Fibrosis in rats has been observed foilowing_inhalation of attapulgite and sepiolite; a remarkably high incidence of mesotheliomas occurred in rats following inhalation of erionite. Long-fibred attapulgite induced mesotheliomas, f ollowing intrapleural and intraperitoneal administration. Wollastonite also induced mesothelioma after intrapleural administration. Erionite induced extremely high incidences of mesotheliomas following inhalation exposure and intrap1eura1 and intraperitoneal administration. ____ The length, diameter, and chemical composition of fibres are important determinants of their deposition, clearance, and translocation, within the body. Available data also indicate that the potential of fibres to induce mesotheliomas following intrapleural or intraperitoneal injection in animal species is mainly a function of fibre length and diameter; in general, fibres with maximum carcinogenic potency have been reported to be longer than 8 pm and less than 1.5 pm in diameter. 1.1.5. Effects on man _____ Epidemiological studies, mainly on occupational groups, have established that all types of asbestos fibres are associated with diffuse pulmonary fibrosis (asbestosis), bronchial carcinoma, and primary malignant tumours of the pleura and peritoneum (mesothelioma). That asbestos causes cancers at other sites is 1ess well established. Gastrointestinal and laryngeal cancer are possible, but the causal relationship with asbestos exposure has not yet been firmly established; there is no substantial supporting evidence for cancer at other sites. Asbestos exposure may cause visceral arid parietal pleural changes. Cigarette smoking increases the asbestosis mortality and the risk of lung cancer in persons exposed to asbestos but not the risk of mesothelioma. Generally, cases of malignant mesothelioma are rapidly fatal. The observed incidence of these tumours, which was low until about 30 years ago, has been increasing rapidly in males in industrial countries, _ As asbestos - related mesothelioma became more widely accepted and known to pathologists in western countries,, reports__of mesothelioma increased. The incidence of me sothelioma prior to, e.g., 1960, is not known. Mesotheliomas have seldom followed exposure to chrysotile asbestos only. Most, but not all, cases of mesothelioma have a history of occupational exposure to amphibole asbestos, principally crocidolite, either alone or in amphibole-chrysotile mixtures. There, is strong evidence that one non-asbestos fibrous mineral (erionite) is carcinogenic in man. This fibrous zeolite is likely to be the cause of localized endemic mesothelioma in Turkey. Non -ma1ignant thickening of the visceral pleura is frequently assoc.ia ted with asbestosis. Thickening of the parietal pleura, sometimes with calcification, may occur in the absence of detectable asbestosis. It is seen in those occupationally exposed http ://\vw\v. inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 10 of 129 to asbestos and also occurs endemically in a number of countries. but the causes have not been fully established. Tremolite fibre has been implicated as an etiological agent in some regions. 1.1.6. Evaluation of health risks At present, past exposure to asbestos in industry or in the general population has not been sufficiently well defined to make an accurate assessment of the risks from future levels of exposure, which are likely to be low. A simple risk assessment is not possible for asbestos. In making an assessment, the emphasis is placed on the incidence of lung cancer and mesothelioma, the principal hazards. Two approaches are possible, one based on a comparative and qualitative evaluation of the literature (qualitative assessment), the other based on an underlying mathematical model to link fibre exposure to the incidence of cancer (quantitative assessment). Attempts to derive the mathematical model have had limited success. Data from several studies support a linear relationship with cumulative dose for 1uncL cancer and an exponential relationship with time since first exposure for mesothelioma. However, the derived "coefficients" within these equations cover a wide range of values from zero upwards. This numerical variability reflects the uncertainty of many factors including historical concentration measurements, fibre size distributions associated with a given fibre level, and variations in the activity of different fibre types. Furthermore, smoking habits are rarely well defined in relation to bronchial cancer. The' variability may also reflect uncertainty in the validity of the models. These factors have complicated the Quantitative extrapolation of the risk of developing these diseases to levels of exposure such as those in the general environment, which are orders of magnitude below levels of exposure in the populations from which the estimates have derived. _____ The following conclusions can be drawn on the basis of qua1itative assessment: (a) Among occupational groups, exposure to asbestos poses a _____ ___ health hazard that may result in asbestosis, lung cancer, and mesothelioma. The incidence of these diseases is related to fibre type, fibre dose, and industrial processing. Adequate control measures should significantly reduce these risks, (b) In para-occupational groups including persons with household contact,__those living in the vicinity of asbestos-producing and -using plants, and others, the risks of mesothelioma and lung cancer are generally much lower than for occupational groups. The risk of asbestosis is ... .___ very low. These risks are being further reduced as a result of improved control practices. (c) In the general population, the risks of mesothelioma and lung cancer, attributable to asbestos, cannot be quantified reliably and are probably undetectablv low. Cigarette smoking is the major etiological factor in the production of lung cancer in the general population. The risk of asbestosis is virtually zero. (dj On the basis of available data, it is not possible to .......... assess the risks associated with exposure to the majority . _____ .of. other natural mineral fibres in the occupational or http://www.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 11 of 129 ___ general environment. The only exception is erionite for which a high incidence of mesothelioma in a local popu1ation has been associated with exposure. 1.2. Recommendations for Further Research The molecular and__cellular mechanisms associated with both the f ibrogenic. and carcinogenic action of asbestos are not known. In addition, precise epidemiological data and reliable exposure data to establish dose - response relationships for asbestos fibres are lacking. There should be further studies on: (a) the significance of the physical and chemical properties of asbestos and other mineral fibres (fibre dimension, surface properties, and contaminants) with respect to their ____ biological effects; {b) the biological significance of the durability of mineral fibres in the body; (c) the differences that exist between varieties of asbestos with respect to the induction of malignant tumours; (d) the induction of malignant tumours by well-characterized samples of other natural mineral fibres, especially ____ asbestos substitutes; i_e) immunological, cellular, and biochemical responses to natural mineral fibres (including their action as initiator and/or promotor); (f) prevalence and incidence of disease in large cohorts of more recent workers with reliably-measured exposure; and tg) improvement and international standardization of methods of monitoring exposure to asbestos and other fibrous materials , 2 . I DENT ITY, PHYSICAL AND CHEMICAL PROPERTIES, SAMPLING AND ANALYSIS 2.1. Identity; Physical and Chemical Properties of Asbestos Minerals As best os is a collective name given to minerals that occur naturally as fibre bundles and possess unusually high tensile strength, flexibility, and chemical and physical durability. Fibre bundles may be several centimetres long. Bundle diameters may yary_ significantly, but tend to be in the millimeter range. This has given rise to a technical grading based on fibre bundles. 1 engt h s_,_ and diameters. However, when these fibre bundles are manipulated, they may break down into smaller units, a portion of which have dimensions in the submicron range. The asbestos minerals are not classified on a mineralogical basis, but rather on a commercial basis because of their unique properties. Therefore, the asbestos variety commercially known as crocrdolite is referred to in the mineralogical literature as riebeckite. The asbestos variety called amosite is known mineralogically as grunerite. All other asbestos types are referred to by their proper mineral names. The properties usually attributed to asbestos as controlling both its stability in the environment, and its biological behaviour, include fibre length and diameter, surface area, chemical nature, surface properties, and stability of the mineral http: "www. inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 12 of 129 within a biological host. The physical and chemical properties of asbestos have been widely discussed in the literature (Allison et al., 1975; Selikoff & Lee, 1978; Michaels & Chissick, 1979; US NRC/NAS, 1984; Langer & Nolan19851. Two basic, mineral groups, serpentine and amphibole, contain i mp ortant asbestos minerals including the 6 minerals of special interest 1iseed in Table 1. These groups are hydrated silicates with complex crystal structures. The typical chemical composition of_ the individual types of asbestos within these groups is provided in Table 1. 2.1.1. Serpentine group minerals - chrvsotile Chrysotile is a sheet silicate composed of planar-linked silica tetrahedra_with an overlying layer of brucite. The silica-brucite sheets are slightly warped because of a structural mismatch, resulting in the propagation of a rolled scroll that forms a long ho11ow tube. These tubes form the composite fibre bundle of chrysotile. Table 1. Physical and chemical properties of common asbestos minerals5 Characteristic Theoretical formula Chrvsotile Crocidolite- ---- Mg, (Si,0J (OH) Na,FeII_FeIII,, (SisO^MOH), Chemical analysis (range of maior consitutents (%) 1 Si02 38 - 42 49 - 56 Amosite Anthophvllite- Trei (Fe, Mg), (Si_Q0,,) (OH), (Mg, Fe), Ca,Mc (SiD0,,) (OH), (Sio0,, ' --- -- 49 - 52 53 - 60 55 A1.0, -F--e-z-0-3, FeO MgO CaO Na~0 (0 - 2) e (0-5) JO - 3) 38-42 (0 - 2) (0 - 1) (0 - 1) 13 - 18 3 - 21 (0 - 13) (0 - 2) 4-8 (0 - 1) _____ (0 - 5) 3 5 - 40 5-7 (0 2) (0 - 1) (0 - 3) (0 - 5) 3-20 17 - 31 . (0 - 3) (0 - 1) (0 (0 (0 20 10.. (0 N.ZC- T 11.5 - 13 1.7 - 2.8 Colour usually white to pale green yellow*, pink- blue Decomposition 450 - 700 temperature- C} 400 - 600 Fusion temperature of residual mater_ia 1 ( C) 1500 1200 1.8 - 2.4 1 ight grey to pale brown 600 - 800 14 00 1.5 - 3.0 white to grey pale brown 600 - 850 1450 1.5 whi gre 95 C 131 http://www.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 13 of 129 Table 1__(contd) . Characteristic Chrvsotile Crocidolite- Density (q/cm-) 2.55 3.3 - 3.4 Resistance to acids undergoes fairly rapid attack good Resistance to alkalis very good good Mechanical properties of fibre as taken from rock samples Tensile strength 31 V10 ` kg/crrk) 35 .Average) (103 psi) (440) (495) Younq1s modulus (10- kq/cm-) 1620 1860 (Averaqe) (10' psi) (23) (27) Texture -......... - ------------------------------- usually flexible, silky, and tough flexible to brittle and touqh Amosite2 3.4 - 3.5 attacked slowly good 17 (250) 1620 (23) usually brittle AnthoDhvllite- 2.85 - 3.1 very good Trei 2.9 ver very good goc (< 7) (< 100) _ 5 (< . usually brittle usu ___ bri Table 1_ (cp_ntdl^_ Characteristic Chrvsotile Crocidolite^ Main producing countries Canada, China, ...Italy,. South Africa, Swaziland, USA, USSR, Zimbabwe South Africa Amosite2 South Africa AnthoDhvllite- Mozambique USA Trei Ita USA -___From: CEC (1977) . s Mineralogical name of crocidolite is riebeckite. .Mineralogical name of amosite is grunerite. 3 Anthophyllite asbestos is the proper term, as with tremolite and actinolite. - Bracketed figures denote common elemental substitution found in asbestos mineral f.. _ From serpentinized dolomite deposits. 3 Dehydroxylation or dehydrogenation accompanied by disruption of crystal lattice strengths Commercial exploitation of anthophyllite discontinued. ......... The chemical composition is uniform in contrast to that of the http: Avww.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 14 of 129 a mghibole asbestos varieties. Some trace oxides (Table 1) are always, present as a result of contamination during the formation of the. minera 1,__in_the host rock. Some of these trace elements may be structurally accommodated within the tetrahedral site of the silica 1ayer__(as in the case of aluminum substituting for silicon) , or the octahedral site of the brucite layer (as in the case of nickel or iron substituting for magnesium), or may exist as major elements within minor concentrations of discrete mineral phases intercalated in the fibre bundle (e.g. ,__magnetite) . Organic impurities have not been observed in virgin chrvsotile (Harington, 1962). Chrvsotile fibrils are long, flexible, and curved, and they tend to form bundles that are often curvilinear with splayed ends. Such bundles are held together by hydrogen bonding and/or extrafibril solid matterChrvsotile fibres naturally occur in lengths varying from 1 to 20 mm, with occasional specimens as long as 100 mm. .Some of the physical properties of chrvsotile are shown in Table_1^ Exposure to acid results in the liberation of magnesium ions and the formation of a siliceous residue. Chrvsotile fibres are almost completely destroyed within 1 h when placed in 1 N hydrochloric acid at 95 C (Speil & Leineweber, 1969). Chrvsotile is highly susceptible to acid attack, yet is more resistant to attack by sodium hydroxide than any of the amphibole fibres. _____ Chrvsotile dehvdroxvlates partially and gradually; dehydroxvlation mainly occurs at approximately 600 - 650 fo11owed.by.recrystallization to fosterite and silica at - 820 C. C about 810 2.1.2. _ _ Amphibole group minerals The amphibole minerals are double chains of silica tetrahedra, c.ros s -1 inked with bridging cations. The hollow central core typical, for chrvsotile is lacking. Magnesium, iron,_calcium, and sodium have been reported to be the principa1 cations in the amphibole structure (Speil & Leineweber, 1969). Some physical properties are summarized in Table 1. _____The amphibole structure allows great latitude in cation rep1acement, and the chemical composition and physical properties of various amphibole asbestos fibres cover a wide range. Only rarely does the composition of a field sample coincide with the assigned theoretical or idealized formula. However, theoretical compositions are used for identifying the various fibres as a marter of convenience (Table 1) . Whereas the comminution of chrvsotile fibres may produce separated unit_fibrils (which are bound by weak proton forces and/or interfibril amorphous magnesium silicate material), the breakage (both parting and cleavage) of amphiboles occurs along defined crystallographic planes. Parting along some of these surfaces may result in fibrils of amphibole, 4.0 nm in diameter (Langer & Nolan, 1985) . Thes.e mechanisms of amphibole breakage are important biologically with regard to resultant particle number, surface area,.and general respirability (all of which control penetration to target cells and delivered dose), and also with regard to expressed chemical information contained on the fibre surface http://www.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 15 of 129 (Ha rlow e t al., 1985). In a crystallographic study of amosite a s b e s tos and its physically-different counterpart, grunerite, size distri by tions were different when they were comminuted in an identical manner. This factor controls both quantity and quality of dose (Harlow et a1., 198 5). 2 . 1 . 2 . 1 Crocidolite (Riebeckite asbestos) Crocidolite is represented by the "idealized" empirical formula provided in Table 1. Iron can be partially substituted by Mg-- within the structure. Typical crocidolite fibre bundles easily disperse into fibres that are shorter and thinner than other amphibole asbestos fibres, similarly dispersed. However, these ultimate fibrils are generally not as small in diameter as fibrils of chrvsotile. In comparison with other amphiboles or chrvsotile, crocidolite has a relatively poor resistance to heat, but its fibres are used extensively in applications requiring good resistance to acids. Crocidolite fibres have fair to good f1exibilitv, fair spinnabilitv, and a texture ranging from soft to harsh. Unlike chrvsotile, crocidolite is usually associated with organic impurities, including low levels of polycyclic aromatic hydrocarbons such as benzo( a )pyrene (Harington, 1962). Only about 4% of asbestos being mined at present is crocidolite. 2 . 1. 2 . 2 Amosite (Grur.er: re asbestos) _____ The characteristics of amosite are given in Table 1. The Fe~ to Mg--1 ratio varies, but is usually about 5.5:1.5. Amosite fibrils ape generally larger than those of crocidolite, but smaller than particles of anthophyllite asbestos similarly comminuted. Most amosite fibrils have straight edges and characteristic right-angle fibre axis terminations. 2 .1.2.3 Anthophyllite asbestos ____ Anthophyllite asbestos is a relatively rare, fibrous, orthorhombic, magnesium-iron amphibole (Table 1), which occasionally occurs as a contaminant in talc deposits. Typically, anthophyllite fibrils are more massive than other common forms of asbestos. 2 . 1 ,_2_^4_ Tremolite and actinolite asbestos The other fibres mentioned in the text include tremolite asbestos, a monoclinic calcium-magnesium amphibole. and its ironsubstituted derivative, actinolite asbestos. Both rarely occur in the asbestos habit, but are common as contaminants of other asbestos deposits; actinolite asbestos occurs as a contaminant fibre in amosite deposits and tremolite asbestos as a contaminant of both chrvsotile and talc deposits. Tremolite asbestos fibrils range in size but may approach the dimensions of fibrils of crocido1ite and amosite. 2.2. Identity.- Physical and Chemical Properties of Other Natural Mineral Fibres Many minerals, other than asbestos, exist in nature with a fibrous habit. Still others comminute to produce particles with a f ibro_us form. _ Some enter the environment through human activities and others through natural erosion processes. These have become inc re a singly important because they have been linked with human disease in a limited number of instances (as with the case of erionite associated with mesothelioma in Turkey) and because they http:/7\vww.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 16 of 129 have been suggested as substitutes for asbestos, 2.2.1. Fibrous zeolites Zeolites are crystalline aluminosilicates in which the primary "building blocks" are tetrahedra consisting of either silicon or ad urn ini um atoms surrounded by four oxygen atoms. These tetrahedra combine, linked together by oxygen bridges and cations, to yield ordered three-dimensional frameworks. Although there are more than 30 known natural zeolites, only four are fibrous (chabazite, c 1 inoptilolite , erionite, and mordenite) i.Table 2) . Erionite fibres are similar in dimension to asbestos fibres, tnough they are probably shorter in length on average (Suzuki, 1982 ; Wright et a ; . , : 98 8 , . Table 2. Typical formulae of some fibrous zeolites5 ChabaziteCa (Al^Si^ .,) x 6 H.,0 Clinoptilolite (Na0KaCa) (Al^SipO??) x 7 H.,0 Erionite(Na^K^CaMg) 4 ? (AlpSi2^0^2) x 27 H?0 Mordenite (Na2K2Ca) (Al2Silc024) x 7 H20 a From: Mumpton (1979) . wollastonite)">2.2.2. Other fibrous silicates (attapulgite, sepiolite, and ihe chemical composition of these minerals is: palygorskite (attapulgite) : MgcSi8O20(OH)2(H20)4 x 4H20 (Barrer, 1978); sepiolite: ______MgaSi1 20,n (OH) 4 (H.,0) 4 x 8H?0 (Barrer, 1978); wo 11 a s t onite: __ CaSi03 (Ullmann, 1982) . Certain clay.minerals, such as sepiolite and, especially, attapulgite, may occur in forms that are similar to both chrysotile and amphibole asbestos fibrils. Under the electron microscope, they may appear to have a hollow tube structure, or have an appearance of an amphibole lath. Meerschaum represents a massive form of fibrous sepiolite. The surface of attapulgite resembles that of chrysotile in that it is hydrated and protonated. Attapulgite consists principally of short fibres of the mineral palygorskite (Bignon et al__1980) . Wol lastonite ha_s received considerable attention as a possible substitute for asbestos .___ The basic structure of this mineral is an infinite silicon oxygen chain (Si03). Calcium cations link the infinite chains together (Leineweber, 1980) The properties of wo11astonite as well as its biological effects have been discussed in several papers (Korhonen & Tossavainen, 1981; Huuskonen et al.. 1983a,b). Relevance of physical and chemical properties to biolocrical effects http://w\v\v. inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 17 of 129 For respirability, the most important single property of both asbestos and other fibrous minerals appears to be fibre diameter. The sma1ler the fibre diameter, the greater the particle number per unit :r.ass of dust; the more stable the dust aerosol, the greater the inhalation potential and penetration to distal portions of the lung. Once within the tissue, fibre length, surface chemistry, and physical and chemical properties are the likely factors controlling biological activity (Langer & Nolan, 1985). wollastonite)">2.3. Sampling and Analytical Methods ____ Collection and preparation of samples from the environment and subsequent analysis of asbestos and other natural mineral fibres or application of direct measuring methods are required for the assessment of human exposure, evaluation of control measures, and control of compliance with regulations. Sampling strategies and analytical procedures must be adequately planned and conducted. Calibration of instruments and quality control are essential to ensure accuracy and precision. Detailed descriptions of the collection and preparation of samples and of analytical procedures are beyond the scope of this document (Asbestos International As sociation, 19B2 ,__1984; EEC, 1983; ILO, 1984) . 2.3.1. Collection^ and preparation of samples The collection and preparation of samples from air, water, and biological and geological media require different strategies and specimen preparation techniques. However, once in a suitable form for analysis, the instrumental methods required are virtually identical. 2.3.1.1 Air _____ The identity of fibres in the work-place is usually known. This is not true in the general environment, where fibre identification is generally necessary. The ratio of asbestos fibres to total respirable particles varies widely, ranging from 1; 10-3 to 1:10" (Nicholson & Pundsack, 1973; Lanting & den Boeft,1979). In addition to fibre identification and concentration, it is important to focus on fibre size and its relation to inspirabilitv and respirabiJLity_LFig ^ 1J_. The upper limit of the geometric diameter of respirable asbest_os__fibres is 3 urn, obtained from the cut-off of the alveolar fraction of spherical particles (aerodynamic diameter of 10 urn; specific gravity 1 g/cm3) (Fig. 1) and the average specific gravity o f _ a sbestos (3 g/cm3) . While, in some countries, the inspirable fraction as a whole is covered when measuring the concentration of airborne asbestos, only the alveolar fraction (termed "respirable dust")__ is used in the majority of countries (ILO, 1984) . FIGURE_.. 1 p33 ; 4 9; e53_1 bmp The concentration of airborne fibres is expressed either as fibre number concentration, i.e., fibres/ml, fibres/litre, or fibres/m3 (alveolar fraction) in the work-place and/or general environment, or as mass concentration, i.e., mq/m3, in the work place environment and for emission control (inspirable or alveolar fraction) (EEC. 1983; ILO, 1984), or ng/m3 in the general environment (alveolar fraction). http://wvvw.inchein.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 18 of 129 When fibre number concentrations are determined by optical microscopy, particles having a diameter of less than 3 urn, a 1e ngt h-1 o-diame ter_. rat io greater than 3:1,__and a length greater Chan 5 pm are counted, since they are thought to be the most biologically-relevant part of the alveolar fraction (EEC, 1983; ILO, 1984) . However, this conclusion is based mainly on studies on animals involving intrapleural or intraperitoneal administration of fibres, or intratracheal administration. In addition, alveolar deposition is relevant for the induction of pleural and peritoneal mesotheliomas and interstitial fibrosis, but not for the production of bronchial carcinomas in man, most of which develop in the large bronchi. In the past, sampling strategies have not always been representative of workers' exposures. As an initial step, an inventory _of the work-place exposure conditions should be undertaken.___The sampling strategy should be determined by the nature of probable exposure at different work locations. An adequate sampling strategy can, and must be, designed and strictly followed, and should include decisions on "where", "when", and "for how long" to sample, as well as on the acceptable number of samples. The sampling procedure must also be considered so that a sampling plan can be established. Details of sampling strategies and procedures can be found in the literature (US NIOSH, 1973, 1977; Robock & Teichert, 1978; Raihans & Sullivan, 1981; Asbestos International Association, 1982, 1984; Robock. 1982; Valic, 1983; ILO, 1984; WHO, 1984). Specific procedures for the evaluation of airborne asbestos have been developed and some have been standardized and used in different countries (US EPA, 1978; US NIOSH, 1984; Asbestos International Association, 1982, 1984; EEC, 1983; ILO, 1984; ISO, 1984; OECD, 1984). These procedures usually provide guidelines for sampling strategy in addition to collection and analytical p r oc edur e s _. Samples are collected by drawing a given volume of air through a filter for a given length of time, using pumps that are able to provide a constant.and measureable rate of flow. The concentration of the fibres deposited on the filter is subsequently determined. Personal sampling within the worker's breathing zone, as well as static sampling at fixed locations, can be conducted, depending on the purpose of the evaluation. Personal sampling should be used to assess a worker's exposure (e.g., for compliance control and for epidemiological studies). Static sampling is widely applied for the evaluation of engineering control. J3asically, the same principles should be applied in collecting samp1es_for the determination of airborne fibre concentrations in ambient-air (Asbestos International Association, 1984 ; VDI, 1984). However, the sampling strategy (e.g., location of sample collection ppints, duration of sampling, etc.) varies from that in the oc c upational environment (VDI, 1984) . _____The same principles should also be applied in the collection of samples at the work-place to determine mass concentrations (mg/m-) by gravimetric methods (ILO, 1984). 2 . 3 . 1 . 2 Water ___Available technology for determining asbestos in water is described in a US EPA report (US EPA, 1983) . The water sample to / i1 b ^i ___ -- http ://www .inchem.org/documents/ehc/ehc/ehc5 3 .htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 19 of 129 be analysed is initially treated with ozone and ultraviolet r ad iat:or. to oxidize suspended organic material. A capillary pore BP1 ycarbonate filter (0.1 am pore size) is then used to filter the water samp1e._ The filter is prepared by carbon extraction replication and then examined with a transmission electron microscope (TEM). Since some problems may require less sophisticated instrumentation, depending on fibre size, type, and concentration, and to minimize expenditure, a more inexpensive rapid method has been developed to evaluate the need for the detailed analysis of water samples suspected of containing asbestos fibres. This method is not vet in common use. Details of both the full method and the rapid method are given in US EPA (1983) 2 . 3 . 1. 3 Biological tissues Many techniques have been developed for the recovery of mineral dust from human tissues (Larger et al., 1973; Gaudichet et al., 19 80; Poolev & Clark, 1980) These include wet chemistry methods _{e.g., formamide, glacial acetic and other acids, enzyme, alkali, and sodium hypochloride digestion) ,__and physical methods (e.g,, as h ing using both low and high temperatures) for tissue destruction. The recovered residues can be assayed gravimetrically, by light microscopy or by electron beam instrumentation (Langer et al., 1973) . In addition, with the development of the carbon-extraction replication technique, it is possible to analyse, in situ, minerals in tissue slides (Langer et al. , 1972) . 2.3.1.4 Geological samples The preparation of geological specimens (rocks, soils, powdered mineral specimens, etc . )__ for fibre analysis follows standard geological techniques for sample selection, splitting, and chemical-physical mineral separation. Detailed descriptions of the many techniques available is beyond the scope of this document (Bowes et al., 1977). 2.3.2. Analysis In general, the analytical procedures for fibre quantification and identification are applicable to all types of samples. 2_,_3 ^2^1__ Light microscopy Several versions of a method for counting respirable fibres on filters, based on phase contrast light microscopy, have been developed _(Asbestos Research Council, 1971; Asbestos International Association, 1982; US NIOSH, 1984). These are most appropriate for analysis in the occupational environment, where fibre identification is unnecessary. The most widely recommended propedure_is the Membrane Filter Method, based on the Asbestos International Association/RTMI method, which has also been adopted by the European Economic Communities (EEC, 1983) and the International Labour Office (ILO,.. 1984). The same principles are now under discussion for acceptance by the International Standards Organization (ISO, 1984). The determination of fibres by phase contrast microscopy has been widely discussed in the literature (Booker ep_aJU, 1982; Walton, 1982; ILO, 1984; Taylor et al., 1984) . _____ Mineral fibres down to about 0.25 urn in diameter (lower for http t'Avwvv. inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 20 of 129 amphiboles than for chrvsotile) are visible and countable by this met ho_d_.___ Identification of specific fibre types is not possible using this technique and, therefore, every fibre is counted as "asbestos". The detection limit of the method, defined as the minimum fibre concentration that can be detected above the background fibre count, is usually 0,1 fibre/ml. Theoretically, the detection limit can be lowered by increased sampling time, but thi_s cannot normally be achieved in industrial situations because ambient dust levels lead to overloading of the filter. _____ Large systematic and random observer differences in optical fibre counts have been reported using the Membrane Filter Method. These can be reduced by selection of the proper equipment, training of personnel, and inter-laboratory comparisons. Improvement in the counting of fibres can be effected by the automatic evaluation of filter sameles. In principle, such evaluations can be conducted using image analysing systems (Dixon Taylor* 19791 or magnetic alignment combined with scattered light measurements (Gale & Timbrel!, 1980}. & Finally, it must be stressed that the development, improvement, and refinement of the Membrane Filter Method in recent years have led to higher sensitivity and thus to more reliable assessment of levels !n the work-place. 2^3 . 2Electron microscopy _____ Asbestos fibres may represent a very small part of the total number of particles in the general environment, water, and biological and geological samples. Moreover, the types of fibres may not be known, and the diameters of asbestos fibres found may be sma1ler than those found in the work-place environment. Thus, an electron microscopic technique is preferred for the analysis of t hese_filter samples. For example, scanning electron microscopy (SEM1, transmission electron microscopy (TEM, STEM) with energy dispersive X-ray analyser (EDXA), and selected area electron diffraction (SAED) (so-called analytical electron microscopy) can be_applied.__Analytical electron microscopy has been discussed in the specialized literature [ClarkL 1982; Lee et al. , 1982; Steel et al., 1982) . In order to establish a correlation with the results obtained by__p.hase contrast microscopy, the results of any fibre count laspect ratio > 3:1) must contain the following size fraction: fibres greater in length than 5 um with diameters ______between 0.25 um and 3 um, which represent the size fraction recommended for counting by phase contrast microscopy. When required, the following size fractions can also be considered: fibres greater in length than 5 um with diameters of less than 0.25 um; and ____ fibres shorter in length than 5 um with diameters greater than and/or smaller than 0.25 ^m. The results obtained by the electron microscopic assessment of concentrations of total fibrous particles and/or asbestos particles have often only been published for an aspect ratio greater than http:/Av\vw. inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 21 of 129 3:1, independent of length and diameter. These results cannot be compared, since there are few data on the lower visibility limit (magnification) and identification limit with regard to the diameter, and since no correlation with the evaluation criteria for measurements^ in work-place environments can be established. (a) Scanning electron microscopy _____ Fibres with diameters as small as 0.03 - 0.04 um may be visible with this instrument, depending on preparation and instrumentation techniques (Cherry*. 1983).. The scanning electron microscope can be used routinely to identify fibres down to a diameter of 0.2 um, when equipped with an energy dispersive X-ray spectrometry system 1 EDXA) in environments where fibres are known. Limitations may be encountered in environments where different minerals have identical elemental ratios; in this case, selected area electron diffraction (SAED) is required for identification. One advantage of SEM is that the filter (membrane or Nuclepore) can be examined directly within the microscope, without the generation of preparation artifacts. (b) Transmission electron microscopy A modern Transmission Electron Microscope has a resolution of about 0.0002 um, which is more than adequate for resolving unit fibrils of any mineral. The TEM, if equipped with EDXA, can chemically characterize fibres down to a diameter of 0.01 um. In addition, SAED permits the determination of structural elements of crystalline substances. When samples containing large fibres are analysed under similar conditions, the detection limits are comparable for TEM and SEM. As the sensitivity of analytical instruments increases, so does the possibility of error in measurement, e.g., the_incorporation of adventitious mineral grains. This may result in erroneous fibre counts, especially in the analysis of samples with a low mineral fibre content. ______The application of the TEM is very advantageous because of the possibility of structural characterization by means of SAED, which increases identification accuracy (Beaman & Walker, 1978). 2 JS_._2_. 3__ Gravimetric determination ______Various generally-known methods are available for the gravimetric evaluation of filter samples (mg/m-) from the workp1ace environment and exhaust emissions, including the weighing of the filter before and after dust sampling or absorption of ionizing radiation. Qualitative and quantitative infrared spectrometry or Xray diffraction analysis (Taylor, 1978; Lange & Haartz, 1979), to determine the composition of dust, can be carried out on such filter samples. These filters must contain a relatively large mass of dust. The disadvantage of gravimetric determination is that there is no discrimination between fibrous and non-fibrous dusts, and therefore, it is thought to provide a poor index of the health hazards posed by asbestos-containing dust. 2.3.3. Other methods Optical dust-measuring instruments, such as the Tyndallo-meter, the Fibrous Aerosol Monitor, and the Rovco particle counter (ACGIH, 1983); apply the light scattering principle for measuring dust concentrations in. the work-place environment and in stacks of central dust collectors. They are direct-reading instruments to which a recorder can be connected. http://www.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 22 of 129 The advantages of these instruments are: ____ Xa]__ immediate location of dust sources; (b) instant determination of the efficiency of du st-suppression measures; (c) recording of fluctuations of dust concentrations; and (d) determination of short-time peak concentrations. ____ However, these techniques are limited by dust concentration, particle morphology, and the lack of specificity in terms of particle identity. These direct-reading instruments are used mainly for static monit oring, and for the evaluation of engineering control measures. For reliable evaluation of work-place air levels, these instruments should be calibrated with work-place dust samples of known concentration. 2.3.4. Relationships between fibre, particle, and mass concentration There is no general relationship between the results of fibre counts and mass measurements in the assessment of the concentration of asbes tos._and other natural mineral fibres in the various types of environmental media. Several attempts have been made to establish conversion factors between mass measurements and fibre counts (Bruckman & Rubino, 197 5,- Gibbs & Hwang, 1980). Although relationships for individual work-places and specific work practices have been determined, these factors cannot be applied generally. The very wide range of numbers of fibres per unit weight for a given density as a function of fibre size has been calculated by Pott (1978) on a theoretical basis (Table 3). In early analyses for asbestos using electron microscopy, the sample-preparation technique artificially increased the number of fibres, and therefore, the authors usually reconverted fibre counts to mass units. However, using electron microscopy, it is now possible to measure asbestos fibres unchanged and, thus, the conversion is not warranted. Conversion of the results of measurements of number of particles per unit volume (mppcf - millions of particles per cubic foot) obtained with the Midget Impinger into number of fibres per unit volume (F/ml) has presented similar problems (Robock, 1984). While the calculated mean ratios (F/cm-/mppcf) for various industrial settings varied only hetween 3 -^nd B- there we.r.e large variations__within each industry; for example, in the textile industry, the experimentally-determined ratio varied from 1.2 to T1.6 and, in mines, between 0.5 and 47.4 (Robock, 1984), Table 3. The numbers of fibres per ng for different size categories (cy1indrical. fibre shape, density 2.5); diameter/length ratios in the second Une1 Diameter (am) 0.625 1.25 Lenqth Ami_______ 2.5 5 10 20 40 80 0.031 819 200 1:20 409 600 1:40 204 800 102 400 1 : 80 1 : 160 0.0625 204 800 1 : 10 102 400 1:20 51 000 1:40 25 600 1 : 80 12 800 1 : 160 http://www. inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 23 of 129 0.125 51 200 1:5 2 5 60012 8 00____ 6400 ______ 32 0 01600 1:101:20 1:401 : 801 : 16C 0.2 5 12_8 00640.032001600800400200 1:2 .51^51.101:201:401:80 0.5__ 16008004002001005025. 1:2.51 : 51 : 101:201:40 1.0 ________________________________20_Q100502512.5 1:2 , 5 _ ljjj1 : 101:20 2.0 ______ _______ ___2_512.56.25 1:2.5________lj_5_________ 1:10 1:160 1:80 1:40 6.25 1:80 3.21.6 1:20 1.40 From: Pott (1978) 3. SOURCES OF OCCUPATIONAL AND ENVIRONMENTAL EXPOSURE Once liberated into the environment, asbestos persists for an unknown lenqth of time. The release of free fibres into the air through (both. natural and human activities is the most important mode to be considered. The main potential exposure sources are the handling^ processing,__and disposal of dry asbestos and asbestoscont aining products.___ Fibres can also be released through the we a t hering of geological formations in which asbestos occurs or as a result of the disturbance of these formations by man. 3.1._ Natural Occurrence Asbestos is widely distributed throughout the lithosphere, and is found in many soils. Chrvsotile, the most abundant and economically-important form, is present in most serpentine rock formations in the earth's crust and workable deposits are present in over 40 nations; however, Canada, South Africa, the USSR, and Zimbabwe^ have 90% of the established world reserves (Shride, 1973]. On.the other hand,__the various amphibole asbestos mineral types have a comparatively limited geographical distribution, principally in Australia and South Africa. The presence of asbestos minerals as accessory minerals in geological for mation s is quite common throughout the world. However, only a few of these deposits are commercially exploitable. In Europe, the serpentine belt of the Alpine mountain chain contains chrvsotile as well as other mineral fibres. These rocks can be disturbed by weathering, land-slides, or by man during such activities as mining, road construction, and tilling of the soil. ____ The total amount of asbestos emitted from natural sources is probably._greater than that emitted from industrial sources. However,__no measurements concerning the extent of release of airborne fibres through natural weathering processes are available. A study.of_the mineral content of the Greenland ice cap showed that airborne chrvsotile existed long before it was used commercially on a large scale. The earliest dating in the ice cores showed the presence of chrvsotile in 1750 (Bowes et al. , 1977] . ___ There are also some data on levels of asbestos in water supp1ies due mainly to erosion from natural sources (e.q.. drinking-water in areas such as San Francisco, California; Sherbrooke, Quebec,- and Seattle, Washington) . 1:160 http://\v\v\v. inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 24 of 129 Increases in the incidence of asbestos-related diseases (e.g., pleural calcification and mesothelioma) in areas in Bulgaria, Czechoslovakia, Finland, Greece, and Turkey have served as a surrogate ind i c ator of exposure to other natural mineral fibres (e,ganthophyllite,__tremolite, sepiolite, and erionite) . The results of such studies are discussed more fully in section 8 (Burilkov & Michailova. 1970; Constantopoulos et al., 1985). In the. Federal Republic of Germany and the USA, asbestos emissions have.been detected in quarries (Carter, 1977; Spurnv et al., 1979b), and from quarried rocks used as road gravel (Rohl et al., 1977), 3.2. Man-Made Sources 3.2.1. Asbestos Activities resuiting in potential asbestos exposure can be divided into four broad categories. The first category is the mining and milling of asbestos. The second is the inclusion of asbestos in products that are currently being developed or and cement articles, and the manipulation of these products (e.g., replacement of brake shoes and insulation materials). The third potential source includes construction activities (cutting and other mani pulations), particularly the removal (e.g, tear-out or stripping) or maintenance of previously-installed asbestos in buildings or structures, and the demolition of asbestos-containing buildings or structures. The fourth is the transportation, use, and disposal of asbestos or asbestos-containing products. In each case, appropriate work practices and control measures to prevent or control the release of asbestos must be implemented (ILO, 1984). 3. 2. 1.1 Production The. world production of asbestos increased by 50% between 1964 and 1973, when it reached a level of nearly 5 million tonnes. The projected world demand for asbestos, based on historical consumption figures and usage patterns through the mid-1970s, indicates more than a doubling by the year 2000, However, world production figures for the period 1979-83 showed a decline in production (Table 4[,__ Fig,__ 2 shows a drastic decline in major asbestos uses in the USA in the period 1977-83. The only substantial increase in asbestos demand seems to be occurring in developing countries (Clifton. 1980), and in some European countries. Industrial Minerals (1978) reported that the market for some natural mineral fibres, other than asbestos, is growing rapidly as a result of the constant search for asbestos substitutes. This is, in part, a result of the legislative restrictions on asbestos in some countries. Table 4. World production figures on asbestos (tonnes)5 Country 1979 1980 1981 1982 Afghanistan Argentina Australia Chrysotile Brazil Bulgaria Canada Chrysot:le 4000 1371 1261 1280 1218 79 721 138 457 600 92 418 170 403 700 45 494 138 417 400 18 587 145 998 600 1 492 719 1 323 053 1 121 845 834 249 1983 1350 20 000 158 855 700 820 000 http://www.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 25 of 129 China 140 000 131 700 106 000 110 000 110 000 Table_; \coned. ] Country 1979 1980 1981 1982 1983 Cyprus Chrysotile Czechoslovakia Egypt India Amphibole Italy Japan Chrysotile Korea, Republic Mozambiaue South Africa Amosite Crocidolite Chrysotile Swaziland Chrysotile Taiwan Turkey of USAfc USSR Yugoslavia Zimbabwe Chrysotile 35 472 564 238 32 094 143 931 3362 14 804 789 39 058 118 301 91 828 34 294 2957 38 967 93 354 2 020 000 9959 259 891 35 535 617 316 33 716 157 794 3897 9854 800 51 646 119 148 106 940 32 833 683 8882 80 079 2 070 000 10 468 250 949 24 703 388 325 27 521 137 000 3950 14 084 800 56 834 102 337 76 772 35 264 2317 2833 75 618 1 105 000 12 206 247 503 18 997 342 310 19 997 116 410 4135 15 933 800 43 457 87 263 81 140 30 145 2392 23 283 63 515 2 180 000 10 748 197 682 17 288 325 325 17 288 139 054 4000 12 506 800 40 656 87 439 93 016 28 287 2819 22 596 69 906 2 250 000 9663 153 221 World Total 4 800 000 4 700 000 4 300 000 4 000 000 4 100 000 ^ From: BGS (1983) . e Sold or used by producers. Note: In addition to the countries listed, the Democratic Peoples Republic of Korea and Romania are also believed to produce asbestos. 3.2.1.2 Mining and milling Asbestos ore is usually mined in open-pit operations. Possible sources of particulate (asbestos) emissions include: drilling, blasting, loading broken rock, and transporting ore to the primary crusher or waste to dumps. Subsequently, the ore is crushed and may lead to exposure from the following emission sources: unloading ore from the open pit, primary crushing, screening, secondary crushing, conveying and stockpiling wet ore. A drying step follows, which involves conveying the ore to the dryer building, screening, drying, tertiary crushing, conveying ore to dry-rock storage building, and dry-rock storage. The next step is the milling of the ore,___ In well-controlled mills, this is largely confined to the mill building and presents very little emission to the air because the mill air is collected and, usually, ducted through some particulate matter control device. Few attempts have been made to quantify fibre emissions from mining and milling operations. FIGURE 2 ; 4 6 ; 51; e5 3_2 . bmp 3.2.1.3 Uses http://www.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 26 of 129 Asbestos has been used in thousands of applications (Shride, 197 3) The wav in which asbestos has been incorporated into various end-products is illustrated in Fig. 3. There are wide variations in the pattern of use of asbestos in various countries. For example, in some countries, the production and application of some of these asbestos products has been discontinued, in part, because of serious health risks associated with their production. In some countries, there are also secular trends in the pattern of usage, i ,_e. , decrease in the production of insulation and increase in the manufacture of friction materials. The products in group I cannot all be regarded as end-products but are generally used in conjunction with water as insulating plasters, cement, or spray mixtures. The greatest use of asbestos fibres lies in the manufacture of composites (group II). The cement variety, i.e., asbestos cement, constitutes a major component of this group. Other products of major importance are friction materials. insulation boards, millboard and paper, reinforced plastics, and vinyl ti1es_ and sheets. Asbestos can be spun into yarn and woven into cloth. The resulting textile products (group III) can be used for further processing into friction materials, packings, and laminates, or may find direct applications such as insulation cloth, protective clothing, fire protection, and electrical insulation, A list of the most important asbestos-containing products and their approximate fibre contents is given in Table 5. The references in the right-hand column refer to Fig. 3. It should be noted that the extent to which respirable fibres are produced depends on the type of asbestos product and how it is manipulated. 3 . 2.2. Other natural mineral fibres _____ Other natural mineral fibres may be present in air in respirable form or may become respirable as a result of manipulation.___ The dimensions of these fibres are comparable those of asbestos. with (a) Fibrous zeolites Erionite has been mined in the USA for use in ion-exchange processes, for the retention of nitrogen in fertilizers, and for use in concrete aggregate or road surfacing. Some of these applications, as well as natural weathering, may lead to significant fibre_.concentrations in the local air (US NRC/NAS, 1984). Fibres may also be found in drinking-water as a result of natural weathering. rIGURE 3;41;58;e53_3.bmp Table 5. Asbestos products and asbestos contents5 Approximate asbestos content (% weight) Asbestos fibre type- Reference to Fig. 3 1. Asbestos-cement building products 10 - 15 C, A, Cr II-6 2 . Asbestos-cement pie s s u:e, sewage, and drainage pipes 12 - 15 C, Cr, A 11 - 6 http://www.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 27 of 129 3 . Fire-resistant insu1ation bonrds 25 - 40 4 . Insulation products includinq spray 12 - 100 5 . Jointinqs and packings 25 - 85 6 . Friction materials 15 - 70 7 . Textile products not included in (6) 65 - 100 8 . Floor tiles and sheets 5 -- 7.5 9 . Moulded plastics and battery boxes 55 - 70 10 . Fillers and reinforcements and products made thereof (felts, _millboard, paper, filter pads for wines and beers, underseals, mastics, adhesives, coatings^ etc. 25 - 98 A, c 11 - 6 , 11 - 5 A, C, Cr C, Cr 1-1. 1-2, 1-3,. 1-4, II - 5 11 - 8 , III-18 C c, Cr c c, Cr c. Cr 11-10 III II - 9 11 - 9 , 11-10 ___ II- 7, 11-11 a. From: CEC (1977) . D A = amosite (not used in all countries); C = chrysotile; Cr = crocidolite (not used in all countries). (b) Palvgorskite (attapulgite) Available data on the production of attapulgite in various countries are presented in Table 6, Tab1e_6. World production of attapulgite and sepiolitea Country Annual production of attapulgite (tonnes) Annual production of sepiolite (tonnes) France unknown 2500 India 10 000 Seneqal 16 700 Spain 50 000 236 000 JSA__ _ 700 000 Modified from: Biqnon et al. (1980). The USA is the biggest producer and consumer of attapulgite: consumption currently exceeds 700 000 tonnes and is almost triple chat of asbestos. The consumption figures for various uses of attapulgite_in the USA are listed in Table 7. An additional 100 000 tonnes is exported from the USA each year (US Bureau of Mines, http://www.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 28 of 129 198 2) . 8imila. r data for other countries are not available. Table 7. Uses of attapulqite in the USA- Use 1981 consumption (1000 tonnes) Drillinq mud Fertilizers Filtering (oil and qrease) Oil and qrease adsorbents Pesticides and related products Pet waste adsorbent Medical, pharmaceutical, cosmetic inqredients Other uses 173.5 50.2 18.7 178.2 106.5 105.8 0.06 79 .5 Total 712.46 3 From: US Bureau of Mines (.1.982) In France, attapulqite is used in drugs for the treatment of gastrointestinal diseases (Bignon et al., 1980); in the USA, it is a component of non-prescription antidiarrhoeal drugs (Physicians' Desk Reference, 1983) . The potential environmental effects of attapulqite were reviewed by the US NRC/NAS (1984). It was stated that, when used in such products as pet waste adsorbents, fertilizers, and pesticides, substantial amounts of attapulqite could be released into the air. Attapulqite has also been found in water supplies (Millette.et a1 1979b) . ..(c) Sepioli te _____ Available data on the production of sepiolite in several countries are presented in Table 6. ____ Minerals that contain sepiolite are used as cat litter. 3.2.3___Manufacture of products containing asbestos 3 . 2 . 3 .1 Asbestos - cement products Throughout the world, the asbestos-cement industry is the largest user of asbestos fibres.Asbestos-cement products contain 10 . - 15% asbestos, mostly in the form of chrysotile, though limited amounts of crocidolite may be used in large-size asbestos-cement pipes_,__to give the required strength as well as to increase the speed of production. The most important products are asbestos cement pipes and sheets. Products are primarily manufactured in wet processes. ___ Possible emission sources are: (a) the feeding of asbestos fibres into the mix; (b) blending the mix; and (c) cutting or machining end products. Emissions may range from negligible to significant according to the dust control measures and technology. Emissions can also occur from sources other than processing operations, such as the improper handling and/or shipment of dry materials containing asbestos and during the cutting or machining of., end-products. Recently, control measures have been developed and approved in the Federal Republic of Germany (Berufsgenossenschaftliches Institut fur Arbeitssicherheit, 1985), which have reduced airborne levels in the immediate vicinity by 1 - http://www.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 29 of 129 2 orders of magnitude, generally, to less than 1000 fibres/litre. 3 .2 .3 ,2 Vinyl asbestos floor tiles ______The second largest user of asbestos fibres in the USA is the asphalt and vinyl floor tile manufacturing industry. This type of tile__has found increased use in many countries because of its durability and impermeability to water. 3 . 2 . 3 . 3 Asbestos paper and felt Pro ducts classified as asbestos paper and felt range from thin paper to 1 cm thick millboard, which contains up to 97% asbestos. The feed__for paper machines is prepared by mixing short chrysotile fibres with water and binders. Since papermaking is a wet process, little asbestos dust is generated during manufacture. However, finishing operations, such as slitting and calendering, may be sources of dust emission,___The use of asbestos paper and felt is declining in some countries. 3.2.3.4 Friction materials (brake linings and clutch facings) Moulded brake linings are used on disc and drum-type car brakes. Woven brake linings and clutch facings for heavy use are made from high-strength asbestos yarn and fabric reinforced with wire; this material is dried and impregnated with resin. In the moulding process, the asbestos fibres and other constituents are combined with the resin, which is thermoset. Final treatment involves curing by baking, and grinding to customer specifications. Emissions may range from negligible to significant depending on dust control measures and technology. 3.2.3.5 Asbestos textiles _____ Asbestos textiles are used in the manufacture of fire-resistant garments_,__sealing materials, wicks, and thermal insulation, or as an intermediate product in brake linings, clutch facing. insulation, and gaskets. Asbestos textile manufacturing is the dustiest_of all asbestos-manufacturing processes, and dust emanating from this process is more difficult and costly to control. However, during the past decade, emissions have been substantia11y reduced in countries in which improved control measures and technology have been implemented, 3.2.4 Use of products containing asbestos Few data are available on fibre emissions during the use of products containing asbestos or other mineral fibres. In most construction materials and consumer products, the fibres are firmly bound or encased in a solid matrix and are not expected to be released under normal conditions, but may be emitted during manipulation or renovation of such materials or products (e.g., fibre levels measured by light microscopy in the vicinity of such activities as removal of pipe lagging containing asbestos or the sanding of asbestos-containing drywall topping and spackling compounds^ay approach or exceed current occupational exposure 1imits) (Fischbein et al., 1979; Sawyer & Spooner, 1979), 4. TRANSPORT AND ENVIRONMENTAL FATE 4,1__ Transport and Distribution Once in the environment, fibres are mainly transported and http:/Avww. inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 30 of 129 distributed, via_air _and,.water. 4.1.1 Transport and distribution in air A: rborr.e minera 1 fibres are stable and may travel significant distances from the site of origin. Airborne asbestos fibres, for example, have aerodynamic diameters that are generally less than 0,3 and, therefore, their sedimentation velocities are very low. Measuremen ts__c oncerning the transport and distribution of specific mineral fibres have been made under certain environmental conditions and at specific locations (Laamanen et al., 1965; Heffelfinger et al., 1972; Harwood & Blaszak, 1974; US EPA, 1974) _____ Caiculations using a dispersion model from a point source (Harwood & Blaszak, 1974) indicated that concentrations of airborne fibres of small dimension decreased very slowly with increasing distance. This study underscores two important characteristics of ambient air fibre burden: (a) fibres are transported great distances from point sources; and (b) fibres in ambient air are small in size, requiring electron beam instrumentation for detection. 4.1.2 Transport and distribution in water ____ Long-range transport of asbestiform fibres in water has been reported. Cooper & Murchio (1974) concluded that chrvsotile fibres presentin tap-water in San Francisco, California, were actuallv introduced at a reservoir many km south of the city. Nicholson (1974) attributed the presence of amphibole fibres in the municipal water supply of Duluth, Minnesota, to the transport, over 96 km, of taconite tailings from a Silver Bay mining operation. In this instance, transport resulted from bottom currents in Lake Superior. 4.2 Environmental Transformation, Interaction, and Degradation Processes ____ Mineral fibres are relatively stable and tend to persist under typical environmental conditions. However, asbestos fibres may undergo chemical alteration as well as changes in dimension. For example, chrvsotile, and to a lesser extent amphibole, asbestos fibres are capable of chemical alteration in aqueous media. The magnesium hydroxide content of chrvsotile is partially or wholly removed by solution, depending on time, temperature, and pH. An insoluble silica skeleton of the fibre remains. Grunerite fibres, of which amosite is the known commercial form, have been reported to react with water, losing some iron on extended exposure to lake water,- the fibres appeared partially degraded and broken when examined microscopically (Kramer et al., 1974). ____ The comparative solubility of selected mineral fibres has been studied and a general trend determined: chrvsotile > amosite > actinolite > crocidolite > anthophvllite > tremolite (US NRC7NAS, 1977) .__Because of their high adsorption properties, it is thought that some mineral fibres may adsorb and carry various organic agents present in the environment, 5. ENVIRONMENTAL EXPOSURE LEVELS Asbestos is ubiquitous in the environment because of its http ://w\v\v. inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 31 of 129 extensive industrial,, use and its dissemination through erosion from natural sources,__Other natural mineral fibres also occur in the environment and may, at times, be present at similar or even higher concentrations than asbestos, depending on local conditions. Since the size distributions of such fibres are often similar to those of asbestos, it is likely that distribution patterns in the environment will also be similar. It is difficult to compare available data on airborne fibre levels because of inconsistencies in both the methods of sampling and analysis, and the expression of results. In most countries. for instance, airborne fibre concentrations in the work-place are expressed as fibre/ml or mg/m-. For concentrations in ambient air, fibre/litre, fibre/m-, and ng/m- are commonly used. Fibre concentrations in biological materials are usually expressed in fibre/g or in ng/g of the dry tissue. In this section, the available data will be discussed in terms of occupational, para-occupational,(household and neighbourhood), and general .environmental__(air and other media) exposure. 5.1 Air 5.1.1 Occupational exposure Exposure levels,for,different types of asbestos and other mineral fibres vary considerably within and between industries. ______This discussion will be limited to data obtained by the Membrane Filter Method and expressed as fibre/ml. On the basis of a review of historical data, ranges of levels in various industries without or with poor dust suppression measures are illustrated in Fig. 4. In recent years, concentrations in many countries have been much lower than those illustrated because of the introduction of engineering controls. For example, results of more recent personal manufacture of asbestos-containing products in the United Kingdom between 1972 and 1978 indicate that, in most cases (54 - 86.5%), levels were below 0.5 fibres/ml (Table 8) . Data from various branches of the asbestos industry in France (Table 9) , indicate levels that are achievable by current dust control methods. The reduction in levels over time is even greater than is reflected by the data, because of the increased sensitivity (3x) the,currently-used Membrane Filter Method, compared with the sensitivity of previously-used methods for the determination of airborne asbestos. of FIGURE, 4i50;31;e53_4.bmp However,__it should be noted that there are countries in which effective dust control measures have not been introduced; current levels in these countries may approach those illustrated in Fig. 4 (Oleru, 1980). Table 8. Asbestos levels in different manufacturing industries in the United Kingdom, 1972-785 Industry___ ________________Number of Percentage of results-- results<0.5 (fibres/ml) Asbesto_s. cement84.586.595.098.5 Millboard/paper13587.098.299.6 <1.0< 2.0 http://www.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 32 of 129 Friction materials Textiles Insulation board 900 1304 545 71.0 58.5 54.0 85.5 80.7 72.5 95.0 95.0 88.6 -- From: Health and Safety Commission (1979) . - 4 -h s amp1e s. Table 9. Asbestos fibre concentrations in 1984 in various branches of the asbestos industry in France- Branch ................... ....... Fibre concentrations (fibre/ml)Total -------------------------------------------------------------------------------- number of < 0.5 ____ 0.5-11-2> 2points Asbestos cement Numbers-261LI61279 Percentage 93.5 3.92.10.3 Friction materials Numbers249845_583 96 Percentage62.821.213 . 82.0 Textile Numbers Percentage 81 65.3 25 20.1 17 13.7 1 0.8 Others Numbers Percentage 41 73.2 14 25.0 0 0 1 1.7 Total Numbers Percentage 632 .... ...... 1347811855 73.9 15.6 _______9_,_11.2 124 56 a . From: AFA (1985) . r Numbers,of points in work-place areas. 5.1.2 Para-occupational exposure ______Members of the families of asbestos workers handling contaminated work clothes (a practice which should be discouraged), and, in some cases, members of the the general population may be exposed, to., elevated concentrations of airborne asbestos fibres. Asbestos has been used widely in building materials for domestic application (e.g., asbestos-cement products and floor tiles), and e1evated airborne levels have been measured during the manipulation of these materials (e.g., home construction and renovation bv the homeowner). In this and the following section, only data obtained bv electron microscopy will be considered, because of the necessity of identifying asbestos and distinguishing it from other inorganic fibres that may also be present in ambient air. In addition, only data obtained using direct preparation methods without alteration of the ..fibrous material and reported as fibre number concentrations will be : r.c 1 uded . . Asbestos levels in the air of mining towns in Quebec have been http://www.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 33 of 129 determined recently by transmission electron microscopy using direct_transfer sample preparation techniques. Samples were collected in June 19 83_ at 11 sites in 5 mining communities located downwind from asbestos mines. Sampling was also conducted at a control site in Sherbrooke, Quebec.__ The overall mean asbestos concentrations in the samples from the mining towns were 47.2 fj. b re s/litre (total) and 7.8 fibres/litre (> 5 urn). Mean values for each of the sites sampled ranged up to 97,5 fibres/litre (total) and 20.6 fibres/litre__(> 5 ^m) . For the control community, the mean values were lower - 14.7 fibres/litre (total) and_0_. 7 fibres/litre (> 5 fim) (Lebel, 1984). ______Measurements were carried out in 1983 and 1984 in various mining areas in Canada and South Africa (Robock et al. , 1984; Selles et al., 1984) using scanning electron microscopy with energy dispersive X-ray analysis (Asbestos International Association. 198_4 Total inorganic fibre and asbestos fibre concentrations, using the counting criteria used in the Membrane Filter Method .(_>.5 um in length; < 3 urn in diameter; aspect ratio > 3:1) and evaluated in the same laboratory, are shown in Table 10. ______Levels of asbestos in the vicinity of industrial sources in Austria have also been reported (Felbermaver & Ussar, 1980). Applying the counting criteria described above, levels in samples taken in the vicinity of an asbestos deposit in Rechnitz averaged 0.2 fibres/litre _[range 0 -__0.5 fibres/litre) . In the vicinity of an asbestos-cement plant (Vocklabruck) , the mean concentration was 0.5 fibres/1itre (range 0_- 2.2__fibres/litre) . Table 10. _ Fibre concentrations in mining areas of Canada and South Africa--^-- Area ...___ Locations Concentration (fibres/litre. _______________________ __________longer than 5 jj.m) Total inorganic___________________________________________ Asbestos Canada (Quebec area) Residential(JJ3.2l. 8 ___areas near(2J3.10.9 asbestos mines (3) 0.9 0.2 South Africa Downwind mill . .Ail (2) ___ (3) (4) (5) (6) 600.0 81.6 8.6 300.0 10.6 4.9 600.0 80.3 8.6 3 00.0! 9.3 2.4 Residences of asbestos mine workers (1) (2) (3) .....ill .. ..15). (6) 6.3 7.4 2.7 11.0 3 .2 8.1 6.0 7.1 2.0 11.0 3 .2 7.3 Table 1_0_ (contd . ) Area Locations Concentration (fibres/litre. lonqer than 5 um) Total inorganic Asbestos Residential(JJ1.0o . 8 http :/Avw\v. inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 34 of 129 areas near asbestos mines (2) (3) (4) (5; . _ _ (6)............. . 0.6 1.1 0.4 Near a magnesium mine 1.5 Near an iron ore mine 1.5 o Jo CO`,co 0.3 0.7 0.2 0.2 0.5 0.1 0.3 - From: Robock et al. (1984) and Selles et al. (1984). - Practical limits of error. 95% (Poisson's distribution). for the calculated concentrations of fibres/litre depend on the number of fibres found in 1 mm- of the total filter surfacej__for 0.1 fibre/litre, the range is 0.002 - 0.6 fibres/litre; for 1 fibre/litre, the range is 0.5 - 1.8 fibres/litre1. Unprotected tailing dump. J Truck loaded with soil. In general, the data indicate that levels of airborne asbestos fibres (> 5 ftm in length) in residential areas in the vicinity of indus.trial sources are within the range of those in urban locations (up to 10 fibres/litre) or, in some cases, slightly higher. 5.1.3 Ambient air Available data on asbestos levels in ambient air, determined by a variety of sampling, instrumental, and counting techniques, we re reviewed by Lanting & den Boeft (1979) . Levels were significantly lower than those in the occupational environment. More recent data on levels of asbestos in outdoor air, determined by currently-accepted techniques, are presented in Table 11. Only levels measured as fibre count concentrations are presented as these are relevant to health effects. On the basis of these data, it can be concluded that levels of asbestos fibres (length > 5 urn) at remote locations are generally less than 1 fibre/litre. ... Levels in urban air generally range from < 1 up to 1_0_ fibres/litre (occasionally, levels exceed this value). Mean concentrations of other inorganic fibres of the same dimensions are generally up to an order of magnitude higher, or occasionally more. Recently, there has been concern about potential exposure to asbestos in the air of public buildings with friable surfaces of sprayed asbestos-containing insulation. Sprayed asbestos was used extensively between the 1940s and 1970s on structural surfaces (to retard collapse during fire)__and on ceilings (for purposes of acoustic and thermal insulation and decoration) . The results of available studies on asbestos levels in indoor air are presented in Table 12. These values are usually within the range of those found in ambient air__(i.e., generally do not exceed 1 fibre/litre, but may_be higher, up to 10 fibres/litre) . 5,2___ Levels in Other Media Asbestos is introduced into water by the dissolution of asbestos-containing minerals and ores, from industrial effluents. atmospheric pollution, and asbestos-cement piping. The presence of asbestos fibres in drinking-water was first reported in Canada in http://www.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 35 of 129 1971 (Cunningham & Pontefract, 1971) since when surveys of asbestos concentrations in various public water supplies have been conducted in Canada (Canada, Environmental Health Directorate, 1979), the Federal Republic of Germany (Meyer, 1984), the United Kingdom (Commins, 1979), and the USA (Millette et al., 1980). On the basis of a compendium of published and unpublished surveys in which 1500 water samples from 406 cities in the USA were analysed (using various sample-preparation techniques), it was concluded that the majority of the population consumes drinkingwater containing asbestos fibre levels of less than 1 x 10-/litrea (Millette et al.,_1980) .___ In some areas, however, levels of between 1 and 100 x 10s fibres/litre were recorded and levels as high as 600 x 10- fibres/litre were reported for one water supplycontaminated with amphibole fibres from the processing of iron ore. A nation-wide survey of asbestos levels in drinking-water from 71 1 ocations, across Canada (serving 55% of the population) was the has is for an estimation that 5% of the population receives water containing levels higher than 10 x 10- fibres/litre, about 0.6% receives water having more than 100 x 10- fibres/litre (Canada, Environmental Health Directorate, 1979) . Levels as high as 100 x 10- fibres/litre in some areas were attributable to erosion from natural sources. Levels in drinking-water supplies in the United Kingdom have been reported to range up to 2,2 x 10- fibres/litre (Commins, 1979). The size distribution of asbestos fibres in water supplies differs from that of airborne asbestos. In general, fibre lengths are much shorter; median values of 0.5 - 0.8 um have been reported (Canada, Environmental Health Directorate, 1979) . Available data also indicate that the release of fibres from asbestos-cement piping is related to the aggresivity of the water (Canada, Environmental Health Directorate, 1979; Meyer, 1984), and that convent i ona 1 . t reatment processes involving chemical coagulation fo1lowed by. fi11ration effectivelv reduce levels in drinking-water supglies^ Table 11. Fibre concentrations in outdoor air Area ----------- --------- Concentration Total inorqanic (fibres/litre) a Asbestos Total > 5 um Counting criteria.,. Referenc AUSTRIA Leoben (heavy traffic) 7.0 4.6 lenqth: > 5 urn diameter 0.2 - 3 um (SEM) Schalchham (low traffic) 1.7 0.1 lenqth: > 5 urn diameter 0.2 - 3 um (SEM) Villaqe with 4.6 asbestos-cement roofing _____ _______ ---------------- ----- ---------- Villaqe without asbestos - cement roofing 4.3 < 0.1 < 0.1 lenqth: > 5 um diameter 0.2 - 3 um (SEM) lenqth: > 5 um diameter 0.2 - 3 um (SEM) http.VAvww.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 36 of 129 Remote rural areas 1.4 <__0_ALlength: > 5 um diameter :_________________ 0.2 - 3 um _______________(SEM) Table 11. (contd.J Area ___ _____ ____ Concentration (f ibres/litre) a----------- counting criteria Total________ __________ Asbestos inorganic Total > 5 um Referenc CANADA Ontario Metropolitan Toronto <2-9 length: > 5 um diameter: all (TEM) Southern Ontario <2-4 length: > 5 um diameter : all (TEM) Toronto (busy intersection) 0 - 13b length: > 5 um diameter: all (TEM) Mississauga 0 - 11^ length: > 5 um diameter: all (TEM) Oakville 0 - 8b length: > 5 um diameter: all (TEM) Bracebridge (remote rural location) 0 - 2- length: > 5 um diameter: all (TEM) 231 O 1 Peterborough Quebec Sherbrooke 0.7 length: > 5 um diameter: all (TEM) length: > 5 um diameter: all (TEM) Table 11. icontd.)_ Area ___ Concentration (fibres/litre)a---------_________ ______TotalAsbestos inorganicTotal> 5 um counting criteria GERMANY, FEDERAL REPUBLIC OF Wanne-Eickel______________ - 300 m downwind 90.0_( from asbestos - _ _...... __ j cement plant I 700 m downwind from asbestos - 70.0 i_I.O2.0length: > 5 um Jdiameter: 0,2 - 3 um j;(SEM) j _40_^8length: > 5 fj.m Jdiameter: 0.2 - 3 um .Referent http://www.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 37 of 129 cement plant 1000 m downwind from asbestoscement plant 60.0 (SEM) 4_ ___ _______ 0_.__6length: > 5 um ______________ diameter: 0.2 - 3 /im (SEM) Dortmund dwelling area crossinq with heavy traffic Gelsenkirchen Diisseldorf 30.0 60.0 J all lengths > all diameters L 13 < | 1 18 0.2 0.9 _________________ | ... 1 50.0 1 1 io 5.0 ....... .. _ .... . 1 _[ - -------20.0 1 1 ... ----- |1- 16 ____ -- 1.0 _ _________ |_ _! -- length: > 5 um diameter : 0.2 - 3 /im (SEM) length: > 5 um diameter : 0.2 - 3 /im (SEM) calculated length: > 5 um diameter : 0.2 - 3 um (SEM) calculated length: > 5 um diameter : 0.2 - 3 um (SEM) Table 11. (_cpntd._l Area Concentration (f ibres/1 itre) a-----------Total____ _____________Asbestos inorganicTotal> 5 tan counting criteria SOUTH AFRICA Johannesburg (centre/traffic)3 . 20.2length: > 5 fim diameter: 0.2 - 3 urn (SEM) Lanqa (asbestos-cement1.70.2length: > 5 um appl i cat ion)diameter: 0.2 - 3 um (SEM) __ Soweto (asbestos-cement '! . 4 _ _ ___ _ _________ 0.2length: > 5 um ..appl ic.3tion)____ __________________________________________________________________________diameter: 0,2 - 3 um _____(SEM) Frankfort _ (rural]0 2< 0.1length: > 5 um _ ____ _(SEM) at Cape Point (reference) ____ < 0-1< 0.1length: > 5 fim .... ___diameter: 0,2 - 3 um USA ____ California diameter: 0.2 - 3 um (SEM) Upwind of< 0.2 - 11 an asbestos plant ______ length: all diameter: all http://www.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 38 of 129 a Practical limits of error, 95% (Poisson's distribution), for the_calculated con fibres/litre depend on the number of fibres found in 1 mm- of the total filter fibre/litre, the range is 0.002 - 0.6 fibres/litre; for 1 fibre/litre, the rang fibres/litre^ p____951%_confidence limits. Table 12. bevels of asbestos fibre concentrations in indoor air Area____ _________________ Number of Concentration5 samples(fibres/litre) Counting criteria Refere Canada In 3 public buildinqs with amositecontaining insulation not < 2h applicable lenqth: > 5 um diameter: all Chatfi In 7 public buildings with chrysotilecontaining insulation not < 4 to < 9 - applicable In 19 public buildinqs with asbestoscontaininq insulation 14 0 tc1 0 . 3 lenqth: > 5 um diameter: all lenqth: > 5 um diameter: all Chatfie Pinchi Germany, Federal Reoubli c of Sportinq halls (sprayed crocidolite 45 Schools (sprayed crocidolite) 5 Public buildinqs (asbestos-cement air ducts) 5 Public buildinqs (asbestos-cement sheets' 3 Public buildings (sprayed asbestos) Homes (electrical storage heaters) 0.1 to 1 . 1 0.1 to 11 . 0 0.1 to 0 . 2 0.1 to 0 . 2 1.0 to 10 . 0 0.1 to 6 . 0 lenqth: > 5 um diameter: 0.2 - 3 am Instit Fibrou (1984) lenqth: > 5 um diameter: 0.2 - 3 fim lenqth: > 5 um diameter: 0.2 - ---- ------- -- 3 Instit Fibrou (1984) Instit Fibrou (19 84) lenqth: > 5 um diameter: 0.2 - 3 am Instit Fibrou (1984) lenqth; > 5 um Lohrer diameter: 0.2 - 3 am lenqth: > 5 um Lohrer diameter: 0.2 - 3 am a Practical limits of error, 95% (Poisson's distribution), for the calculated con fibres/litre depend on the number of fibres found in 1 mm~ of the total fiIter ____ fibre/litre (range 0.002 - 0.6 fibres/litre) and for 1 fibre/litre (range 0.5 - c 95% confidence limits. The extent of asbestos contamination of solid foodstuffs has not been well studied because a simple, reliable analytical method is lacking. Foods that contain soil particles, dust, or dirt almost certainly contain asbestos fibres. Foodstuffs may also contain asbestos from water or from impure talc, which is used in coated rice, and as an antisticking agent for moulded foods (E i senberq, 1974 ) .___ Asbestos may also be introduced into foods from impure mineral silicates, such as talc, soapstone, or pyrophvllite, used as_carriers for spray pesticides (Kay, 1974) . http: www,inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 39 of 129 A S3 best: os f ib r ess hav e been det ect e d_]n b overages . Concentrations of 0.151 x 10- fibres/litre have been found in some Eng 1 ish beers (B_i 1 es & Emerson, 1968.)_, and concentrations of 4.3 6^6 x_10- fibres/litre have been recorded in Canadian beers (Cunningham & Pontef ract,__ 197Jjy__levels between 1.7 and 12.2 x 10fibres/litre have been found in soft drinks.___ It has been suggested that asbestos filters used for the clarification of beverages and other 1iquids may have contributed to the asbestos content. However.the_presence of asbestos in the water used to constitute these beverages has complicated interpretation of the data. a Unless otherwise specified, levels in drinking-water are all ____fibres visible by TEM. 6. DEPOSITION, TRANSLOCATION, AND CLEARANCE Although most of the data concerning the deposition. translocation, and clearance of fibres have been obtained in studies with asbestos, it is likely that other natural mineral fibres behave in a similar manner. 6 ^ .1 _ Inhalation In 1966,__the.. ICRP Task Group on Lung Dynamics (1966) published a iur.g model. t.hat_.subdivided the respiratory tract into three compartments the nasopharynx, the tracheobronchial, and the pulmonary or alveolar region. The deposition, clearance, and translocation of particles in each of these three compartments was described. This scheme of pathways was modified for fibres by Bignon et al. (1978) as shown in Fig. 5. FI Gy _RE_ 5j_ 3 3 ; 5 3; e5 3_5 . bmp 6.1.1Asbestos 6.1.1.1 Fibre deposition (a) Models Th e re_ _ a re five mechanisms of deposition of particles in the respiratory tract (i.e., inertial impaction, sedimentation. interception, diffusion, and electrostatic precipitation). .. Sedimentation is determined principally bv the aerodynamic diame ter of particles. The geometric diameter and density of a fibre largely determine the aerodynamic diameter with fibre length being of secondary importance. It has been estimated that an asbestos fibre of 3 fim diameter would have approximately the same settling velocity as a 10 um sphere with a density = 1.0 g/m- (Timbrell, 1982) and thus. it is generally agreed that all asbestos fibres with a diameter greater than 3 um are not respirable. However, it should be noted that._this_cut-off value is relevant only for asbestos and other fibres of similar densities.___For more information concerning the deposition of_. airborne particles in the respiratory tract, see Stober et al. (1970) and Doull et al. , ed. (1980)^ Interception is most important for longer fibres (Timbrell, 1972) .___ Fibres are more subject to interception at bifurcations in the lower respiratory tract than isometric particles because of the http://www.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 40 of 129 p_robabi1itv of nonaxial alignment and entrainment in secondary flow patterns.___ The branching of the lower respiratory tract in animals is generally less symmetrical than that in human beings. Therefore,__there may be interspecies differences in airborne fibre deposition. [b) Experimental data Studies of deposition patterns and efficiencies in hollow airway casts of the human bronchial tree using monodisperse spherical particles have shown that: (a) the deposition efficiency per airway generation increases distally, reaching a peak in the second to fifth generation, and decreases subsequently with generation number down to at least the eighth generation; particle size and flow rate determine in which generation the peak deposition occurs; and (b) the deposition of inhaled particles per unit surface area is generally much greater in the vicinity of the bifurcations than at other surfaces (Schlesinger et al., 1977, 1982 ; Chan & Lippmann, 1980) . Detailed quantitative data on deposition patterns and efficiencies for fibres at specific airway sites are not available. In the .absence of such data, it is reasonable to assume that the deposition will be similar, though probably higher, for fibres, than for particles of more compact shapes, and that the additional deposition of fibres through interception will increase the amount without radically changing the pattern of deposition. Harris & Fraser (1976) give a quantitative comparison for selected fibre lengths^ _____ Experimental evidence indicates that penetration into the alveolar part of the rat lung decreases sharply for glass or asbestos fibres with aerodynamic diameters exceeding 2 urn and that deposition in the tracheobronchial airways increases with increasing fibre length (Morgan et al., 1980). ______Timbrell (1972) studied the deposition of asbestos fibres in hollow airway casts of pig lungs extending to the respiratory bronchioles. The author found that, for comparable mass concentrations of UICC asbestos-__ there was about 5 times more bronchial airway deposition for the "curly" chrvsotile fibres than for the straighter amphibole forms. This was attributed to the effective increase in chrysotile diameter due to the diameters of the curl" and to the greater probability of amphiboles to be a1igned parallel to the airway axes by the shear flow. These results were consistent with those of additional studies described in the same paper, in which retention in the rat lung was measured one day after a 10-week inhalation exposure. The retention of 3 types of UICC amphiboles was about 6 times greater than that of 2 types of UICC chrysotiles. The deposition of chrvsotile asbestos in the peripheral lung airways of rats exposed for 1 h to 4.3 mg respirable chrvsotile/mwas studied by Brody et al. (1981). In rats killed immediately after exposure, asbestos fibres were rarely seen by scanning electron microscopy in alveolar spaces or on alveolar duct surfaces, except at alveolar duct bifurcations. Concentrations were relatively high at bifurcations nearest the terminal bronchioles, and lower at the bifurcations of more distal ducts. In rats killed http: AA/ww. inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 41 of 129 after 5 h, the patterns were similar, but the concentrations were reduced.. 6_._1____Fibre clearance, retention, and translocation The fate of fibres deposited on surfaces within the lungs depends on both the site of deposition and the characteristics of the_fibres. Within the first day, fibres deposited in the tracheobronchial airways can be carried proximally on the mucous surface. to the larynx, and can be swallowed (Fig. 5) . It has been suggested, though not proved, that a small fraction of the fibres might penetrate the epithelium of the tracheobronchial tree. In the non-ciliated airspaces below the terminal bronchioles, fibres are cleared much more slowly from their deposition sites by various less effective mechanisms and pathways, which can be classified into 2 broad categories, i.e., translocation and disintegration. ______Translocation refers to a change in the location of the intact fibre primarilv along the epithelial surface: (a) to dust foci at the respiratory bronchioles; (b) on to the ciliated epithelium at the terminal bronchioles; or (c) into and through the epithelium, with subsequent migration to interstitial storage sites or along lymphatic drainage pathways. Short fibres (generally < 5 urn), ingested by alveolar macrophages as well as unincorporated fibres, may be translocated. ______Disintegration refers to a number of processes, including subdivision of the fibres along parting planes (either in length or diameter), partial dissolution of components of the matrix, which creates a more porous fibre of relatively unchanged external size, or surface etching of the fibres, thus changing external a Standard reference samples of asbestos collected in 1966 .___ experimental use under the auspices of the Union Internationale ...Centre le.Cancer. .dimensions., Uni ike amphibole fibres which are less soluble in lung fields, chrysotile fibres undergo partial dissolution within the 1un g s aft er _fibr11lation {i.e.,__f ibre splitting along the fibre length!..,___Predominant changes ir. the fibre, with time, include a decrease ir. magnesium, and an increase in iron content (Langer et a_l..,,, 1970, 1972! . Mg2^ contributes to both the structural integrity and the positive charge of the fibre. The process of 1eaching._can_cause fragmentation and more rapid disappearance of chrvsotile from the lung compared with that of amphibole types of asbestos {Morris et al, 1967). ____ The results cf studies of the short-term retention and clearance of asbestos in rats, reported by Wagner & Skidmore 1965, , indicated that over a period of 2 months following a 6-week period of exposure to about 30 mq/m3 of respirable dust, the clearance patterns for chrysotile. amosite. and crocidolite could each be described bv single exponential functions. However, the rate..of clearance for chrysotile was higher bv a factor of 3 than that for amosite and crocidolite. In addition, the retention of ohrysotile. as measured a few days after the end of the 6-week exposure period, was only about one third that of the amphiboles. Later work by Wagner et al . <1974,? indicated that, after prolonged exposure. - 12 months! ._the lung burden of chrysotile reached a clateau, whereas a continued increase was observed for the 3Tp.hi_bcles_.. _ This difference was attributed to the enhanced v 1 ea rar.ce rate cf chryso111 e Fig 6 ! . http://www.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) In a study, on rats conducted by Middleton et al . (1979;, the retent ion of chrysocile was approximately one quarter that of the imphiboles and appeared to be related to the airborne asbestos I v e 1 during dusting; at higher airborne levels (1.3 -__9.4 ng/m3 ) , the retention of chrvsotile was lower than of the amphiboles. .FIGURE . eg. 3 2; 3.2; e 5 3 .bmp Muhle et al. (1983; investigated the effects of cigarette smoke on the retention.of UICC chrysotile__(type A) and UICC crocidolite in. rats., Result,? showed a doubling of crocidolite fibres in the lungs of the cigarette smoke exposed group compared with animals not_ exposed to cigarette smoke. A plateau was found for chrvsotile as in the study of Wagner et al. (1974). This plateau was not influenced by cigarette smoke. This difference between the two fibre types can be. explained bv a higher deposition rate of enrysotile in the upper airways compared with crocidolite and a decrease in deep lung clearance induced bv cigarette smoke. There is_some evidence that tracheobronchial clearance is not influenced bv cigarette smoke (Lippmann et al., 1980). In man, smoking reduces long-term deep lung clearance (Cohen et al.. 1979) . 2n trie, other hand, . the results of studies reported by Morgan et al. .1975,__1977a;. who performed single exposures administered through a head mask, neither confirmed the fast clearance nor the lower retention o_f chrysot i_le, Middleton et al. (1979) concluded that clearance could be described in terms of an exponential model, though somewhat modified compared with that used bv Morgan et al. . 191 ] a. . ___ Tne. clearance model used to describe the results of these s.noi t term studies was not applicable to long-term (1-vear) inhalation studies, .Davis et al., 1978'. It was suggested. theref.or.e^ t_hat the observations in long-term studies should be exp 1 a: red ..by an impairment of the clearance mechanism in lungs with Available data indicate that fibre length is an important determinant of clearance. While results of studies with asbestos are not available. Morgan & Holmes (1980) studied the effect of fifare length on the retention of glass fibres in rat lungs bv means of serial sacrifices. The 1.5 um diameter glass fibres were administered bv intratracheal instillation. The macrophage-mediated mechar.ical clearance was less effective for fibres IQ um in length than for 5 pm fibres. It was ineffective for fibres of 30 pm or more As supporting evidence. Morgan et al (1980) cited the work cf Timbrell & Skidmore (1971) on the dimensions of anthophyllite fibres in the lungs of Finnish workers. The results of their study suggested that the maximum fibre length for mechanical clearance was 17 um. Resuits of studies bv Pooley & Clark (1980) indicated that the size distribution of amosite and crocidolite fibres in airborne -u:u_ies_was simi.ar to tnat found m organs. Later it was noted that, the proportion of longer fibres of both minerals found in the :una was increased, probably because of the more efficient clearance of the shorter fibres. It was difficult to compare the size distribution of airborne chrvsotile with that in the lung because of the breakdown of chrysotile fibre aggregates and fibre The effects .of. intermittent exppsu_re.. to.._high doses of asbestos .uefineu by the autnor as pea.k_. on fibre retention in. the lungs of rats were studied by Davis et al . ; 1980b,- . Four groups of rats -uha_eu be.22 preparations of amosite or chrysotile. Two of the die -pis. were exposed respectively to the 2 asbestos types for 5 da vs/week,__7 h/day.__for 1 year. The 2 other groups were treated with atosite and chrvsotile. respectively, at 5 times the previous http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 42 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) dose, _but__for only 1 day per week for 1 year.__ The results showed that after.the. 12-month inhalation period, the levels of both chrysotiie and amosite in lungs were similar regardless of whether "peak" (1-dav/week exposure) or "even" (5 days/week exposure) dosing had been used. During the following 6 months, asbestos was cleared from the lungs of the "peak" chrysotiie group more slowly than tnat from the lungs of the "even" chrysotiie group, but clearance from the "peak" amosite group was faster than that from the "even" group. The movement of inhaled fibres from the epithelial surfaces into the lymphatic and circulatory systems was described by Lee et al. ,1981) . Groups of rats, hamsters, and guinea-pigs inhaled cocassium octatitanate (Fybex), potassium titanate (PKT), and UICC amosite. The mean diameters (0.2 - 0.4 ^m) and lengths (4.2 - 6.7 ym, were nominally similar ..for all three types of fibre. Numerous dust_celIs were transported to the tracheobronchial and mediastinal 1 yrrph nodes., where some, dust cells penetrated into the blood or lymphatic circulation. The dust cells migrated directly from the - y"p k n :ies met ad^ a cent, med : as t i r.al adipose tissue. Dust-laden g i a r. t c e 1 _1 _s we re occasionally found in the liver, and there was widespread migration of the fibres into other organs, without any sianificant. tissue response. On the basis of these results, it was proposed that lymphatic vessels were a main route of dust cell migration.... However.__it is most unlikely that the pathways that were demonstrated to.be important in this study represent the predominant routes for clearance at exposure levels normally encountered in the ambient and occupational environment. It is more 1ikely that they may be important following exposures to massive.concentrations of dust__.3100 fibres/ml; . More experimental work with lower concentrations of fibres is necessary. ..... In the inhalation study of Brody et al. (1981) (section 5.1.1.1;, the examination of tissues by transmission electron microscopy revealed that chrysotiie fibres deposited on the bifurcations of the alveolar ducts were taken up, at least partially, by type I epithelial ceils during the 1-h inhalation exposure. In the 5-h period after exposure, significant amounts were._cleared from the surface, and taken up by both type I epithelial cells and alveolar macrophages. In the 24-h follow-up exposure, there was an influx of macrophages into the alveolar duct bifurcations. These observations suggest that there may be direct fibre penetration of the surface epithelium. Thus, in summary, available data indicate that chrysotiie is more likely than the amphiboles to be deposited in the upper airways of the respiratory tract. In addition, chrysotiie is i:earea more efficiently from the lungs; thus, there is greater retent ion of the amphiboles. Fibre length is an important de.cerminant of clearance, with shorter fibres being cleared more readily, and cigarette smoking affects deep-lung but not i acn.ecbi cnchial clearance. . There were, no consistent effects on clearance and_ retention of fibres with intermittent exposure to n-uh doses compared with continuous exposure to lower levels. 6 , 1,2 Ferruginous bodies _____ Mineral fibres inhaled and retained in the lungs may become coated with a segmented deposit of iron containing protein, forming club_.shaped ferruginous bodies (Davis. 1964 ; Milne. 1971). Those for which the core is asbestos are commonly called asbestos bodies. Using light microscopy, they have been found in large numbers in individuals occupationally exposed to asbestos (Ashcroft & Heppleston, 1973) and, using optical and electron microscopy, in the .lungs of most adults who have lived in urban areas (Thomson & Figntn et al . , 19FQ; Selikoff et al . , 1972; Davis & Gross, 1973; Oldham. 1973). Probably fewer chan 1% of the fibres in.. tr.e lung become coated 'Gaensler & Addington, 1969) . No http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 43 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) ef i o 1 oqicaI_sign lficance has been attributed to the format ion of cstbod:es ; their occurrence_alone merely indicates exposure to_asbescos and not necessarily the presence of disease (Longlev, 1969; Milne, 1971; Churg & Warnock, 1980) . 6 -.1 . 3 Concent _of _ fibres in the respiratory trace l' he mi.per a 1... fibre content of organs of deceased persons who had been occupationally exposed to asbescos has been investigated. doer, determinations, require tissue digestion procedures that do not change the fibre structure, and sophisticated analysis to identify -_i.tics.__The reported mineral content in the .urgs of workers exposed to fibres ranged from 1 to 10 q/kg (dry AkLigct:.levels...in. the general population are about 0.3 g/kg (dry weigh:. .Beattie &_ Kno_x 1961' . Mo tone1 usions.concerning the regional distribution of fibres in the.lung can be drawn on the basis of available data (Le 3ouffant, 1980; Sebastien et al., 1980b? . 6 . 2 Inaescion _____ An important question in the evaluation of the possible risks associated with the inaestion of asbestos is whether fibres can migrate from the lumen into and through the walls of the gastrointestinal tract to be distributed within the body and subsequently cleared. There is considerable disagreement coneerning. this subject, largely because of the difficulty of controlling external contamination of tissue samples in available studies and. because of limitations in existing analytical techniques - ____ Detailed reviews of the available data have been published .Cook. 1953; Toft et al., 1984). It is not possible to conclude with certainty that asbestos fibres do not cross the gastroincest;nal wall ... ._However, available evidence indicates thatL f t : r. :vr. aces :t is extremely limited.__Cook (19831 has suggested that 10 3 tc 1_0 7 of ingested fibres penetrate the gut Wdi ; . There is no.available informat ion on the bioaccumulation/ retention of ingested asbestos fibres. Simulated gastric juice has been shown to alter the physical and chemical properties of choysotile. fibres and, to a lesser extent, crocidolite fibres .Seshan,..198 3__.. Available data concerning the possible elimination of asbestos in the urine of human beings are contradictory and inconclusive (Cook & 01 son , 19 7 9; Boat man, 1982; .. 7.__ EFFECTS ON ANIMALS AND CELLS 7.1__Asbestos For a pollutant, such as asbestos, where there is a great deal of information on the human health effects associated with exposure, the results of toxicological studies are important, not only to assist in assessing the causality of associations observed m epidemiological studies, but also to elucidate the mechanisms of tcxicity, to define biologically important physical and chemical p rooertles, and to develop hypotheses for further epidemiological sfudyu.. The results of toxicological studies on asbestos have also . 3 i :'.-u . r. f c i magi cr. or. pose response relat ipnships and the role cf _i.ibre type, size, and shape m the pathogenesis of asbestosr e la t e d.. a pseas es . _ However, con cl us ions c oncerni r,g the importance cf these variables are necessarily limited, because of the uucu::y to adequately characterize fibre size in the administered . j. . In tne following section, the results of recent studies .a:- e:;pr.as.zta, since experimental methods have improved ::or.s i do rabl y in. the., past few. years . http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 44 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 45 of 129 7 . ... . Floroqer.ici ty 7.1.1. i Inhalation Da:3 concerning the ibroqeni ci t y of inhaled asbestos in animal Flbrosis has been_observed i_n many animal species (e.g., guinea pigs, rats.__hamsters, monkeys', following inhalation of both chrysotile and the amphiboles. In several of the studies, the incidence and severity were approximately linearly dose-related 'Wagner et al., 1974. 1980; Wehner et al., 1979) and, as has been observed in human studies, there was progression of the disease fc11owing_cessation of exposure (Wagner et al., 1974. 1980). In genera1, it has been observed that shorter fibres are less fibrogenic (Davis et al. 1980a). The results.jpf the early studies regarding the relative fibrogemcitv of various fibre types are confusing and contradictory mainly because, usually, only the airborne mass coneentrations were measured; the numbers or size distribution of the fibres were not considered. In addition, there may have been surface artifacts in the. mineral, produced during sample preparation, which blunted activity. Table 13. Inhalation studies - fibrogenicitv 3cec.es Number Protocola Results References J ii!. e a PA 3. and Vervet monkev 16 24 guinea Dias, 2 4 rabbits, and 3 4 Vervet monkeys in exposed aroups exposure to - 30 000 o/ml of chrvsotile .7 10% fibres > 10 p.m. , anosite, or crocidolite from South African mills for various periods of time (e.g.. up to 24 months for auinea-pias exposed to chrvsotile; lifetime for rabbits and Vervet monkevs exposed to chrvsotile. but onlv 14 months for these species when exposed to amosite) asbestos bodies present in all 3 species exposed to all 3 types; chrvsotile exposure caused fibrosis in guinea-pigs and monkevs but not in rabbits: amosite caused asbestosis in all 3 sDecies; it is difficult to draw conclusions concerning the relative cathoaenicitv of the different fibre tvoes because of the various periods of exposure and lack of characterization of fibre sizes Wagner (1963a! SFF W. s ta r rat total of 1013 rats; group sizes of 19-38 qrouDS exDosed to 9.7 14.7 mg/m3 of UICC amosite, anthophvllite. crocidolite. chrvsotile (Canadian). or chrvsotile (Rhodesian) for periods of 1 dav, 3, 6, 12. or 24 months less asbestosis for amosite than for the other dusts: progression of asbestosis following cessation of exposure for all dusts Waqner et al. (1974! SFF w h: t e ,. . ; : 3 t tl th e Han groups of 48 an:ma1s study designed so that both mass and fibre number could be examined; 5 groups exposed to 10 mg/m3 UICC chrvsotile. crocidolite. or amosite (550 fibres/ml amosite > 5 um; 390 fibres/ml chrvsotile > 5 am or 430 fibres/ml crociaolite > 5 am, for 12 months chvsotile caused far more fibrosis than either amDhibole. even when the fibre numbers were similar Davis et al. (197R! Table 13 . _____ . 'contd.'1 Scecies Number ``a = tr ..... . totai of 96 Protocola two groins exposed for Results sliaht Dulmor.arv fibrosis Wehner http://www. inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 46 of 129 Svnan aolden hamster exposed and 96 control animals 3 h/dav, 5 davs/week to either 1 uq/litre (5-13 fibres/ml, > 5 um) or 10 uq/litre (30-118 fibres/ml. > 5 um) A/C aerosol (chrvsotile content 10.5%) for up to 15 months only in the 15-month exposure et al. qroup; hiqher incidence and (1979) severity with increased dose after 5-month exposure to 10 uq/litre dose; increased incidence of sliqht emphysema after exposure to the 10 uq/litre dose for 6 months - after 15 months, no difference between exposed and control qrouos; authors suqqested that the minimal resoonse miqht be due to chanoes durinq processinq of the fibres that decreased the toxicity Aa t _ : a . not see- ci f ied arouos sizes of _ i to ar.. rr,a -v s -------------- --- -- ------------- desiqned to comDare the oathoioqical effects of exposure to UICC samples with those of factory samples; 4 qrouDS exDosed to UICC amosite. UICC chrvsotile. factorv amosite, or factory chrvsotile at 10 mq/m3 for 12 months; animals permitted to complete life span factory amosite more fibroqenic than UICC sample Davis et al. (1980a) Table 13. (contd.) Number Protocola Results SPF Wistar rat z z the AF/HAN strain arouo sizes of 48 animals - studv desiqned to compare the oathoioqical effects of peak dosinq to those of even dosinq; 2 qrouos exposed to either UICC amosite at 10 mq/m3 or UICC chrvsotile at 2 ma/m3, 7 h per dav. 5 davs Der dav. 5 davs ter week for 1 year and 2 qrouDS exDosed to either amosite at 50 mq/m3 or chrvsotile at 1C mq/m3. 1 dav each week, for l vear levels of oeribronchial fibrosis qenerallv lower for "oeak" dosinq qrouos than for "even" dosinq qrouos; levels of interstitial fibrosis sliahtlv hiaher followinq "peak" dosino References Davis et al. (1980b) Caesar ;ar. derived /A s t a r 1 at Group sizes of 24 6 and 12 months exposure' and 46 3 mentns exposure exposure for periods of 3. 6. or 12 months to SFA chrvsotile (430 fibres/ml > 5 um), Grade 7 chrvsotile .1020 fibres/ml > 5 um) or UICC chrvsotile (3150 fibres/ml > 5 um) at 10.8 mq/m3 oroqression of fibrosis after end of exposure for arouDS inhalinq all types for 6 or 12 months.- UICC Droduced at 2 samples in all 6 aroups a Unless otherwise specified, exposures were for 6-8 h/dav. 5 davs/week. However, in an inhalation study by Davis et al. (1978), chrysotile caused more lunq fibrosis in rats than either : . : :.e :r amosite, even when the fibre numbers (lenoth > 5 urn' in the dust clouds were similar. The authors snaaested that the Great er fibroaenicitv of chrysotile miqht be related to the fact that chrvsotile clouds contained manv more fibres over 20 ^m lono. Th e observation that shorter fibres are less fibrooenic was confirned in a studv bv the same arouD, in which rats were exposed for 12 mo n.ths to 10 ma/m3 of either short-fibred (1% > 5 um) or lcr.cr- f ibr ed (30% > 5 um) amosite (Bolton et al . , 1983a). .1.2 Intrapleural and intraperitoneal injection Fibrosis has also been observed following intrapleural (Smith Waqner et al. (19R0) http://www.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) et al . , 1965; Burger & Engelbrecht, 1970; Davis, 1970, 1971, 1972) and.mtraperitoneal injection (Jagatic et al., 1967; Shin & F i rrn i nger 19 7 3_ Engelbrecht & Burger, 1975) of asbestos. The results of these studies have confirmed that short fibres are less f icrogen.c .Burger & Engelbrecht, 1970; Davis, 1972! . 1 ._3 1 r.gest ion Several ..studiesof the effects of ingested asbestos on prol.: rerat ion and other biochemical variables in the epithelial ce_l_ls of the gastrointestinal tract have been conducted (Amacher et l?"!; F: -" v . 5. Varr.es, 19^6; Jacobs et al . . 1911' . Although sore changes ..e.g., an increase in incorporation of tritiated tr.vmidinel have been noted in some studies at various times fo1lowing administration,. no consistent pattern has emerged. __ The histopathological effects of ingested asbestos on the gastrointestinal wall have been examined, but the results of these studies, have also been contradictory. Though Jacobs et al. (1978) Y-'-l 1 :gh: and electron microscopic evidence of cellular damage m the intestinal mucosa of rats fed 0.5 or 50 mg of chrvsotile per dav, for 1 week or 14 months, no pathological changes were found on light and electron microscopic histological examination of tissue sections of the gastrointestinal tract of rats that had consumed approximately 250 mg of UICC amosite, chrysotile, or crocidolite, per week, for periods of up to 25 months (Bolton et al., 1982a). Similarly, tissue examination by light microscopy did not reveal any pathological changes in the wall of the small intestine of Wi_star rats that had consumed 100 mg UICC amosite, daily, for 5 days .Meek St Grasso, 1933.' . 7.1.2 Carcinogenicity ion Exposure conditions in inhalation studies approach more closely ihe nrcurnstances _of human exposure to asbestos and are of most relevance for. the assessment of human health risks. The results of the most significant inhalation carcinooenicitv studies in various animal species are Presented in Table 14. Although fibrosis has been observed in several animal species following inhalation of different types of asbestos 'section 7.1.1 , a consistently ir.reased incidence of bronchial carcinomas and pleural mesotheliomas has been observed only in the rat. an extensive and well conducted and controlled series of 'n = 19 - 58'. tc! the 5 UICC asbestos samples at concentrations ranging from 10 to 15 mg/m3. for periods ranging from 1 dav to 24 months 35 h/week). Exposure had very little effect on average survival Average survival times varied from 669 to 857 davs for exposed animals and! from 754 to 803 days for controls. In the exposed animals, there were 50 adenocarcinomas, 40 squamous cell carcinomas, and 11 mesotheliomas. None of these tumours aDDeared critr tc 3CC days from the first exposure, and the incidence of lung cancer was greatest in animals surviving 600 days. On the basis of analyses of the severity of asbestosis in animals with turnoy r s..taking_.survival into account, it was concluded that the an.;male with lung tumours had significantly . P < 0.001) more asbestosis than those without. Seven malignancies of the ovarv and rigro of m.al e gem to - urinary organs were observed in the exposed groups of approximately 700 rats. No malignancies were observed at these sues m controls. These differences were not statistically icar.t and the incidence of malignancy at other sites was different from that in the controls. No data on the i_t_ ext ra - pulmonary sites and is dose were provided. http://www .inchem.org/documents/ehc/ehc/ehc 5 3 .htm Page 47 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 48 of 129 1:. ji study by Davis ec.al. ..J..97S, rats were exposed - ~ v yq ^( .~ru : do 1 : t e , or arnosite at 2.0 or 10.0 ma/rn3 for 12 months. All malignant pulmoriary tumours occurred in chrysotile- exccseu animals ___The authors suggested that, the greater care:nogenic;ty of chrysotile might be related to the fact that hrys"' : 1 <= ''r.ouncd many more fibres over 20 in length.__ In addition to the lung tumours, extraoulmonarv neoplasms included a relatively large number of peritoneal connective tissue malignancies, including a leiomvofibroma on the wall of the small intestine. The relationship between these tumours and exposure to asbestos is uncertam, however. In a recent study, inhalation of short-fibred arnosite (1% > 5 am' at 10 ma/m3 did not produce fibrosis or pulmonary tumours in Wistar rats ;n = 48}. In contrast, there was extensive fibrosis ana over 30% incidence of tumours in a group similarly <exposed to ;cr.~ fitred arnosite '30% > 5 urn.- 11% > 10 am) (Davis et al. . in press.' . Table 14. Inhalation studies - carcinogenicity SpeciesNumber .................. ProtocolaResult s____________ ______________________ Reference rat, 12 `.controls^ ; exposure to chrysotile,increased lung tumourReeves et al. i acc ___ 2 C__ 6.9___.exposed.. crocidolite, or arnosite forincidence in rats (7-9% in(1974) guinea pig, ______________________ 4 h/dav, 4 davs/week. forthose with adequate survival gerb11,_______________________________2 years,- mean concentrationrecord) mouse ___ ______ ________ = 50 mg/m3; light microscopic ______ ______ fibre count of chrysotile: 54 ___ ___ fibres/mlarnosite : 864 fibres/ml, crocidolite: ____________ 1105 fibres/ml SPF Wistar rat total of 1013 rats; group sizes of 19-58 groups exposed to UICC arnosite, anthoohvllite, crocidolite, chrysotile (Canadian). or chrvsotile (Rhodesian), at 9.7 - 14.7 ma/m3. for periods of 1 dav. 3, 5, 6, 12, or 24 months. for 35 h/week higher incidence of tumours Waaner et with 12 months exposure than (1974) with 6 months, but little difference following 12 and 24 months exposure; of 20 tumours which metastasized. 16 were in chrvsotile-exDOsed qrouDs, 3 in crocidolite-exoosed groups and 1 in anthoohvllite-exDosed qrouns: of 11 mesotheliomas. 4 occurred following exposure to crocidolite and 4 followina exposure to Canadian chrvsotile 2 mesotheliomas occurred following 1-dav exposures: positive association between the._.incidence of asbestosis and lung cancer; no association between exposure and gastrointestinal cancer incidence Tacie 14 ^contd.._ Specles Syr_lan golden hamster Number Protocola Results - - ___ ___ _ ___ ____________ ________________________ 102 animals per group .._____ ______ animals exposed to UICC Canadian chrvsotile at 23 uo/litre for 7 h/dav. 5 davs/week. for 11 months; half of animals also exposed for 10 min 3 times a dav to cigarette smoke for duration of their life span; one 10 out of 12 lung adenomas found in 510 hamsters. occurred amona the 102 animals (1975. 1979) Wehner (1980) of larvnaeal lesions arid maliqnant tumours siqnificantlv http://www.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 49 of 129 control group exposed to smoke + sham dust, one exposed to sham smoke + sham dust lower in asbestos + smokeexposed group than in smokeexposed control group probably due to significantly shorter life scan in asbestos - exposed animals Wistar rat of the Han strain qioup size = 4 R experiment designed so that both mass and fibre number could be examined; 5 groups exposed to UICC chrysotile. crocidolite. or amosite at 2 or 10 mg/m3 (550 amosite fibres/ml > 5 urn: 390 chrvsotile fibres/ml > 5 um or 430 crocidolite fibres/ml > 5 am) all malignant pulmonary neoplasms occurred in chrvsotile-exposed animals; the authors suoaested that the greater pathogenicity of chrvsotile miqht be due to greater number of fibres > 20 um in length Davis et al. (1978) ;-3c.e 1-5. .ccntd._ - c. ~ rat (strain net see cified' Number group .s l.ze __= 4ft Protocol a Result s Reference . ______ ________________________________ _____________ designed to compare the pathological effects of exposure to UICC samples with those of factory samples; 4 groups exposed to UICC amosite. UICC chrvsotile. factory chrvsotile produced similar levels of lung pathology to those produced bv UICC sample except that a slightly smaller number of bronchial carcinomas was Davis et al. (1980a) factory amosite, or factory produced by the factory dust; chyrsotile at 10 mq/m3 for 12 little carcinogenicity with months; animals permitted to complete life scan both amosite samples; based on the analysis of fibre sizes in each of the samples, authors concluded that "while fibroqenicitv and carcinogenicity both depend upon the presence of relatively long fibres in dust clouds, different lengths are involved in each process and tumour oroduction reauires the largest fibres SrF Wistar rat, af.' ha:; .: i: r. aroup size = 48 study designed to compare the no differences in the Davis et al. pathological effects of "peak" incidence of pulmonary (1980b) dosing with those of "even" neoDlasms between "Deak" dosina dosing,- 2 groups exposed to groups and "even" dosing groups; UICC amosite at 10 ma/m3 or the authors concluded that no UICC chrvsotile at 2 mg/m3, indication that short periods 7 h/dav. 5 davs/week for of high-dust exposure in an 1 year and 2 groups exposed asbestos factory would result to amosite at 50 mg/m3 or in significantly greater hazard chrvsotile at 10 mo/m3 than would be indicated bv the 1 dav/week for 1 year raised overall dust counts for the day in auestion (there were. however. 2 bronchial carcinomas in the "peak" dosing amosite qrouo and none in the "even" dosinq qroup) Sceci es Number Protocola Results carrier _ .grcup sizes = exposure for periods oftumour yield significantlyWagner et al protected.. 24 ,.6,, and. 12 .... either 2L 6. or 12 months to greater with UICC chrysotile(1980) http://www. inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 50 of 129 Caesar ian___months exposure) SFA chrvsotile (430than with Grade 7 derived and 48 '3 _____fibres/ml > 5 qm) or UICC Wi.st.ar_ rat months exposure) chrysot i le !3150 fibres/ml ______ > 5 |im.__________ at 10.8 mq/m3 a Unless, otherwise., specified, exposures were for 6-8 h/dav. 5 davs/week. The results of inhalation studies impart some useful mrcrmation concerning dose - response relationships and the c3rcinogen.ic. potential of asbestos of various types and fibre s i zes_.__ An., approximately linear relationship between the incidence of 1 png. cancer..and dose has been found in several studies (Wagner et al . , 1974. 1980; Davis et al., 1978) and, although insufficient numbers of mesothellomas have been produced in inhalation studies co draw definitive conclusions, it has been noted that most have peer, found m animals that received a high total dose of asbestos ,,Davi_s , 197 9' .__ However, the incidence following a short period of exposure T.e., 1 day) has been greater than would be expected on -he has:? ~f a 1 inear hypothesis for the dose - response relationship (Wagner et al. . 1974). It is also of interest to note that in two studies Davis e t al . , 1978; Wagner et al., 1980),, all of the mesotheliomas observed (3) occurred in the qroups exposed for the shortest period. 7.1.2. 2 Intratracheal instillation _____Factors that affect the deposition of fibres in the respiratory tract are not taken into consideration in studies involving mtracracheal 1 mection and therefore it is difficult to extrapolate the results directly to man. In addition, the greater incidence of infection following exposure bv this route often complieates the interpretation of the results. However, the resul_ts of. such investigations have confirmed the observations in _:.na*at - in studies ... . Furthermore, significantly-increased incidences cf _po..th .mesothelioma and lung cancer have been observed in dogs conconitantly exposed to cigarette smoke (inhalation) and asbestos . ir.t rat racheal ly / 'Humphrey et al . , 1981), 7 . 1 2 . 3 Direct administration into body cavities - Wagner ,15 5 2_....f irst reported that "it is possible to produce tumours wmch appear to be arising from the mesothelial cells of the pleura bv inoculating certain dusts into the pleural cavities of rats__ Since then, numerous studies involving the injection or implantation of asbestos into the pleural or peritoneal cavities of various species, have been conducted: the results of the most important of__tnese studies are summarized in chronological order in Table 15. Table 15. Intrapleural and intraperitoneal administration studies Species Wistar rat Number 11 aroucs; 10 animals/aroup Protocol Results intrapleural infection of 50 mg of 3 samples of crocidolite from South African mines. 3 samples from mills in the same region. 2 samples of chrvsotile from mines. 1 sample of amosite. 99.9% pure silica dust or pure carbon black - -- - 30 months after exposure. pleural mesotheliomas in 2 crocidolite-treated rats, 1 chrvsotile-treated rat. and 1 rat receivina Dure silica: authors concluded "it is possible to produce tumours which aDDear to be arisinq from the mesothelial cells of the Dleura bv inoculatinq certain dusts into the pleural cavities of rats" Reference Wagner (1962) Golden hams t er 15 animals/ exposed group.15 untreated intrapleural infection of 25 mg of soft chrvsotile 'averaae fibre length 67 am). granulomatous inflammation and fibrosis in hamsters receivina all 3 types; 5 (1965) http:,/www.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 51 of 129 cp_nt.roIsharsh chrysotile (36 /im) and tumours, possibly _ampsite 8_ grn; ; also softmesotheliomas; 2 in harsh ___________________ chrysotile in diet (10 q/kq) chrysotile-treated hamsters (10 q/ka) of chrysotile-and 3 in amosite-treated ________________________treated animals; amosite _______hamsters ________________________ ! 10 g/kq) in diet of amosite____________________ treated animals S?F..wistar 48 males, 48intrapleural injection ofappreciable proportion ofWagner & : 31 and.. _ females/exposed 20 mg of Transvaal amositeanimals treated with all types Berry ''..standard'1 group(91% < 5 am in length)of asbestos developed a rapsuperfine grade of Canadian__________________________________________ mesothelioma; large number of chrvsotile (92% < 5 um), tumours found in animals North West Caoe crocidolite receiving crocidolite (SPF: (70% < 5 urn); extracted 86/94, standard: 62/91); fewer crocidolite (86% < 5 um). tumours in amosite-treated silica or saline group (SPF: 38/96, standard: 26/84) and period between inoculation and development (1969) Species Number SPF Wistar rat a r. u " standard" rat .conta.' -ft-a's. cathoaen 11 ee CsborneMendel rat - 2a3 -T- _ - 'contd.' Species Number SPF Wistar 12 - 36 rat Protocol Results Reference of mesothelioma much longer than with the other 2 types: authors note "the high incidence of these neoplasms following the inoculation of chrvsotile was unexpected" 'SPF: 61/96. standard: 62/90! 40 ma of 17 materials applied on a fibrous glass vehicle to cne pleura including 3 tvoes of asbestos in 7 forms, 6 types of fibrous glass, 2 tvnes of silica. etc; 2-vear observation period amosite.chrvsotile, and 4 Stanton & different tvpes of crocidolite Wrench (1972) produced eauallv high incidence (58-75%) of mesotheliomas: hand-milled crocidolite not exposed to extraneous oils or metallic mining yielded dose- related tumour responses comparable with those of a standard reference milled crocidolite; standard crocidolite caused fewer tumours (20-32%) when reduced to submieroscooic fibrils; pulverized fragments of mill and nickel metal and fibrous glass vehicle alone did not induce tumours: 2 forms of fine fibre-qlass milled to approach length of asbestos fibre produced moderately high incidence (12-18%); authors concluded "the simplest incriminating feature for both seems to be a durable fibrous shape, perhaps in a narrow range of ---------------------------------------- __________________________________________ ................................. Protocol - - ________ __________________________________________ Results intrapleural iniections of 0.5. 1. 2. 4. or 8 mg of SFA chrvsotile and crocidolite (from Northeast Cape mine): the risk of develooina a proDortional to dose for both (3 <317) http:/Vw\vw. inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 52 of 129 Rat strain n-r spec ; : : ea. Mendel : a: exoosed arouD intrapleural iniection of SFA chrvsotile and crocidolite; 20 mg of Canadian chrvsotile of the UICC standard reference samDles. SFA chrvsotile. or samples, crocidolite was the saline (control): intrapleural most carcinogenic and removal iniection of 20 mg of the 5 of oils bv benzene extraction UICC samples. brucite or did not alter the barium sulfate; intrapleural carcinogenicitv of these iniections of ceramic fibre, samoles; results were fibre glass, glass powder. consistent with the hvoothesis aluminium oxide, and 2 that finer fibres are more samples of SFA chrvsotile carcinogenic 3 intrapleural iniections of 20 mg of chrvsotile from filters at 2 USSR mines 95% fibres < 5 urn in lengthy mesotheliomas in 46% of the exposed rats Shabad <et al. (1974) ' ' "C'1 or" 3' ' "" r 5 fibrous glass vehicle of 40 mg of 17 samoles of fibrous materials of diverse tvoes or dimensional distribution fibres < 1.5 um in diameter and > 8 um in lenqth yielded highest orobabilitv of pleural mesotheliomas Stanton et al. (1977) Scecies Osborne Xendel rat Wi s tar : a Num.be r Protocol Results Reference 30 - 50 in each exposed group Dleural imDlantation on a fibrous glass vehicle of 40 mg of 37 samoles. which were variations of 7 fibrous materials; fibre-size distributions similar to asbestos Dercentaae Drobabilitv of Dleural mesotheliomas ranaed from 0 to 100%. lesions in groups with low orobabilitv of tumours were highlv cellular and fibres were comoletelv contained within macrophages; lesions in high tumour orobabilitv groups were relatively acellular with an abundance of collagen and free. lonq fibres in interstitial tissue Stanton & Lavard (1978) total or: 1086 mtraperitoneal iniection of 9 fibrous dusts .chrvsotile, milled chrvsotile. crocidolite. oalvgorskite. nemalite. gvosum. 3 tvoes of glass fibres' and 8 granular dusts; miected doses between 2 and 100 mg,- observation period 30 months fibrous dusts (except soluble Pott et al. gvosum fibres) induced (1976a) maliqnant tumours of the Deritoneum (6 ma chrvsoti1p-77%: 2 mg crocidolite-39%; 2 mg glass fibres JM 104-27%); clear dose- response relationships for chrvsotile and 2 tvDes of class fibres; reduction in carcinoqenicitv of chrvsotile after milling to very short fibres; carcinogenicity greatest for fibres with length > 3 [j.m and diameter < 1 urn; durability of fibres also important contd.. ' Result s Reference ,._inhalation of 3000 WLM radon all animals developed lungLafuma et al. . one month anatumours including 7(198 0) intrapleural iniection ofmesotheliomas, authors http://www.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 53 of 129 2 mq chrvsotile after 71 davs concluded "svnerqistic effect obvious" 10 whole body irradiation - 230 extraDulmonarv tumours in rads for 1 dav and irradiated controls and in rats intraDleural iniection of receivinq asbestos orallv and 2 mq chrvsotile after 125 bv intraoleural iniection: no davs or 150 rads and 1% specific localization in chrvsotile in diet for 6 asbestos exposed animals months af ter _3S_ days Harrier protected Caeserianderived Wi s tar rat 48/exoosed arouD; 48 in control qroup intrapleural iniection of 20 ma of SFA. UICC Canadian or Grade 7 chrvsotile allowinq for different survival times, SFA was about twice as carcinoaenic as Grade 7, which was 3 times as carcinoqenic as UICC sample; results not well correlated with results of an inhalation study with these materials Warmer et al. (1980) S?F male Soraoue Dawlev rar. 16 in HC1treated chrvsotlieexposed aroun: > 32 m all other exposed qroupS; 32 control animals intrapleural iniection of 20 mq untreated UICC chrvsotile A or 4 samples leached to various extents (10 - 90% Mq removed) bv oxalic acid or HCl; also crocidolite or qlass fibre in life-time observation period. a total of 68 pleural mesotheliomas. 1 lunq cancer, and 9 peritoneal mesotheliomas in the total of 304 animals.- proportion of cancer lower than expected because of earlv deaths from infection; carcinoqenicitv of chrvsotile with 44% Mq removed; authors concluded "size is not the onlv factor involved in the induction of pleural cancers bv mineral flores" Monchaux et al. (1981) .15... . _ Species \TEDH rat Number Protocol Results Reference intraoleural. intraoeritoneal. and intratracheal administration of 2 mq of UICC Canadian or Rhodesian chrvsotile. with or without ancillary radiation treatment (1000 rads-whole bodv) or iniection of 1 mq 3-MC a siqnificant incidence (3.8%) of mesotheliomas in 159 rats treated with asbestos alone; this incidence increased to 11.8% in animals also receivina radiation treatment (borderline statistical siqnificance) and 25.5% in animals also administered 3-MC (siqnificant increase) earlv tissue responses were similar to asbestos reactions without specific Datholoaical chanaes attributable to radiation or 3-MC Warren et al. (1981) ce^ie v,' i s t a r rat _____ 3 arouDS, 20 ar.imais/grou^. intraoeritoneal iniection of 50 mq milled UICC crocidolite (fibre lenqths 3 - 5 urn). amorphous UICC crocidolite, or saline life-time observation: 8 mesotheliomas (40%) in amorphous crocidolite-exoosed qrouD; 3 mesotheliomas (15%) in fibrous crocidolite-exoosed qroup and none in saline qroup; statistically siqnificant difference.- author questioned the fibrous structure of asbestos as the predominant cause of Deritcneal Kolev (1982) http://wvvw.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 54 of 129 mesothelioma and suggested that submicroscopic particles might be important in induction of tumours Table_15. (contd.) Species. NumberProtocolResultsReference Ar/HAN Wistar rat 7 groups. 32 animals/qrouo intraperitoneal iniection of 25 mg of 5 samples of UICC chrvsotile and factory amosite collected from airborne asbestos clouds of inhalation study production of mesothelial Bolton et al. tumours in 94 - 100% of the (1982b) animals in 6 groups; chrvsotile more carcinogenic than amosite; heated chrvsotile (850 C) least carcinogenic; some correlation between carcinogenicity and fibre lenath; aood correlation between carcinogenicity and in vitro cvtotoxicity ASi HAN . 17_ groups!__________ m t rapen toneal injection of mesothelial tumours in 0 - 96% Bolton et al. S?F Wi.star..19-48 animals0.01 - 25 mg elutriated UICC of animals; graded dose(1983b) per group ___chrysotile and crocidoliteresponse for both chrvsotile _ ______ _______ and crocidolite; for a given __________________________ ______ _____ ____________ dose, more tumours in . ........... ... .. ________ _____________________________________________________ chrvsotile than in __________________ __________________ _crocidolite-exposed groups _____ The introduction of massive doses into body cavities does not simulate the route of exposure of man to fibrous dusts such as asbestos. However, such studies have made it possible to clarify a number of questions that could not feasibly be investigated using the ir.r.alation model, since insufficient numbers of mesotheliomas occur following exposure by this route. The most important contribution of such studies has been to focus attention on the importance of fibre size and shape in the pathogenesis of asbestosassociated diseases. In 1972, on the basis of their study involving intrapleural implantation of 17 fibrous materials in rats, Stanton .& Wrench first hypothesized that "the simplest incriminating feature for both carcinogenicity and fibrogenicitv seems to be a durable fibrous shape, perhaps in a narrow range of size". On the basis of the results of further studies. Stanton & Layard (1978) prepared a model in which carcinogenicity was expressed as. a function of fibre length and width; in general. fibres with maximum potency were longer than 8 urn and less than 1.5 t* ... u_u:: vtei .Waic.oi et al . . 1573; Stanton et al . , 1977' . .In an. extensive study. Stanton et al . (1981) implanted 72 dusts con.tai.ning fibres of various sizes in the pleura of Osborne-Mendel rats.__The correlation coefficients for the logit of tumour prctab:1:ty with the common logarithm of number of particles per -"i--rc-gram :n different dimensional ranges are presented in Table -5 .__ Tr.e . prooability of the development of pleural mesotheliomas was highest for fibres with a diameter of less than 0.25 am and lengths greater than 8 ^m. However, probabilities were also "relatively" high for fibres in other size categories (i.e., with diameters of up to 1.5 ^m and lengths greater than 4 urn). The authors.also noted that there might be a low level of tumour response for fibres outside these size ranges. Table 16. Correlation coefficients of logit of tumour probability with common logarithm of number of particles per microgram in different dimensional. .rangesa Fibre diameterFibre length ium) .,, pjm; < 4 )( > 4 - 8 )( > 8 ) http://www.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) > .4.--0.28-0.30 > 1 . 5_ ___ 4-JhJS-0.240.13 15Q_L0J0.450.68 < 0,25 __..................0_. 20(L_630J30 a. ._Frcrn:__Scancon__ec_ al . [1981! . Tu m rx'.er,s:vQ se' ios of studies involving ir.traper11or.ea 1 = rwu & r r i ear i cns_ ,1972. ana Poet et al. (1976a) induced .peritoneal mesotheliomas in Wistar rats injected with iiffeier.t varieties of asbestos, fine class fibres, and nemalite ~\2goes i um nydroxide. . Few or no .tumours developed fol lowing similar_to. one of the forms of asbestos. Very few tumours developed to1lew;na administration of 100 mg of UICC chrysotile fibres shortened bv ball-milling for 4 h, compared with 6.25 mg of the oriaina1 sample. The results of further studies confirmed that tumour incidence for relatively low doses__y0,_5__c,_2_mg' of dust samples with a sufficient number of durable long and thin fibres was high. Turn,our incidence for unstable.__long, thin fibres (e.g., '.cached fibres and slag wool' was much lower (Pott et al. , 1984). On the.basis of some of these studies, a working hypothesis on the carcinogenic potency of fibres as a function of length and diameter was developed and is presented in Fig. 7. For example, this model predicts that 100 fibres, 2 urn in length. have the same carcinogenic potency as 4 fibres, 5 um in length, or 1 fibre, 20 urn in lenath 'hypothetically). Again, it should be noted that there may be a low level of tumour response for fibres outside the size range indicated on the diagram. In addition, on the basis of the result_s of these studies, it has been concluded that the physical ana chemical constitution of fibres influences the carcinogenic niter.', ill mstfar as it determines the stability m the...body. F13 'J F. E 7; 3 5 ; 4 i; e 5 3 _ ~ . bmp ____ These observations concerning the importance of fibre size and shape in tumour induction have given rise to speculation that "ay ucr caused bv cnvsical irritation caused bv fibres mat are. car_ried to. the pleural surface bv both lymphatic transport within macrophages or by direct penetration of free fibres (Davis. 19 81,- Craighead & Mossman, 1982 . A great deal of attention has cee.n focused on this 11 carcinogenic subset" of fibres. However, there 5, re., still several unanswered questions concerning the -V-. ; i.pres w_m me cr iticai rar.ae l cr me so me 11 oma nduct_i.cn .Harington, 1_9_8..1_ . Acid leaching of chrysotile significantly decreased the : aremegem c potency after intrapleural injection in rats 'Morgan et al.. 1977b; Lafuma et al.. 1980: Monchaux et al.. 1981); it is uncertain whether these effects are a function of change in fibre size or number, chemical modification, or other factors. In several other studies on mice and rats (Roe et al.. 1967; Wagner et al., 1973'. variation in the trace metal content did not have any effect on carcinogenic potency (Gross & Harley. 1973). _ ResuIts of studies involving intrapleural or intraoeritoneal :r.jecticn,_ cr. implantation have also imparted some information on dose response relationships, the relative potency of various fibre types, and the t ime course of the development of asbestos - related disease. Tr.ere was evidence of., a dose - response relat ion ship for ".al ignar.t tumour, incidence, following exposure to both chrysotile :.r.o rrcridoi i te, m several of the studies !Wagner et al. , 1973..y;:r. h Hubert. 1574; Bolton et al . . 1983b). Fig. 8 shows the rearessicn line for dose response relationships after : r.t rape r i tor.ea I injection, of chrysotile, crocidolite. and glass http ://\v\v\v. inchem.org/documents/ehc/ehc/ehc53.htm Page 55 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) flores _ .Johns Manville 104). derived from the results of Pott et a 1 1976a;, Bolton et al . (1983b), and Pott et al . (1984), showing a somewhat higher potency of chrysotile. In. several studies,., crocidolite was more potent in the induction. pi., mai ignant neoplasms than an equal mass of chrysotile .Qross__& Harley.* 1973; Wagner et al . , 1973: Engelbrecht & Burger, 1975Monchaux et al . , 1981). However, other studies did not confirm the higher potency of crocidolite (Wagner & Berry, 1969; Stanton &. Wrench*. 1972' , while in two more recent studies, . :.: y s was round more potent in inducing mesotheliomas than an equai_. mass of crocidolite ^Bolton et al. , 1983b) or amosite (Bolton et al., 1982b;. The distribution of fibre sizes was not well characterized m these studies, and the need for caution in the interpretation of such results cannot be overemphasized. For example, the similar incidence of mesotheliomas in groups of rats exposed to UICC crocidolite (2.83%) and Canadian chrysotile (2.9%) m the inhalation studies of Wagner et al. (1974) contrasted with the authors' observation in an earlier study that 3 times as many malignant neoplasms resulted in the crocidolite-exposed group following intrapleural injection of equal masses of the 2 samples. Data available from studies involving intrapleural injection also indicate that the lifetime risk of mesothelioma is greater in animals exposed at a younger age. Berry St Wagner 11976) injected doses of ecual masses of crocidolite into the pleura of two groups of rats, one at the age of 2 months and the other at the age of 10 months. In the group exposed at the earlier age, 40% developed mesothellomas: in the second group, the incidence was only 19%. The former, group., also., experienced a longer latency period. There ,_is still some controversy concerning the histological nature g__.ma 1 ianant tumours induced by the intrapleural and ne i1 . n.ccu 1 at ::r. o_f_ an ima l_s .Karington, 1981,' . In .u-;:;: leicuyuamic factors that affect fibre deposition, defence mechanisms that determine the differential retention of fibres within the lung.*__and factors that determine penetration of fibres from the alveolar space to the pleura were not taken into consideration in this experimental model. However, the results of :ye 1 anta.tion _studies can be integrated with the observations from other investigations that finer fibres are more likely to penetrate to the periphery of the lung, and that short fibres (< 5 urn) are more effectively cleared from the lungs bv macrophages than long fibres, which cannot be phagocytosed by single cells (Harington, 1981' .___ However, the need for caution in the extrapolation of the resul_ts_of intrapleural injection studies to predict the potency of various fibre samples with respect to the induction of mesotheliomas and other types of cancer, such as lung cancer, must be emphasized. In a recent study, described in Table 15, tumour incidences following intrapleural injection and inhalation of the same samples of chrysotile were not well correlated (Wagner et al., 198 0) .. The authors suggested that problems of aggregation of fibres,.m the suspension prepared for intrapleural injection. might have resulted in different size distributions. 7 ._2.. 4 Ingestion Studies on the _effects of ingested asbestos on animal species nave peep., reviewed Toft et al. . 1984), and the results of the most recent and extensive of these studies are presented in Table 17. . up me oasis of their review, Toft et al. >1984) concluded that tnere wps no copelus_iye..evidence from the toxicological studies conducted to date, that ingested asbestos is carcinogenic. The res u it. s of .ear 1 y_s tu d i.e s_ we re inconclusive becaus e of shortcomings -_p. sp.ugy design; many of the investigations were conducted for relatively short periods of time with insufficient numbers of test hUp://\vw\v.inchem.org/documents/ehc/ehc/ehc53.htm Page 56 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 57 of 129 ana control animals, and the studies were not designed to allow measurement of dose - response relationships. In addition, the administered asbestos was often not well characterized. In later, more extensive studies, increases in gastrointestinal tumour incidence were observed in some of the test groups in some of the studies; however, these increases were not observed consistently. Moreover, there was no evidence of a dose-response relationship in any of tne studies. _____ The Task Group noted that, in a recent well-conducted study, the incidence of benign epithelial neoplasms was significantly higher in comparison with pooled controls from contemporary asbestos feeding studies in the same laboratory (US NTP, 1985).___However, the increase was not statisticallv-significant in corneari son. with concurrent controls and was limited to one sex. In addition, the study was not designed to investigate exoosureresponse re_lationships. It is of interest to note that no increase m tumour incidence was observed following administration of short-range chrysotile, which was composed of size ranges more similar to these found in drinking-water. _Spme__of the toxicological studies on ingested asbestos that haye been conducted recently by various investigators have been very extensive _Tonham et_. al . , 1980; McConnell, 1982a,b). However. there have seen several criticisms concerning the suitabi lityy.wi th resuect it extrapolation, tc man cf tne vehicles m which asbestos :.c*_s._p_c_c._, tne Line size oi tne aammistered asbestos, and the fat content of the animal diets. 7.1.3 In vitro studies _____ The effects of mineral dusts and especially of asbestos fibres on cell cultures have been investigated intensively over the last decades. According to Allison (1973), 4 cell types are potential targets for asbestos in vivo: (a) macrophages, (b) mesothelial cells, which undergo malignant transformation, (c) fibroblasts, which p 3 r t: c ipat e ..in the fibrooenic reaction, and (d) pulmonary epthe 1 _i_al_.cells, _ which can also undergo malignant transformation. These cells, proliferating cell lines, and erythrocytes have been used in vi trp. scudies . ___ The present position is that, with the combined use of several test systems, the findings can be used to predict, with some certainty, the fibrogenicity of dusts and fibres in vivo. Prediecion of carcinogenicity is less reliable, but the findings may be of some use in predicting mesothelioma. As the tests can be completed within a few weeks, they may be usefully employed in the select ion of materials to be tested in vivo. The tests are also of use. ir.._t he s tuay of _ mechani sms . Table 17. Toxicological studies - ingested asbestos Species Number of Protocol ------------------ -- test animals Svnan Golden 60 hamster 0.5 mg amosite/litre drinking-water over the lifetime Results no tumours 60_______________ 5 mg amosite/litre___________ 3 malignant tumours including __________________ drinking-water ______ _______ a peritoneal mesothelioma. 2 ________________________________________________________ early squamous cell carcinomas _________ __ of the forestomach 6050 mg amosite/litre in1 malignant tumour; authors drinking-water over the concluded "tumours not treatment- Reference Smith et al. (1980) http://www.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 58 of 129 1ifetime related Ma 1 e__w l_s t a r252 50 mg amosite per week1 malignant tumour in gas trieBolton et al. rat __ _ _______ in dietary margarinemuscle layer_____________________ (1982a) __ _ supplement, for periods up to 25 months 2_5 _________________________ 250 mg chrysotile per1 pleural histiocytic tumour; _______ _____ week in dietary margarine significant increase in supplement, for periodsincidence of benign tumours in _______________up to 25 monthstissues other than the gastro- _ ______ ___ ____________ intestinal tract; authors concluded unlikely that these benign tumours were treatment-related ________ __ _________ because of lack of evidence of ______ ______ ________widespread penetration or ________ __ _________________ ________________ dissemination of fibres 2 5............ __ 250 mg crocidolite perno primary malignant lesions of ___ week in dietary margarine the gastrointestinal mucosa supplement, for periods ^up to 25 months Table 17. ' contd.) Species___________ Number of______Protocol test animals Results Reference F_344_i.at...5.0010% chrvsotile m the5 tumours including 1 mesothelioma; Donham et al ___________ .___diet over the lifetimeincidence not statistically(1980) ____________ significantly greater than in ___ _____ _______ ___________________________________________ ________________ control group Syrian_golden hamster 250 males1% amosite in the dietno adverse effects on body weight____________McConnell 250 females fed to nursing mothersgain and survival; no(1982a) ___ _and over the lifetime of statistically-significant increase the pups ____________ ___________ in tumour incidence ..................... 250 males1% short-range chrvsotile significant increase in adrenalMcConnell 250 females (98% < 10 am incortical adenomas in males,- not(1982b) length) in the diet fed to considered to be treatment r.-.rs;ngmothers and ever related __ ................ _....... tne lifetime of tne pups ___ _______ 2 50 males1% intermediate rangesignificant increase in adrenal ............................ .. 2 5.3__females___chrysotile (65% > 10 pm cortical adenomas in males and __in length) in the dietfemales,- not considered to be ___ fed to nursing motherstreatment - related and over the lifetime of ____ ______________________ the pups F 344 rat250 males1% tremolite in the diet no overt toxicity and no adverseMcConnell 250 females fed to the dams and over effects on survival rate; noet al. the lifetime of the pups statisticallv-significant increase ____ ____ ________________________________ in tumour incidence (198 Tah_ie_._i7__.'.contd . ; Spec: P 3-44 Number ot___ .ProtocolResults_ test animals Reference 250 females... 1% amosite in the dietno overt toxicity and no adverse .250 males____ _fed_.to. the dams and over effects on survival rate,- no_______ _ ... .............. the lifetime of the pups statisticallv-signif icant increase ............... ..... ..in tumour incidence in the gastro............... . intestinal tract; the biological __ ______ __________________________________ significance of increases in McConnell et al. (1983) hUp:7\vw\v. inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 59 of 129 ___________________the rates of C-cell carcinomas of the thyroid and monocytic leukaemia in male rats is questionable ? 3A4 rat 250 rr.al.es __1% short-range chrvsotile no overt toxicity and no adverseUS NTP ... . : :i 1 eo ,, j 8 % <. :o ir, lengtr. effects on survival rate; no(1985) in the diet fed tosignificant increase in tumour nursing mothers andincidence _over the lifetime of the pups 250 females 250 males 1% intermediate range chrvsotile (65% > 10 urn in length) in the diet fed to nursing mothers and over the lifetime of the duds no overt toxicitv and no adverse effects on survival rate; increase in benign epithelial neoplasms in large intestine of males.- insignificant when comDared with concurrent controls (88). but sicmificant when compared with pooled controls (524) ____ Reviews have been made by Harington et al (1975), Beck (1980). and Gormlev et al. (1980), and, more recently, these assays have rece;ved particular attention 'Schluchsee Meeting, 1985) . 0.1.3.1 Haemolysis Although haemolysis alone is not a good predictor of in vivo patr.ogep.esi5_.Richards et al . , 1980). it is a useful model for the interaction of) mineral dust with cell membranes. The haemolytic activity of fibres is related to size (Schnitzer & Pundsack, 1970), and surface charge ."zeta potential") (Harington et al. . 1975; Light & Wei. 1980) . Chrvsotile induces haemolysis more rapidly than ip.-- jirphictles .Schnitzer & Pundsack. 1970; Harington et al . . 1zl.....Haemolysis bv cnrvsocile fibres may be related to the ad sorption of the red blood ceil membranes on the fibres and not to an interact;on between magnesium from the fibres and sialic acid from the red blood cells -Jaurand et al. , 1983). 7.1,3.2 Macrophages Because of their important role in fibrogenesis, macrophages have been intensively investigated in cell cultures. The cultured macrophages are usually derived bv bronchioalveolar lavage or from the peritoneum after appropriate stimulation. _____ Two types of cytotoxic effects in macrophages have been observed: ,a) a rapid form that can occur within minutes of contact between fibres and macrophages and reflecting interaction with the membrane, . and (b) a delayed effect that occurs within days .A - -; sen, . The effects are more marked with chrvsotile than w: : h am.pr. ;pple .fibres__ .Harington et al . ,__ 1975) . .Aliisop. ) 1973) investigated the limits of the size of fibres that can be.ingested, by phagocytosis. Irrespective of the type of a s b e s tos,.. short__fibres (< 5 ^m) were readily and completely taken up by phagocytosis, whereas long fibres (> 25 am) were not. The cells attached to, or enveloped the ends of, the latter, but p_cr_ticns_ remained outside the cells. The long fibres caused localized damage to the cell membrane while they were being phagccytcsed; in addition, energy metabolism. was increased 'Beck et . Invizusly, litres with a. length that exceeds the cell o:^me:er rema:n partially ext rapellular . In macrophages and in macrophage like cells j? 388_D ), long 1' asbestos fibres caused increased permeability to two lysosomal enzymes (beta-glucuronidase. beta-galactosidase) and to the cytoplasmic '-rzy-e 1 act: c_ acid dehydrogenase (Beck et al . . 1972; Davies. 1980). This enzyme release is coupled with an increase in permeability to http://www. inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) extracellular dyes, and often occurs in the absence o cell death. Asbestos fibres interfere with the normal digestion of secondary lysosornes, resulting, in some cases, in accumulation of acid hydrolases. Ater membrane damage by asbestos fibres, the lysosomal enzymes can also leak into the cytoplasm. Partly-damaged alveolar macrophages may lead to cellular malfunction in the lungs. Asbestos fibres also_stimulate the secretion of proteolytic enzymes such as elastase -White & Kuhn, 1980). If these enzymes are not "c ;ry ere-";' scree by antiproteases, lung tissue damage can occur. 7 . : . 3_. 3. Fibroblasts _____Beck et al . .1971', reported that long fibres of chrvsotile were net. completely phagocytosed by proliferating mouse fibroblasts. type L.925, In lung fibroblast cultures, chrysotile has been shown to be highly cytotoxic when first added and to induce biochemical and morphological a 1terations _'Richards & Jacoby. 1976). It has also peer...sr.pwn that,_i lung ibroblast -1 ike cells are continuously exposed to small quantities of chrysotile. their ability to syr.t r.es . :,c collagen is increased .Hext et al. . 1577 ; .___ Fibroblasts undergo a ma t u r a t i_o n p r o ce s_s _ ie a ding to. rapidcel iu lar aging . ? . 1 . 4 . 4 . . Ce_i 1 lines and interaction with DNA _____ The UICC reference samples of asbestos have not shown mutagenic activity in bacterial assays (Chamberlain & Tarmy, 1977; Light & Wei, 1980), possibly because of the lack of uptake of fibres by this type of cell. Asbestos - induced sister chromatid exchanges in cultured Chinese hamster ovarian fibroblast cells have been reported by Livingston et al. ;1980~ and in Chinese hamster cells by Sincock & Seabriaht . 1575! and Huang f!979) In Huang's study, it was reported that amosite, crocidolite, and chrysotile were weakly mutagenic. At 10 apu -Is. ug fiore/rru, chrysotile completely inhibited cell growth Livingston et al., 1980); cells exposed to amosite and crocidolite propiierated.only at the lower concentration. Crocidolite significantly elevated the sister chromatid exchange rate and larger (> 5 /am) chromosomes were most sensitive. The chromosomal aberrations found in Chinese hamster cells by Sincock et al. (1982) could pot be detected in primary human fibroblast or in human _In tracheal epithelial cells, chrysotile and crocidolite did not ca.use.breakaoe..of DNA .Mossman et al. , 1983). Hahon & Eckert .1576! found that exposure to asbestos fibres resulted in an almost 90% depression in viral interferon induction in cell monolayers. .. For a review of the effects of asbestos on epithelial cells. p 1 eura 1 mesg_thelial cells, and other cell-lines see Beck (1980! . 7_, l .3.5 Mechanisms of the fibrogenic and carcinogenic action of asbestos An overview of possible mechanisms of the fibrogenic and carcinogenic action of asbestos is presented in Table 18. Fibrogenic potential .When macrophages interact with silica, they produce a :ibrcblast-stimulating factor (Heppleston & Styles, 1967). The incom.plete phagocytosis of asbestos fibres may induce the same process Beck et al..__ 1972; . There is some evidence that the -mmune_system is stimulated by the effects of mineral dusts on the "A : : r-^rn:? S V:gl:am; 1582! ; the authors supposed .that cr.is process was mediated, by., the production of interleukin-1. http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 60 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) which _al so., st imulates fibroblasts. However, Miller et al . ',1978) ccr.cluded from their studies_that quartz and crocidolite had quite d if_f e rent biological effects on the _ macrophages and that the bevl-lop met of p._. 1 me nar y_fibrosis might, to some extent,__be caused dv_.di f f erent mechanisms in each instance . ei.r ir . Some possible mechanisms of act;on_of asbestiform_fibres in the development of fibrosis (F). mesothelioma ,.'d , and 1 ung cancer , C, Mechanism or possible important effects . ., Disease - : p . . a j _ . j -- 5 * S , release, of enzymes, and________________ F, C, M tree radica-S effects o:t.he immune_.s/stemF, C_, M Effects on cell differentiationF, C, M Alteration in cell proliferation processesa F. C, M Interact 1 on with DNAC, M Adsorption and transfer of ____ _____C polycyclic aromatic hydrocarbons -> Increase not only in cell proliferation cut effects on intracellular processes. seen as._DNA_.or protein synthesis . The _release of oxygen-free radicals after incomplete phagccytosis_ of .fibres, may cause peroxidation of membranes and damage ..to macromolecules iMossman & Landesman, 1983; . This could j L..ss.::le "eciuo: s n of the induction c f_ .asbes tps.- related uiseases. Carcinogenic potential .-The_mechan 1 sms...o f_.c arcinogenesis of asbestos are not well -.uei iLX'j. However, several hypotheses have been proposed, and these wi11 be discussed briefly in the light of the experimental find:ngs__lust reviewed. For a more detailed discussion, see US NRC/NAS ! 1984 ) There, is no convincing evidence from cellular tests that asbestos initiates tumours through direct interaction with DNA '.genctoxi c.icy; . Fewer data are available concerning the genotexicity of the other asbestiform mineral fibres,- however. enor.ite has been reported to induce unscheduled DNA repair in some mammalian cell lines (Poole et al., 1983). Another hypothesis is that.asbestos does not induce tumours through direct interaction with DNA, but may act as a promotora. For the purposes of this discussion,_mesothelioma and lung cancer will be considered Me so r hel i ~>:na It has been hypothesized that .asbestos, initiates mesotheliomas. since mere is no evidence from experimental studies that asbestos .-.ty :uv-r r.a'oral mineral fibres prompt e_ mesot hel iomas initiated by otter ...agents . _ Furthermore,__there is no association between Broking.and mesothelloma incidence in asbestos workers !US NRC/NAS. le-4, . This hypothesis is strengthened .by the observation of . n: -upre.ne^p* a st i c reactions of mesotheiial cells following the http://www. inchem.org/documents/ehc/ehc/ehc53.htm Page 61 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) .n;r ap 1 eural ori.ncraoeritoneal injection of long fibres in animal species :US NRC/NAS , 1984) . __ Available data also indicate that it is fibres of a specific size that act: .as ,initiators of mesothelioma. Durable, longer (> 5 and thinner '< _ 1 ,um) fibres of various minerals induce high peso):hel.ioma rates after intrapleural and intraperitoneal administration, while, under the same circumstances, granular dusts or thick or short fibres _of_..the same materials are considerably less potent , Indeed, there is a clear quantitative relationship between fibre size distribution and carcinogenic potential. In addition to the fibre concentration and size, durability .so1i11ing, solubility, disintegration). and migration activity account for the variations observed in mesothelioma incidence in animals. ..b/ hung cancer In.the case of bronchogenic cancer, there is evidence that factors ctr.er than fibre size,, such as adsorbed environmental pel 1 uta_nt s .poiycycl ic aromat ic hydrocarbons . etc! . and tobacco smoke, car. cor.tribute to..the., total carcinogenic potential of minera_l. i. pres The ref ore, _ the extent to which results regarding the g.uantitacive relationships obtained in the intrapleural and in_trapentoneal injection studies on animals may be extrapolated to., bronchial___cancer___is not clear. Some important reservations are necessary. Wagner et al. (1980) did not find the same order of rank for the carcinogenicity of three chrysotile varieties after mhalat con .and.. intrapleural infection in rats. However, there is some evidence from inhalation studies..that longer fibres are more ;:arc logger.;c . Some authors see similarities between asbestos and premotors such as phorbol_ester ITopping & Nectesheim, 198 0; Craiaheaa Sc Mossman, 1982/ For the purposes of this document, a promotor is defined as an agent that increases the tumoungenic response to a genotoxic carcinogen, when applied after the carcinogen, without being carcinogenic itself. 7.1.3. 6 Factors modifying carcinogenicity ....One of the mechanisms proposed for the induction of lung cumeurs by asbestos fibres is the adsorption and transfer of po 1 y cy c 1 ic a r oma.t i c hydrocarbons _ into cells ("carrier hypothesis"). Squa1 mi11igram amounts of crocidolite asbestos, carbon, hematite, and kaolin have been compared for their ability to bind and release the radiolabelled polycyclic aromatic hydrocarbon and jmetnyicnoianthrene ,3MC;, into culture medium (Mossman & Oraighead.^.. 1982' .__ Asbestos did not adsorb more 3MC or release g.reater amounts of the hydrocarbon than the other materials. _The results of Bogovski et al (1982) showed low lung-tumour :es in.rats after intratracheal instillations of either .z: , a .pyrene or ohiysotiie, alone .6.1,% after 5 x 5 mg izo , a .pyrene, 3.7% after 5 x 1 mg chrysotile. 2.6% in the itrol group. . The instillation of. a Texture .of the 2 substances r^ueo. -i.C.%_lur.g tumours, and the addition of phenol ;i% in lyglycml. , 78.9% lung tumours. However, the tumour yield 11 owir.g exposure to a mixture of chrysotile and benzo( a ) pyrene =__lower m the studies of Smith et al. (1970) on hamsters and of lev 1.19721 _ on_ rats.__ After intraperitoneal or intrapleural eccions, the chrysotile-induced tumour rate was not augmented benzol a )pyrene (Pott et al., 1972; Pylev, 1980). _____ A svncarcinogenicity in man of polycyclic aromatic hydrocarbons and. chrysotile was proposed when organic substances containing http://wvvw.inchem.org/documents/ehc/ehc/ehc53.htm Page 62 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 63 of 129 benzOj_a 'pvrene were found in chrvsotile (Harinaton. 1962; Pylev & Snabad^ i973.' . However, the amounts were very low (2 - 240 uq benzo( a )pyrene per kg chrvsotile). The doses of benzo/ a )pyrene given in the studies of Bogovski et ai. (1982) were 107 bo 109 tirt.es higher than would be received if administering equal amounts of natural chrysotile. Thus, it appears very dubious that rentamination with polycyclic aromatic hydrocarbons enhances the carcinogenicity of asbestos significantly. Lakowicz & Bevan (1980) reported that the adsorption of benzo ( a )pyrene on chrvsotile and anthopnyllite greatly enhanced their rates of uptake in the liver microsomes,__compared with a microcrystalline dispersion of benzo( a ) py r er.e_.__ Croc idol ite. from which the natural organic substances had peer, removed by extraction, produced a_tumour incidence after :n:rapleu:al adm;nistration in rats similar to that produced by ,.:.i: t aieu samples .Wagner L Berigy 1969.; Stanton & Wrench, 1972' . Therefore, available dat_a do not provide conclusive support for the "carrler. hypo thesis_ 9.2 Other Natural Mineral Fibres There is a paucity of toxicological data concerning natural mineral fibres other than asbestos. The results of some available studies are presented in Tables 19 ( in vivo studies) and 20 ( in vitro studies). Only oreliminary___in vitro studies have been conducted with some : cue natural mineral fibres. The results of such assays vary considerably depending on the test system employed and factors that influence the pathogenicity of mineral dusts in vivo (e.g.. deposition, clearance, and immunological reactivity) are absent in vicro. Thus, such studies should be considered as only the first stage of a multi-tier toxicological test protocol for the assessment of potential hazards for human health. _____ The results of preliminary in vivo studies involving. intrapleural or intraperitoneal administration to animals are available for some natural mineral fibres. However, introduction into body cavities is_ an unnatural route of exposure that does not -a>e ;n:c account deposition and clearance in the respiratory tract,.__but such studies do provide important information on the characteristics of particles that influence pathogenicity and the relative potency of various fibre types i_xp_~s_: e co.nd.11 ions m inhalation studies approach most closely the circumstantes of human exposure to natural mineral fibres and are most _ relevant for the assessment of health risks to man. However, or 1y two.such studles involving exposure to natural mineral__fibres other than asbestos__f erionite, attapulgite, and sepiolyte' have been_conducted to date. 1 r.tei pretat ion of the small amount of toxicological data on natural, mineral fibres other than asbestos is also complicated by the fact that, in some studies, only the mass of the administered material has.been determined, while the origin of samples and fibre count or size distribution has often not been reported. _ In this section, the available data are discussed according to mineral type under the following headings: attapulgite, sepiolite, wellastonite, and erionite. Table 19. __ In vivo studies - natural mineral fibres other than asbestos Fibre type . Source and fibreProtocolNumber Species ResultsReference size distribution -teiygorskite___Spanish; fibre size inhalation of40.F 344 fibrosis grade at 3Wagner .Apt apu la; t e_. distribution not10 ma/m3 for 12________________ ratmonths-. 3.3 (control-.(198 2) reported _ _moirths; 4 animals _________________ 1.1), 6 months: 2.6 _________ sacrificed at 3.________(control: 1.0), and http://www.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 64 of 129 6. and 12 months 12 months: 3.5 control; l.l) Attapulqite Atcapulaite Spanish; fibre size distribution not reported (without ultrasonication) ................- -- intrapleural inoculation of unspecified dose.animals observed for life span 40 Spanish; fibre size distribution not reported 'with ultrasonification) intrapleural inoculation of unsoecifled dose; animals observed for life span 40 F 344 rat 10 mesotheliomas; 16 survivors at unspecified time period followina administration Waaner (1982) F 344 rats 5 mesotheliomas (chrvsotile B: 9 mesotheliomas). 22 survivors (chrvsotile B: 19 survivors) at unspecified time period followina administration Waaner (1982! two samples from intrapleural Attapulqus. Georqia: implantation of Duritv > 90% 40 ma; animals "composed entirely observed for 2 of short fibres vears of consistently small diameter 3 0-50 Osborne- tumour incidence 2/29 Mendel (7%) for both samples rat Stanton et al. (1981) Actaonilaite source not reported; intraDeritoneal 33-34 fibre lenath < 5 iniection - am 70% 3 x 25 ma; animals observed for life scan Wistar rat 76.5% of animals developed tumours chrvsotile A - 54.5%); mesotheliomas in 70.6% (chrvsotile A - 48.5% mesotheliomas); first tumour - 257 davs (chrvsotile A - 323 davs) after iniection Pott et al . (1976a) Table 19 . : ccntd.. r; bre type . Source and fibre size distribution Protocol Number Species Results Reference Seotol ite Sepioiite Spanish; fibre size distribution not reported inhalation of 10 ma/m3 for 12 months; 4 animals sacrificed at 3. 6, and 12 months 40 Soanish; fibre size distribution not reported (without ultrasonification) intrapleural inoculation of unspecified dose; animals observed for life span 40 F 344 rat F 344 rats fibrosis arade at 3 months: 3.1 (control: 1.1), 6 months: 3.1 (control: 1.0), and 12 months: 3.2 (control: 1.1) Waaner (1982) 0 mesotheliomas: 19 survivors at unspecified time period followina administrated on Waaner (1982) Wollastonite 4 samples from Canadian mine: onlv one sample completely, fibrous fibres "relatively i.arae." intrapleural implantation of 40 mq; animals observed fer 2 years 30-50 Osborne- tumour incidence 5/20 Mendel (25%). 3/21 (14.3%). rats 2/25 (8%). 0/24 et al. (1981) Ericnite New Zealand frequency of fibres < 0.5 am in diameter and > 4 am m lenath = 1.9% inhalation of 10 mq/m3 for 1 vear; 4 animals sacrificed at 3, 6, and 12 months 40 F 344 rat no mesotheliomas in the animals not sacrificed 8 months after exposure (1982) urionite Oreaon - freauenev of fibres < 0.4 inhalation of 10 mq/m3 7 h/dav. 40 F 344 rat mesotheliomas in 27 (96.4%) of the 28 et al. http://www.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 65 of 129 urn in diameter5__days_ per week,_________________ ___ animals not sacrificed(1985) and > 5 jjm in for 1 year;. 4_________________________________ 12 months after j-. 3 * 3 r.: ma 1 s sacrificed exposure; mean survival ____________ at 3, 6, and 12time 580 davs ____months Fibre typeSource and fibreProtocolNumber Species ResultsReference size distribution Frionite New Zealand freauencv of fibres <0.5 um in diameter and > 4 um in lenqth = 1.9% intrapleural inoculation of 20 mq; animals observed for life span 40 F 344 rat 6 mesotheliomas; 20 survivors at unspecified time period followina administration Waaner (1982) Erionite Oreaon - freauencv of fibres < 0.5 - d- er and > 4 u.t, m lenqth = 9.5% intraoleural inoculation of 20 mg; animals observed for life span 40 F 344 rat 40 mesotheliomas (100%); mean survival time 390 davs Waaner et al. (1985) Ericnite Karain - freauencv of fibres < 0.5 um in diameter and > 4 um m tenqth = 2.9% intrapleural inoculation of 20 mq; animals observed for life span 40 F 344 rat 38 mesotheliomas (95%) mean survival time 435 davs Waaner et al. (1985) " sedimentarv erionite" source and fibre size d:s t r:bution net reported intrapleural iniection of 25 mq; animals observed for life span 40 SDraque- incidence of mesothel- Dawlev iomas after 67 weeks - rat 52.5% (UICC Canadian chrvsor.ile: 0% mesotheliomas) Maltoni et al. (1982a.b) Erionite source not reported intraperitoneal 10 Swiss maliqnant peritoneal Suzuki averaae lenqth 1 um iniection of (95% < 8 um): 10 or 30 mq; albino male tumours in 6 out of 10 (60%) 8 - 22 months (1982) averaae width 0.1 animals observed mouse after administration; um (94.4% < 1 um) for life span malianant peritoneal tumours in 2 out of 4 (50%) chrvsotile- treated controls between 9 and 16 months . 3 to: 1 fi\ Tabl 9 -- . contd . Fibre tvne ......... -- - - Erionite Source and fibre size distribution "sedimentarv erionite" ,* source and fibre size distribution not reported Protocol Number Species Results intraperitoneal iniection of 25 mq; animals observed for life scan 40 Soraque Dawlev rat incidence of mesotheliomas after 67 weeks 2.5% (UICC Canadian chrvsotile: 2.6% mesotheliomas) Reference Maltoni et al. 1982a.b) Erionite naturallv-occurrina from Colorado. USA intraperitoneal 50 BALB/c iniection of mouse 10 ma; animals observed for life span___________ __________________________ peritoneal mesotheliomas in 21/42 dissected animals (50%) between 7 and 23 months after exposure (1984) c.r ionite natural lv-occurnna from Nevada. USA intraperitoneal iniection of 0.5. 2, or 10 ma,animals observed for life scan 50 BALB/c mouse peritoneal mesotheliomas in 6/18 (33%) qroUD). 24/44 (55%) (2-mq qroup). (38%) (10-ma arouD) (1984) http://www.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 66 of 129 Table 20. In vitro studies - natural mineral fibres other than asbestos FTbre._cyp_e Source and fibreResultsReference size d istribution At tape: ia11 e Spanish; thinnest fibres Q.02 - more haemolytic in humanBiqnon et al. C.03 fim wide; mean length.....................red blood cells than UICC -> C.8 jim and .aspect___ ... ________ . chrysot l le_ A . __________ ratio >__ 17 (I960) Attapulgite . ______ . 11 short - f ibre" ; source andcytotoxic in mouse peritoneal distribution of sizes notmacrophages but not in A 549 reportedand V79-4 cells Chamberlain et al. (1982) "long fibre";__source and _distribut.ion of sizes not reported cytotoxic in all 3 cell types (see above) Attapulgite relatively pure sample fromminimal inhibition ofReiss et al. mine in Atcapulgus, Georgia;colony - forming efficiency "fibres of small or smallerof 1-407 cells (16% vs 54% diameter range, than diameter _ for equal dose of amosite) range tor clirysoti.e" {1980) Attapulgite source and fibre sizealteration in thymidineLemaire et al. distribution not reportedincorporation by lung _________ _________ __ ________________ fibroblasts at 48 h; 63% of ____ that observed for chrvsotile B (1982) Table 20. 'contd_.J Fibre type __ Source and fibreResultsReference size distribution " 1 ` r.tt reported; "short not cytotoxic in mouseChamberlain et al. (1982) fibre" .90% < _0_. 5 grrh _peritoneal macrophages.- __________________ __ ____ _A549 or V79-4 cells .................................... source not reported; "long-cytotoxic in all 3 cell ___ ______ ..fibre."__(90% < 3.5 urn)types (see above) Wcl last cr.it e source and fibre size_________________ no release of lysosomalPailes et al. distribution not reported . enzymes nor damage to membrane__in rabbit alveolar ___ _________ _____ ______ macrophages exposed to _____ ________ _ _____________________________ ________________________ 250 ug/ml; far less cytotoxic than chrvsotile (1984 ) Eri o_ru t e_____ _ Oregon; 6.2 x 103 fibres/^gincrease in morphologicalPoole et al. of dust; median lengthtransformation and unscheduled *1.7 pm. 4.3% > 6 urnDNA repair synthesis __ in C3H10T1/2 cells and _____________ unscheduled DNA repair _____ synthesis in A549 cells; ___ ____ more active than UICC ._____ chrysotile and crocidolite (1983) 7.2. 1 . I Palygorskite (Attapulgite) v.- t:. m: nary results of an inhalation study indicate that e u---gr_ee. _oi i.trosis for animals sacrificed following exposure to Span:sh. a11apu 1 a_ite for 3. 6, or 12 months was similar to that for tu.tuIs exposed to crocidolite (Wagner. 1982). The fibre size distribution, cf the attapulgite and the administered dose were not http://www.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) reported in the early published account of the preliminary results In..a . _s:.udy_._ 1 nyolvmq intrapleural administration in rats .Wagner, 1982]Spanish attapulgite was less potent in inducing mesothelial rumours chan equal masses of UICC .chr.ysqtile_.Bj_.. while.,. -u_,JhwU.e: .rvu,virig inti apex i toneai infection of atcapulqite qf._unreported origin (Pott et al. . 1976a), it was more potent than ::iiys_tile A. The fibre size distribution of the attapulaite samples ..was not specified in the first of the above two studies, while, in the second. 30% of fibres were more than 5 um in length. In a further study, the incidence of tumours following intrapleural implantation of attapulgite in rats was low (7% versus 48.3% for VICC crocidolite); this low value was well correlated with the low piic-pc.rtion of fiores m the critical size range (< 0.25 um in diameter,__ > 8 um in length' in the administered material (samples from the mine in Attapulgus, Georgia) (Stanton et al., 1981). The results of in vitro assays of the toxicity of attapulgite nave been somewhat contradictory. However, the fibre size dpst ribut ions of the administered samples have not been reported in tne published accounts of most of the studies. Attapulgite has been more haemolytic in red blood cells than UICC chrvsotile A (Bignon et al . , 1980; and UICC B ;Nolan & Langer, personal communication, 1985) it should be noted, however, that this is not considered to be a particularly good predictive assay for the in vivo cathogenesis of mineral dusts..In another assay, the alteration in up _i at _ it. by lung f icrublasts. exposed to attapulgite was._6 3%__cf_..chat observed for chrvsotile B Temaire et al . , 1982) and "minimal inhibition" of the colony - forming efficiency of 1-407 cells py attapulgite )16% versus 54% for an equal dose of amosite) has peer, reported 'Reiss et al . , 1980). it pas a.s^ peer, reported that *'short fibre" attapulgite is cytotcxpc for mouse peritoneal macrophages but not for A549 and V_i 9 4 cells,,. whereas__" long-fibre1' attapulgite is cytotoxic in all 3 cell types .Chamberlain et al., 1982). On the basis of the correlation of the results observed in previous in vitro studies in these cell lines and in vivo investigations, it has been inferred_by Chamberlain et al. (1982) that "short - fibre" a11acu -g.ite may be__"flbrogenic" in in vivo studies, whereas "long- - ui.c" attapulgite may be "fiorcgenic and carcinogenic" . Using P38SD1 cells, Lipkin (1985) did not find any cytotoxic effects with short-fibred American or French attapulgite. Attapulgite fibres have also been shown to bind environmental carcinogenic pydrccarbuns such as benzo( a )pyrene and nitrosonornicotine (Harvey et al., 1954.. 7.2 .1 . 2 Sepiolite The. preliminary results of an inhalation study indicate that cue degree cf fibrosis for anj._m.als sacrificed after exposure to sepiolite for 3. 6. or 12 months was similar to that for animals exposed, to crccidply_te (Waor.er. 1982) . Additional details on the were not reported in the early published account of the preliminary resuits of this study. So mesothelial tumours were reported in 40 F 344 rats, at an upspeci_faed_penod prior to study completion, following :p: raoleural administration of sepiolite (Wagner. 1982) . 11 Short fiore" sepiolite was not cytotoxic in mouse peritoneal macrophages. Ad 4 9,_ or . V7 9-4 cells, whereas "long-fibre" sepiolite was cytotoxic :r. all three systems .Chamberlain, et _al .198 21^. 7 ..2 . 2_.. Woliastomte I XL studies involving the intrapleural implantation in rats of 4 samples of woliastomte from a Canadian mine, the mesothelial http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 67 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) ..'0 Y.ui ic-d. J b - 21 % : idol ce;! Stanton et al., 19811^ Ir. in vitro studies, wollastonite has been relatively non toxic in the cell systems studied to date. There was no release of lysosomal enzymes nor damage to the membrane in rabbit alveolar macrophages exposed to wollastonite. at doses much greater than the concentrations of chrvsotile known to be cytotoxic in this system IPailes et al.. 1984). In addition, wollastonite was found to be far less haemolytic in red blood cells than asbestos (Hefner & Qe.hrmg, 1975; Vallyathan et al. . 1984). and, whereas asbestos inhibits virus-induced interferon production from mammalian cells in culture (Hahon & Eckert. 1976) wollastonite enhances this natural defence mechanism (Hahon et al.. 1980). Recent ..evidence for the in vitro biological activity of wc11as tonice shows that these natural mineral fibres induce effects or. pu 1 mcnary macrophages that may simulate events occurring in the _ _ 1 _ :wir.g dust_ exposure,__such as impaired phagocytic capacity of the exposed macrophages, and serum complement activation, as Treasured by dose-related increases in pulmonary macrophage cne^ctaxis ykarhei.t__.et. al . , 1984 s . 7 .2.3....Fibrous zeolites - enonite In an inhalation study (Wagner et al.. 1985; in which animals were__ exposed for one year to enonite from several sources, at 10 '-a./-3 i h./day, 5 days per week, a remarkably high incidence of mesotheliomas .96.4%) occurred in the animals that remained 12 mpnths after exposure 'sample from Oregon) (frequency of fibres < 0.4 pm m diameter and > 5 am in length = 13.3%) For comparison, mesotheliomas were present in only 15 (1.4%) of 1056 rats exposed in earlier studies to similar concentrations of various forms of asbestos for periods varying from 1 day to 2 years .Reeves et al . , 1974Wagner et al.. 1974 ; Davis et al., 1978). The time to development of the tumours in the Oregon erioniteexposed animals was approximately half of that observed in crocidolite-exposed animals (Wagner. 1982). No mesotheliomas occurred in rats exposed by inhalation to New Zealand erionite _frequency of fibres < 4 gm in diameter and > 4 um in length = 1_._2__ for one year !Waoner, 1982) Ir. studies involving injection into the body cavities of animals. erionite has been extremely potent in the induction of "'e s r " he'. : 11 tumours; indeed one author reported that it _is the "mtst .potent known. ex_oeri_men_ta 1 _carcinogenic agent for the pleural mescthelium" .Yaltoni.ee. a I... , .19 8 2b_.. For example, in a study involving the intrapleural administration in rats of 20 mg of enonite from Oregon, the mesothelial tumour incidence was 100%; fpr samples originating from Karain this value was 95% (Wagner et ? 1 1 ?8JL ,__ The incidence of tumours after 67 weeks, in rats receiving an._intrapleural infection of 25 mg of "sedimentary encr.ite" of unreported origin, was 52.5% (UICC Canadian chrvsotile 3%. .Yaltcni et al.. 1982a.b' . In the same study, the incidence of tumours following intraoentoneal injection of a similar amount of the same material was considerably less (2.5%) (UICC Canadian chrysottie 2.5%) . On the basis of these results, the authors coneTuded.._that there was a different degree of "responsiveness of the_pieura and peritoneum to erionite and crocidolite" (crocidolite was more potent in inducing tumours following intraperitoneal admmiscration! However, a high incidence (6/10, 60%) of malignant tumours has been noted in another study in which 10 mg of erionite average length 1 ^m; average width 0,1 pm) was administered intraperitoneallv to mice (incidence in chrvsotile-exposed animals, 2/4, 50%, .'Suzuki, 1982). No peritoneal tumours were observed in ma1e BALB/c mice that had been administered erionite by a single intrapenconeal injection and had died less than 7 months after exposure. Between 7 and 23 months after administration, there were http: "\v\vw. inchem.org/documents/ehc/ehc/ehc53.htm Page 68 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) mesotheliomas in all the erionite-treated groups: 10 mg Colorado erionite. 21/42 (50%), 10 mg Nevada erionite, 3/8 (38%), 2 mg Nevada erionite, 2 4/44 (55%).__and 0.5 mg Nevada erionite, 6/18 .33%) . Available data also indicate that some forms..of erionite are more toxic in. in vicro systems than crocidolite and chrysotile,___ A sample, of erionite from Oregon increased morphological . ; -: ,v A 3 h 1 ,-T. / 2 tells and msm.edu lea DNA repair synthesis.m A5.49 cells to a greater extent than UICC cnrysotile.and crocidolite (Poole et al., 1983). The authors noted tnat fewer fibres in the sample of erionite administered were in the. "pathogenic11 size range (4.3% > 6 um long, median length 1.7 AUC . compared with the UICC crocidolite, and suggested that there might be some property of erionite that makes it quantitatively -ere active. 7.2,4. Assessment _ Although, m general, the toxicological information is not adecu ate to assess the potential_ risks associated with exposure to most.cf these fibrous minerals, it can be concluded, with some certainty, that some forms of erionite mav be particularly hazardous. This conclusion is based on the observed potency of the mineral in the induction of mesothelial tumours following both intrapleural implantation and inhalation. It has been suggested by one author that erionite mav be "the most danqerous of the natural fibres" 'Waciner. 1982! and bv another that it is the most ootent known experimental carcinogenic agent for the pleural mesothelium Maitom et al. , 1982'. 8,._.. EFFECTS ON MAN 8 . 1 .Asbestos T."f -pid^-^: c 1 ogi ca 1 studies discussed below are categorized acemumg..to. wr.ether tne asbestos exposure was occupational '.mining and mi11 mg, manufacturing, or product application), paratccupaticr.al ..'neighbourhood of an asbestos industrial plant, or heme of an asbestos worker), or exposure of the general population _ a. l r_ _o r.. w a ter' . 8 ,1.1 Occupational exposure .Inhalation c asbestos dust can cause fibrosis of the lung . asbestos is], changes m one or both surfaces of the pleura, brcnchial carcinoma, mesothelioma of the pleura and peritoneum, and possibly, cancers of other sites. 8_;_ 1 . 1 . 1 Asbestosis ______This is clinically diagnosed on the basis of a history of exposure to asbestos, clinical signs and symptoms, chest radiograph appearances, and tests of lung function. These indices show the usual range of severity typical of biological processes, making diagnosis easy and certain in advanced cases, but difficult and uncertain m the earliest stages of the disease. b'r.der recent exposure conditions, asbestosis will rarely be uet_=rstan 1.e^ even m its early stages, in less than 20 years from first exposure. In the maioritv of cases, asbestosis will advance a_t_er cessation of exposure iBerry, 1981; Jones, R.N., et al. , 198C; Navratil, 19S2_4 though early cases do not show any mi - i n - - m. 11, act.: c mange ever many years, provided that mere is no further exposure IGreoor et al. , 1979; Rubino et al.. 1579a; hiddell & McDonald, _JL.980i_. Tr.e 19 E 9.. 3 r 11 is.h Occupational Hygiene Society standard of 2 fiores/ml for chrysotile was based on a retrospective study o a hup:/7www. inchem.org/documents/ehc/ehc/ehc53.htm Page 69 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) factory population,__which did not include those who had left the factory.and .were, still alive (Peto,__ 1978). Further follow-up of a larger population, including ex - employees. showed that the annual incidence of _. crepitations in men with cumulative doses below 100 tibre/nL years was of the order of.2%__(Acheson &. Gardner. 1979) , and a recent analysis suggests that., the lifelong risk of developing '_-a: iy s . j r. s c: asbestos is., may be even higher .Berry et al . ,__197 9; - There is. no substantial evidence that asbestos fibre type in.fluen.ces the frequency or severity of pulmonary fibrosis. However, the risk may be higher in the textile industry than in mining and milling, or in the manufacture of friction products . Me bon. a *C, 1. 9 .... ____ hs deaths due to asbestosis may appear on death certificates under another guise and are most frequently included in deaths due to non-malignant respiratory disease, information on mortality due specifically to asbestosis is usually incomplete. For workers who in the past suffered very heavy exposure, such as_.English textile workers first exposed before 1933 (Knox et al., 1968_)__or. Nort h American insulation workers (Selikoff et al . , 1979). this._dlsti.netion was not important, as the excess risk was so large that the estimated excess was more or less the same by either criterion; but for less heavily-exposed workers, whose mortality -xpe r:-net is "'.ore relevant, for the purpose of estimating risks at lower exposure levels,__neither estimate is satisfactory, as mortality due to respiratory disease varies substantially over time an d be twee n_ _c o untries and social classes, and expected numbers are the i' e.f ere ^rti eliable. Asbestosis mortality in heavi ly - exposed workers is related to time since first exposure and intensity of exposure, but. not to age (Knox et al., 1968). and is increased by t*garette smoking .Hammond et al., 1979).If the risk were -iio.-i: . y : r-d'.ed. :c. intensity, of. expos ur e at lower levels,...th_e.se relationships would provide a basis for estimating low-level risks .Pets, 1975. j_ put. this_ seems ._imp.l.ausl.bie for such a generalized p r pg ryes spue condition.. ".1.1.2 Pleural thirkening, visceral,.and parietal Exposure to asbestos may produce acute or chronic visceral pleurisy, which tends .to. run parallel to the severity of the accompanying asbestosis. and thus, is a feature of those with heavy occupational exposure to asbestos. In contrast, parietal pleural thickening (plaques) is often not associated with asbestosis and tends to occur also in those with only light occupational exposure; it may also be a marker for those exposed environmentally. A high prevalen.ee of pleural plaques in a number of countries across Europe has been attributed to environmental exposure to various mineral__fibres. Pleural changes are related to the time from first exposure rather than to accumulated exposure (Rossiter et al.. 1 972' . Pleural calcification is occasionally seen as a very late conseauence of. occupational exposure. o_. 1.1.2 Bronchial cancer _____The first reports (Glovne, 1935; Lynch & Smith, 1935). suggesting..that asbestos might be related to lung cancer occurrence were followed by approximately 60 case reports over the next 20 F:f - i.s.t epidemiological confirmation of this association 'm= p . r ~ - r-.-i ry ^I 1 1 9" c ' ?: r.?<* then, over 30 cohort studies ::av<r pc-err. carried.out -u industrial populations m several court tries. The maionty have shown an excess lung cancer risk ;McDonaIdL 1984; ,__ but several studies have shown no significant excess mortality from bronchial tumours, even though some mesotheliomas, occurred__(Rossiter & Coles. 1980; Thomas et al.. - p? 2 ;.. .berry __F Newnouse, 1983; Onlson & Hogstedt. 1985; . _____^. Type of asbestos http ://w ww.inchem.org/documents/ehc/ehc/ehc53.htm Page 70 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 71 of 129 Zt is net clear whether chrysotile, crocidolite. and amosite differ m their potential to cause lung cancer. Occupational exposures to these fibres usually occur under different industrial circum,stances and with the exception of mining and milling. mixtures of asbestos fibre types are often present. With regard to mining, Australian crocidolite miners experienced approximately 5 times the lung cancer risk of Canadian chrysotile miners (Hobbs et al , 198CM ; however, it is not known whether the exposure levels or cther risk factors such as smoking were comparable in these 2 populations. In manufacturing, both Enterline & Henderson (1973) and_Hughes & Weill (1980) presented evidence suggesting a lower lung cancer risk from pure chrysotile exposure than from a mixture of chrysotile and amphiboles, but these results were not defini11ve. Recent studies of 2 textile plants, one using chryspt i 1. e_only__'.McDonald et a 1 . ,__1983a).__ the other using a mixture ur.rysoci-e ana ampmooles .McDonald et al . . 1963b', showed no di:rerence. *n lung cancer risk between the two. However, as with the, mining studies,__it is difficult to make such cross-study comp at iscr.s, because. of possible differences in the actual exposure levels ana other, risk factors. In gas-mask manufacture, in the 194 0sthose ,exposed to crocidolite had a greater excess of lung ___ = - :. j .on.- y___._: .i y sc 11 le McDonald & McDonald, 1978. ;b' Industrial processes Cumulative asbestos exposure was estimated for each individual in_10. studies on_ 9 industrial populations, using both duration and -Attrus.tv i :.i orma t ion . i n ..two of__these studies, both on asbestos cernent workers ^Albin et al. .__ 1983; Finkelstein, 1983). the reported results are difficult to interpret. Both had relatively small numbers of lung cancer deaths but substantial mortality from mesothelioma, and both failed to reveal any consistent relationship between the observed excess lung cancer and exposure. The 8 remaining st.udi.es. '.Table 22) revealed approximately linear exposure-response relationships, but the estimated slopes of these lines varied considerably. Much uncertainty is associated with each estimated slope, because of manv factors, including the limited exposure measurements made during the relevant time periods. The estimated slopes, however, exhibit a pattern r.j i c industrial process, with. the. lowest, values reported :or miners ana friction product workers.- the highest for textile workers, . and intermediate values m other manufacturing plants. The .venations m these results may be related to the state and physical treatment of the asbestos in different situations, the u^si . x OL.as._p ,u.s containing asbestos fibres of different physical umensious. A detailed review of other exposure - response estimates for lung cancer in different cohorts has recently been published by the US NRC/NAS. (1984} . .able 21. Standardized mortality ratios for cancers of the lung, gastrointestinal tract. and_ether sites m asbestos workers (number of deaths in parentheses)a Sex .Type of_ exposure Period of observation Standardized mortality ratio for: Lung Gastro- Other intestinal cancer cancer Number Reference of mesothel- Mining. chrysotile 194 6 - 7 5b 1951 -75b 1.03 (9) 1.22 (224) 1.03 (15) 1.03 (209) Q.94 (13) 1.05 (317) 10 Rubino et al. (1979b) McDonald et al. (1980) Mai .ttanuf acture, 1936-77c0.85 (28 )0.91 (18) chrys.c.ti 1 _e____ 19 58 -.7 7b2 . 00 159_] 1.-4 6 125) ____ .. 1 958 77b, c____ 1.49 ' 8 4 ~ ___ 1.14 {59) ................ 19.53__8_3bj. c____ 1.61 1113.1.10 (47? 0.93 1.28 1.16 0.84 (26? (35) {70) (48) 2Thomas et al . (1982 ) 1 McDonald et al (1983a) 0McDonald et al. (1984? 17 Peto et al - (in press? http: ''www.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 72 of 129 Male Manufacture, mixed 1941-79d 1947-80 1944-76 1 . 03 1.96 1.72 (143) (57) (.4 4) . 0.96 1 . 11 1.04 (103) (19) (31) 0.88 1.00 0.9S (77) (28) ( 89'; 8 5 3 Mar.uf actut e, 1941 73 6 .29 1841 2.07 126} 1.62 (42) 11 Berrv & Newhouse (1983) Acheson et al. (1984! Clemmesen & HialarimJensen (1981)e Selikoff & Hammond (1975) Male Insulation, mixed 1943-62b 1967-76 1933 -75d 7.00 4.24 2 . 38 (42) (397) (103! 2 . 99 1.67 1 . 18 (29) (89) (40) 1 . 04 1.98 1.39 (17) (258) (38) 7 102 46 Selikoff et al. (1964) Selikoff et al. (1979) Newhouse & Berrv (1979) 1947 78 0.84 1841 0.83 ;s8' 1 .11 (87) 31 Rossiter & Coles (1980) Male Various 3 . 07 : 5 5; 1 . OS f 16) 1 .29 .13 61 23 F ema.e Manufacture. mixed 1936 - 75 1941 - 79d Female Various 8 .44 (27) 0.53 U6J_____ 1.96 (20) 1.06 (29! 2.06 uar___ 1 . 28 (15) 1 ,. 62 (33) 0 .,85 (51) 21 2 0 ,. 99 U90i_ 7 a __ From: Doll & Peto (1985). b___Twenty or more years after first employment. c Some little exposure to amphiboies. d___Ten_or more years after first employment. e Cases of cancer and incidence ratios, not deaths. Mancuso & Coulter (1963); Weiss (1977): Newhouse Sc Berrv (1979); Finkelstein (1983) Newhouse & Berrv (1979) Berrv Sc Newhouse (1983) Mancuso Sc Coulter (1963 Acheson et al. (1982): Peto et al. (in press) - x yes'-re response relationships t o r__b r o n ch i a 1 cancera Loca t Process F ibre __ ___ tvoe Slope for increased Conversion factor lung cancer riskbimppct to fibre/ml) ' f ibresl____ (mppcfauthors other ml years) years} Reference Canada USA minina/ miilinq chrvsotile 0.0014 1 5 McDonald et al (1980) Connecticut friction chrvsotile products 0.000 anv McDonald et al. (1984) Louisiana cement mixed 0.0044 1 Hughes & Weill products_______________________________________________________________ ________________________ (I960) Pennsvlvania textile mixed 0.051 - 1 3 5 McDonald et al. (1983b) South Carol mac textile chrvsotile 0.023 - 0.082 0 . 051 NA _ NA 3 5 3 5 Dement et al. (1982) McDonald et al. (1983a) U:u Led__Ki:igdcin mixed. ....______________0^0 0_58___-_____________ -____ __________ -___-___--___-- ... .:5 . --___ r3(1973) l Enterline & Henderson http:/Avww. inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 73 of 129 area, not _ friction___chrysotile 0.00058 stated ... ___products(1983 ) ______________NANABerry & Newhouse a__ Mod i_f i.ed_. f rom : Canada, National Health and Welfare (1984); report__of Committee of Experts. b Adjusted to relative Xisk..pr . SMR =_...l .at_ .zero dose . NA - nut ape 1: cabI.e . u::;cge::s Because of a lack of information on smoking in most cohorts, it has fceen possible to compare the lung cancer risk associated with asbestos exposure at different levels of smoking exposure in only a few studies. Although there is evidence of an effect of asbestos in the absence of smoking, it is not clear whether the effects of "he 2 carcinogens are multiplicative or additive (if multiplicative, then asbestos exposure at a given level would multiply the risk among various smoking groups by the same const.antif additive, then the risk due to asbestos exposure would be added arithmeticallv to the smoking risk) . A review of the available studies 'Saracci, .1981, and _a ..recent iepor: .cased, on the Canadian mining population .Liddell et al., 15 8.3. suggest that the joint effect of these two exposures is probably more than, additive but not always multiplicative. I f asbestos acts, at least in part, as a promoter rather than an initiator of lung cancer, then exposures other than personal smaxing may also be important. In particular, passive smoking, air uu1._t_uv, cr ionizing radiation may olav a role, but no human data are availacle, as yet, concerning the combined effects of these 5 . 1 . 1 . 4_.. Mesothel loma The maionty of Known cases of mesothelioma arise as a result of occupational or paraoccupational exposure to asbestos or other fiprous minerals, but all series have shown some cases where no such fibre exposure has seemed probable. It has been suggested that it is likely that there are other causes of mesothelioma (Peterson et al. , 1984) . No association with smoking has been observed 1McDonaid,. 1984) . ,a_____ Fibre type No reliable exposure - response information is available for mescthelioma. The 8 studies with adequate measurements of exposure inter.sitv and duration showed only a small number of cases of mesothelioma., and, in at least 4 of the 7 populations studied. . AL-i-:e wjs to mixeg r ipre types .___ Semi quantitative data .New no,se u Berry, 1979; Seidman et al . , 1979; Hobbs et al . , 1980) have .suggested that increased risk of mesothelioma may be related to the duration and intensity of asbestos exposure. Other factors. particularly the time from first exposure, may also be important ' Rosslter & Coles, 1980; Peto et al., 1982; Browne. 1983a,b). l^rini'ive conclusions cannot be drawn in the absence of ' xg t = u i e response . nf crma t ion__for individual fibre types. However, availacle evidence suggests a substantial dif ference between 'virus1111 e and the amphiboles '.especially crocidclite) in their capacity_.to cause mesothelioma. The evidence is summarized below. fucstantial numbers of cases have occurred in naval dockyard i . t _e.s where amphibole exposure, especially during World War II, was probably heavy (Harries, 1968; McDonald & McDonald. 1578'. Of special interest is the study of Rossiter & Coles 11980) at Devonport dockyard in which 31 cases of mesothelioma ...___ were observed among a total of 1043 deaths ( P << 0.001), but no excess of ..lung...cancer http://www. inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) 2_^___Case referent surveys in North America have shown very high risks associated with insulation work that usually entailed exposure to amphibole/chrysotile mixtures (McDonald & McDonald, ___ 1980; Larger (on the basis of tissue analysis), personal coramunica t ion,__ 1985) . 3. Short-term exposure to pure crocidolite of workers engaged in the., ma nu facture of military gas masks in Canada (McDonald & McDonald, 1978) and the United Kingdom (Jones. J.S.P- Et al., ____ 1980) resulted in an extraordinarily high incidence of cases of mesot hel icma . The same was true,__but.po a_lesser extent, in workers in Australian )Hobbs et al., 1980), and South African crocidolite mines )Tolent et _al .1980).., and in an American insulation products_p_lant^ in which only amosite was used ___ .Seidman et al . ,__ 19.79L .In contrast.______very few cases have been iepcipea.among cnrysotile production workers in Canada, Italy, S o u t h A_f r icat. and. _ the USSR. -s . studies or. workers in 2 textile plants in the USA showed a 50 fold greater.lung cancer excess than in chrysotile miners. In one of these plants, only chrysotile was used, and there ____ was one case of mesothelioma,- m the other, small quantities of amp in oo.Ie were,, used, and there were 20 cases of mesothelioma. In._a third plants manufacturing friction products from chrysotile only, there was little or no excess of lung cancer _____ and no mesotheliomas ^McDonald & Fry, 1982; McDonald, 1984) . 5, Cases of mesothelioma in 4 asbestos factories in the Province _____of Quebec were all associated with the use of amphibole McDonald, 198 0) . 5.. . Electron microscopy case - referent surveys in North America .McDonald et al., 1982) and in the United Kingdom (Jones. J.S.P. Et al., 1980), have shown a substantial excess of amphibole fibres in the lung in mesothelioma cases compared with controls, but no difference in chrysotile fibres. However. van at ions in the persistence of different fibre types in the lung complicate the interpretation, of .the results of tissue 7. In a friction products plant studied by Berry & Newhouse (1983' in which only chrysotile was used (except in a well-defined ire a of...one workshop, where crocidolite was processed for 9 years,, the only excess mortality comprised 10 deaths from p 1 e..rql_...mesothelioma, 8 or perhaps 9 in men who had worked with the crocidolite. 8.. Five cases of mesothelioma were reported bv Acheson et al. ,1982. among 219 deaths in women who had manufactured military ps masks containing crocidolite) compared with 1 case .among 17_7_._ de.a_t ns m women manufact urmg civilian masks )conta ining chrysotile.^. this, woman had also worked with, crocidolite in _____ another factory where other cases of mesothelioma occurred. 9. .. There were 5 cases of mesothelioma among 136 deaths. 20 or more years. afte r , first employment, in a London insulation products factory in which only amosite was used (Acheson et al, 1981). .... An .i. r. d i c a cipn_. of the different risks for both pleural and peritoneal mesothelioma is shown in Table 21, in which studies with the relevant information are listed. In terms of absolute numbers of_mesot he1ipmas. greater risks were associated with crocidolite and pc_ssipiy amosite exposures than with chrysotile exposure alone. Execsn_e tc mixed f_ipres_ger.era 1 ly resulted_m an intermediate risk..... Result s of studies not r ep or t_i ng the mesothelioma site are "cr.s; stent with these findings... The reasons for .the different mesothelioma risks associated http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 74 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) with different__fibre types could include differences in the mymcal dimensicns of the fibres and the possibilities of higher ef receive.. doses_,_ increased peripheral deposition, and/or longer tissue persistence for ampin bole exposure than for chrvsotile. ,b. In Just! ial process Current i r.i or mat ion does not suggest an important differential in ..risk according to the industrial process. 3.1.1.5 .Other cancers Many cohort studies on different populations have suggested thaz cancer at sites other than the lung, pleura, and peritoneum has re.su Ited_.from_. occupational exposure to asbestos. In contrast, other studies have shown no excesses of cancer at other sites. [a) Gastrointestinal cancers In 18 cut of 30 cohort studies on asbestos workers, the number of deaths from gastrointestinal cancer exceeded the number expected; in the 12 remaining studies, there was no excess 'McDonald. 1984). SMRs for gastrointestinal cancer in various cohorts are presented in Table 21. However, these excesses are difficult to assess because of confoundina factors such as social - - ^ ^ ] geographical variations, and because of possible misdiagnosis. Moreover, there is no evidence of dose-related effects. Thus, a causal relationshio with asbestos has not been established. This subject has been reviewed recently by Acheson & Gardner . 1 9.8.3, , the Ontario Royal__Commission on Asbestos (1984). and Dol l & Pe.t.o ,19 8 5 - The excess of kidney cancer observed by Selikoff et al. nas not been supported by any other study so far. A causal relatlcnship has not been established. (1979) Laryngeal cancer ____ Evidence concerning this cancer is conflicting. In addition to the.srnal1_excess noted by Selikoff et al. (1979). 2 case-control studieSj...one_in Liverpool by Stell & McGill (1973;. and the other m Toronto by Shettigara & Morgan__ .19751 . produced evidence of increased risk. On the other hand, there was no excess in Quebec mem mu mailers .McDonald et al . , 1980, , and the results of a case-con.tro 1 study__in London bv Newhouse et al. (1980) were also negative. However. Doll & Peto (1985) concluded that "on the present evidence, we conclude that asbestos should be regarded as one of the causes of laryngeal cancer". Again, the relationship, though plausible, has not been firmly established. The excess, if anyy_.would be small in comparison with bronchial cancer. (d) Other sites Among._ 1nsulation workers, 252 deaths were certified as due to " r '.in'c-i", hot "1 cf ihese were reclassified on review as meso.thelioma and 28 as lung cancer (Selikoff. 1982). Reanalysis of -. m--. bis suggested that a substantial part, and perhaps all, of me myarer.;. excess .du e.._t c._o t r. er. cancers can be attnbuted to r:.: sdiaonos.s .___Two sites particularly liable to be certified ir.correctly_ are the pancreas and liver,- 16 of the 49 deaths mi timed as.._du.e. tc pancreatic cancer were, in fact, due to perm on e a 1 rn.es o t he 11 pma Selikoff & Seidmann, 1981). There is, cherefore, 1111le evidence of a causal relationship between -rents tr.i inters p.f these ether sites. There have been three studies in which there was an excess mortality, from., ovarian, tumours m workers exposed to mixed fibres hup :</www.inchem.org/documents/ehc/ehc/ehc53.htm Page 75 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) .Acr.escn et a' ., 1982: Wiqnall & Fox, 1982: Newhouse et al. , 1980), but, :r. :wo ocher studies. no increase was found iAcheson et al. , 1 982 ^ oercy.i Newhouse,. ...15_83_. 8 . 1 . 1 . 6 _ E\iteccs. on_ the immune system Changes in immunological variables have been observed in rumoms * masc.escosis and in experimental animals exposed to asbestos; however the significance of these changes in the etiology of asbestosis is not clear. It is also important to note that, though few data are available, it is possible that exposure to other particles mav effect similar changes. Perms et al. (1965) reported a significant increase in ;heumaci: factors in asbestos workers with diagnosed asbestosis. Increases in non-organ-specific anti-nuclear antibodies and rheumatoid factors have also been reported bv Turner-Warwick & Parkes ..1970), Lange et al. (1974), Kagan et al. (1917b), and , zkcvj ,1982. ir. addition, changes characteristic of . .me: s c . 11 a ,.. pulmonary . fibrosis, such as increased -syeps the immunoglobulins IgA, IgG, IgM. IgE, and complement ccmpcner,ts 3 and 4 ,'Lange et al. . 1974; Kagan et al. , 1977a; Lange, 1982; have been observed in patients with asbestosis. On the basis of these observations, it has been concluded that asbestos can trigger immunological mechanisms that are involved in lung fibrosis .Huuskpnen et al., 1978; Lange, 1980)- A decrease in the number of 7 tells .Kang et al., 1979; Kagan et al. , 1977a!, defects in cell- mediated immunity, and a deficiency of the generation of the migration mhibition factor !MIF~ have also been shown in persons _asbestosis !Lange et al 1978! It has been suggested that changes m T-cell suboopulations affect immunoregulatorv phenomena >;.tt a resulting decrease in T - cel 1 - mediated immunity and increase m 9 tell activity. This could explain the known increased preduction of autoantibodies, hypergammaglobulinaemia. and increase in immune complexes noted in patients with asbestosis '.Salvaggio, 1982) . ____ A detailed review of immunological changes associated with asbestosis and a discussion of the important role of alveolar macronhages in the etiology of this disease has been published by Kagan '1980!. ______The immunological status of individuals with asbestos-related car.cers has been described in only a limited number of reports Pam.acnander et al . , 1975; Haslam et al. . 1978) . These studies : m. me mitogenic lymphocyte response is impaired in such patients. 8.1.2 Para-occupatlonal exposure 8 .1. 2.. 1 Meighbourhood exposure Pleural calcification has been associated with exposure to asbestos . in the environment. An increased prevalence of pleural calcification was observed in a Finnish population residing in the vicinity, cf an anthophvllite mine (Kiviluoto, 1960), and similar coseryations were made in populations living in the vicinity of an antr.cphy 1111e mine .in. Bulgaria .Zolov et al . , 1967), an actinolite mine ;n. Austna .Neuberger et al . 1982;, and an asbestos factory m Czechoslovakia (Navratil & Trippe. 1972). There is some evidence, mainlv from case series and retrospective case-control studies, that the risk of mesothelioma may be increased for individuals who live near asbestos mines or factories: however, the proportion of mesothelioma patients with neighbourhood exposure to asbestos varies markedly in different ser.ies In an early review, of 33 cases of mesothelioma in the Northeast Cape province of South Africa (Wagner et al., 1960). http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 76 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) approximately 50% were individuals with no occupational exposure who had lived in a crocidolite-mining area. In 1977. Webster further reported that, of 100 cases of mesothelioma in South Africa with no _iidentified occupational exposure. 95 had been exposed to crocidolite and only 1 to amosite (Webster, 1977). Newhouse & Thompson (1965) observed 11 otherwise unexposed cases (30.6% of patients in the series) who had lived within 0.5 mile of an "asbestos factory" using mixed amphiboles in London.. ...Data...on._ca.se s :s .s -cseiveu : r. the neighbourhood c.f .shipyards, were reviewed _by._3ch.l_ig. & Main '1973' . who reported 38 cases of "non- occupatipnal" mesothelioma, which occurred during a 10-vear period :n residents. i.n_the vicinity of a Hamburg asbestos plant. However. in a study conducted in Canada, excluding individuals with occupatipnal or household exposure to asbestos, onlv 2 out of the 2 54 _ y3 .7s%) cases of mesothelioma recorded in Quebec between I960 and 1976 lived within 33 km of the chrysotile mines and mills .McDonald. 19801 . In addition, in a systematic investigation of aii_._2.0.1 cases of mesothelioma and 19 other pleural tumours reported to the Connecticut Tumour Registry, between 1955 and 1977, and 604 randomly selected decedent controls., .t_her_e was no association net ween :no i der.ce and neighbourhood, exposure ,Teta et al . , 1983 ' . Few data are. available on the length of residence of the patients in the vicinity of the plants in these studies. Out of 413 notified cases of mesothelioma in the United Kingdom in 196667, 11 individuals (2.7%). who were not asbestos workers and who did not have household exposure . had lived within one mile of an asbestos factory for neriods of 3-40 years. In a review of cases of mesothelioma in 52 female residents of New York state, diagnosed between 1967 and 1968. three otherwise "unexposed" patients (5.8%) lived within 3.6 km of asbestos factories for 18 - 27 vears (Vianna & Fcian, 1978! . In most of the studies, there were few data concerning the t vee of asbestos to which neighbourhood residents Vie re exposed. e r _ 1 eg;ca 1 a ep.idem.iolo.g_i cal studies have been conducted to investigate the relationship between exposure to asbestos in the environment and disease 'Fears. 1976; Graham et al.. 1977; Pampalon et al. . 1982; Siemiatvcki, 1983) . On the basis of the analysis of cancer incidence data from the Quebec Tumour Registry, the risk for resi denis of asbestos-mining communities was from 1.5 to 8 times greater.than that for those in rural Quebec counties, for 10 different cancer sites among males, and for 7 sites among females. The higher.risks.m males were attributed, in part, to occupational n: c.i--. Tr.eie was mcreased risk cf cancer of the pleura in both sexes, wnicn cecreased...w: tr. increasing distance of residence from the asbestos,mines. The authors emphasized the limitations of t.neir study and recommended that information concerning other exposures and lifestyle factors should be considered in more powerful case-control studies. An additional ecological study has been completed (Pampalon et al., 1982; Siemiatvcki, 1983). Mortality between 1966 and 1977 in agglomerations (several municipalities) around the asbestos-minino communities of Asbestos and Thetford Mines was compared with that of the Quebec copulation A statisticallv-sianificant excess of a____ For the purposes of this document, an ecological _____ epidemiological study is one in which exposure is assessed for _____ populations rather than individuals. ng t'iIps in these agglomerations was attributed to ,, c T ya: expos re . A telephone survey indicated that 75% of the ..men., in these communities had worked in the mines (Siemiatvcki. 1.93.3..., For women, whose exposure had been confined to the environment or,__in some cases, to environmental exposure and family TP.nt.act.,__there were no statistically-signifleant excesses of http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 77 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) n.ci: .!-ty du<=- t.c call causes__.standard mortality ratea. SMR = 0.89;, all cancers IS MR = 0.91). digestive cancers ,(S M R = 1.06), respiratory cancers ,SMR = 1.07', or other respiratory disease 'SMR = 0.56. . Similarly, there were no .signi ficant excesses __when the me r ta 111y__ rate at age less than 45 was considered or when the ref.erence_ populat ion was jronf ined to towns of similar size^ 'Jnf or t ur.at eiy, ..very few causes .of mortality were examined in this study, and the classes were fairly broad. The authors concluded that the .results...were .consistent with the hypothesis of no excess risk, though an SMR gf 1.1l_._4______ for lung cancer could not be ruled out m such a s_tudy. In a recently-completed study, no significant differences in the incidence of cancer of the lung or stomach were found in two Austrian .towns.,__one. near natural asbestos deposits and one with an asbes.tos cement production plant, in comparison with local and .national population statistics tcommunity size and agricultural index were taken into consideration; (Neuberger et al., 1984). In another ecological study conducted in the USA, in which cuere was some attempt to control for the urban effect, 3eograchical gradient and socioeconomic class, there was no correlation between general cancer mortality rates and the location of asbestos deposits (Fears. 1976). Ecological studies such as those described above are considered to be insensitive, because of the large number of confounding v : hr I es , which are difficult to eliminate , In addi t ion, t.rue excess cancer .risk is probaoly underestimated m such studies, because, of. .population__ mobr i_i py_ p.v_e_r _a_ latent period of_ several decades . _?olissar, I960' .___Case control and cohort studies are generally more powerful than ecological epidemiological studies. fcec.ause exposure and outcome are assessed for individuals rather *. nun ::r copulations. One relevant cohort study has been conducted. Mortality data for men who lived within 0.5 miles of an amps it e factory in Paterson, New Jersey in 1942 were compared with data in 52.06. male residents of a similar Paterson neighbourhood with no assestos plant (Hammond et al.. 1979). All men who worked ip..the factory were excluded. Approximately 780 (44% of the "exposed", population! and 1735 ;46% of the "unexposed" population' uied during the 15 year period 1962 76. With respect to total -pains, deaths from cancer .all sites combined!, and lung cancer. mortality, experience..was _s 11ght l_y. worse in the "unexposed" P ecu - a. tp on d u ring t his period. Therefore, there was no evidence of increased risk attributable to neighbourhood exposure. a ___ Ratio of the number of deaths observed to the number of deaths expected, if the study population had the same structure as the standard population. In summary, available data indicate that the risk of Pleural p_lagues and mesothelioma mav be increased in populations residing in..the vicinity of asbestos mines or factories. However, there is r.o evidence that the risk of lung cancer is increased in similarly'.-xp_5"_-u copulations . However, it should be noted that, m the past, a;rborr.e _fibre levels near asbestos facilities were generally much higher than they...are today. For example, Bohlig & Hain (1973) ' v.ct: tr.ed that before the second World War, there was "visible sr.owfa 11-like air pollution" from an asbestos factory in Germany. 11.s a 1 sc claimed that, 20 years ago in Quebec mining _:r. i: . es , " snow l:ke_films of asbestos" accumulated regularly .Siemiatycki,_ 1983i -.1.2.2 Household... exposure Measurements made_ by Nicholson et al. 11980} in the homes of ` - un; _ a:. ;, sr.uweu teat ticre u.'.r.cer.tratipns were several times http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 78 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) higher in the_former chan the latter. Studies of both Newhouse & Thompson. .^1_96_5J__ in the United Kingdom and of McDonald & McDonald , 1960.' m North America showed more cases of household exposure in ; -har. : r. '"r.trcls, after exclusion of . ; a .. i u- de-m-c 1 eg : ca 1 surveys have specif ical ly addressed the question. Vianna & Polan (1978) studied the asbestosexposure history of all 52 histologically confirmed fatal cases of mesothelioma in females in New York State (excluding New York Ci_tyJ_,__ in_ 1967-77, with matched controls. Excluding 6 cases exposed at work. 8 others had a husband and/or father who worked '.vi th asbestos; none of their matched controls had a history of domestic exposure whereas the reverse was true in only one pair. Information on latency was not given, but 2 of the 8 whose husbands were asbestos workers were aged only 30 and 31 years, respectively. In a study bv Anderson et al. (1979), over 3100 household cot.tacts of 1664 surviving employees of the Paterson amosite a s bestos plant, were identified in the period 1973-78. From over 2300 still living, 679 subjects who themselves had never been exposed, to asbestos occupationally, and 32S controls of similar age distribution, were selected for radiographic and other tests. Small opacities and/or pleural abnormalities were observed in 35% cf tne.household contacts and 5% of the controls. Pleural changes were more frequent than parenchymal changes ... The readings were made by 5 experienced readers and though the interpretation was bv consensus, it was made without knowledge of exposure category. The mortality experience of this population of household contacts is a1so under_study; the method has not vet been adequately described but at least .5. cases of mesothelioma and excess mortality from lung cancer..nave been reported. -.*. Jenera. population exposure lacInhalation Pleural calcification has been associated with exposure to mineral fibres in the environment. Increased prevalence has been observed in populations living in the vicinity of deposits of anthophyllite, tremolite, and sepiolite in Bulgaria (Burilkov & Michailova, 1970), and tremolite deposits in Greece (Bazas et al. , 1981; Constantopoulos et al.. 1985). However, increased prevalence of pleural calcification has also been observed in populations without any identifiable asbestos exposure (Rous & Studenv, 1970). ______There is very little direct epidemiological evidence on the effects of urban asbestos air pollution. The question was addressed_to .some extent in analyses of the extensive surveys of malignant mesorhe1lal tumours undertaken by McDonald & McDonald '158.01 in. Canada during the period 1960-75, and in the USA in 1972. 1ystematic ascertainment through 7400 pathologists yielded 668 cases whi;h,..with controls, were investigated primarily for cc.piticcs' factors. After exclusion of those with occupational, . - . c , -1. :u:u:p r.eighbourhood exposure, the places of residence of. women were examined for the 20 to 40-year period before death. cf 146 case control pairs. 24 cases and 31 controls had lived in rural.areas only, and 82 cases and 79 controls had lived in urban areas only. These very small differences could easily be due to change, .qupte apart from the greater likelihood of case recognition ..ic.u. mra. amas and me cor. 11 idu t ion of exposure in the immediate neghcgur.hgcd .cf plants, such as that in Paterson, New Jersey - Some indication of the possible impact of general atmospheric air pollution can be obtained from the study of sex differences in the trends of mesothelioma mortality. This approach was explored m a recent analytical review bv Archer & Rom (1983) and McDonald .1985). The industrial exploitation of asbestos began early in the present century and accelerated sharply during the period http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 79 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) before and during the first world war. Given the usual latency for mesothelioma of 20 - 40 years, it might be expected that the effects of asbestos exposure would be seen in the 1950s, especially in men. There are several sets of data from Canada. Finland, the United Kingdom, and the USA, which show that mortality in males was indeed rising., steeply (up to 10% per annum), whereas in women, it is doubtful whether there was any increase.___ Since there was eviuence that both occupational and domestic exposure accounted for some cases in women, there is little room 1eft for any material effect attributable to general environment exposure. Ingestion It has been postulated that asbestos fibres in drinking-water, and perhaps also in food, could conceivably increase the incidence of..alimentary cancers in populations exposed over many years. This is a ccmple_x question, as the exposures are intermittent and the ,c:'.:e:r lacior.s v a r_y . .. However, even m industrial cohorts, the association of asbestos exposure with alimentary cancer is irregular McDonald, 1984,. and net wholly, convincing '.Acheson & Gardner,. 1933_... ___ Icoiygicai epidemio1oq1ca1 studies have been conducted in several areas with relatively high concentrations of asbestos and similar mineral fibres in the drinking-water supplies in Duluth, Canadian cities, Connecticut, Florida, the San Francisco Bay area, and Utah. Only one relevant analytical epidemiological study has been conducted, the locale of which was Puget Sound. Washington. The results of these studies have been reviewed (Marsh. 1983; Toft et al.. 1984' and are presented in Table 23. In 5 of the areas (Connecticut, Florida, Quebec, the San Francisco Bav area, and Utah?, the contaminating fibres were predominantly chrysotile in concentrations ranging from below detection to 200 x 106 fibres/litre. In the sixth population !Duluth), exposure was to an amphibole mineral in a similar range of,concentrations, though it is not clear to what extent the particles were .truly asbestos, There has been no consistent evidence of an association between cancer incidence or mortality and ingestion of asbestos in drinx:ng -water m the studies conducted in Canada (Wigle. 1977; Tof_t ..e t_a_l_ __1951!Connecticut 'Harrington et al.. 1978: Meigs et l?c" , ruliuh. 'Mason et al., 1 974 ; Levy et al . , 1976; Sigurdscr. ep_ai_. , l_9__8i,_, Florida .Millette et al . , 1983), and Utah Sadler et al,, 1981!. However, all of these studies had ~" 'V : al., 1 984.' . The Duluth and Connecticut s; ..pies potn had the disadvantage of relatively recent onset of _ u e .1 955 .in Duluth, mostly since 1955 m Connecticut; and in Connecticut and Florida, asbestos fibre concentrations in most water supplies were very low (< 106 fibres/litre). The Canadian studies included localities with longstanding exposures to high concentrations of asbestos (> 100 x 106 fibres/litre), but the populations at risk were relatively small and cancer incidence data were not available. Ip the.ecological epidemiological study conducted in San Francisco, there was evidence of an association between exposure to asbestos in drinking-water and the incidence of gastrointestinal ,ante: ,Kanarek et al., 1980; Conforti et al., 1981). This study .cad several advantages including long-standing, relatively high but variable concentrations of asbestos in water supplies, a large population at risk, i.e.. the power of the study was good, and oooulation-based cancer incidence data (Toft et al.. 1984). However, there.were several confounding factors that complicate _ r.t ercr et at ion. of the results of the San Francisco Bay area study. Fear, a - y s i stak: ng_ population density into account, reduced the sioni f icar.ce of the relationship observed between ingested http:/ 'www.inchem.org/documents/ehc/ehc/ehc53.htm Page 80 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 81 of 129 a see s t o s_. ar.d .cancer... .1 n males and increased the significance of Che assoclation for females (Conforti,_1982.Li___ Graphical reanalysis of the data also indicated that there were differences in cancer incidence within San Francisco compared with the surrounding census tracts,- this "San Francisco effect" may undermine the significance cf the association that was observed in the California study .Tarter, 1982:, Table. ,23_^__ Epidemiological studies: asbestos in drinking-water Study .area____ Fibre type___ Population andStudy designResultsReference exposure Minnesota amphibole_______ 100 000ecological: comparison of no evidence ofLew et al. 'mine tailings) exposed to 1 - 65 x 106 fibres/ litre for 15 20 vears age-adiusted cancer incidence rates (1969 -74) in Duluth with those in Minneapolis and St. Paul increased risk of gastrointestinal cancers due to the presence of asbestos (1976) Siaurdson et al. (1981) : Siaurdson (1983)' amphibole (mine tailings - 100 000 ex- ecological: determination no evidence of exposed to 1 - 65 x 106 fibres/ litre for 15 20 vears of SMRs (1950-69) for Duluth with comparison population (Minnesota! increased risk of gastrointestinal cancers due to the presence of asbescos Mason et al. (1974) Tcr.r.ert icut chrvsotile 530 000 tasbestoscement pice) exposed to 1 x 106 fibres/ litre for 20 vears -------- ecoloaical: determination authors attributed of standardized cancer incidence ratios (193573) from Connecticut Tumor Registry data; largely negative results to low concentrations of asbestos fibres in towns grouped bv exposure to asbestos in drinkingwater and copulation density; multiple regression analysis with a series of independent variables concerning population density. socioeconomic status. and drinking-water quality drinking-water Harrington et al. (1978) ; Meias et al. (1980) tie 23 , (contd.) Study area___Fibre type Population and exposure Study design chrvsotlie 200 000 ecological: comparison asbestos exposed to < 10 of SMRs for 7 cancer rent pipe. . x _1G6 fibres/________ sites among 3 exposure __________________litre; long-___________groups_________________________ _ s tandinq contamination 40 years; cnryscti.e activities! 30 000 ex- ecological comparison exposed to 200 x of observed to expected -106 fibres/____________ cancer mortality (1964- Results Reference no evidence for an Millette association between use of A/C pipe and deaths due to gastrointestinal and related cancers. limited sensitivity et al. (1983) and analysis no consistent. convincing evidence of Wigle U977) http://www.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 82 of 129 litre; long-73), calculated on theincreased cancer standingbasis of Quebec mortality risks attributable contamination_________ rates specific for sex,_______to ingestion of _[ 80 years) _______ site, period,__and agedrinking-water _____ ______ _________ ________________________________________ contaminated bv asbestos Table 23. (contd.) udv area Fibre tvpe ------------------- ----------------------- Population and exoosure Study design Results Reference Quebecchrysotile______ 25 000 inecological: comparisonno consistent.Toft 'contd.]. . 'miningThetford Minesof ASMRs (1966-76)convincing evidence activities and 100 000 in for 71 municipalities ar.i C V' >- V~ y- r~ V 0. across Canada stratified erosion) exposed to 100 by asbestos concent- et al. of increased cancer risks attributable to x 106 fibres/ litre; longstanding contamination ; 80 vears! z - - - --......... -- -- rations in drinking water, use of chlorination; ASMRS for Sherbrooke compared with those for 7 municioalites ingestion of drinking-water contaminated bv asbestos with low concentrations of asbestos in drinking-water matched for water source !surface) . use of chlorination, and population size; stepwise multiple regression analysis with 13 independent variables concerning socioeconomic status, drinkinq-water quality, and mobility (1981): Wiqle et al. (1981) California .Bav Area chrvsotile 3 000 000 exposed to 36 x 106 fibres/ litre longstanding contamination i 60 years) n ecological: determination evidence of of standardized cancer positive incidence ratios for 722 census tracts (1969-74) from Third National Cancer Survey data.census tracts aggregated associations and relationships between asbestos concentrations in bv asbestos concentration and income or education; log linear regression analysis with 6 independent variables drinkinq-water and (1980) : et al. (1981) : Tarter (1981) 2 7 . ^cn r a . Study area Fibre tVDe Pooulation and exposure Study design Results Utah chrvsotile (asbestoscement DiDe) 24 000 exposed to unknown concentrations for 20 - 30 vears ecological: comparison of cancer incidence data from Third National Cancer Survey data for several Utah communities Dositive association for gall bladder cancer (1981) control for sex. socioeconomic status http://\vww. inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Page 83 of 129 chrvsotile population of Seattle, Everett. and Tacoma met roDolitan areas exposed to 200 x 106 case - control: determination of odds ratios for cancer incidence (1974-77) and mortality (1955-75) in two groups of census fibres/litre; longstanding contamination 60 vears! r tracts aggregated according to asbestos estimates of length of exposure for cases in high-exposure area; 2 control groups Studies, such as those described above, are considered to be insensitive because_of the large number of confounding variables. .u. - U i l__i . t. to eliminate, and the potential to und.erestimate, cancer risk due to population mobility over a latent tericd cf several decades.In the more powerful case-control study conducted m the Puget Sound area, which included data on individual exposures based on length of residence and water source. there was no consistent evidence of a cancer risk due to the 1r-iShstion of asbestos in..drinking-water . ____ Thus, the studies conducted to date provide little convincing evidence of an association between asbestos in public water suppltes and cancer induction. - . J N'atuiii Mineral Fibres _____The qresent review of minerals that may occur in fibrous form will be confined to the fibrous clays, fibrous zeolites, and woiiastcnite. Although the effects of human exposure to these fibres should be described m the same sequence as those for asbestos, it is...not possible with the very scanty epidemiological ;ata available. Instead,.. such information, as exists, will be '-xan.meg under 4 mam mmeralogical headings. 8.2.1 Fibrous clays 1.2.'..: Falygorskite '.attapulgite; 1 n e _. t: - _ zo; pal eft e cts of__these mineral fibres were reviewed by 3igr.cn et a_l_. ,15 8 0, . They mention only a 41-year-old man with pu_Tc.nary f icrosis who had. been exposed for 3 years in attapulgite :;:i_n i r.g m France, and a 6 0 year- old woman treated for 6 months with a drug.containing attapulgite. who was excreting fibres in the urine. They state that there have not been any epidemiological stugies__of attapulgite workers. However, surveys are in progress m the USA. S .2.1.2 Sepiolite There appears to have been only one epidemiological survey of worksrs exposed to sepiolite. i.e.. a radiographic study of 63 men enaaged in trimming sepiolite stones in Eskisehir, Turkey, in the manufacture of souvenirs. They had been employed from 1 to 30 years .me a n_. 1.1.9 years), and 10 showed radiographic evidence of u u1n c nary _fibres is However, more than half of those with fibrosis came from dusty., rural, .regions that^_were__ri ch in tremolite asbestos a.n.g. cep_l.ite deposits; silica ar.d deatom particles were also present .Bar ; s et al_. , 19.80, . population density and migration authors concluded that study did not provide evidence of a cancer risk due to the inaestion of asbestos in drinking-water Polissar et al. (1982) ade of wollastonite-mine and -mill workers http://www. inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) r. New York Slate and of workers exposed to this mineral, .in a Finnan limes t.one quarry. In the. American s tud i.es. _ IS has by .eC_a.L_, 1 979; Hanke et a_l . , 1.98 4^ , 57 workers were examined in 1976 and 1982. Three cases of category 1 simple pneumoconiosis were found and statistical analysis suggested that the more heavily exposed dad u s: jn t : cant ly greater decline in peak expiratory flow.__ In the Finnish surveys .Huuskonen et al., 1983a,b;, slight pulmonary : . i : . s I-- t t it <-d r n.:: ; 1 og: ca 1 ly ;n 14 men, and bilateral P1 eurai_changes in 13 men out of 46__exposed for 10 years or more. Frel minary ne.sul.ts_ from a cohort study on 238 of the quarry worjcey.'s showea no excess mortality, but__the authors noted that one woman with 20 years exposure died from a malignant retroperitoneal "-s^ncl'.ymal tumour, 30 years after f irst .employment^ 8.2.3__ Fibrous zeolites - erionite ______The remarkable incidence of mesothelial tumours in some remote Anatollan villages was first reported by Baris (1975) . The results of intensive environmental and epidemiological studies have since seen described .Bans et al . . 1978. 1979; Lilis, 1981; Saracci et ah , 19 8 2j_ Sebast len et al . . 1983) . In Karain, with a population of less than 600 in 1977, 42 cases of malignant mesothelioma occurred during the previous 8 years. In Tuzkoy, a larger village of 2729 inhabit ants 5 km awav. at least 27 cases occurred in the period 1 978 8 0 Artvmli, & Barr l s , 1979} .___Both sexes were equally affected and at ..an appreciably younger age than is usual in 7 coup at; c n a 1_. cases . .... A ithough many quest ions remain unanswered, there appears to be little doubt that this disastrous situation was largely attnbutable to environmental exposure, from infancy, to ftps zeoldte fibres of volcanic origin, which occur in local dust and which,.haye. been iden.ti f_i ed_in .the 1 ung tissue of patients . The elemental composition of most of these fibres was consistent with m-ni'o. L:-^le asbestos outcropping is used in this area of . i *" .Fen* e i a i . , n 8 ^ . 5 EVALUATION OF HEALTH RISKS FOR MAN FROM EXPOSURE TO ASBESTOS AND OTHER NATURAL MINERAL FIBRES 9.1. As rest os 9.1.1 General considerations ___ The results of extensive epidemiological and toxicological s tud i e s .. have . confirmed that health risks due to asbestos exposure a r e_mair.ly associated with inhalation. The risks from ingestion seem, to be negligible, bv comparison. Estimation of the risks from asbestos is more complex than for most other substances because of the nature of the material. Asbestos is a crystalline, relatively insoluble material of several d;.ffere.nt__t_yp_es, the biological effect of which is influenced bv s ever a 1 .. factors including the diameter and length of the fibres and the length of their retention in the lung. The sources of the fibre, and the wav they are manipulated in the various processes ' ' ~ : n . ng t o f ip. a 1 de_m.pl: t ion. markedly influence the hazards. Therefore,.. it is. .not. possible to make a simple risk assessment or ler.vaiion of d_pse_ resppn.se curve for asbestos. ___ The principle asbestos - related hazards for man are two types of resellatory cancer: bronchial carcinoma and mesothelioma; the - " ; ; f~ p : be pleural surfaces and may also occur in the peritoneum.. Bo.th.._t.ypes _of..cancer progress rapidly and have low survival rates, and the detection of these health effects would be : e* at _ ve ) y ..easy,__if it were net for the fact that many cases of cror.chia: Car.cer.car.,.. m general, be attributed to cigarette c c.pk.i_r,g . At present, it 1.s not possible to separate cases grcc.i f:rally. due to smoking or to asbestos exposure. There is epidemio 1 pgica 1. evidence of a more than ..additive effect on lung http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 84 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) cancer risk w i t_h _ concurrent exposure, to. asbestos and cigarette smoke. .Thus, overal1. smoking is a manor contributory factor to the bronchial cancer risk attributed to asbestos exposure. Until about 30 years ago, mesotheliomas were so rare that they were not recorded separately in national cancer statistics. It is now known that the majority of these tumours are related to asbestos exposure but not to smoking. However, studies of several groups of mesothelioma cases have consistently shown a small proportion in which a link with exposure to asbestos could not be identified historically, or, in some cases, could not be associated with excess asbestos fibres in the lungs. In addition to the respiratory cancers, asbestos inhalation pauses fibrosis of the lungs asbestosis). In the early part of the century, this was the principle asbestos related health risk, because lung cancer was rare -'presumably because there was little smoking).__With very heavy exposures to asbestos, the disease became manifest,, within, as short a period as 5 years.___ At lower dust levels.__the_ disease may not appear for 20 years from first exposure... In some countries, conditions have greatly improved and UP is likely that asbestosis will no longer be the cause of significant asbestos - related mortality. The incidence of a_s.bestosys among, asbestos-exposed workers appears to be declining. Jacccson et al. .1984) have reported a low prevalence of detectable X lay snanot?s in asbestos workers initially employed in 1971 or _atei to fibre .levels meeting current standards m the United Kingdom. There is no epidemiological evidence suggesting that asbestosis has resulted from exposure in the general environment. From this it will be seen that the risk of cancer has recently become the health risk of main concern in relation to asbestos. This concern has been increased bv the belief that there mav be no threshold for manv carcinogens below which there is; no risk. but this "no threshold" hypothesis has not been proved in the case of asbestos. It mav be that the risk is <epidemiological 1 v undetectablv low at the concentrations of airborne asbestos that can be measured only at the high sensitivity of electron _____ The need to consider the full implications of the "no threshold" hypothesis for the induction of cancers by asbestos has 1ed to.much effort to use past experience with high level occupational exposures to predict the possible hazards at much 1 ewer 1 eveIs whereno. excess risks have actually been observed. T h _ s_ ape - i_e s noth to the occupational setting '.to set occupational exposure limits) and to possible risks in the general environment. ____ T h e re a re two broad approaches to assessing health risks.- Tr.c qualitative approach, making use of a variety of empirical 2, The quantitative approach, using mathematical models based on the numerical data on the environmental levels of asbestos in the past and the incidence of asbestos - related cancers. 9.1,2_ Qualitative approach 5.1.2.1 Occupational ______There are several studies concerning occupationally exposed croucs )sectlon 8) in which the conditions in the past have not -'5..s-`-d a detectable increase in bronchial cancer and in which the lexers :f those involved, the time since first exposure, and the T'cmp: z eness of fo22ovv'-up were such that even a moderate increase in bronchia1 cancer risk should have been detected. The experience m these factories suggests that it may be possible to use asbestos http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 85 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) under particular circumstances with no detectable excess of bronchial cancer^ ______Mesocheliomas are not necessarily related to bronchial cancers. Detection occurs many years after first exposure, the latency period often being longer than that for bronchial cancer. Mesotheliomas have appeared more frequently in subjects with exposure to amphiboles than in those exposed to chrvsotile. 9 . 1 . 2 . 2 Para occupatignal.exposure Mesothelioma, mortality has been found to be elevated in pop ; 1 at:ons exposed in an indirect or para occupatxonal manner. .:.cse iicie. exposures originated from mining and milling '.relations, from factories releasing fibres into neighbourhoods, or 1rom asbestos carried home on the clothing of workers. However, leve.is. associated with such exposures appear to be extremely variable, and. it is. not possible to derive quantitative estimates o f_ _ risk from these data. I_n_ severa 1 studies, excess risk of lung cancer from paracrcupatipnal exposure has not been reported. For many years, in the cast, environmental pollution in the chrysotile asbestos mining areas was very high with reports of "snow-like" conditions persisting for long periods. However, studies on such populations have not shown any significant asbestos - related excess of cancers 'section 8) Conditions in recent years have been improved by the : r.r c d u c 11 on . of adequate control measures. Marked differences in mesothelioma incidence have been observed in southern Africa, The incidence was very high in the crocidolite mining areas, very low around the amosite mines, and apparently undetectable in the chrysotile areas of Zimbabwe and Swaziland (Wagner, 1963b; Webster, 197 7 . 53 general, copulation exposure cne.oenera1 environment. the Task Group concluded that: a. the ma~or fibre type observed in the general environment is chrysotile; the average fibre concentration ranges over ,, f magmtuae from remote rural to large urban _a ' e a s !b} chrvsotile fibres in the general environment are virtually all less than 5 um in lenath and possess diameters that require electron microscopy for visualization; these fibres nave .r.ct beer, characterized m work-place environments, nor have they been considered in computing dose - response _estimates for human disease; and .c) the risk of mesothelioma and bronchial cancer, attributable to asbestos exposure in the general population, is undetectably low; the risk of asbestosis is practically _____ nil . 9__, 1 .3 Quantitative approach _____ Assessment of health risks from exposure to asbestos fibres must take into account all the previously discussed factors r egara.r.g cne physical and chemical properties of the fibre types, measurements of exposure, and biological response m both human Pm pngs ...and .an lmals. On this bas^s, the Task Group emphasized specific prmcipies and then commented on the most frequently cited assess me r. t me dels... .a. Fibre type - is-: luc_p believed that ar.y risk model for mesothelioma must distinguish among the fibre types. http: //www. inchem. org/document s/ehc/ehc/ehc 5 3 .htm Page 86 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) The human data reviewed by the Task Group indicate that the ashestos_irelated diseases observed in the work-place are a function c r*:hr-- ^ ypc. The amphiboles have been associated with .;soes t - s ~ s , ne 1 icma , ana lung cancer. The association of cnrysotile with the first two diseases has also been established, but its association with mesothelioma is less clear___Of the total of__32.0 .mesothe Ilomas reported for all cohort. studies on asbestos- exposed .workersj...only. 12 occurred in workers exposed to chrysotile alone.,__ though the majority of workers studied were exposed to cnrysotile. The mesothelioma incidence in chrysotile-exposed workers appeared to be less than that in workers exposed to crocidolite or amosite. However, animal studies have not shown conclusive evidence of a lower carcinogenic potency of chrvsotile. (b) Fibre size and amount ______The importance of fibre size in the etiology of disease has been well demonstrated by asbestos implantation and inhalation studies on animals. Occupational exposure in different industries involves exposure to a range of fibre dimensions, and these dlfferences in fibre size, both length and diameter, mav be resporsible for variations in lung cancer rates observed in different industries. Short fibres (< 5.0 pim) appear to be less active biologically than long fibres (> 5.0 urn) of the same type. However, there are limited data for human populations on the contribution to health effects associated with exposure to fibres much shorter than 5 um. The Task Group believed that extrapolating disease experience m the work-place, derived on the basis of measureverts of long fibres, to the ambient air, which contains mainly short fibres, introduced a major variable of unknown Historically, work-place exposures to asbestos have been "easured using a variety of non-specific methods. Currently, such "easurements are made, m most cases, by using membrane filter collection and subsequent analysis bv phase contrast light microsccpy. With phase contrast light microscopy, the number of fibres per volume of air are determined. However, by convention, only fibres > 5 um in length, with diameters smaller than 3 ^m, and .having an aspect ratio of > 3:1 are counted. These fibres 'were chosen because they were believed to represent the biologically-relevant part of the respirable fraction. In addition, there is no comparability between the results obtained by the Membrane Filter Method and those obtained bv any other currently available methods (especially those expressed in mass units! As a consequence, pooling of data obtained using different methods is inappropriate. Thus, the size of the data base that can be used to construct reliable dose - response relationships is severely reduced. The Task Group believed that, even in the occupational setting, dose-response relationships are ill-defined in ...terms..of fibre size, fraction of biologically-relevant dust. and f i.pre dose For this, last parameter, the use of cumulative dose.max tot be appropriate m calculating dose - response rel_ationships . .c! Mechanism of action Once inhaled, chrvsotile tends to split longitudinally and degrade chemically. As a result, its residence time in the lung is shorter than that of other asbestos types. Residence time in 1_._cc ^ .s ror.siiered tc be an integral part of dose. In addition. asbestos max act as a promotor (section 7.1.3.5). These factors have .net beer, t.aken. into, account in models for quantitative risk 9..1.3.1___Bronchial cancer http:/Avww. inchem.org/documents/ehc/ehc/ehc53.htm Page 87 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) __At. low_levels of asbestos exposure, such as those that occur in the general environment, the excess cancer incidence is too low to be_.decected directly. Kfforts to provide an estimate of what they might be, using the incidence observed at high occupational levels and then extrapolating downwards to the effects at low or very low 1eve 1sx__has been carried out using a linear model relating incidence and dose (concentration x time). The validity of such linear extrapolation cannot be proved for such low levels, but fits reasonsbly well with the response observed at higher levels. It is likely that it overestimates rather than underestimates the risk at low levels. _____ The most widely-used model for the effects of asbestos exposure on lung cancer incidence assumes that the relative risk is increased in approximate proportion to both the intensity .fibre/ml) and duration of exposure, irrespective of age, smoking habit, or time since exposure.__This can be summarized by the I .d, f , a. sx__ = I a. s) x (1 + K x d x f)(1) AU L where, I .d,f,a,s) denotes lung cancer incidence among asbestos A worker? "a" who smcke "s'1 cigarettes per; day and have been excise:. ::r a tcial durat ion of "d" years at an average level of "f" ficre/ml. I denotes lung cancer incidence at the same age "a" U _n an. unexposed population with similar smoking habits, and K is a L constant, characteristic of the mineral type and distribution of f Tore dimensions of the asbestos. The relative risk, which equals 1__:v- K x d x f, is thus increased in proportion to d x f, the cumulative dose (fibre/ml years). ______There are many uncertainties in using this formula. For example, there are no surveys in which there have been reliable and comparable fibre counts going back to the time when the observed occupational groups were first exposed. In the small number of surveys with dust estimations extending 20 or more years into the past, the indices of dust levels are not comparable, for example, particles per cubic foot in the chrvsotile mining and milling industry..and fibres/ml in the textile industry, obtained using entirelv_d ifferent dust samplers. Confident conversion from one to the other measurement is not possible as different dust parameters were measured, and the conversion factor, when obtained, varied for different processes within the industry (section 5). Different authors have used different conversion factors. In bq^atior, _,__ K , the "constant", represents a number of o:o;og:cally important variables such as.fibre type, size uistricut ion of the airborne fibre, and the rate of lung clearance cf the fibres, etc. These may well differ between different surveys. Cigarette smoking is such an important factor that it is included in the model, but for many of the surveys, information about the number of cigarettes smoked was not available. Smoking habits, which may be rising in some developing countries and falling in industrialized countries, will render the predicted figures even less reliable. If smoking levels are rising, a higher m.sil ..te excess risk can be expected in the future, unless the as testes.. dust levels are reduced. ______The reservations concerning the reliability of the model indicate that it can be used to obtain only a very broad apc r ox ima c ion of the lung cancer relative risk. The different values of the extrapolated risk estimates (generated predicting ex.eess cancers per mi 1 lion people in the general population) varied http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 88 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) over many orders of magnitude (US NRC/NAS. 1984}. 9 . 1 . 3 . 2 Mesothelioma For both pleural and peritoneal mesothelioma, the incidence has been reoorted to be approximately proportional to between the 2.6th and 5th power of time since first exposure to asbestos, and to be independent of age or cigarette smoking habit. Such a model predicts that the ef feet._o_f .each day of exposure adds to overall incidence and is proportional to the intensity of exposure on that day. More formally.,., the predicted incidence rate (I), t years after ::st exposure, is proportional to t4-(t-d)4, where d is duration of., expesure .Peto et al. . 1982'. These predicted incidence rates are roughly proportional to the duration of exposure for a period of up to.5 or 6 years, but the effect of further exposure falls progressively. According to the model, there is little increase in risk after exposure lasting beyond about 20 years (Peto, 1983) . The suggested model for the prediction of mesothelioma incidence .I. is thus: 1 ' t, f = K x f _x M Lt 4 - ( t -d) 4 ) _______________ __________________ (2) where t_ denotes years since first exposure, f is the level of expo sure in fibre/ml, and d is duration of exposure in years. The constant K depends on the type of fibre and the distribution of M fibre dimensions of the asbestos. .. As with the lung cancer model, there are reservations with the mesothelioma model. Some of the uncertainties raised for lung cancer also apply for mesothelioma. Additionally, the dose- response relationship indicated bv the formula 'Equation 2) is not supported by all of the data available, and fibre types are not i - s t;:: g.sr.ed.___ Th_; s. last feature led the Task Group to the cor.ci-Sion that the K value, which has been generated from M~ ^montoo_e ana mixed fibre data, cannot be used for chrvsotile. ______The Task Group concluded that anv number generated (number of cases per million people) will carry a variation over many orders of.magnitude !For more information, see US NRC/NAS. 1984) . 9. 1.3. 3 Risk assessment based on incidence of mesotheliomas in ........Because of the many sources of uncertainty and consequent error i r. risk est mat len based on extrapolation, it_is necessary to reconsider the possibility of some more direct approach. The ir.ridence of ma 1 lonant mesothelioma is a relatively specific indicator of mineral fibre exposure. If observed in a standardized manr.er for a sufficient length of time and in a large enough population, this index could have considerable sensitivity. In particular, the incidence of mesothelioma in women, if combined with case-referent field studies to estimate the contribution of direct and indirect occupational factors, could be used to assess the risk of asbestos exposure in the general environment (section B'; . This approach was explored in recent analytical reviews bv Archer & Rom (1983) and McDonald (1985) . The industrial exploitation of asbestos began early in the present century and accelerated sharply during the period before and during the first wer id., war. Given the usual latency for mesothelioma of 20 - 40 Aui, it might oe expected to see the effects of asbestos exposure in the . 1950s. especially in men. There are several sets of data f:~- Canada, Finland, the United Kingdom^__and the USA, which show that....mortal lty ir. males is rising steeply '.up to 10% per annum) . wr.eieas 'women,., it is doubtful whether there is anv increase. Fir.ue mere is evidence, that both occupational and domestic exptsure account for some cases in women, there is little room left http://vvww.inchem.org/documents/ehc/ehc/ehc53.htm Page 89 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) for any material, effect attributable to general environmental expc s uie.__However, the. sensitivity of this approach needs to be evaluated. 9-1-4 Estimating the risk of gastrointestinal tract cancer 3eca.use_._of,. the, inconsistent findings on gastrointestinal tract cancers and lack of data on exposure-response, the risk for this disease cannot be estimated. 9.2 Other Natural Mineral Fibres _____ Despite the scanty epidemiological information on populations exposed to many natural mineral fibres, the results o laboratory research suggest that all mineral fibres of similar size, shape, and persistence, mav well carry the same or greater risks for man. Until there is information to the contrary, it may be prudent to m.ake this assumption. However, on the basis of available data, it can be concluded that some forms of fibrous zeolites (e.g., erionite) are particularly hazardous, causing mesothelioma in exposed populations 3 . 3 Conclusions 9.3.1... 1. Occupational risks ______Among occupational groups, exposure to asbestos poses a health hazard that mav result in asbestosis, lung cancer, and mesothelioma. The incidence of these diseases is related to fibre type, fibre size, fibre dose, and industrial processing. Adequate cor.trol measures should significantly reduce these risks. 9_. 3 . 1 .2 Para-occupational risks In para occupational groups, which include persons with household contact and neighbourhood exposure,__the risk of mesothelioma and lung cancer is generally much lower than for occupational groups. Risk estimation is not possible because of the lack of exposure data required for dose-response characterization. The risk of asbestosis is very low. These risks are being further reduced as a result of improved control practices. 9.3 .1.3 General population risks In the general population, the risks of mesothelioma and lung can per... at tributable to asbestos cannot be quantified reliably and : ::.uu*y de i et up 1 y lew. Cigarette smoking is the major etiological factor in the production of lung cancer in the general popu1at ion The risk of asbestosis is virtually zero. 5.3..2... Other mineral fibres ______On the basis of available data, it is not possible to assess the risks associated with exposure to the majority of other mineral fibres in the occupational or general environment. The only exception is erionite, for which a high incidence of mesothelioma in a.lpca.1 copulation has been associated with exposure. 11. PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES The carcinogenic risk of asbestos was evaluated in detail in December 19 7 6. by., an International Agency for Research on Cancer Working Group iIARC, 1977). and this evaluation was reconsidered in http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 90 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) .cy _ anocr.er Working Group , IARC, 1982, ___ The summary evaluation from the later monograph is reproduced here. 1."There was sufficient evidence for carcinogenicity to humans. ______Occupational exposure to chrysotile, amosite, anthophyllite. and mixtures containing crocidolite has resulted in a high incidence of lung cancer. A predominantly tremolitic material mixed with anthoohyllite and small amounts of chrvsotile also caused an increased incidence of lung cancer. Pleural and peritoneal mesotheliomas have been observed after occupational exposure to crocidolite. amosite, and chrysotile asbestos. Gastrointestinal cancers occurred in increased incidence in groups_ exposed occupationally to amosite, chrysotile. or mixed fibres containing crocidolite. An excess of cancer of the larynx was also observed in exposed workers. Mesotheliomas have occurred in individuals living in the neighbourhood of asoestos factories and crocidolite mines, and in people living with asbestos workers. Cigarette smoking and occupational __ exposure to asbestos fibres increase lung cancer incidence independent 1y when they, occur together, they act mult ipl icat_ively_" G} ARCy 1977: . I. "There was sufficient evidence for carcinogenicity to animals. _A.il types._of. commercial asbestos fibre that have been tested are carcinogenic to mice, rats, hamsters, and rabbits, creducing mescthe11gmas.and lung carcinomas after inhalation exposure and after administration mtrapleurally, i n.t rat racheal ly.t.. or int raperi toneal 1 v"__ } IARC, 1977x . 3. "There was inadequate evidence for activity in short-term tests. Asbestos was not mutagenic in Salmonella typhirnurium _____ or Escherichia coli (Chamberlain & Tarmv, 1977). It has been claimed to be weakly mugtagenic in Chinese hamster cells iHuang, 1979). but negative results in rat epithelial cells were published recently (Reiss et al., 1980). It has been .... reported that asbestos produces chromosomal anomalies in _____ mammalian cells in culture (Sincock & Seabright, 1975; Huang et al.. 1978), but this may be secondary to toxic damage. No increase in chromosomal anomalies was seen in cultured human ceils treated with asbestos (Sincock et al.. 1982). Sister chromatid exchanges were not increased in treated Chinese hamster cells (Price-Jones et al.. 1980). No data on humans ______were available." 10_. 2 ,__ CEC . .. in 197 7a group of experts evaluated, for the Commission of European Communities,__the public health risks of exposure to asbesccs :CEC, 1977} . The main conclusions of the report may be summarized .as follows: _____ bronchial carcinomas occur in asbestos-exposed workers, more or less independent of the type of asbestos: smoking increases the risk considerably; ____ larynx carcinoma may be associated with past asbestos ______exposure; evidence of a causal relationship is not proven; ______ gastrointestinal carcinomas have a slightly higher incidence in occupationally exposed workers, also in those with severe but short periods of exposure; the geographical distribution in the general population is not consistent with that of para-occupational and neighbourhood exposure ___ ______to asbestos; the incidence of mesothelioma is probably related to the ______ type of asbestos; an effect of smoking is not evident; ...tnere exist indications that intermittent even short-term __ _____ exposure mav suffice to induce a mesothelioma after a long http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 91 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) latent period; the prevalence of mesothelioma shows a typical geographical distribution increased in regions with shipyards, heavy industry, asbestos industry, and some asbestos mines (especially crocidolite); occurrence of mesothelioma is much more specific (although not absolute.' for previous asbestos exposure than _occurrence of the other malignant tumours mentioned above; u.ctt is general agreement that the risk of mesothelioma is fibre related in the order crocidolite > amosite > chrysotile > anthophyllite, but the magnitude of the dif ference .in risk is not well established; there exists a qualitative dose response relationship, insofar that.__in the occupational setting, the risk decreases with decreasing exposure; the intensity and/or duration of asbestos exposure necessary to induce a malignant tumour probably is the lowest/smallest in the case of mesothelioma; at present, there is no established evidence of general "true" environmental exposures of the public causing an increased incidence of asbestos-related tumours by inhalation or ingestion, but such a risk cannot be conclusively excluded on present evidence; there is no theoretical evidence for an exposure threshold below which cancers will not occur; ___ there is no consensus vet whether only fibres longer than 5 urn carry a biological risk, whereas the general public is exposed relatively much more to short fibres (< 5 ^m) : the relationship between short and long fibres varies widely with the source of the fibrous dust; and -i - - .ciown whether some groups or members of the general .public have a high susceptibility. .. .from yihis^ _i_t can be concluded that it is impossible to come to a re11able quanto-tatijye assessment of the risk of malignancies for the general ouplic: present evidence does not point to there being a..threshp 1 d _ 1 evei. of dust exposure below which tumours will never occur. It is very likely that there is a practical level of exposure below which it will be impossible to detect any excess mortality or morbidity due to asbestos, despite the presence of this mineral in the tissues, especially the lung. Thus, it is possible that there is a level of exposure (perhaps already scnieved in the general public) where the risk is negligibly small. REFERENCES ACQIH (1979) Asbestos identification and measurement. Proceedings of a Topical Symposium, Cincinatti. Ohio, American Conference of Governmental Industrial Hygienists. ACGIH .1983', Air sampling instruments for evaluation of atmcspheric contaminants. 6th ed., Cincinatti, Ohio, American Co r. f e r e n c e of Governmen tal Indust rial Hygienists. A1HE31N, S . C . & CARCNER, VL J_, __ Ai?.Z S_ The ill-effects of asbestos ;r. health, in-. Final Report of the Advisory Committe ~n Ashesi-s, London, Health and Safety Commission, Vol . 2. pp. 7 S3. ACHFTLN^ A,L_, & GARDNER, N!. J. (1983) Asbestos.- the control _ http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 92 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) 1 i;ni n for asbestos, London,. Health and Safety Commission. ALHESON, .0. , BENNETT, C., GARDNER. M.J-, & WINTER, P.D. .1951; Mesothelioma in a factory using amosite and chrvsotile asbestos... Lancet,__2 : 1403 -1405 . ACHES.0NL E.D.. GARDNER, M.J., PIPPARD. E.C.. & GRIME. L.P. .15321 Mortality of two groups of women who manufactured gas masks .from chrvsotile and crocidolite asbestos: A 40-year follow up.. ind. Med., 39: 344-348. ACHESON^JO.Jlu ^ GARDNER,. M.J., WINTER, P.D., & BENNETT, C. '1984) Cancer in a factory using amosite asbestos. Int. J. Epidemiol., 13: 3 -10. A FA ,1985' Report on dust measurement records to Asbestos Intematicnal Association, London, Association francaise de 11Amiante. AL3IN, M. JAKOBSSON. K., ENGLAENDER, V.. RANSTAM, J.. WELINDER, H. WESTRUP, C.. & MOLLER, T. (1983) Mortality and cancer morbiditv m a cohort of asbestos - cement workers. In: Proceedings of the 6th International Pneumoconiosis _ Conference, Bochum, 20-23 September, 1983. ALLI SON,__A,C. .1973) Experimental methods of cell and tissue culture: effects of asbestos particles on macrophages, mesotheiial cells, and fibroblasts. In: Boaovski, P., Gilson, ... .T ,mn i e 11, V. .__ & Wanner, J.C.. ed. Biological effects of asbestos. Proceedings of a Working Conference, Lyons, 2-6 October, 1972, Lyons. International Agency for Research on C a nee r,__pp_8 9 93 'IARC Scientific Publications No. 8). ALLISON, A . C . , HARINGTONJ .S. , & BADAMJ, D.V. ;i975; Xir.era* f ipies; chemical, physiochemicai and biological p r o c eities.__Auv. Pharmacol. Chemother., 12: 291-402. A.YA0HER , D.E.. ALARIF, A., & EPSTEIN, S.S. .1974' Effects of invested chrvsotile on DNA synthesis in the aastrointestinal tract and liver of the rat. Envi ron. Health Persvect., 9: 319-324. AXACHER, D.E.. ALARIF, A., Sc EPSTEIN, S.S. (1975) The dosedependent effects of ingested chrvsotile on DNA synthesis in the aastrointestinal tract. liver,__ and pancreas of the rat. Environ. Res. ,__10: 208-216 ANDERSON, H.A. .1983'. Family contact exposure. In: Proceedings of the World Symposium on Asbestos, Montreal, Canadaj .25-27 May, 1982, Montreal, Canadian Asbestos In.format ion. Centre, pp . 349-362. ANLFF\'N, H . A , L1LIS, R . . DAUM, &. SELIKOFF. I , J . _1_97S1 Asbestosis among household contacts of asbestos factory workers. Ann. NY Acad. Sci., 330: 387-399. ARCHER, J . E _ & ROM, W.N. (1983) Trends in mortality of d i f f u s,e . ma 1 igr.ant mesothelioma of pleura. Lancet, 2; 112-113. Ar:vNLI, Y. L_BARRIE, Y.I ..1979; Malignant mesotheliomas .u a small_.yillagge._in the Anatolian region of Turkey. J. Natl .Cancer , 6 3: 17 - 2 7 , ASBESTOS INSTITLTE . 19 7 9_. __ Annual report, Neuss, Federal Recur 1 ic of Germany^. _2.B._g_. asbestos INTERNATIONAL ASSOCIATION (1982? Reference method for the determination of airborne asbestos fibre http ://\vw\v. inchem. org/documents/ehc/ehc/ehc 5 3 .htm Page 93 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) _ concentrations at workplaces by light microscopy (Membrane Filter Method), London, Asbestos International Association, 14 dp (AIA Health and Safety Publication RTM No. 1) . ASBESTOS INTERNATIONAL ASSOCIATION (1984? Method for the determination of airborne asbestos fibres and other inorganic fibres by scanning electron microscopy, London, Asbestos International Association. (AIA Health and Safety Publication RTM No. 2;. ASBESTOS RESEARCH COUNCIL (1971) The measurement of airborne asbestos dust by the Membrane Filter Method. Rochdale. United Kinadom, Asbestosis Research Council (Technical Note No. 1). ASHCROFT, T. & HEPPLESTON. A.G. (1973) The optical and electron microscopic determination of pulmonary asbestos fibre concentration and its relation to the human pathological react,:;:-. U. Clin. Pathol., 26.: 224._2.3d AUERBACH, 0., HAMMOND, E.C.. SSLIKOFF. I.J., PARKS, V.R., KOSLCW. H0, & GARFINKEL, L. {1977) Asbestos bodies in lung parenchyma in relation to ingestion and inhalation of mineral : icers . Environ .... Res . , 14 : 286 - 304 . EAR. S , . ..jA Pleural mesotheliomas and asbestos pleurosis due to environmental asbestos exposure in Turkey. Hacettepe Bull. Med. Sura.. 8: 165-168. BARIS, Y.I. s1980; The clinical and radiological aspects of 185 cases of malignant pleural mesothelioma. In: Wagner. J.C.. ed Biological effects of mineral fibres. Proceedings of a Symposium held at Lyons. 25-27 September, 1979, Lyons, International Agency for Research on Cancer. Vol. 2, pp. 937-945 (IARC Scientific Publications No. 30). BARIS, Y.I, SAH1N, A.A. . OEZESMI, M,, KERSE. E.. 0E2EN, E., KCTACAN, ALTINOERS, M., & GOEKTEPELI , A. (1978) An ontbreak cf pleural mesothelioma and chronic fibrosing pleurisy in the village of Karain/Uerguep in Anatolia. Thorax, 33: 181 - 192 , BARIS, Y . I . L .ARTVINLI, _M_., & SAHIN, A.A. ; 1979' Environmental mesothelioma ln Turkey. Ann. NY Acad. Sci. , 330; 423-432 . BARIS, Y .1 SAH I_M ^ A.A. , & ERKAN, M . L .jl980.' Clinical and r ad p Ion real study of seoiolite workers. Arch. Environ. Healths 35j 343 - 346 . BARI Y . I . . SIMONATO. L., SARACCI . R.. SKIDMORE. J.W. & ARTVIMTI, M . : 158i;_.Malignant mesothelioma and radiological chest abnormalities in two villages in central Turkey. Lancet, 1: BARBER, R . M . .1978 ZecC i tes and clay minerals as sorbents and molecular si eves, London. New York. San Francisco. Academic Press, 497 pp. BAZAS. T.. BAZAS. B., KITAS, D., GILSON. J.C-, & MCDONALD. C.C.(1981) Pleural calcification in North-West Greece. Lancet, 2: 254. BEAMAN, D.R. & WALKER. H.J. (1978) Mineral fibre identification using the analytical transmission electron 'drcsocpe. In: Gravatt,. C.CU, et al. , ed. Proceedings of a . Workshop cn Asbestos: Definitions and Measurement Methods. Hash . n peer. DC, Nat local Bureau.. .o f_._ Standards, pp. 249-269 (NBS ip --r'^C.^CaliOr. No. 5 C 6 . . http:,, wwvv.inchem.org/documents/ehc/ehc/ehc53.htm Page 94 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) BEATTIE, J. & KNOX, J.F.(1961) Studies of mineral content and _ p article size dis tri but ion in the lungs of asbe stos. textile, workers_^... In; Davis., C.N. , . ed. _Inhaled particles and yappurSi._N.ew. York, Pergamon Press, pp . 419-433 . BECK, E .G.__ ' 1_9 8_0J Experimental pathology in vitro studies re1ated to asbestos and other mineral fibres. In: Wagner, J A3ed. Biological effects of mineral fibres. Proceedings of a Symposium held ac Lyons, 25-27 September, 1979, Lyons, International Agency for Research on Cancer, Vol. 1, pp. 3 8 5 4 0 0...' I ARC. Scientific Publications No. 30) . BECK, E.3. , BR'JCH, . J . L FRIEDRICHS,. K. -H. , HILSCHER, W. , & POTT, F. ,197; Fibrous silicates in animal experiments and re_ culture morpnoiogical c.e.1.1 and tissue reactions according to different physical chemical influences. In: Walton, W.H., ed. Inhaled particles. III. Proceedings of an International Symposium, London, 14-23 September,__ 1970, Old Woking. Surrey, Unwin. Vol. 1, PP. 477-487. 3ECK, E.G., HOLT, P.F., & MANOJLOVIC. N. (1972) Comparison of_.the effects on macrophage culture of glass fibre, glass powder, and chrvsotile asbestos. Br. J. Ind. Med.. 29: 280-286. BEGER, P,J, (1933) [On asbestos bodies and pseudoasbestos bodies.] Virchows Arch., 290: 280-353 (in German). BERRY, G. (1973) Hygiene standards theory and application. In: Bogovski, P., Gilson. J.C., Timbrell. V.. & Wagner. J.C.. ed.Biological effects of asbestos. Proceedings of a Working Tourerence* Lyons* 2-6 October, 1972, Lyons, International Agency for Research on Cancer, pp. 145-149 (IARC Scientific Pub1ications No 8). BERRY, G. '1981' Mortality of.workers certified by pneumccpniosis. medical .panels., as having asbestosis. Med., 38: :?0 137. Br. J. Ind. BERRY, G. & LEMINSOHN, H.C. (1979? Dose - response relationships for asbestos related disease: implications for hygiene s tan d a r ds .... P a r t_ _1_Morbidity .___ An n. NY Acad. Sci . , 330: 185-194. RF-FY, m. 5, NFWHCV9E, M.L. (1983.' Mortality of workers manyfaccuring fryc.tion materials using asbestos. Br. _J. Med. , 40j _1 7^ Ind. BERRY. G. & WAGNER. J.C. (1976) Effects of age at : roc til st.ipn or. occurrence. of. mesothelioma in rats.___ Int. J. Cancer,_ VI1 _477 . 3ERRY, G.. GILSON, J.C., HOLMES, S., LEWINSOHN, H.C., S.A. (1979) Asbestosis: a study of dose-response relationships in an asbestos textile factory. Br. J. Med., .3 6: 98 -112 . & ROACH. Ind. 3ERUFSGEN0SSENSCHAFTEN INSTITUTE FUR ARBEITSSICHEREIT (1985) [Saf_ety rules for dust generating handtools in contact with asbestos cement. 1 Hauptverb. Gewerbl. Berufsgenoss. Zh. . 1 April,1 : 616 (in German) . 3 35 .1 9,5 3.. Bri tish Seel ogi cal Survey world mineral statistics ia?a-6j: anmveisary issue. BI.GNGN, J, , GONI , J.. BONNAUD. G.. JAURAND. M.C., DUFOUR, G., u iN 3F 3N,_ M . C . .19 7C. Incidence of pulmonary ferruginous o.odies. m France. __Environ. Res., 3: 430-442. . N , _ . , J E::A_w I I T), _F..^. U GATE I CHET . _A.(19 7 8; http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 95 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Measurement of asbestos., retention in the human respiratory stem legated to nealth effects. In: Proceedings of the Workshop, on Asbestos.- Definition and Measurement Methods, July 1977, Gaithersburg, Maryland, National Bureau of Standards. pp 119 (National Bureau of Standards Special Publication 506.' . BIGNON,. ..J . t SEBASTIEN, Pw GAUD I CHET, A.. & JAURAND, M.C. '.1980!___ Biological effects of attapulgite. In: Waoner. J.C., edBiological effects of mineral fibres. Proceedings of a _Symposium held at Lyons, 25-27 September, 1979, Lyons, Internatlonal. Agency for Research on Cancer,__Vol. 1, pp. 163-181 (IARC Scientific Publications No. 30). BILES. B. & EMERSON. T. (1968? Examination of fibres in beer. Nature (Lond.), 219: 93-94. BLEJER. J.P. occupational 9 2 .3 7 .. & ARLON, P.F. (1973) Talc: a possible and environmental carcinogen. J. Occup. Med., 15: BOATMAN, E. ,1982! Analysis of urines from residents drinking water containing asbestos in the Pacific Northwest. Paper presented at the US EPA Summary Workshop on Ingested Asbestos, Cincinnati, Ohio, 13-14 October. BOATMAN, E.S., MERRILL, T., O'NEILL, A., POLISSAR, L., & MILLETTS. J.R. (1983) Use of quantitative analysis of urine to assess exposure to asbestos fibres in drinking-water in the Puget Sound region. Environ. Health Persvect., 53: 131-139, BOBYLEVA, A, T. BUKHANTSEVA, R.M., LOVTSOVA, S.E., & SADILOVA, the city of Asbest and its effect on children's health. envircn. Healthy 2: 727, Arch. 5QG0VSKI. P-, KUENG. A., & WINKMANN. F. (1982; [Phenols, ^"h^r components of oil shale tars .and asbestos as factors modifying the action of benzo( a )pyrene.1 Arch. Geschwulstforsch., 52: 49-55 (in German). BOHLIG, H. & HAIN, E. (1973) Cancer in relation to environmental exposure, type of fibre, dose, occupation, and duration.of exposure. In: Bogovski. P., Gilson, J.C., & Wagnert J.C., ed. Biological effects of asbestos. Proceedings of a Working Conference, Lyons, 2-6 October, 1972, Lyons, International Agency for Research on Cancer, dp, 217-221 (IARC Scientific Publications No. 8). BELTON, R.E. & DAVIS, J.M.G. (197$) The short-term effect of pro! o ng e d _ as b estos ingestion m rats. Ann. Occup. Hyg., 19: 121 128. BOLTON, R.E., DAVIS, J.M., & LAMB, D. (1982a) The pat biological effects of prolonged asbestos ingestion in rats. Environ. Res., 29: 134-150. 30ETON, R.E., DAVIS, J.M.G., DONALDSON, K., & WRIGHT, A. ,1982b) Variations, in the carcinogenicity of mineral fibres. V, Inhaled particles. Ann. Occup. Hyg., 26: 569-582. F-1 70 N, R.E. , VINCENT, J.H., JONES, A.D., ADDISON, J., & 1ELKETT, S.T. ,1983a. An overload hypothesis for pulmonary c .1 e a r a r.ce _ pf__..UIC C amosite fibres inhaled by rats. Br. J. Ind. Med., 40: 264 272. BOLTON, R.E., DAVIS, J.M.G., MILLER. B., DONALDSON, K., & WRIGHT (1983b; The effects of dose of asbestos on http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 96 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) mesothel iorra . product ion in the laboratory rat. In: Proceedings of zhe 6 th International Pneumoconiosis Conference, Bochum, Federal Republic of GermanyL 20-23 September, 1983,... Beraban 3erufsqenossenschaft, International Labour Office, pp. 1029- 1035 BONSER, G.M. & CLAYSON. D.B. (1967) Feeding of blue asbestos to rats. Br. Emp. Cancer Campaign, Res. Rep.. 45: 242. BOWES, D.R-, LANGER. A.M., & ROHL, A.N. (1977) Nature and range of mineral dusts in the environment. Phil. Trans. R. Soc. London A, 286: 593-610. BREEDING,,.. J L!1974' Potential hazard from eating rice rated a : t r. glucose and talc. J. Am. Med. Assoc., 228: 101. 3RJTISIH OCCUPATIONAL HYGIENE SOCIETY (BQHS):i968; Hygiene s tar.dard for chrvsotile asbestos dust. Ann. Occuo. Hyg. , 11: 47 59 . BRODY, A.R-, HILL, L.H:, ADKINS, B., & O'CONNOR, R.W. (1981) Chrvsctile asbestos inhalation in rats: deposition pattern and lie a r tier, of alveolar epithelium and pulmonary macrophages. Am. Rev. Eespir. Dis12 3p 670-679, BROWNE L K. !1983a^ Asbestos - related mesothelioma: epidemiological evidence for. asbestos as a promoter. Arch. srcOWNE, K_. ! 198 3b' The epidemiology of mesothelioma. Gccup. Med., 33: 189-194. J. Soc. BRUCKMANN, J. & RUBINO, R.A. (1975) Asbestos, rationale behind a proposed air quality standard. J. Air Pollut. Control Assoc. , 25: 1207-1215 . BURGER, B.F. & ENGELBRECHT, F.M. (1970) The biological effects of long and short fibres of crocidolite and chrysotile A after intrapleural injection into rats. S. Afr. Med. J., 44: 12 6 6. EURILKOV, T. & MICHAILOVA. L. '1970) so. 1 .and.. endemic pleural asbestosis . Asbestos content in the Envi ron . Res . , 3: 443-451 3YK0M, J.C., HODGSON, A.A., & HOLMES. S. 119691 A dust survey carried out in buildings incorporating asbestos-based materials m their construction. Ann. Occud. Hva., 12: 141-145 CANADA. ENVIRONMENTAL HEALTH DIRECTORATE (1979) A national ._survev for asbestos fibres in Canadian drinking-water, Ottawa, Environmental Health__Directorate, Canada. CANADA, .NATIONAL HEALTH AND WELFARE___'.1984) Rapport du comite d'exceizs charge d'ir.former le ministere de la sa_n.ee na cional e du bi en -etre social sur le fondement scientifigue des normes relatives a 1'amiante dans les milieux de travail, Ottawa. National Health and Welfare, CARTER. L.J. '1977; Asbestos: trouble in the air from Maryland Rock Quarry. Science, 197: 237-240. CARTER, R.E. & TAYLOR, W.G. (1980) Identification of a particular amphibole asbestos fibre in tissues of persons exposed to a high oral intake of the mineral. Environ. Res. 21: 65 93. cue .1977; Public health risks of exposure to asbestos, Oxford. Pergamon Press Ltd (Report of the Working Group of http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 97 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Experts to the Commission of the European Communities) (EUR 5 6 5 3 e CHAMBERLAIN, Y. & TARMY. E.M. (1977) Asbestos and glass fibres in bacterial mutation tests. Mu tat. Res., 43: 159-164. CHAMBERLAIN, M.. DAVIES. R-. BROWN, R.C-, & GRIFFITHS, D.M. (1982) In vitro test for the pathogenicity of mineral dusts. Ann. Occup. Hvq . , 26: 583 - 592 . CHAN, T.L. & LIPPMANN, M. (1980' Experimental measurements and empirical modelling of the regional deposition of inhaled particles in humans. Am. Ind. Hyg. Assoc. J. , 41: 399-409. CHATFIELD1 E . J_. il_982 ' Prospects for new methods of analysis and measurement cf_. fibres in environmental samples. In-. 7: "ceeJir.gs of the World _Sympos iigm on Ashes cos, Montreal,__ A::a i-i, If l"7 May, 1932, Montreal, Canadian Asbestos Information Centre, pp 401-418. CHATFI ELD, E.J. (1983) Measurement of asbestos fibre concent rations in ambient atmospheres (Report prepared for the Royal Commission on Matters of Health and Safety Arising from the Use of Asbestos in Ontario, Toronto, Ontario). CHATFIELD. E.J., GLASS, R.W., & DILLON. M.J. (1978) Preparation of water samples for asbestos fibre counting by electron microscopy, Athens, Georgia. US Environmental Protection Agency. 132 do (EPA Report No. 600/4-78 - 001, PB 2 8 C 18 3 ' CHERRY, J. (1983) An investigation of the reproducibility of counting and sizing of asbestos fibres by SEM. In: Proceedings of the 4th International Colloquium on Dust-Measuring Technicues and Strategy. Edinburgh, Scotland, 1982. CHURG. A. &. WARNGCK, M.L. ;i98Q) Asbestos fibers in the general population. Am. Rev. Respir. Pis., 122: 669-687. 1 LARK, R . L ... ^ 1982^_____ MSHA Standard method for fibre identirication by electron microscopy, Washington DC, National :: -fa a . c f r t dr.car ds.L cc . 2Q7-21Q . NBS Special Publication No. CLEMMENSEN. J. 5c HJAL1GRIM -JENSEN. S . tl981) Cancer incidence arr.gng 568.5. asbestos c ement workers followed from 1943 through 1976. J. Ecotoxicol. Environ. Saf., 5: 15-23. CLIFTON, R.A. 119 7 5 ' Asbestos. In: Minerals yearbook 1973, Washington DC, US Department of the Interior, Bureau of Mines, CD. 171-179. ~LIETCN, R.A. 193 0', Asbestos. In: Minerals yearbook 1978-1979. I. Metals and minerals. Washington DC. US Lecartment of the Interior. Bureau of Mines, dp. 91-101. CLI ETON, R.A. (1985) Asbestos. In: Mineral facts and .problems, Washington DC, US Department of the Interior (Bureau of Mines Bulletin No. 675). CCER IN,__ p L., PALEKAR, L.D., & COOK, P.M. '1982' Tumorigenesis by a ferroactinolite mineral. Toxicol. Lett., 13: 143 :8C: ,'CLE, D.A., STEVENS R.H. , & WILL, L. A. ''1982) Icent _ f icat icn of carcinogens by measurement of cell-mediated immunity.... .11__ Immunity to asbestos - induced rat peritoneal "e - : t r.e 1 i oma . Envi rgn. Res . , 28 : 77 - 83 http://www, inchem.org/documents/ehc/ehc/ehc53.htm Page 98 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) COHEN^_D_^_ ARAI, S-. & BRAIN. J.D, (1979) Smoking impairs long-term dust clearance. from_the lung.z Science, 204: 514-517. COX.VINS, B.TU , 1979i __ Asbestos in drinking-water: A review, Medmenham, United Kingdom, Water Research Centre, 36 pp (Water krsearm Tecunical Report TR_ 10 0,... Cali forma Bay area study. Presented at Che US EPA Summary _Workshop on _Inchested Asbestos, Cincinnati , Ohio, 13-14 October, 1982. CONFORTI, P.M., KANAREK, M.S.. JACKSON. L.A., COOPER, R.C., & MURCHIO, J.C. (1981) Asbestos in drinking-water and cancer in the San Francisco Bav Area: 1969-1974 incidence. J. Chron. Pis., 34: 211-224. CONSTANTOPOULOS, S.H., GOUDEVENOS, J.A., SARATZIS, N,. DANGER, A.X., SSLIKQFF, I.J.. & MOUTSOPOULOS, H.M. (1985? Metsovo luno: pleural calcification and restrictive lung function in Northwestern Greece and environmental exposure to mineral iibre as etiology. Environ. Res., 38: 319-331. COOK, P.M. (1983) Review of published studies on gut penetration by ingested asbestos fibres. Environ. Health Perspect., 53: 121-130. COOK, P.M. & OLSON, G.F. (1979) Ingested mineral fibres; elimination in human urine. Science, 204: 195-198. CO K, r , X . ,__GLASS, G .., &. TUCKER, J.H. ,1974,. Asbestiform tn'prnbcle "_iper a_l s : detection and measurement of high concentrations m municipal water supplies.__ Science, 185: S53 S55 . CIO PER, R . C... &. MURCHIO, J.C. :1974.` Preliminary studies of asbestiform fibres in drinking-water. In: Proceedincs of the Fifth Annual Conference on Environmental Toxicology, Dayton, Ohio, Wriaht-Patterson Air Force Base, Aerospace Medical Research Laboratory, pp. 61-73 (AMRL-TR-74-125) CRAIGHEAD, J.E. & MOSSXAN, B.T. (1982) The pathogenesis of asbestos-associated diseases. New Engl. J. Med., 306(24); 1446 - 1455 . CRALLEY,__L.J. .1971) Electromotive phenomenon in metal and mineral particulate exposures: relevance to exposure to -crest is and occurrence of cancer. Am. Ind. Hyg,, Assoc. J.. 32: 653-661. CRAPO, J.D., BARRY, B.E.. BRODY, A.R., & O'NEILL, J.J. 1950; Morphological, morphometric and microanalvtical studies_ on lung tissue of rats exposed to chrvsotile asbestos m inhalation chambers. In: Wagner, J.C.. ed. Biolopical effects of mineral fibres. Proceedings of a Symposium held at Lyons, 25-27 SeptemberL 1979, Lyons, International Agency for Re sea rch on Cancer, Vol . 1, pp. 273 - 283 ; IARC Scientific Pup1ications No, 301. IRA WEIRD, N.P. & COWIE, A.J. '1984; Quality control of ; - - -. i-ibie .v-tts in the United Kingdom: the pres e n t. .posit i on . _ _, Ann.__Occup. Hyg. , 28 : 391 - 398 . CUNNINGHAM, H.M. & PONTEFRACT, R.D. (1971) Asbestos fibres in beverages and drinking-water. Nature (Lond.), 232: 332. CUNNINGKAX, H,X_._^ MOODIE, C . A. , LAWRENCE. G.A.. & PONTEFRACT. http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 99 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) RJD. .\1977_L. Chronic effects of ingested asbestos, in rats . .Arch . Environ. Con tarn... Toxi col. , 6: _50.7 \ 513 ._ DAVIES,. R.__^19.80, The effect o mineral fibres on macrophages. _In: Wagner,__J.C.. ed. Biological effeccs of mineral fibres.__Proceedings of a Symposium held at Lyons, 25-27 September, 1979, Lyons. International Agency for Research on Cancer, Vol. 1, pp. 419-424 (IARC Scientific Publicat ions No. 30) . DAVIS, J.M.G. (1963) An electron microscopy study of the effect of asbestos dust on the lung, Br. J. Exd. Pathol., 44: A 54 . DAVIS,__j.M.G. (1964? The ultrastructure of asbestos bodies from human lung. Sr. J. Exp. Pathol45: 642-646. DAVIS... J.M.G. (1970) The long-term fibrogenic effects of chrysotiie and crocidolite asbestos dust injected into the pleural cavity of expenmental animals .Br. J. Exp. Pathol. , 51: 517. DAVIS, J.M.G. '.19711 Epithelial outgrowths from lung tissue foilowing intrapleural injection of asbestos dust in experimental animals. Int. J. Cancer, 7: 238-248. DAVIS,... J . M . G . . 1972 (__ The fibrogenic effects of mineral dust ircectec into the pleural cavity., of...mi_ce^.__Br. J. Exp. Pa t hoi. , 5 3 : 19 3. DAVIS,__J.M.G..1979! Current concepts_____in asbestos fiber Pathogenicity. In: Lemen, R. & Dement, J.M, ed. Dusts and di sease, Park forest.. South, Pathotox Publishers Inc. DAVIS, ._J.M_._G, (1981' The biological effects of mineral fibres. -Ann. Occup. Hyg. , 24: 227. DAVIS, J.M.G. & GROSS. P. (1973) Are ferruginous bodies an ;ndication of__atmospheric pollution by asbestos? In: Bogovski, ?. ,__GiIson, J.C., Timbrell, V., & Wagner, J.C., ed. Biological effects of asbestos. Proceedings of a Working Conference, Lyons, 2-6 October, 1972, Lyons, International Agency for Research on Cancer, pp. 328-242 (IARC Scientific Publications no^_..8;_, DAVIS, J.M.G,, BECKETT,.. S.T., BOLTON, R.E., CODLINGS, P., & MIDDLETON,. A.P.(1978; Mass and number of fibres in the pathoger.esis. of asbestos related lung disease in rats. Br. J. Cancer L 37 :_ 673-688.. DAVIS, J.M.G., BECKETT, S.T., BOLTON, R.E., & DONALDSON, K. A comparison of the pathological effects in rats of "he OTCC reference samples of amosite and chrysotiie collected rom the factory environment. In: Wagner, J.C., ed. Biological effects of mineral fibres, Lyons, International Agency for Research on Cancer. 285 pp (IARC Scientific Publication No. 30. . DAVIS, . J.M,G^ BECKETT, S.T., BOLTON, R.E., & DONALDSON. K. -1980b' The effects of intermittent high asbestos exposure (peak dose levels) on the lungs of rats. Br. J, Exp. Pathol., 61: 272-280. DAVIS,_ fh M.G., ADDISON, J., BOLTON, R.E., DONALDSON, K., JONES,. A. D . ,__ & SMITH. T. (m press) The pathogenicity of Iona versus short fibre samples of amosite asbestos administered to rats by inhalation and intraperitoneal injection. Br. J. Exp, Pathol. http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 100 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) DEMENTJ. M. HftBRTR. R.L.. SYMONS. M.J.. 5, SHY, C. (1982) Estimates of dose-response for respiratory cancer among chrvsotile asbestos textile workers. In; Walton. W.H., ed. Inhaled darticles. V. Proceedings of an International Symposium, Cardiff, 8-12 September, 1980, Oxford, Pergamon Press, pp. 869-883 ( Ann. Occup. Hyg., 26: 869-887). [)_r_XQN, R.N. & TAYLOR, C.J. (1979) In: Johari, 0., ed. _Asbestos fibre counting by automatic image analysis. Scanning electron microscopy, SEM Inc., AMF 0 1 Hare , pp_.__3 61.-_366__ (JL 0CLEA _R^__ ; 1955' Mortality from lung cancer in asbestos workers. 3r. J. Ind.. Med. , 12 : 81 -86 . POLL, R.. & PETO, J. ;i985)_____ Effects on health of exposure to asbestos, .Vendor., United Kingdom Health and Safety Commission, Her Majesty;_s Stationery Office. DON'HAM, K.J., BERG, J.W.. WILL. L.A., & LEININGER, J.R. ,1960. The effects of long-term ingestion of asbesto.s_._on the ccTcr. of F 344 rats. Cancer, 45: 1073. OOUEE, __J . , KEAASSEN , . C . D., & AMDUR , M.O., ed . ;1980) Casaretc and Doull's toxicology. The basic science of poisons, 2nd ed., New York. MacMillan Publishing Co., pp 1-778. DUNNIGAN. J. (1982) Modification of asbestos fibres; biological considerations. In: Proceedings of the World Symposium on Asbestos, Montreal, Canada, 25-27 May, 1982, Montreal. Canadian Asbestos Information Centre, pp. 390-394. ElSEN3ERG, W.V. (1974' Inorganic particle content of foods and drugs.Environ. Health Perspect., 9: 183-191. FEMES, P.C. S SIMPSON, M.J.C. '1977} Insulation workers in Belfast. A further study of mortality due to asbestos exposure .1540 75:. Br. J. Ind. Med., 34: 174-180. ENGSL3RECHT, F.M. &. BURGER, B.F. (19751 Mesotheliai reaction to asbestos and other irritants after intraperitoneal infection. S. Afr. Med. J49: 87-90, FNTEELINEP_^.E ,_ & HENDERSON, V. (1973) __ Type of asbestos and respiratory can cer_in the asbestos industry. Arch. Environ. Health, 27: 3 12;.- 317. EPSTEIN, S.S. & VARNES, M. (1976) The short-term effects of ingested chrvsotile asbestos on PNA synthesis in the pancreas and other organs of a primate. Experientia (Basel), 32: 602 -604 . ERDR5ICH, L.S. (1983) Comparing epidemiologic studies of ingested asbestos for use in risk assessment. Environ. Health Perspect., 53: 99-104. EUROPEAN ECONOMIC COMMUNITIES (1983) Council directive on the protection of workers from the risks related to exposure to a $ bps t os. at. work, Brussels, EEC. FEARS, T.R. [1976) Cancer mortality and asbestos deposits. Am. J. Epidemiol. ,__ 104(5): 523 -526. FEEEERMEYER, w. '1583) [VDI Conference on fibrous dusts: neas-rement, effect, correction. Strassbourg, 1582.] . YkJ- - eeri ch te, 475: 143-146 'm German) . http ://ww\v. inchem.org/documents/ehc/ehc/ehc53.htm Page 101 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) FELBEKMAYER, W, & USSAR, M. (1980) fEnvironmental damage by di smtegrazion of asbestos cement sheeting under~ che i nfl uence of__bhe weather, ] Leoben, Austria,__ Institute for UmweItschutz and Emissions fragen jin German). FINKELG7EIN, M .M.. .198 31___ Mortality among long-term employees f asbestos cement factory. Br. J. Ind.._Med._.j._.40_i -c FI M . B .. &_ HALLENBECKt__ W_. H. ;1985) Detection of chrysotile asbestos m workers' urine. Am. Ind. Hyg. Assoc. J., 46: 162 169. ?X3CHBE_IN A, , ROHL, A.N., DANGER, A.M., & SELIKOFF, ._197S____ Dry wall construction and asbestos exposure. Hyg. Assoc. J., 40: 402. I.J. Aw. Ind. FQERSTER, H. (1983) [Natural fibre emissions in the Federal Renublic of Germany.1 VDI-Ber., 475: 373-376 (in German). FOWLER. D.?. : 1977) Disposal and emission of asbestos in the USA, Menlo Park, California. Stanford Research Institute. FRIEDRICHS. K.H. (1983) fVDI Conference on fibrous dusts: tneasurement, effect, correction, Strassbourg, 1982.1 VDI-Berichte, 475: 113-116 fin German). GAENSLER, E.A. & ADDINGTON. W.W. (1969) Asbestos in f errugir.ous bodies.___New Engl. J. Med., 280: 488-492. GALE, E.W. & TIMBRELL, V. .1960. Practical application of niir.e: : c. a 1 ignment .of. rnir.eral _.f :bres_ .for., hazard evaluat ion . I r.; Viagr.er, G.C-, ed. Biological effects of mineral fibres. Proceedings of a Symposium held at Lyons, 25-27 September. 197 9, Lyons ,__International Agency for Research on Cancer. Vol, X,. p . S3 -60. 'IARC Scientific Publications No. 30; . GARDNER, .M . J ._ ;19S3. Tumour incidence after asbestos exposure in Great Britain with special reference to the cancer risk of the r.on-occupational population. VDI-Ber., 475: 165 - 19 (D GACDICHET, _ A., , SEBASTIEN,__P_! . CLARK. N.J.. & POOLEY, F.P. ..i 96 0. I dent; f i cat ion and quant ification of asbestos fibres in. human tissues. In: Wagner, J.C., ed. Biological effects of mineral. fibres.,.. Proceedings of a Symposium held at Lyons, 25-27 September, 1979, Lyons, International Agency for Research on Cancer, Vol. 1, pp. 61-68 (IARC Scientific Pub1icat ion No. 30) . GAZE, R. (1965/ The physical and molecular structure of asbestos. Ann. NY Acad. Sci., 132; 23-30. GI3BS, G.W. (1979? Etiology of pleural calcification: a study of Quebec.chrysotile asbestos miners and millers. Arch. env_i_ron . Heal 34j 76 - 8 3, GI_BBS_, G.W. & HWANG, C Y_.__;1980' Dimensions of airborne asbestos fibres... In: Wagner, J.C.. ed.___Biological effects of minera 1_ fibres Proceedings of a Symposium held at Lyons, 25 2~ September, 1979, Lyons. International Agency for Research on Cancer^ Vol. 1. pp, 69-78 ;1ARC Scientific Publ i cat icr.s No .__3 0). GI_BEL, W., LQHS. K., HORN, K.-H., WILDNER, G.P., & HOFFMANN. F. . ,.l?76j [Experimental studies on the carcinogenic activity of asbesc c. s fibres.]. _ .A rch Geschwuls t borsch., 46: 437-442 -in German. . http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 102 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) GLOYNE, _S_. R. . ,19_35_. Two cases of squamous carcinoma of the lung occur mg m ..asbestosi s.. Tuberculosis, 17: 5. GORMLEY, I.P., BROWN. R.C.. CHAMBERLAIN, M., & DAVIES, R. Hvg , 23: 225 -228 . GRAHAM, S. i!981) Methodological problems in ecologic studies of the asbestos - cancer relationship. Environ. Res., 25: 35-49. GRAHAM, S., BLANCHET, M., & ROHRER, T. (1977? Cancer in asbestos-mining and other areas of Quebec. J. Natl Cancer . Inst. , 59 'A ) : 1139 -1145 GREGOR. A.. PARKES. R.W.. AU BQIS, R., & TURNER-WARWICK. M. ;i979' Radiographic progression of asbestosis: preliminary report . .Ann. NY Acad. Sci . , _330 : 147 - 156, lEOGS, P. & HARLEY, R.A. !1973) Asbestos - induced mcrathoracic tissue reactions. Arch. Pathol., 96: 245-250. GROSS, P., TREVILLE, R.T.P. De, TOLKER, E.B-. KASCHAK. M., & BAB YAK, __M. A_.___A967) Experimental asbestosis. The development of Tung cancer in rats with pulmonary deposits of chrvsotile asbestos dust. Arch. Environ. Health, 15: 343-355. GROSS. ?., RUSSEL, A., HARLEY, R.A., SWINBURNE, L.M-, DAVIS, J . m . , &. GREENE, _W_,3 1974; Inoested mineral fibers. Do they petetrate tissue or cause cancer?__ Arch. Environ. Health, 29: iu; 14c. GEQTK, D.H., KOMMINENI, C., & MACKEY. GR (1980) Carcinogenicity of beryllium hydroxide and alloys. Res , 21: 63 -84 . Environ. GYLSETH. B.. BAUNAN. R.. & BRUUN, R. (1981) Analysis of morganic fiber concentrations in biological samples by scanning electron microscopy. Scand. J. Work environ. Health, 7: 101-108. HAHON, N. & ECKERT, H.L. (1976? Depression of viral interferon induction in cell monolayers by asbestos fibres. Environ. Res. , 11: 52 -65 . HAHON, N... BOOTH, IA. , BOEHLECKE. B.A., & MERCHANT. J.A I960 Enhanced viral interferon induction by the mineral wollastonite. J. Interferon Res.. 1: 49. HAHN, E. , DALO'GEN, P., BOHLIG, H., DAHBERT, A ., & HING, I . 1974 Rescrosoective studv of 150 cases of mesothelioma in Hamburg area. Int. Arch. Arbeitsmed., 33: 15 -37 . HALLENBECK. W.H. & PATEL-MANDLIK. K.J. (1979) Presence of fibres in the urine of a baboon aavaaed with chrvsotile mueslis. Environ. Res.. 20: 335-340. tlALLEN3ECKt_ W.H., CHEN, E.H., HESSE. C.S., PATEL-MANDLIK, K., i w^lFF, A . H . . 197 SIs chrvsotile asbestos released from asbestos-cement pipe into drinking-water? J. Am. Water Works As see, _ 7 0 : J7 102 . HAMMONS, E.C , SELIKOFF, I.J., & SET OMAN, H. (1979) Asbestos exposure, cigarette smoking, and death rates. Ann. NY Acad. Sci , 330: 473 -490 . HANKE, W., SEPULVEDA, M.J., WATSON, A., & JANKOVIC. J. http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 103 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) 1984) Respiratory morbidity in wollastonite workers. ind. Med., 41; 474-479. Br, J. HARINGTON, J.S. (1962) Natural occurrence of oils containing 3.4-benzpyrene and related substances in asbestos. Nature (Lond.) . 193: 43-45 . HARINGTON, J.S. (1981) Fiber carcinogenesis: epidemiological :bservat:cr. and the Stanton hypothesis.___ J. Natl Cancer Inst., 67: 977 - 989 . HARINGTON. J.S., ALLISON, A.C., & BADAMI, D.V. (1975) Mineral f ibre.s :. chemical, ohvsico chemical, and biological proper ties... Adv. Pharmacol. Chemo ther. , 12: 291-402. HARRIES, ?.G. 1968' Experience with asbestos disease and its control in Great Britain's naval dockyards. Environ. Res., 11: 261-267^ HARRINGTON, . CRAUN, G.F.. MEIGS. J.M.. LANDRIGAN, P.J., FTANNERY, J.7., & WCODHULL, P.S. ,1978) An investigation of :: asbestos cement pipe for puciic water suppl.y_and ire mlicence of gastrointestinal cancer m Connecticut __9 5_5 7 3... Am. J. Epidemiol., 107:__ 96 . HARLOW. G.5., KIMBALL. M.R.. DOWTY. E.. & LANGER, A.M. '1985) Observations on amosite/grunerite dusts. In: Proceedings of the 2nd International Congress on Applied Mineralogy in the Minerals Industry, Los Angeles, California, 22-25 February, 1984. California. The Metallurgical Society of HARRIES. F.G. (1968? Asbestos hazards in naval dockyards. Ann . _ __Occujd ^ Hyg. , 11: 135-145. HARRIS, R,L. & FRASER. D.A. (1976) A model for deposition of liners in the human respiratory system. A/n. Ind. Hyg. Assoc. J. , 37 ; 73 -89. HARVEY. G.. PAGE, M.. & DUMAS. L. '1984) Binding of environmental carcinogens to asbestos and mineral fibres. J. Ind. Med., 41: 396-400. Br. HARWOOD. C. & BLASZAK, T. >1974) Characterization and control of asbestos emissions from open sources. Research Iiiangle Pair,_North Carolina, US Environmental Protection Agency, 195 pp EPA Report No. 650/2 -74 - 090, PB 238925; . HAS LAN, P.L., LVXOSZEK, A., MERCHANT, J.A., & TURNER WARWICK., . l ? 7 6 . wVinpnGcvte responses to phytohaenagalumn m patients with asbestosis and pleural mesothelioma. Clin. Exp, immunol 31: 173 188. HEALT H AND SAFETY COMMISSION (1979) Asbestos volume 1: final report of the advisory committee, London. Her Majesty's Stationary Office. HEFFELFINGER. R., MELTON. C., St KIEFER, D. (1972) Development of a rapid survey method of sampling and analysis for asbestos in ambient air. Research Triangle Park. North Carolina, US Environmental Protection Agency. 4 pp (Report No. HEFNER.,R . . & GEHRING. P.J. (1975) A comparison of the r e*a: :ve rates of nemo lysis induced by various fibroaemc and pcn_fibrogenic particles with washed rat erythrocytes in vitro. Am. Ind. Hyg. Assoc. J., 36: .734.. http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 104 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) HE ID ERMANNSL_ G..(1969? fHazard of silicosis bv the technical usage of finelv grained materials.1 Staub-Reinhalt. Luft:, 2 9(2? : 4 5 - 48 (in German). HEIDERMANNS, G. '1973/ [DeterminaCion of asbestos content through optical and chemical analysis procedures, radiography ana infra red soectrographv.1 Scaub-reinhalt. Luft, 2: 66-70 tin German . HENDERSON, V. I . Sc ENTERLINE, P.E. (1979) Asbestos exposure: factors associated with excess cancer and respiratory disease mortality. Ann. NY Acad. Sci., 330: 117-126. HEPP LE STON . A.G. 6 STYLES. J.A. (1967! Activity of a tatrcpr.age factor in collagen formation bv silica. Nature (Lond.) , 214: 521-522. HEXT, P.M. , HUNT, J.. DODGSON, K.S., & RICHARDS, R.J. (1977) ihe effects of lona-term exposure of lung fibroblasts strains to chrysotile asbestos. Br. J. Exp. Path., 58: 160-167. HILDING. A .C., HILDING, D.A., LARSON, D.M.. & AUFDENHEIDE, A.C. (1981 ) Biological effects of ingested amosite asbestos. tacomte t. ailings, diatomaceous earth, and Lake Superior water m rats . Arch. Environ. Health, 36: 298. HILL. J.W.. ROSSITER, C.E.. & FODEN. D.W. (1984) A Dilot respiratory study of workers in a MMMF plant in the United Kingdom. In: Biological effects of man-made mineral fibers, Proceed in qs of a WHO/IARC Conference, 20-22 April, 1982, Copenhagen , World Health Organization, Vol. 2, dp. 413-419. H055S, M.S -T.. WOODWARD, S.D., MURPHY. B.. MUSK. A.W., & ELDER, J.E .1980' The incidence of pneumoconiosis. mesothelioma, and other respiratory cancer in men engaged in ".u.u'.j ana milling crocidolite in Western Australia. In: Waar.er. J.C., ed. Bioloaical effects of mineral fibres. Proceedings of a Symposium held at Lyons, 25-27 September, 1979, Lyons, International Agency for Research on Cancer, Vol. 2 , pp. 61c 62" (TARC Scientific Publications No. 3Q)_. HOLT, P.F. 1982 r wail. Translocation of asbestos dust through the Environ. Res., 27.2. : 255 260. HOLT, P.F. . MILLS. J., & YOUNG. D.K. (1964) The early effects of chrysotile asbestos dust on the rat lung. J. Pathol. Bacterid.. 87: 15-23. HOLT, P.F. . MILLS. J.. & YOUNG. D.K. (1965) ExDerimental asbestosis with four types of fibre: importance of small particles. Ann. NY Acad. Sci.. 132s: 87. HOLT, P.F. . MILLS. J.. & YOUNG. D.K. (1966) ExDerimental asbestosis in the guinea-oia. J. Pathol. Bacterid., 92: 185. HR0M2K. J. (1962) The mass incidence of characteristic pleural changes in citizens of the western part of the former Juhlava region.___ Rozhl. Tuberk., 22: 405-415. HUANG, S.L. (1979) Amosite, chrysotile, and crocidolite ascestos are .mutagenic in_ Chinese hamster lung cells. Mu tat. Res. , 68 :__ 2 6 5 - 274. HUANG, S, _L. _L SAGGIORO, D., MICHELMANN. H., & MALLING, H.V. 115 7 3; Genet 1c effects of crocidolite asbestos in Chinese namster lung cells Mutat. Res., 57: 225-232. HUGGINS, CUW., DENNY, M.V., & SHELL, H.R. (19621 Properties http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 105 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) of pa 1ygorskite,__an asbestiform mineral, Washington DC, department of the Inferior. US Bureau of Mines (Report of Investigat Ion 6 07 1) . HUGHES,_ J. St WEILL, H. {1980) Lung cancer risk associated wit h _manu facture of asbestos - cement products. In: Wagner, ed . 3iological effects of mineral fibres.__Proceedings of -a. Symposium held at Lyons, 25-27 September, 1979, Lyons, International Agency for Research on Cancer. Vol 2, pp. 6 2 7 -6_35._LiARC Scientific Publications No. 30). HUM PHRE Y, E.W., EWING, S.L.. WRIGLEY, J.V., NORTHRUP, W.F., keesten,._ t,e, , mayer,. . j.e., & vargo, r.l. ;i98i) The production of malignant tumors of the lung and pleura in dogs from intratrachea1 asbestos instillation and cigarette smoking . __ Cancer,__ 47.8): 1994-1999. HURLBLUT, C,S. 11971)____ Dana's manual of mineralogy,__ 18th ed., N'ew York,.. John Wiley and Sons, 579 pp. HUUSKpNEN, M.S,^._ RAESAENEN, J.A.. HAERKOENEN, H., & ASP, _._157s____ Asbestos exposure as a cause of immunological stimulation. Scand. J. Respir. Pis., 59: 326-332. S. HUUSKPNEN, M. .S., TOSSAVAINEN, A., KOSKINEN, H., 2ITTING, A., KORHQNEN- 0.. NICKELS. J.. KORHONEN, K., & VAARANEN, V. , 1983a.: Wollastonite exposure and lung fibrosis. Environ. Res. , 30 : 291-304. HUUSKPNEN, M . S .., JAERVISALO, J-, KOSKINEN, H. . NICKELS, J.. RAESAENEN, J . . t ASP. S. f1983b) Preliminary results from a cohort of workers exposed to wollastonite in a Finish I:~estcne quarry. Scand. J Work environ. Health, 9: 169- 175. I ARC ) 1577) Asbestos, Lyons, International Agency for Research on Cancer. 106 do (IARC Monographs on the Evaluation of Csroincgeni c_Ri.sk of. Chemicals to Man, Vol.__14) . o.RC .1582, _ Chemi ca_l s, industrial processes and industries _ associated with cancer in humans. Lyons. International Agency for. Research on Cancer, Suppl. 4, p. 52 \IARC Monographs on tre. Evaiu.at.ion . of. Carolnoger.ic Risk of Chemicals to Man, ICC .1 934. _ Safety i_n the use of asbestos, Geneva. I rt'-: Labour Office, ca .__120 pp . I LO Code of__Practice' . inoustrial minerals {1973) Vol. 133,....pp, 1 _9_-_31 . Mineral fibres: a review, London, I NSC: CUTE. FOR.. APPLIED FIBROUS DUST RESEARCH :i984) reports,__Neuss, Federal Republic of Germany. Test I SO '1981) Si2e definitions for particle sampling: recommendations of ad hoc working group appointed by Committee TC.146_cf_ the International Standards Organization. Am. Ind. Hyg. Assoc. J., 42: A/64-A/68. I SO..1584) Proposed analytical method for determination of asbestos fibres in air, Geneva. International Standards 'T roar, i zat i on . JACOBS, R . , COPGSCNj___K .. S . ^ _RI CHARDS , _R . J ) 19_7 7_) A preliminary study of biochemical changes m the rat small . r ;es t.i r.e_ foil owing long term inges cion of__chrvsot l le asbestos. Br. J. Exp. Pathol. , 58: 541-549. JACOBS.,.. R , HUMFHRYS, S.. DOGSON, K.S., & RICHARDS, R.J. http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 106 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) 19"7?. Light and electron microscope studies, of the,rat digestive tract following prolonged and short-term ingestion of__chrysotile asbestos . Br. J.__Exp. Pathol., 59: 443-453. JACOBSON,. M;MILLER, B.G.. & MURDOCK. R.M. (1984) Experience with the ILO 11980) classification in an epidemiological study of asbestos workers' chest radiographs. In: Proceedings of the Vlth International Pneumoconiosis Conference. Bochum, Federal Republic of Germany, 1983, Berobau-Berufsaenossenschaft. do. 868-881. JAGATIC, J.. RUBNITZ. E., GODWIN, C., & WEISKOPF, W. (1967) Tissue response to intraoeritoneal asbestos with preliminary report of acetate toxicityof heat-treated asbestos in mice. Environ. Res., 1: 271-230. JAURAND, M.-C., MAGNE, L., 5, BIGNON, J. (1983) Mechanism of haemolysis bv chrvsotile fibres. Toxicol. Lett., 15: 205-211. JOHN, W., BERNER, A., SMITH, G., & WESOLOWKI, J.J . (1976) Experimental determination of the number and size of asbestos fibres in ambient air. Sonnafield. Viramia. US National Technical Informat ion Service. ~.NLuS, _ .S . ? . , ROBERTS, G.H. . POOLEY. F.D. . CLARK . N . J . , SMITH, P.G.. OWEN, W.G., WAGNER, J.C., BERRY, G., & POLLOCK, D.J. 1980' The pathology and mineral content of lungs In cases of mesothelioma in the United Kingdom in 1976. In: Wagner, J.C.. ed. Bioloaical effects of mineral fibres. ProceedinQs of a Symposium held at Lyons, 25-27 September, Lyons, International Agency for Research on Cancer, Vol. 1. pc. 187-199 (IARC Scientific Publications No. 30) . JONES, R.N., DIEM. J.E.. GLINDMEYER. H.. & WEILL. H. (1980! Progression of asbestos radiographic abnormalities: rel.at ions hips to estimates of dust exposure and annual decline in 1 ur.a function. In: Wagner, J.C., ed. Biological effects of mineral fibres. ProceedinQs of a Symposium held at Lyons, 25-27 September, 1979, Lyons. International Agency for Research on Cancer, Vol. 2, pp. 537-43 (IARC Scientific Publications No. 30). KAGAN, E. (1980) The alveolar macrophage: immune derangement and asbestos - related malignancy. Sem. Oncol., 8(3): 258-267. KAGAN, E., SOLOMON, A., COCHRANE, J.C., BEICHSNER, E.I.. G LG G KMANN t__ ROCKS , P.H., & WEBSTER, I. (1977a: I.mmunc 1 oaical studies of patients with asbestosis. 1. Studies of ceil mediated immunity,.. Clin, Exp. Immunol., 28: 261 -267. KAGANj. E, J___SOLOM_ONJ..._A . , COCHRANE, J.C., KUBA, P., ROCKS, P.H., Sc. WEBSTER. J. '1977b: Immunological studies of patients with asbestosis. II. Studies of circulating lymphoid cell number ar.a humoral immunity. Clin. Exp. Immunol., 28: 268-275. KANAREK. M.S.. CQNFORTI, P.M.. JACKSON. L.A.. COOPER. R.C.. & MCECH10, JC. ; 19 8 0 Asbestos in drinking-water and cancer incidence m the San Francisco Bay Area. Am. J. Epidemiol., 112: 54 - 72. KANAREK, M.S., CONTORT I , . ?, M . , .. Sc JACKSON, L . A . (198K r y-r t : - e asbestos ficers ir. drinking water from a.see st cs -ceme n t pipe ^. Environ. Sci. Technol . , 15: 923 -925. KANG,,. K.-Y., SERA, Y., OKOCHI, T., & YAMAMURA, Y. (1974) T_lymphocytes in asbestosis. New. Enal. J. Med., 291: 735-736, KAJFMANN, R., HILLENKAMP. F., & WECHSUNG, R. (1979) The http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 107 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) 1 aser nicroprobe mass analyser (LAMMA) . 6: 109-121. Med. Proar. Technol , KAY, G.H. (1974) Asbestos in drinking-water. Works Assoc., 66: 513-514. J, Am. Water KEENANR.G & LYNCH, J.R. 11970) Techniques for the detection, identification, and analysis of fibres. Am. Ind. Hvq. AssoC J , 31: 587-597. KIM, W.S., CARTER, J.W., & KUPEL, screenina test for asbestos. Am. 15c 201. R.E. Ind. ',1981) _ Quick Hvg. Assoc. J. . 42: KIVILUOTO, R- (I960; Pleural calcification as a roentgenologic sign of non-occupational endemic anthcphyllite asbestosis. Acta radiol.. 194(Suppl.): 1-67. KIVI lj'JOTO , R . , MEURMAN, L.O. , & HAKAMA, _ M . Q197 9J_ Pleural p.^c-es and neeplasia m Finland. Ann. NY Acad. Med., 330: KNOX , J.F., HOLMES, 5. , DOLL, R. , & HILL,. I . D . 11.96 8Q Mortality from lung cancer and other causes among workers in an asbestos textile factory. Br. J. Ind. Med.. 25: 293-309. KOLEV,__K. (1982) Experimentally-induced mesothelioma in white rats in response to intraperitoneal administration of amorphous crocidolite asbestos: preliminary report. Environ. Res., 29: 123-133. KORHONEN, K. & TOSSAVAINEN, A. (1981? FWollastonite - a fibrous industrial mineral.! Finnish). Vuoriteollisuus, 39: 38 -45 (in KOSKINEN. H., JAERVISALQ, J., HUUSKONEN, M.S., KOIVULA, T., MUTANEN, P., & PITKAENEN. E. (1983) Serum lysosomal enzyme activities l.n silicosis and asbestosis. Eur. J. Resp. Pis., 64: 182-188. KRAMER. J., MUDROCH. 0.. & TIHOR, S. (1974) Asbestos in the environment, Burlington, Ontario, Research Advisory Board. International Joint Commission and Environment Canada, 50 pp. KuSCKNEE,M., LEE, R., ROBECK, G.G., ROSSUM, J.R., SCENE ILERMANN, M.A., & TAYLOR, E.W. -1974) A study of the crcoler. cf asbestos in water. __J. Am. Water Works Assoc. , 66; LAA.MANEN, A.N., NORC, L.. & RAUNIO, V. -1965) Observations on atmospheric air pollution caused bv asbestos. Ann. NY. Acad. Sci . . 132: 240-251. LAFUMA, J.. MORIN. M.. PONCY. J.L.. MASSE, R.^ HIRSCH. A.. BIGNON. J.. 4 MONCHAUX. G. (1980) Mesothelioma induced by intrapleural iniect.ion of different types of fibres in rats; synergistic effect of other carcinogens. In: Wagner. J.C.. ed. Biological effects of mineral fibres. Proceedings of a Symposium held at Lyons, 25-27 September, 1979, Lyons, Ir.ternational Agency for Research on Cancer. Vol. 1. pp. 3 1 1 320 (IARC Scientific Publications No. 30) LAKOWICZ, J.R. & BEVAN, D.R. (1980? Benzo ( a ?pyrene uptake into rat liver microsomes: effects of adsorption of benzo, a .pyrene to asbestos and non-fibrous particulates. Chem.~biol. Interact., 29: 129-138. LANJE, A._ .. .--I,___ An epidemiological survey of immunological http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 108 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) abnormal11ies in asbestos worXers^. 1. Nonorgan and a...:. :.;laa;cant icodies . _ E/tvi ron . Res . 2 2 :. ,._162L.,_1C7_5... LANGE, A119821___ Anergy and autoimmuni ty_. in asbestos - exposed peop 1 e ., Arch .__Immunol. The r. Exp., 30: 211-218. LANGE t B. & HAARTZ, J.C. (1979) Determination of microgram quant ip ;es of asbestos by X-ray diffraction: chrvsotile in thin dost layers of matix material. Anal. Chem., 15: 520-525. LANGE, A., SMOLIK, R., & ZATON5KI, W. (1974) Autoantibodies and. serum.immunoglobulin levels in asbestos workers. Int. Arch. Arbeitsmed., 32: 313 325. LANGE, A., CHMIELARCZYK, R.S.W., GARNCAREK, D., & GIELGIER, Z_.L1975 ' , Cellular immunity m asbestosis. Arch. Immunol. Ther. Exp26: 899-903. LANGER, A.M. & NOLAN, R.P. (1985) Physicochemical properties of minerals relevant to biological activities: state of the art. In: Beck, T. & Bignon, J., ed. Proceedings of the 3rd International Workshop on In vitro Testing of Mineral Dusts, October, 1984, Berlin, Heidelberg, New York, Springer-Verlag. LANGER, A. M . , RUBIN, I . SELIKOFF, I .J. (1970) Electron microorobe analysis of asbestos bodies . In-. Shapiro, H.A., ed. Pneumoconiosis. Proceedings of the International Conference, Johannesburg, 1969, Capetown, London. Oxford University Press oy . LANGER,.. A . M . I.B., SELIKOFF, I.J., & POOLEY, F.D. 1972. Chemical character izat ion. of uncooked asbestos fibres frc-m the lungs of asbestos workers by electron microprobe analysis. J. Histochem. Cytochem., 20: 735-740. LANGER,. A.M.. ASHLEY, R., BADEN, V., BERKLEY, C., HAMMOND, E . C . , ...MACKLER.,., A.D.. MAGGIORE, C.J., NICHOLSON, W.J., ROHL, A . N . ,. . RUBIN,, LE,. SASTRE, A., & SELIKOFF, I -J. '1973) 1 dent..i f icaticr. of asbestos in human tissues. J. Occup. Med., 15 : 287 295 . LANTING, R.W. Sc DEN BOEFT, J, ',1979) Atmospheric pollution by asbestos fibres, Luxembourg. Commission of the European Communities. 180 dd ;CEC ReDort EUR 6768 EN. ReDort G 908 . November 1979; . LEBEL, J. (1984) Review of fibre concentrations in Quebec asbestos mining towns, Quebec, Quebec Asbestos Mining Association. LE BOUFFANT. L. (1980) Physics and chemistry of asbestos dust. In: Wagner, J.C., ed. Biological effects of mineral fibres. Proceedings of a Symposium held at Lvons. 25-27 September, 1979, Lvons. International Agency for Research Cancer. Vol. i, pp . 15-33 (IARC Scientific Publications No. LEE, K.?., BARRAS, C.E., GRIFFITH, F.D.. WARITZ. R.S.. & LAPIN, C.A. (1981) Comparative pulmonary responses to inhaled inorganic fibres with asbestos and fiberglass. Environp . Res., 24: 167 -191 . LEE, E . C . , KELLEY, J,F..WALKER, J.S. ;i982; Cons i dera t i ons i_n._ the analysis and definition of asbestos . using electron microscopy, Cincinnati. Ohio, American Co nf e r ence _g.f Governmental Industrial Hygienists, pp . 132-137 .NEE Special Publication No. 619_v . http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 109 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) : 1980) wool and vitreous fibers . In. Wagner. J.C.. ed. Biological effects of mineral fibres. Proceedings of a Symposium held at Ivons, 25-27 September, 1979, Lyons, International Agency for Research or. Cancer, Vcl . 2. CD. 881 900 (IARC Scientific Publications No. 30). EMAI RE, I . . GINGRAS, D. , & LEMAIRE, S. 11982) Thymidine incorporation bv lung fibroblasts as a sensitive assay for biological activity of asbestos. Environ. Res., 28: 399. LEVY. B.S.. SIGURDSON. E .. MANDEL. J.. LAUDON. E.. & PEARSON, J. '1976' Investigating possible effects of asbestos on city water: surveillance of aastorintestinal cancer in Duluth. Minnesota. Am. J. Epidemiol./ 103:362. LIDDELL, F.D.K. (1983) Tumour incidence after asbestos exposure in the general population of Canada. VDI-Ber., 475 : 179 -183 . LIDDELL, _F . D_, K . & MCDONALD, J . C . _ 198 0 , Radiological findings as predictors .of mortality in Quebec asbestos workers .. Br. J. Ind. Med., 37_l_ 257 267 . LIDDELL, F.D.K., THOMAS. D.C., GIBBS, G.W., & MCDONALD. J.C. 1983. Fibre exposure and mortality from pneumoconiosis, respiratory and abdominal malignancies in chrvsotile production in Quebec, 1926-75. Presented at the Third International Symposium on Epidemiology in Occupational Health, Singapore, September 1983. LIEBEN, J. S FISTAWKA, H. .1967, Mesothelioma and asbestos exposure . . Arch.. Environ. Health., 14: 559 - 568. LIGHT, W.G. & WEI, H.T. '1980' Surface.charge and.a molecular basis for asbestos toxicity. In: Brown, R.C. Et al.. ed. The in vitro effect of mineral dusts, London. Academic F.ress , _pp . 139 - 145 . LI LIS_,__ R (1981) Fibrous zeolites and endemic mesothelioma in Cappadocia, Turkey. J. Occup. Med., 23; 548-550. LIPKIN, L.E. (1985) Failure of attapulgite to produce tumours: prediction of this result by in vitro cytotoxicity test. In: Beck, E.G. & Bignon,__J., ed. In vitro effects of mineral dusts, Berlin, Springer-Verlag. L_I FPMANN, , y. . , YEATES, D.B. , & ALBERT, R. E. :i980` Deposition, retent.ion, and clearance of inhaled particles. Br. J. Ind. Hed. ,. 37 : 337 362 . LJVINGSTQN, G.K.. ROM, W.N.. & MORRIS, M.V. (1980) Asbestos-induced sister-chromatid exchanges in cultured Chinese hamster ovarian fibroblast cells. J. Environ. Pathol. .Toxicol,, 4(2/3': 373-382. LCHRER, W. ,198 3. [Asbestos - exposed interiors: analysis and evaluation of.. r isk__pgtent_ials.,.l. _ Staub-Reinhal t. Luft, 43: LONOLEY. 5.0. '1969/ The many faces of asbestos disease. Med. J. Aus t., 56: 1063 - 1066 . LYNCH. K.M. & SMITH, W.A. (1935) Pulmonary asbestosis. III. Carcinoma of lung in asbestos - silicosis. Am. J. Cancer, 24: 56. LYNCH, K.M.. MCIVER, F.A.. &CAIN, J.R. (1957) Pulmonary tumours in mice exposed to asbestos dust. Arch. Ind. Health, http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 110 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) 15: 207. MCCQNNELt. _.EE. (1982a)____NIEHS carcinogenesis bioassay of ampspte_asbestos in Syrian golden hamsters. Presented at Summary Workshop on Ingested Asbestos, Cincinnati, Ohio, 13-14 October, 1982, Cincinnati, Ohio, US Environmental Protection Age n cy. Health Effects Research Laboratory. MCCCNNEL,... E . E ... ''1992b'__NIEHS carcinogenesis bioassay of hrysot i le a s b esto s _ in Syrian golden hamsters. Presented at Summary Workshop,, on ingested. Asbestos, Cincinnati, Ohio, 13-14 Octobert. 1982,.. Cincinnati, Ohio. US Environmental Protection Aaency, Health Effects Research Laboratory, MCCONNELL, E . E . ,__RUTLER^ H.A., ULLAND, B.M.. & MOORE, J.A. 198?. Chrcr.ic effects of dietary exposure to amosite asbestos and trenipl.it.e in F344 rats. Environ. Health Perspect., 53: 21 - 44 , MCCONNELL, E. E. WAGNER,. J.C.. SKIDMORE, J.W., & MOORE, J.A. ,1984, A. comparable _study. of the fibrogenic and carcinogenic effects of UICC Canadian chrysotile B asbestos and microfibres ."V. B:-ring: cal effects of_.man-ma.de mineral fibres, Proceedings of a WHO/IARC Conference, 20-22 April, Copenhagen, World Health Organization , Vol. 2, up. 234-250. MCDONALD, A.D. & FRY, J.S . (1982) Mesothelioma and fiber type in three American asbestos factories preliminary report. Scand. J. Work environ. ,Health . 8(SuddI. 1): 53-58. MCDONALD. A.D. Sc. MCDONALD , J.C. (1978) Mesothelioma after crocidolite exposure during gasmask manufacture. Environ. Res., 17: 340 -346 . MCDONALD, A.D. Sl MCDONALD . J.C. (1980) Malignant mesothelioma :n North Amen ca. Cancer,, 4 6 : 1650-1656,. MCDONALD, A.L . , . MCDONALD^. 2 . C & POOLEY, F.D. ,1932' Mineral fiore content of .Lung m mesotheiial tumours in North America. In: Walton,. W. H _. , ed,_. I_nhale^d partjcl_es_,__VL. Prgceedings pf an_Internatlonal Symposium, Cardiff, 8-12 September, 1980^ Oxford, Pergamon Press, pp. 4 17-422 ' Ann occup_. Hyg. , 26: 417-422! . MCDONALD,. _A,. D. , FRY, J.S., WOOLLEY, A.J., & MCDONALD. J.C ,1283a. Dust exposure m an American chrysotile textile p ' ,= r r . Br. J. Ind. Med., 40: 361-367. MCDONALD , A.D. FRY. J.S.. WOOLLEY. A.J.. & MCDONALD, J.C. 1983b) Dust exposure and mortality in an American factory using cn rvsotile, amosite. and crocidolite in mainlv textile t a " 1 f a ~ ure. Br. J. Ind. Med. , 40: 368 - 374. MLuONAi-D . A.D., FRY, J.S.. WOOLLEY, A.J., & MCDONALD, J.C. "1984) Dust exposure and mortality in an American chrysotile asbestos friction products plant. Br. J. Ind. Med., 41: 1 51.^l_5 7 . MCDONALD , J.C. (1980) Asbestos-related disease: an epidemiological review. In : Wagner. J.C.. ed. Biological _effects of mineral fibres. Proceedings of a Symposium held at . Lyons, 25-27 September, 1979, Lyons, International Agency for Research on. Cancer, Vol . 2, pp. 587r601 (IARC. Scientific P..indications No. ,.30... MCDONALD, . C . .19 6 4. . Mineral fibres and cancer. iVc Z--- A - :.gacci e,__13.; 39 5_3jJ2^ Ann. Acad. http://www. inchem.org/documents/ehc/ehc/ehc53.htm Page of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) U.O. .i?S5[ exposure to. asbestos. Health implications, of environmental Environ. Health Perspect., 62: 319 328. MCDONALD, J. C.._&_ MCDONALD. A.D.(1977) Epidemiology of Tie so the 1 i cma from est imated incidence. Prev. Med., 6: 426-446. MCDONALDC .__ & MCDONALD. A.D. 11981) Mesothelioma as an index.of. asbestos impact. In: Peto, R. & Schneiderman, M.. ed. Quant:f:nation of,occupational cancer. Cold Spring Harbor. Cold Spring Harbor Laboratory, pp . 73-82 (Banbury Report 9) . MCDONALD. J.C.. LIDDELL. F-D.K.. G1BBS, G.W., EYSSEN, G.E., MCDONALD . A.. DJ__ i 1980 )___ Dust exposure and mortality in chrysptile mining, _1910_-_1975^___ Br. J. Ind. Med., 37: 11 -24. & MALTONI, C., MINARDI. F.. & MORISI. L. (1982a) The relevance of the experimental approach in the assessment of the oncogenic risks from fibrous and non-fibrous particles. The ongoing pronect of the Bologna Institute of Oncology. Med. Lav. , 73 (4) 394-407 . MALTONI, C . MINARDI. F.. & MORISI. L. (1982b) Pleural mesotheliomas in Sprague-Dawlev rats bv erionite: first experimental evidence. Environ. Res., 29: 238-244. MANCUSO, T.F. & COULTER. E.J. (1963) nea..cn__studies. The cohort approach, an i.-tts-c? -cmpany. Arch. Environ. Methodology in industrial with special reference to Health, 6j. 210-22.6_l MARFELS. H., SPURNY, K.. BOOSE. C.. SCH05RMANN. J., OPIELA, H., ALTHAUS, W. ,__& WEISS. G. (1984a) [Measurements of fibrous_dusts in ambient air of the Federal Republic of Ternary. Measurements in the vicinity of an industrial aub-Reinkal t_. Luf t. 44j_ 259-263 (in German). SPURNY, K., BOOSE, r SCHOERMANN, J . . OPIELA. H., ALTHAUS, W .&_ WE ISS . G . (19 8 4b; [Measurements of fibrous dusts m ambient air of Federal Republic of Germany. * I_ M e a s u reme nts on a busy crossing of a large town.] Scaub-Reinhalt. Luft, 44: 410-414 (in German). MARSH, G.M. 1983) Review of epidemiologic studies related to ir.gested asbestos. Environ. Health Perspect., 53: 49-56. MASON. T.J., MCKAY, E.W.. & MILLER. R.W. (1974) Asbetos-like fibres in Duluth water supply: relation to cancer mortality. J. Amu. Med_, Ass_oc. , 228 : 1019 . MEEK, M.E.__ & GRASSO, P- (1983) An investigation of the P.enetration of ingested asbestos into the normal and abnormal intestinal mucosa of the rat. Food Chew. Toxicol21: 193-200 MEEK, M.E., SHANNON. H.S.. &. TOFT, P. (1985) Case study: Aset sits in. t cxicoioaical__risk assessment. In-__Cl ay son, D . B . , Krewskl, D. , & Munro, I , ed. Toxicolocrical risk assessment, Bp c a_ Raton. Florida. CRC Press, Vol. 2, pp. 121-165. MEIGS, J.W., WALTER, S.D^ HESTON... J . FM ,, MILLETTE, J.R. . SPA UN, G.E., WOODHULL. R. _S . , & FLANNERY, J.T. U980) Ash-'-sic? c^er.t pipe and cancer in Connect i cut 1955-74.___J._ envircn. Health, 42: 187 . MEYER, . E. _1984_1[Presence of asbestos fibres in drinking >;acer . 1 In-. Fischer,. M. Meyer, E . , ed.fAssessment of the raneer_ri_sk. from asbestos. 1, Munich. Medizm Verlag, do. 62-78 .in. lercan..;. MEYLAN. W.M,, HOWARD, P.H., LANDS, S.S., & HANCHET. A. http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 112 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) 97 81____ Chemi ca 1 _ marke t _ inpu c/ou tp ut analysis of selected eh em_ica_l subs t_an ces t o as sess source of environmental contaminationdsbescos^ Washington DC. US Environmental Prot ect: on.. Agency , EPA Report .No..__ 560/6 - 7 8 - Q 0 5) . MICHAELS. L. & CHI SSICK. S.S., ed. (1979) AsbesCos: propercies, applications, and hazards,___New York, John Wiley and Sons, 553 dp. MIDDLETON. A.P., BECKETT. S.T., & DAVIS. J.M.G. (1979) Further observations on the short-term retention and clearance of asbestos by rats, using UICC reference samples. Ann. Occuc. Hvo. , 22: 141- 152 . MILLER. A.. DANGER, A.. TIERSTEIN, A.. & SELIKOFF, I. (1975) "Non - specify, cy interstitial pulmonary fibrosis.__New Engl. J. W i. , 2 92 : : 9 * . MILLER,. A.5. ,1976, Asbestos fibre dust and gastrointestinal r.al ignancies . Review of literature with regard to a cause/ef feet relat ionship_J.. Chron. Pis . s__3_lj__2 2 - 33. >L L L ER, . K _.j_i 978 ' _ The effects of asbestos on macrophages. CRC Crit. Rev. Toxicol., 5: 319-354. MLL LER. K.. WEBSTER, I., HAND FI ELD, R.I.M., & SEINE. M.I. , 1976____U1 trastructure of the 1 ung in the rat following sxpes-tre to crccidolite asbestos and quartz. . J. Pa thol . , 124 : . 39 . MILLETTE, J.R.. CLARK. P.J., & PANSING. M.F. (1979a) Exposure to asbestos from drinkincr-wa ter in the United States, Cincinnati, Ohio. US Environmental Protection Agency. Health Eff ects Research Laboratory. Office of Research and Deve1coment. 86 pp (EPA Report No. 600/1-79-028). MILLETTE, J.R., TWYMAN, J.D., HANSEN, E.C., CLARK, P.J., & PANSING. M.F. (1979b? Chysotile, palygorskite, and hallov site in_dnnking-water. Scanning Electron. Microsc., 1: 579-586. MILLETTE, J.R., CLARK. P.J., PANSING. F.M., & TWYMAN, J.D. '.19.8 0] . . Concentration and size of asbestos in water supplies. _Envi ron. Health Perspect., 34: 13 - 25 . M _ L--E i - E , J . R . , CRALfN , G F . ,_STOEER, J.A., KRAEMER, D . F . , TOCS TENANT, . H . G HILDAGCh. E. , DU30ISE, R.L.. & BENEDICT. J. .1 98 3. Epidemiology study of the use of asbestos - cement pipe for the distribution of drinking-water in Escambia Countv, F1 or i da . . _. Environ. Health Perspect. , 53: 91-98. MI LNE,. __J . E . H_._ ; 197Developmental changes in asbestos bodies arid .their significance. Trans. Soc. Occup. Med., 214: 118-121. MCATAMED, F,, ROM, W.N., & CASEY, K.R. (1981? Early response to injected f ibrous enonite in the mouse peritoneum and rat lur.g. Am. Rev. Respir. Pis., 123;Annual Meeting Supplement': 14_4... abstract.' . MONCHALX, .G^,_. BIGNON. J., JAURAND, M.C., LAFUMA, J., SEBASTIEN, P.. MASSE, R., HIRSCH, A., & GONI, J. (1981) Mesotheliomas in rats following inoculation with acid-leached cnrysotileasbestos and other mineral fibers. Carcinogenesis, 2 : 229 236. MORGAN,.. A . , 19 7 9? Fibre dimensions: their significance in tr.e. deposition and clearance of inhaled fibrous dust. In: Leme.n, R. & Dement, J.M.. ed. Dusts and disease. Park Forest South, Illinois.__Pathotox Publishers Inc., pp. 87-96. http://vvvvw.inchein.org/documents/ehc/ehc/ehc53.htm Page 113 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) MORGAN. A. & CRALLEY. L.J. (1973) Chemical characteristics of asbestos and associated trace elements. In; Boqovski, P.. et al., ed. Biological effects of asbestos. Proceedings of a Working Conference, Lyons, 2-6 October, 1972, Lyons. International Agency for Research on Cancer. pp. 113-118 (IARC Scientific Publications No 8) . MORGAN, A & HOLMES. A. (1980) Concentrations and dimensions of coated .and uncoated asbestos fibres in the human lung. Br. J, Ind. Med. , 37 : 25. 32 .. MORGAN, A-,.. EVANS. J.C.. EVANS. R.J., HOUNAM. R.J., HOLMES, A..&_D_pYLE, S . G (1975^ Studies on the deposition of inhaled fibrous material in the respiratory tract of the rat and. its subsequent clearance using radioactive tracer techniques_.__..I_.I^_Deposition of the UICC Standard Reference Samples of Asbestos.___ Environ. Res., 10: 196-207. MORGAN, A., EVANS, J.C.. & HOLMES, A. (1977a) Deposition and clearance of _inhaled fibrous minerals in the rat. Studies .s:\j i ^ i. ;a ' \ . ve 'rater technique. In: Walton,.. W. H_._, e.d Inhaled parei cles . J_V. _ParL^.L.\..roceedings_of_an__Incern3.tional_ Svmoosium , Edinburgh. 22-26 September, 1975. Oxford, Pergamon Press, dp. 259-272. MORGAN, A. , DAVIS, P., WAGNER, J.C., BERRY, G . , & HOLMES, A. 1977b' T he biological effects of magnesium- leached chrvsotile asbestos. Br. J. Exp. Pathol., 58 : 465-473 MORGAN, A. , BLACK, A., EVANS, N., HOLMES, A.. Sc PRITCHARD, J.N. (1980 ) DeDosition of sized alass fibres in the respiratorv tract of the rat. Ann. Occup. Hyg., 23: 353-366. MORRIS, 7 . G . , ROBERTS, W.H., .3 I OVERTON, R. E, , SKIDMORE. J.W. . WAGNER, C.C., a..TOOK, G . W... . 15_6.7_ Comparison of dust retention ,in_ specif ic pat.noqen free and standard rats. In: Day. i es,__C . N . , ed . Inhaled parti cles and vapours, London, Rsraamcn. Press, Vol . 2 , pp. 2 05-213. MOSSMAN_ B_,TM & CRAIGHEAD. J.E. (1982) Comparative cocarcmogenic effects of crocidolite asbestos, hematite, kaolin, and carbon in implanted tracheal organ cultures. Ann. occupy. Hyg26(1-41: 553-567. MOSSMAN, B.T. & LANDESMAN, J.M. (19831 Importance of oxygen _f ree. radical.s_in asbestos - induced miury to airway epithelial cells. Ches t,._ 83 50 51. MOSSMAN, 3.J.., EASTMAN. A. , LANDESMAN. J.M., & BRESNICK.__ E,. 1563 .___ Efleets of crocidolite and chrysotile asbestos on cellular uptake, metabolism, and DNA after exposure of hamster tracheal epithelial cells to benzof a )pyrene. Environ. Health 7orerect . , 51: 3 3 1-336 ,. MUHLE, H., SPURNY, K., & POTT, F. (19B3) [Inhalation experiments on retention, lung clearance, and migration of asbestos and glass fibres in dependence of cigarette smoking.] VDJ-Ber., 475: 247-251 (in German). MCMP70N,_ ~ .A. .1579, Reconnaissance study of the association _ f zed : : es w: : h -resothel i cma cancer occurrences in central Turkeyj Brqckpqr.t, New .York,__ State University College, 49 pp, NAVRATI L, M i_S82_[Asbestos of the lung and its ccnpl i ca tio_ns2 ]__Prague, Avicenum ; in Czech; . NAVRAT IL, .. M. & JE2KOVA. Z. (1982) Antibodies against http ://\vw\v. inchem.org/documents/ehc/ehc/ehc53.htm Page 114 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) pulmonary tissue in individuals with long-term exposure to asbes. tos... dust . Cas . Lek. Ces . , 121: 1608-1611. NAVRATIL.,.. M. & TRIPPE, F. (1972)___ Prevalence of pleura1 calcification m persons exposed to asbestos dust,.. and in the ler.eral population m the same district. Envi ron. Res. , 5 NEVBERGER. M - , .RABER, A , t. &. FR I EDL, . H . jT. {1982) [Epidemiology of asbes tos - linked lunc? diseases in Austria . XV'ith Congress of the Austrian Society for Lung Diseases,] : u'.:'., pp . 1.1 ^ 1 3 6 ,: r. German. . NEUBERGER, M.. KUNDI, M., & FRIEDL, H.P. (19B4? Environmental asbestos exposure and cancer mortality. environ. Health, 39: 261-265. Arch. NEWHOUS5, M.L. & BERRY, G. (1976) Predictions of mortality from mesothellal tumours in asbestos factory workers. Br. J. ind. Med., 33 : 147-151. NEWHQUSE, M.L. & BERRY, G- (1979) Patterns of mortality in ashestos factory workers in London. Ann. NY Acad. Sci., 330: 53 -60 . NEWHQUSE, M.L. & THOMPSON, H. (1965) Mesothelioma of pleura and peritoneum following exposure to asbestos in the London area Br. J. Ind. Med., 22: 261-269. NEWHOUSM ._L, , GREGORY, M.M.. & SHANNON, H. (19B0j___ Etiology of_ carcinoma of the larynx. . In: Wagner, J.C., ed Biological effects_cf min.eral._fibres. Proceedings of a Symposium held at Lyons, 25-27 September, 1 tsrar . n or. ..dancerVoT fuelmatters No. 30. . 1979, Lyons. International Agency for 2_,_ _d_d 687 - 695__( I ARC Scientific NEWHOUS E, M, L_. , OAKES , D . , & WOOLLEY, A. J.(1985; Mortality : v/elieis and other craftsmen at a shipyard in northeast "rj: m Br. T. Ind. Med., 42: 406 410. NICHOLSON, W.J. (1974) Analysis of amphiboleasbestiform f. i_b res mmuni cip a 1 water _ suppl les .___Environ. Health Perspec t., 9: 165.173, NICHOLSON, W.J. (1976) Case study 1: asbestos - the TLV approach.__ Ann. NY Acad. Sci., 227: 152-169. NICHOLSON, W.J. & PUNDSACK, F.L. (1973) Asbestos in the environment. In: Bogovski, P., Gilson. J.C., Timbrell, V., & Wagner. J.C., ed. Biological effects of asbestos. Proceedings of, a Working Conference, Lyons, 2-6 October, 1972, Lyons, International Agency for Research on Cancer, pp. 126-130 (IARC Scientific.Pub1ications No. 8). N1 CFT-LSC N, W.C., MAGGIORE,. C.J., & SELIKOFF^ Asbestos.contamination of parenteral drugs. 1 7.1.-173, I . J. >19121 Science, 177: NI CHOLS ONWJ SELIKOFF, I.J., SEIDMAN, H-, LILIS, R., & 1 IRMLY, ?, ,1_5 7 9_. Long-term mortality experience of chrysct: le miner s___and. millers m Thetford Mines, Quebec. Ann. AT Acad.' Sci . , 330 : 1 1 21 . N I CHOLS ON, W J . ROHL, A.N., WEISMAN, I., & SELIKOFF.__ I . J. . . -j turn - joUjS ms _ - n c e r. t r a.t _ c n_s in tn.e United In: Wagner, J.C., ed. Biological effects of mineral Li .scoldings ut a Symposi urn held at Lyons, 25-27 . September, 1 9 7 9, _ ..Lyon s_,__ International Agency for Research on http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 115 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) 1; I : OECD ;i934^ Control of toxic substances in the atmosphere asbestos. Pans. Organisation for Economic Cooperation and Develcpmenc ;Environment Committee: Air Management Policy Group ENV/AIR/81.18, 2nd Revision). OHLSON_C .-G. & HOGSTEDT, C. (1985) Lung cancer among asbestos cement workers. A Swedish cohort study and a review. Br. J. Ind.. Med., 42: 397-402. 0LLHAM, P.D. 11973' A trial of techniaues for counting asbestos bodies in tissue. In: Boqovski, P. Et al__ ed. Biological effects of asbestos. Proceedings of a Working Conference, Lvons. 2-6 October, 1972. Lyons, International Agency for Research on Cancer, pp. 45-49 (IARC Scientific Publications No_L_ 8 T OLE RUj__H . G .__ 19801 Pulmonary function of control and indus.trially-exposed Nigerians in asbestos, textile, and toluene isocyanate foam factories. Environ. Res.. 23: 137 ItS. ONTARIO ROYAL COMMISSION.ON ASBESTOS 11984' Report of the _Roya_l _ Conwiission on Matters of Health and Safety arisincj from the use of Asbestos in Ontario, Vol.__One__ two, and three, :.\ Ir.tjiit Minis try c tr.e At t orr.ey __3enera.l . i AI LEO ( W_.H . JULY. 0 , J.. RESNICK. H., & CASTRANOVA, V. ,1989, Relative effects of asbestos and wollastonite on alveolar macrophages, J. Toxicol. Environ. Health, 14: 497. PA.MPAL0N, R.. SIEMIATYCKI , J., & BLANCHET, M. (1982) Er.v: ronrr.ental asbestos pollution and public health in Quebec L'Union Medicale du Canada, 111: 475-489. PERN15, B. & VIGLIANI, E.C. (1982) The role of macrophages and immunocvtes in the pathogenesis of pulmonary disease due to mineral dusts. Am. J. Ind. Med. , 3(2): 133-137. PERNIS. B., VIGLIANI. E.C., & SELIKOFF, I.J. (1965) Rheumatoid factors in the serum of individuals exposed to asbestos. Ann. NY Acad. Sci., 132: 112-120. PETER SONJUT GREENBERG. S.D., & BUFFLER, P.A. (1984) N ona sb est os__ r elated malign ant mesothelioma. Cancer, 54; 1E.1, J. .1978, The hygiene, standard _for.__chrysot.i_le asbes_t_os_.__ Lancet, 1: 484-489. PETOt T . 198.G___ Lung cancer mortality in relation to measured dust. 1 eve 1 s__in an asbestos textile factory. In: .- , , "i. I1.. Tgi'/ul effects of mineral fibres Proceedings of a Symposium held at Lyons, 25-27 September, 1979, Lyons, International Agency for Research on Cancer, Vol. Li- 8 ^ 9 3 2 C .IARC Scientific Publications No. 30:. PETO, J. (1983) Dose and time relationships for lung cancer and mesothelioma in relation to smoking and asbestos exposure. Lj.. f.cachings of a Symposium on Asbestos, BundeSQesund- heitsamt, West Berlin, 17-19 February, 1982, Berlin, Dietrich Reimer Verlag, pp. 126-132. PETO, J.. SEIDMAN, H-, & SELIKOFF, I.J. (1982) Mesothelioma mortalicv in asbestos workers.- implications for models of carcinogenesis and risk assessment. Br. J. Cancer, 45: 124 -135. http://www.inchem.org/documents/ehc/ehc/ehc53.htrn Page 116 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) PETO. J.. DOLL. R.. GOFFE. T.. & CLAYTON. R. (in press) Mortality of workers in a Rochdale asbestos textile factory. Ann. . Occup. Hvq. PHYSICIANS' DESK REFERENCE (1983) Physicians' desk reference for nonprescription drugs, 4th ed. , Oradell, New. Jersey.,. POLISSARx. L. '1980) The effect of migration on comparison of disease, rates in geographic.. studies_ in. the United States. Am. J. Epidemiol., Ill: 1975. POL! SSAR. L . , . SEVERSON, R.K., BOATMAN, E.S.. Sc THOMAS. D.B. . 1.982) _Cancer incidence in relation to asbestos in d r i n k i ng_ wa t e_r _ in the Puget Sound region. Am. J. Epidemiol., 116 3IA-- .19'^.. Electron ncroscope characteristics pi .Ml-, asbest.s hhv. Sr. J . Ind. .Med . 2?.j. POO LEY, F. D. & CLARK, N.J. (1979; Quantitative assessment of inorganic fibrous particulates in dust samples with an analytical transmission.electron microscope.__Ann. Occup. Hvq., 22: 2 S j - 2 7 1 . POOLEY. F.D. & CLARK. N.J. (1980) A comparison of fibre dimension in chrysotile, crocidolite, and amosite particles from samples of airborne dust and from post-mortem lung tissue specmens. In: Wagner, J.C.. ed. Biological effects of mineral fibres. Proceedings of a Symposium_held at Lyons, 25-27 SeccemberL 1979, Lyons, International Agency for Research on Cancer, Vo.lL i, pp. 79-85 [IARC Scientific Publications No. 3c; . POOLE, BROWN ( R.CtJ_ TURVER, C.J., SKIDMORE, J.W.. & JR 1 rr 1 OHS , D_._M. .1 983,____ In vitro qenotoxic activities of fibrous erionite. fir. J. Cancer, 47: 697. R.QXX, F. ! 1978) Some aspects on the dosimetry of the carcinogenic_ potency of asbestos and other fibrous dusts. Staub - Reinh. Buft, 38: 486-490. LETT, F. .198C. __ [Animal experiments . 1 In: Urr.wel tbundesamt ed. iAir quality criteria - environmental burden by asbestos i r, 1 -'her' fire fibrous dusts,] Berlin, E. Schmidt., pp . . 3 3 3 360 Umweltbundesamt. Berichte 7/80) (in German). POTT, F. & FRIEDRICHS, K.-H. (1972) fTumours of the rat af_ter _..intraperitonal injection of fibrous dusts. 1 Naturwiss., 58 'in German) . POTT, F., HUTH, F., & FRIEDRICHS, K.-H. f1972) fTumours of the rat__after intraperitoneal injection of milled chrysotile and benzol a ) pyrene. 1 Zbl. Bakt. Hvq.. I. Abt. Prig. B. , 155: -15 3 -469 ; in German) . POTT, F . , FRIEDRICHS, K.-H., Sc HUTH, F. (i976a) [Results of " ' O. yp-r : "'er.-s --naming the carcinogenic effect of. fibrous, dusts and their interpretation with regard to the car.c i nogenes is _i n __hurrLans_. j___ Zbl. Bakt. Hvg. ,__ I_. Abt. Orid. B. t__ 162; 4 57 5C5 . m German. . PCTT, F_._, DOLGNER, R., FRIEDRICHS, K.H., & HUTH, F. (1976b) Effec oncologique des poussieres fibreuses. Experiences sur ie.s_an:maux et leurs relations auec la carcmogenese humaine. Ann. Anat. Pathol . , 21:. 237. http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 117 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) POTT, F . , HUTH, F & gPURNEY , K. ; 19 8 0 :__ Tumor induction after mtrapentoneal miection of fibrous dusts. In: Wagner, j,Ced..___Biological effects of mineral fibres. Proceedings of a Symoosium held at Lyons, 25-27 September, 1979, Lyons, Inter na. t _i on a i Agency . for Research on Cancer. Vol. 1, pp . 3 37 34 2 . ^IARC Scientific Publications No. 30). rO_; i_j__._r_._j_ . SCHL1PKOETSR, H.W., ZIEM, U., SPURNY, K., & HUTH, F.'1984;___ New results from implantation experiments with mir.eral _f ibres . In.- Biological effects of man-made mineral fibres. Proceedings of a WHO/IARC Conference, Copenhagen, 20-22 April, 1982, Copenhagen, World Health Organization, Vol. 2, pp ... 286 .302 , POTTS, H.J., EEDERER, T.S.. & GEHRING. P.I. (1978) Hemolysis of washed rat erythrocytes in vitro by dust particles. Am. Ind. Hyg. Assoc. J., 39: 497. PRICE-JONES. M.J., GUBBINGS. G.. & CHAMBERLAIN, M. (1980) The genetic effects of crocidolite asbestos: comparison of chromosome abnormalities and sister-chromatid exchanges. Mutat. Res., 79: 331-336. PYLSVL ..N L 197 2)[Morphological lesions in rats lungs, - ;id -.ted cp. pat. r acheal i n_; ec t ion of chrysotile asbestos alone and with benzo; a ipyrene.l Vopr. Oncol., 18: 40 -45 Russian. . jin PYLEV, L.N. (1980) Pretumorous lesions, lung and pleural tumors induced bv asbestos in rats, Syrian golden hamsters, ar.d monkey Macaca rhesus. In: Wagner, J.C., ed. Biological effects, of mineral fibres. Proceedings of a Symposium held at Lycr.Sj 25-27 September, 1919. Lyons, International Agency for Ruses:cr on Cancer,. Vol . 1, pp , .343_3_55__ ; I ARC Scient i f ic Pubi i cat_ipns . No.. . 3 PYLEVt L.N. & SHA5AD, L.M. '.1973) Some results of experiment a 1 studies in asbestos carcinogenesis. In: Bogovski, P.. Gilson. J.C., Timbrell, V., & Wagner. J.C., ed. Biological effects of asbestos. Proceedings of a Working Conference, Lyons, 2-6 October, 1972, Lyons. International Agency for Research or. Cancer, pp, 99- 105 (IARC Scientific Publications No. 8; . RAHMAN, Q., VISWANATHAN, P.N., & ZAIDI, S.H. (1977) perspectives on the biological effects of asbestos. Res. , 14: 487-498 . Some new Environ. RAJ HANS, G . S . &_BRAGG, G.M. '1978; asbestos dust control, Ann Arbor, Sc i_en.pi fit Publ ishers, 191 pp . Engineering aspects Michigan, Ann Arbor of RAjHANS, G.S. & SULLIVAN, J.L. 11981) . Asbestos sampling and , j_.analysis Ann. Arbor Michigan. Ann Arbor Scientific Pup 11 s h e r s.,.. 250 pp . RAMACHANDERK., SCHLECHTER, R., PHELPS. B., & CHAHINIAN, P. _ _1.9 7 5. :mmunocompetence m patients with pleural mesothelioma.___ Proc. Am. Assoc. Cancer Res., 16: 142. RA 7.. , . . .s56. . .u,,: i er. :e of unusual pleural calcification : r. E : r. - arc . Ann Med. Tat. Fear.., 55.suppl. .47) : 1 - 61 . REEVES, A.L., PURO, H.E.. & SMITH, R.G. (1974) carcinooenesis from various forms of asbestos. 8: 178 - 202 . Inhalation Environ. Res.. http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 118 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) REISS, B.. MILLETTE, J.R., & WILLIAMS, G.M. (1980)___ The activity of environmencal samples in a cell culture test for asbestos r.ox.icir.v. Environ. Res.. 22: 315. RICHARDS, R.J. & JACOBY . F. (1976) Light microscope studies on the effect of chrysotile asbestos and fibre glass on the morphology and reticulin formation of cultured lung fibroblasts. Environ. Res., 11: 112-121. RICHARDS, R.J., GEORGE, G.. HUNT. J.. & TETLEY. T.D. (1980) The relationship between the haemolytic potential of certain particulates and their reactivitv at the lung surface in view. In: Brown, R.C. Et al . , ed. The in vitro effects of mineral dusts, London, Academic Press, pp. 323-332. ROBOCK, K. (1979) Based on available data, can we oroiect an acceptable standard for industrial use of asbestos? Absolutely. Ann. NY Acad. Sci.. 330: 205-210. ROBOCK. K. 19 31' [The environmental hazard caused bv the p r uses sing r f asoestos cement products.] Staub-reinhal t. Luft, ROBOCK, K. ,.15.82._ Monitoring the workplace: problems and progress. State-of-the-art (automatic counting methods) and ..oternattonal efforts for standardizing of methods. In: Proceedings of the World Symposium on Asbestos, Montreal, Canada, 25-27 May, 1982. Montreal, Canadian Asbestos Information Centre, dp. 104-116. E0B_0C_K1 K(19 84; [Comparison of different measuring procedures in relation to conditions at the workplace.! In: Fischer, M. & Meyer, E., ed. fAssessment of Che cancer risk from asbestos,] (BBA Schriften 2/84) (in German). ROBOCK, K. & TEICHERT, U. (1978) Techniques, strategies, and results of dust measurement in the asbestos industries. In: Proceedings of the 5th International Conference on Pneumoconiosis, Caracas, 29 October - 3 November, 1978, Seneva, International Labor Office. ROBOCK, K., ISSEROW, L.W., & SELLES, D.J.A. (1984) Research on the concentration and identification of dust particles in ambient air by electron microscopy. General description cf the '-etn.tu. in: Proceedings of the 6th Interna tiona_l Con ferenc_e_ on_ - x i . , rie:u:a,_ E- u tr. Africa . ROE, F . J . 0,_, _ CARTER, R.L., WATTERS, M.A., & HARINGTON, J.S. .1 96 7, Che pathological effects of subcutaneous injections of asoestos fibres m mice: migration of fibers to submesothelial Tissues and induction of mesotheliomata. Int. J. Cancer, 2: 12 8 6 3 3 . ROHO, A.N., LANGER, A.M., & SELIKOFF, I.J. (1977) Environmental asbestos pollution related to use of quarried serpentine rock. Science, 196: 1319-1322. BOH LA,N^_ LANGER, A.M., MONCURE, G., SELIKOFF, I.J., & FISHBEIN, P. .1982, Endemic pleural disease associated with exposure to mixed fibrous dust in Turkey. Science, 216: ROCKER. S.J.. VAUGHAN. N.P., & LE GUEN, J.M. (1982) On the visibi1itv of fibres by phase contrast microscopy. Am. Ind. _ Hygr. Assoc. J. , 43: 505-515. ROSKILL REPORT ON ASBESTOS (1983) Asbestos. IV. The economics. of asbestos, 4th ed. , London, Roskill Information http:/Avww.inchem.org/documents/ehc/ehc/ehc53.htm Page 119 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Services. Ltd. ROSSITER. C.E, & COLES. R.M. (1980) H.M. Dockyard. E e vc r.pc rt : 1947 mort a lity study. In: Wagner, J.C.. ed. Biological effects of mineral fibres. Proceedings of a Symposium held at Lyons, 25-27 September, 1979, Lyons, International Aaencv for Research on Cancer. Vol. 2, pp, 721 ,IARC Scientific Publications No. 30.'. ROSSITER, C.E., BRISTOL. L.J.. CASTIER, P.H., GILSON. J.C.. GRAINGER. T.R., SLUIS-CREMER G.K., & MCDONALD. J.C. (1972) Radiographic changes in chrvsotile asbestos mine and mill workers of Quebec,.., Arch. Environ. Health. 24; 388-400. EGGS, V. & STUDENY, J. ,1970.' Thorax, 25: 2S7C* 284. Aetiology,of pleural plaques. RUBINO. G.F., SCABSETTI, G., DONNA, A.. & PALESTRO. G. '1972' Epidemiology of pleural mesothelioma in North-Western Italy (Piedmont). Br. J. Ind. Med., 29: 436-442. G. . PIOLATTO, G... & ARESINI,, G. (1979a) Radioloqic chanqes afte: cessation of exposure among chrvsotile asbestos miners in Italv. Ann. NY Acad. Sci., 330: 157-161. RUBINO. G.F.. PIOLATTO, G . , NEWHOUSE, M.L.. SCANSETTI, G.. ARESINI. G.A.. . Sc MURRAY , R. (1979b) Mortality of chrvsotile asbestos workers at the Balangero mine. Northern Italy. Br. J. ind. Med.. 36: 187-194. SADLER, T.D., ROM. W.N., LYON, J.L.. & MASON, J.O. (1981) The use of asbestos-cement pipe for public water supply and che incidence of cancer in selected communities in Utah, 196~7-76i Salt Lake City, Utah,. University of Utah 'Graduate t:.tcited -n Marsh, 1983, . SALVAGGIO,.J.E. {1982d Overview of occupational immunologic Gun a disease. J. Allergy din. Immunol., 70: 5-10. SAMUDRA*.. _A, V., HARWOOD. C.F., & STOCKHAM, J.D. (1978) Electron microscope measurement of airhorne_ asbestos co ''.centra: :cr:sL Research Triangle Park_,__Ncrth Carolina. US Er.viron.m enta 1. .Protection Agency. Environmental Sciences Research Laboratory. 49 pp ;EPA Report No. 600/2 - 77 - 178 - Rev , r,3 2 5 5 94 5, . SARACCI, R. (1981) Personal-environmental interactions in occupational epidemiology. In; McDonald. J.C.. ed. Recent advances in occupational health. London. Churchill Livingstone, pp. 119-128. SARACCI, R., SIMQNATO, L., BARIS. Y., ARTVINLI, M.. & SKIDMORE, J. (1982) The age mortality curve of endemic pleural mesothelioma in Karain. central Turkey. Br. J. Cancer, 45: 147-149. SAWYER^,R.N. & SPOONER. C.M. (1979) Asbestos-containing materials in public buildings: a guidance document, Washington DC. US Environmental Protection Agency. SCHLESINGER, R.B. & LIPPMANN, M. {19781 .Selective particle .:-tp and or on c huger.; c carcinoma Envj ron . Res . , 15 : 4 2 4,4 3 1 . S CEDES INGER, _R.. B .. 50HNING, D.E., CHAN, T.L., & LIPPMANN. M. ,157 7,'. . .Part.icle deposition in a hollow cast of the human tracneobrcnchial tree. J. Aerosol Sci8: 429-445. http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 120 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) SCHLESINGER, R . 3., CONCATO. J.. & LIPPMANN. M. .1982) Particle deposition, during exhalation: a study in replicate casts _of_ the human upper tracheobronchial tree. In: Proceedings of _the International Symposium on Aerosols in the Mining and Industrial Work Environment, Minneapolis, Minnesota. SCHLUCHSEE MEETING ,1985)_____ In vitro effects of mineral dusts. I r.: Beck L E..3..& Bignon, ed_.____ Ecological sciences, Berlin, Springer Veriag,_ Vol. Ill, pp . 1-548 (NATO AS!__Series No. G) . SCHNITZER, R.J. & PUNDSACK. F.L. q970) Environ. Res., 3: 1-13. Asbestos haemolysis. 3 EBASTIEN, P., FONDIMARE, A., BIGNQN, J.. MQNCHAUX, G.. DES50RDES, J., & BONNAUD, G. (1977) Topographic distribution of asbestos fibres in human lung in relation to occupational and non-occupational exposure. In: Walton. W.H., ed. Inhaled particles. IV. Part 2. Proceedings of an International Symposium. Edinburgh, 22-26 September. 1975, Oxford, Pergamon Press Ltd, op. 435-446. SE5ASTIEN, P.t BILLON, M.A., JANSON. X.. BONNAUD, G-, & 3IGN0N, J. ,1978' Utilisation du microscope electroniaue a transmission .MET,, pour la me sure des contaminations par . -u'.a.-.r.e. Arcr.. Mai. Prof. Med. Tray.- Secur. Soc. (Paris). 39 : 229 248 SEBASTIEN, P., MASSE, R., & BIGNQN, J. (1980a) Recovery of ingested asbestos fibres from the gastrointestinal lymph in rats. Environ. Res., 22: 201-216. SEBAST I EN, P. , JANSON, X., GAUD I CHET, A. , HIRSCH, A.., & BICN-N, J. Asbestos retention ruman respiratory t isj-.es : cotriparat :ve measurements in lung parencnyma and .in parietal pleura. I n : Wagner , J . C . ,___ed..__ Biological effects of mineral fibres. Proceedings of a Symposium held at Lyons, .25-27 September, 1979, Lyons, International Agency for Research on Cancer, Vol. 1, pp. 237-246 (IARC Scientific Publications No. 30). SEBASTIEN, P., MCDONALD, J.C., CORNEA. G.. & GACHEM, A. (1983) Electron microscopical characterization of respirable airborne particles in a Tunisian phosphate mine. In; ._Proceedings of the 6th International Pneumoconiosis Conference, Bochurrij Federal Republic of Germany, 20-23 Sec center 193_3_,_ _3ergban - Beruf saenossenschaf t, International Labour Office, Vol. 3, pp. 1650-1665. SEIPMAN, H., SELIKOFF, I.J., & HAMMOND. E.C. (1979) Short term, asbestos, work exposure and long-term observation. . ,VV Acad. Sci . , 330.: SI 89 . SEIOMAN, H., SELIKOFF, I.J., & HAMMOND, E.C. (1982) Mortality of brain tumors among asbestos insulation in the United States and Canada. Ann. NY Acad. Sci., 381: 160. SELIKOFF, I.J, 11979) Mortality experience of insulation wiike:s the United States and Canada, 1543 1976 . Ann. NY Acad. Sci . ,. 330.: 91 1 16. SELIKOFF, __,1_982_____ Disability compensation for as'cos tos -associated disease in the United States. New York, Mc..nt Sinai School of Medicine, City University of New York. F?I. pp .Report to the US Department of Labor, Environmental Sciences Laboratory). SFLIKCFF, I.J. & HAMMOND, E.C. (1975) Mult_ipie_risk factors http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 121 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) in environmental cancer. In: Fraumem, J.F.. ed. Persons at high risk of cancer. New York, Academic Press, pp. 467-483^ SELIKOFF, I.J. & LEE. D.H.K. (197B) London, Academic Press,__54 9 pp. Asbestos and disease. SELIKOFF, I.J. & SEIDMAN, H. (1981) Cancer of the pancreas among asbestos insulation workers. Cancer, 47; 1469-1473. SELIKOFF,, I.J., CHURG. J.. & HAMMOND, E.C. (1964) Asbestos exposure and neoplasia. J. Am. Med. Assoc., 188: 22-26. SELIKOFF, I.J., NICHOLSON, W.J., & LANGER, A.M. (1972) Asbestos air pollution. Arch. Environ. Health, 25: 1-13. sfl:k:ff, :. j .,. hammonl, e.cl, & seidman. h. ;i979; y.p rt a 111 y experience of _ insulation workers in the United States and Canada, 1943 19 7.6 _ Ann.__NY Acad. Sci., 330: 91 - 116. SELLES D . J . A . L _ I SSEROWL.W., & ROBOCK. K. (1984) Results o f same _ i r.g i r. m i n i n.g and non-mining areas. In: Proceedings of - (--h I:: ^erna - :mn a 1 Conference on Air Pollution/ Pretoria , Scatr Atr ic.a . SESHAN, K. '.1983' How are the physical and chemical properties of chrvsotile asbestos altered by a 10-vear residence m water and up to 5 days in simulated stomach acid? Envi ron_._ Health. Persoect. ,__53 : 14 3 - 148. SHABAD. L.M.. PYLEV, L.N., KRIVQSHEEVA, L.V.. KULAGINA, T.F.. & NEMENKO, B.A. (1974) Experimental studies on asbestos carcinogenicity. J. Nad Cancer Inst.. 52: 1175-1187. 5HASBY, D.M., PETERSEN. M., HODOUS. T., BOEHLECKE, B.. & MERCHANT. J._ '1979) Respiratory morbidity of workers exposed to wollastonite through mining and milling. In: Lemen. R. & Dement. J.M., ed. Dust and disease. Park Forest South. Illinois, Pathotox Publishers Inc., pp. 251-256. SHETTIGARA,. _ FA T. & MORGAN. R.W. (1975) Asbestos, smoking, ar.d laryngeal carcinoma. Arch, Environ. .Health/..30.: ,517_^519. SHIN, M . L_.. Sc FIRMINGER, H . I . (1973 )___ Acute and chronic effects of mtrapentoneal injection of two types of asbestos in. rats with, a study of the histopathogenesis and .. 11 rest rue: ure cf resulting mesotheliomas. Am. J. Pathol., 70: 2_91... SHRILL, A.F. .1973,. Asbestos. In: Brobst, D. & Pratt, W., e_d. . US. mineral resources, Washington DC, US Department of the 1C,te_ricyr 63 - 72 (Geological Survey Professional Paper 820). SIEMIATYCKI, J198 3 A Health effects on the general pgcu 1 at ion . .rrorpal i ty in t he general population m asbestos mining areas' . In: Proceedings of che World Symposium on _ Asbestos, Montreal, Canada, 25-27 May, 1982. Montreal, Canadian Asbestos Information Centre. SIGURDSCN, E-S. '1983) Observations of cancer incidence surye.i llance in Duluth, Minnesota. Environ. Health Perspect., 53: 61 67 , SIG URD SONE_, E . , LEVY, B.S.. MANDEL. J.. MCHUGH, R., MI Cill ENZI, L. J. , JAGGER, H., & PEARSON, J. (1981? Cancer morbidity investigations: lessons for the Duluth study of possib1e effeets of asbestos in drinking-water. 25: 50. Environ. Res.. http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 122 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) SINCQCK, A.M. & SEABRIGHT, M. (1975) Induction of chromosome changes in Chinese hamster cells by exposure to asbestos f.ibers Nature (Land.), 257: 56-58. A V # CELHAN7Y, J.D. A., & CASEY, G.__ 1198 2J-_. A comparison__of the cytogenetic response to asbestos and glass iibre__m Chinese hamster and human cell lines. Demonstration of growth inhibition in primary human fibroblasts. Mutat. Res. , 101:. 257 - 268 . BMITH,_. W & HUBERT, D.D. '1974) The intrapleural root as a :,r.s ::: s t : "-a t mg car c ir.ogem c i iy . InyKarbe,. E. & Park, J. r . , eg. Experimental lung cancer, carcinogenesis, and bicassav, New York, Springer, pp. 92 101. SMl.7iL._W .E., MILLER, L.. CHURG. J.. & SELIKOFF, I.J. (1965) Mesotheliomas in hamsters following intrapleural miection of asbestos. J. Aft. Sinai _Hosp._j_ 32j 1 SMITH. W.E., MILLER. L., & CHURG. J. (1970) An experimental model for study of carcinogenesis in the respiratory tract. In: Morphology of experimental respiratory carcinogenesis, Oak Ridge, Tennessee. US Atomic Energy Commission, pp. 299-316 (US AEC Symposium Series 21). SMITH. W.E., HUBERT, D-D., SOBEL. H.J.. PETERS. E.T., & DOERFLER, T.E. {1980) Health of experimental animals drinking water with and without amosite asbestos and other mineral particles. J. Environ. Pathol. Toxicol., 3: 277-300. SPEIL, S, & LEINEWEBER, J.P. (196 9) Asbestos minerals in modern technology. Environ. Res., 2: 166-208. S PL'RNY , . K . R . ;1983; Natural fibrous zeolites and their carc:r,caenicity;_ a review. Sci . Total Environ., 30: 147-166. S ? C R X Y, K . R . St GENTRY, . J . W ;.l ,9_8 2_ 1 _ _ Filtration efficiency studies for fibrous particles. In: World Filtration Congress , 1 - -17._Septembert 1982, Philadelphia. Pennsylvania. The kXY A_. K STCE3ER, W.. OPIELA, H., & WEISS. G. (1979a) the eva1uation of fibrous aerosols in remote ambient air. _i. Total Environ., 11: 1-40. PCRXY, _K,, POTT, F., HUTH, F., WEISS. G., & OPIELA. H. ,1579*1-.. [Identification and carcinogenic effect of fibrous accirolite of a quarry.1 Staub - Reinhalt. Luft, 39: 386-389 !m German. . SPURNY, K.R., SCHOERMANN, J.. & KAUFMANN, R. (1981) Identification and microanalvsis of mineral fibres bv LAMMA Fresenius' Z. Anal. Chem., 308: 274-279. STANTON, M.F. & LAYARD, M. (1978) The carcinogenicity of fibrous minerals. In: Gravatt. C.C. Et al.. ed. Proceedings of the Workshop on Asbestos: Definitions and Measurement Methods. Washington DC, July 18-20, 1977, Gaithersburg. Maryland. National Bureau of Standards, pp. 143-151 [National Bureau of gtar.aaids . Special Publication 506. . STANTCN,___M_._F . Sc WRENCH, C.,1972.'______ Mechanisms of mesothelioma 1 P-du c t ior. _wi th asbestos and fibrous glass. J. Natl Cancer Ins t .__ 4 8 :__ 797 - 821 . STAXTCX, M . F. , LAYARD,.. MTEGERIN, A., MILLER. E., MAY. M., & '-'EN'T. E 17'"'. Carcinogenicity cf_ fibrous glass: pleural Response m the rat in relation to fibre dimension. J. Natl http: '\v\\'\\ .inchem.org/documents/ehc/ehc/ehc53.htm Page 123 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) Car.cer Ins c . , 58 : 58 7 - 603 . S.:_AN , LAYARP, M.. TEGERIN. A., MILLER, E., MAY, M., MORGAN, E., i SMITH,. A... ,1981.' Relation of particle t .s : ::" 'a re : r.coen : ct y_ :n amphibole asbestoses and other U. Na t J Cancel Inst . , 67 ; I. : 969 97 5... STEEL, E.3. & SMALL, J ._A . __(.198 5] Accuracy of transmission elect rcn._ mi croscopy for analysis of asbestos in ambient environment. Anal. Chew., 57: 209-213. STEEL, EB., SMALL. J-A-, & SHERIDAN, P. (1982) Analytical errors in asbestos analysis by analytical electron microscopy, Washington DC. National Bureau of Standards, dp. 162-168 (NBS Spec 1 a 1 _ _Pu bl i cation No. 619) . STELL, P.M. & MCGILL. T. (1973) career Lancet, 11_: 416 -417 . Asbestos and laryngeal ST03ER, W. , FLACHSBART. H., & HOCHRAINER. D. {1970; [The aerodynamic diameter .of. latex aggregates and asbestos fibres.1 Staub-Reinhal t. Luft, 30 : 277 285 'in German) . STOREYGARD, A.R. & BROWN, A.L. (1977) Penetration of the smal I intest i na 1 mucosa by asbestos fibres. Mayo Clin. Proc., 52: 809 812 , SULLIVAN, R. &. ATHANASSI ADI S. Y. 11969) Preliminary air pollution survey of asbestos, Raleigh, North Carolina. US S'UNDU.'R, N. & 3YGDEN, A. '.1 938) [Dust content in. asbestosi.s .c.i u uec zi iscestcs bodies, j Arch. Jewebepa thoI_^._...8.i 2 6 'j .m German^ . SUZUKI, J_. .1532; Carcinogenic and fibrogenic effects of zeolites: preliminary observations. Environ. Res., 27: 433-445. SUZUKI. J. & KOHYAMA, N. (1984) Malignant mesotheliomas induced by asbestos and zeolite in the mouse peritoneal cavity. Environ. Res., 35: 277 - 292. TABTAr, M. E. '.1981.- Pattern recognition in the context of an asbestos cancer threshold study. In: Proceedings of Che 13th Annual Symposium Interface: Computer Science Statistic. TARTER, M. '.1552;___ Graphical reanalysis of the California Bay area study. Presented at the US EPA Summary Workshop on Ingesced Asbestost Cincinnati, Ohio, 13-14 October,__1982. TASK.GROUP ON _ LUNG DYNAMICS (1966' Deposition and retention models for internal dosimetry of the human respiratory tract, Health_Phys. ,. _12__:_ 17.3.; 208 (Comm. XI , ICRP) . IAYLCR, D.G., BARON,. P.A.. SHULMAN, S.A.. & CARTER, J.W. I i-i-r. l . f i rat: or. arid count i na_c f asbestos fibres. Am. ..Ind, Hyg_. Assoc. J4 5: 84-88. (A.: _ , y. '.-'.9, Methods for the quantitative determination -iscvstos and cp.art.2 in bulk samples using X-ray dllira c tion.. Analyst, 103: 1009-1020. TETA, M. JLEWINSOHN, H.C., MEIGS. J.W., VIDONE, R.A., MOWAD, L . Z ._ & FLANNERY, J.T. (1983; Occupat lonal and geographic a s s c_c ; a tic ns. _ J. Qccup. Med., 25: 749-755. TREE. I AULT, G_., & GRAND BOIS. L. (1978) Mesothelioma and asbestos i n the. province... of Quebec ..196 9 - 1972 . Arch .__Envi ron . http: "www. inchem.org/documents/ehc/ehc/ehc53.htm Page 124 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) _Heai_ch^_33_:__ 15_-JL 9^ THOMAS. H.F., BENJAMIN. I.T., ELWOOD, P.C., & SWEETNAM, P.M. '1992_) Further follow-up study of workers from an asbestos cement factory. Br. J. Ind. Med., 39: 273-276. THOMSON 1_. J .G. & GRAVES. W.M. (1966) Asbestos as an urban air contaminant^ _Arch, Pathol., 81: 458 -464. TIM3RELL, V. )196 52 The inhalation of__fibrous dusts. Ac ad,... S.c.1 . , _ 13 2 :. _. 255.. .27 3^ Ann. NY t:mBEFLL, V. .1 972, Inhalation and biological effects of asbestos. In: _Mercer,__T.T. Et al.. ed. Assesssment of airborne pa r_t i cl es L Springf 1 eld. Illinois. C.C. Thomas, pp . 429-445. TIMBRELS, V. .1975) cy t.agne.uc 11 elds_, Alignment of respirable asbestos fibres Ann, Occup. Health, 18: 229-311. TIMBRELS, V. .1980) Measurement of fibres in human lung ttssue_. ..In Wagner i... J.C., ed Biological effects of mineral fibres. Proceedings of a Symposium held at Lyons, 25 -27 Strp temperj 1979, _ Lyons , International Agency for Research on Cancer, Vol . l,.pp_. 113 126 ,1 A_RC .Scienp.ifi.fi_c Publications Nc. 3C, TIMBRELL, V. (1982) Retention of fibers in human lungs. In-. Walton, W.H.. ed. Inhaled particles. V. Proceedings of an International Symposium, Cardiff, 8-12 September, 1980, Oxford, Pergamon Press, pp. 347-369. TIMBRELL, V. & SKIDMORE, J.W. (1971) The effect of shape on p_article penetration and retention in animal lungs. In; Walton, W.H., ed. Inhaled particles. III. Proceedings of an International. Symposium, London, 14-23 September, 1970, Old .-.);_.ug , Surrey. Onwi n, Vol. 1, pp .__49-56. TOFT P. , WIGLS. _ D., MERANGER, , & MAO, Y. (1981) Asbestos and drinking-water in Canada.___ Sci^__ Total Envi ron. ,_18_:__ 77-.8.9.,_ TCFT, P., MEEK, M.E., WIGLE, D.T., & MERANGER. J.C. (1984) Asbestos in drinking-waterOttawa, Ontario, Canada. Cep a r t me r. t of N a 11 on a 1 Health & Welfare, Health Protection Kronen ,CRC Critical Reviews in Environmental Control) ^ i ilenc, c .m ., karriscnl. . w.o.,. soloman. a. , & webster, j. A survey of o-.acx mineworkers. of the Cape crocidolite -ires. In: Wagner, J.C., ed. Biological effects of mineral : .- n . > . :-f.-euL -r a Symposium ::eld at Lyons, 2_5_r2_7. Sepcembei , Ia79, Lyons, International Agency for Research or, Cancer, Vcl,_ 2,. pp , 72_3 72_9 .IARC Scientific Publications No. 30.).._ LOPPING,__ D .C. & NETTESHEIM, P. .I960; Two-stage carcinogenesis stud.i_es with asbestos in Fischer 344 rats. J. Natl Cancer Inst., 65:3': 627-630 TOPPING. D.C., NETTESHEIM, P-, & MARTIN. D.H. (1980) Toxic and tumongenic effects of asbestos on tracheal mucosa. J. environ. Pathol. Toxicol., 3: 261-275. CORNER - WARWICK,___M& PARKES, W.R. (1970) Circulating roe-mate-.a... ana antinuclear factors in asbestos workers. 0. 2 : , J.2_ 4 95 ,. Br. OLLMANN'S ENCYCLOPAEDIA_ OF TECHNICAL CHEMISTRY )1982) Wein.heim^_ Deerfield Beach. Basel, Vol. 21. p. 406 (in German). 'JM W E LT 3 ON L E SAM T_ ) UBA).1930.) [Envi ronmental pollution by http: /w ww.inchem.org/documents/ehc/ehc/ehc53.htm Page 125 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) asbestos and other fibrous dusts,] Berlin, Erich Schmidt Verlag, 411 pp (Umweltbundesamt, Berichte 7/80) (in German) US BUREAU OF MINES _/198 2) Minerals yearbook 1981, Washington DC,. US_Department of che Interior, Vol . 1. A yre -m; r.aiy tr j: l on asbestos in the n . V:;. m'h.' r a i rea , Washington DC, US Environmental Protection Agency, Office of Technological Analysis. US.. EPA v1373,.._ Electron microscope measurement of airborne asbestos concentrations. A provisional methodology manual, research Ttiarvgle Park, North Carolina, US Environmental Protect ion _ Agency __ (EPA Report 600/2-77-178) . US EPA_ __1_980_ Ambient water quality criteria for asbestos, Washington DC, US Environmental Protection Agency (EPA Report No. 440/5-80 022, PB 81-117-335? . S EiA 1;-.:.... Asbestos fibre determination in water samples: preparation techniques - improved analytical method and rapid screening, US Environmental Protection Agency (Proiect Summary EP.. 1.. 89/2. :60 Q/S4 - 83 - 044) . US NZOSH (1972; Criteria for a recommended standard: occunational Exposure to Asbestos, Washington DC, US Department of Health, Education and Welfare. Public Health Services and Mental Health Administration, National Institute.for Occupational Safety and Health (PHEW Publication No. 72 - 10267) , US NIOSH... '197.11 - The industrial environment: its evaluation a:: j .ct' i .c , i n c i nn a_t ;, h i c, _ b National Institute of. 0rc-caticna1 Sa_fety and Heait.p. US NIOSH .1977) Asbestos fibers in air. NXQ5H manual of analytical methods, 2nd ed Cincinnati, Ohio, National u.at-tote ioi Occupational Safety and Health,__Vol. 1. US NIOSH '1984) Revised NIOSH asbestos counting method. NIOSH _manual of analytical methods, Cincinnati, Ohio, US National Institute of Occupational Safety and Health. US NRC/NAS .1977' ..... Drinking-water and health, Washington DC, National Research Council,. Safe Dr.ink1.n9__Wa.ter Committee, Nat icna 1_.Academy of Sciences,__DP -13 Q r.l 5l_._ US..NRC/NAS '1984' Asbestiform fibers: non-occupadonal health risks, Washington DC, US National Research Council. Committee on Nonoccupational Health Risks of Asbestiform Piters, pp. 177-180. US NTP H 98 3.J____ Li.fetime carcinogenesis studies of amosite asbestos in. Syrian golden hamsters, Research Triangle Park, North Carolina, US National Toxicology Program (NIH Publication No._ 84 -2505) . US .NTP -.198 5.1____ Toxicology and carcinogenesis studies of chrysotile asbestos in F344/N rats (feed study), Research Triangle Park, Nortn Carolina, US National Toxicology Program, 390 cp .Technical Report Series No. 295; NIH Publication No. VAUI/C, FU___1953' ... ILO encyclopaedia of occupational health and safety,_Vol.,__ 1. Geneva, International Labour Office, p. 601. YAULYATKAN, V. , ROBINSON. V., REASOR, M.J.,__ & STETTLER, F. .1984. Wo I 1 is t or.i te...and asbestos, cytot o.xi c_i t y_.. .__._Ani.-_. Rev. rest;r. Dis.,. 129: A178. http://vvww.inchem.org/documents/ehc/ehc/ehc53.htm Page 126 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) VEREIN RECTSCHER INGENIEJRE .1984.' [Measuring of inorganic ticrous pat Holes m ambient. air - scanning^ ejection.. microscopical, method] _)_in German'' . VI ANNA t. N_. J.. & POLAN, A . K . '1978;___ Non occupational exposure to. a sb.es t o s_ and malignant meso thelioma in females. Lancet, 2: 1 061.10 6 3. VORWALD. A.J., DUNKAN, T.M., & PRATT, P.C. (1951) Experimental studies of asbestosis. Arch. Ind. Hyq. Occup. _Med._^__3 l._Is8_3_^ WAGNER, J.C. ; 1962.' Experimental production of mesothelial tumours py implantation of dust in laboratory animals. Nature (Lend.), 196: 180. WAGNER, J.C. (1963a) Asbestosis in experimental animals. J. Ind. Med., 20: 1. Br. WAGNER, JX, . t.19 63b) Asbestos dust and malignancy. In: Proceedings of... the XIV International Congress of Occupational Health, Madrid, 1963, pp. 3. 1066-1067. WAGNER, J.C. '.1982) Health hazards of substitutes. In: Proceedings of the World Symposium on Asbestos, Montreal, Canada, 25 27 May, 1982, Montreal, Canadian Asbestos Informat ion Centre,__po. 244 -266 . WAGNER, J.C,. i BERRY,. G_. 1569. Mesotheliomas in rats : t.Icwmu inoculation with asbestos. Br. J. Cancer, 23: 5.61 - 5 8 1, 'WAGNER, J.C. & SKIDMORE, J.W. (1965) Asbestos dust deppsition and retention in rats. Ann. NY Acad. Sci., 77 86 . 132: WAGNER,_ JSLEGGS, C.A., & MARCHAND, P. (I960? Diffuse pleural mesothelioma and asbestos exposure in the Northwestern Cape Province. Br. J. Ind. Med., 17: 260-271. WAGNER, J.C., BERRY, G., & TIMBRELL, V. (1973) Mesothelicmata in rats after inoculation with asbestos and other minerals.___ Br. J. Cancer. 28: 175- 185. WAGNER_l_ J.C. , BERRY, G., SKIDMORE, J.W., & TIMBRELL, V. . 1.974j____ The, effects of the inhalation of asbestos in rats. J. Cancer, 29: 252-269. Br WAGNER, J.C., BERRY, G.,, COOKE, T-L., HILL. R.J., POOLEY, E . C . , Zt SKIDMORE, J.W. .1977.' Animal, experiments with talc. In j walton . W.H., ed. Inhaled particles. IV. Part 2. Proceedings gf_ an International Symposium, Edinburgh, 22-26 September19 75, Oxford. Pergamon Press, pp. 647- 654. VIA TIER , J . , BERRY,. G . , SKIDMORE,, J.W. , & POOLEY, F.D. .1380. The. comparative effects of three chrvsotiles by i act: on and. inhalation__in rats. In: Wagner, J.C., ed . Biological effects,of mineral fibres. Proceedings of a Symposium held at Lyons, 25-27 September, 1979, Lyons, International Agency for Research on Cancer, Vol. 1, pp. 363 372. IARC Scientific Publications No. 30; a.AJNER, J.C. 4. SX1LMCRE, J.W,, HILL, R. J . . & GRIFFITHS, D.M. ' 1985 Eriomte exposure and mestotheliomas in rats . Br. J. Cancer, 51: 727-730. WALTON, VI.H.. (1982). The nature, hazards and assessment of http://www.inchem.org/documents/ehc/ehc/ehc53.htm Page 127 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) occupational exposure to airborne asbestos dust:__a review. ..A*V2.`. Occup. Hyg. , 25: 117-247. WARHEIT^IOB, . HILL, L.H., Sc BRODY, A. R. (1984) In vitro efrects of crocidolite asbestos and wollastonite on pulmonary macrophages and serum complement. Scanning Elect. Microscop., 2_:_9 1 9 -_92_6 . WARREN, S.t BROWN, C.E., CHUTE, R.N.. , & FEDERMAN, M. (1981) Nesot_ne_iicrna relative to asbestos, radiation, and methylcnolanthrene. __ Arch. Pathoi. Lab. Med. ,__105 : 305 . WEBSTER, ,1974, The ingestion of asbestos fibres. Er.vi runFerspect . , 9 : 199 202 . WEBSTER,. I. (1977) Methods by which mesothelioma may be diagnosed..,. ..In: Glen, H. W. , ed. Proceedings of Asbestos Symposium, Johannesburg, South Africa, 1977, Randburg. National .Institute, for Metallurgy, pp 3-8. THCT.T, B.A. ,1574, Asbestos fibrils., in Bull. Environ. Tontam. Toxicol . , 11..:. WEHNER, A.P. (1980] Effects of inhaled asbestos, asbestos plus cigarette smoke, asbestos - cement, and talc baby powder in hamsters. In: Wagner, J.C.. ed. Biological effects of mineral . fibres. Proceedings of a Symposium held at Lyons, 25-27 September, 1979, Lyons, International Agency for Research on Cancer. Vol. 1, pp. 373-376 (IARC Scientific Publications No. 3 0'. WEHNER, A_,_P. , BUSCH, R.H., OLSON. R.J., & CRAIG. D.K. (1974) Ij; ves: i_ga t_i or. _ of 00 - caroinogenici ty of asbestos, cobalt oxide, r. i_ c k e 1 ox_i he, _jdi e th ylni trosamine, _ and . c iga ret te smo ke_, Bethesda, Maryland, Richland, Washington, Battelle-No rthwes t_ .Final report.to National Cancer Institute'. WEHNER, A.P., BUSCH. R.H., OLSON. R.J., & CRAIG, D.K. _T.rcr. 1 c inn a 1 at ion of asbestos and cigarette smoke by hamsters..___ Envi ron . Res . , 10 : 368 . (1975: WEHNER, A,P., STUART, B.O., & SANDERS, C.L. (1979) I nr. a 1 at: on studies . with Syrian golden hamsters. Prog. Exp. 7U:". Res., 2 4-. :77. S. WAGGENSPACK1 CO .1975.' If.f 1 pence of 1 '.-jl .ill 1 i j ma_ 1 ~n.<an.cy uSfv in asbestos An. Rev. Respir. Pis., 120: 345-354. WEISBURGER, J.. H. St WILLIAMS, G.M. {1980J Chemical r arc i no-gens. In: Doull, J. Et al . . ed. Casarett and Doull's toxicology, New York, Macmillan Publishing Co.. Inc, pp, 84-136. WE IS5, VO (1977) Mortality of a cohort exposed to chrvsotile asbestos, J. Occup._ Med. , 19: 737-740. WESTOARE. G.E , , SPJ'JT, H.J., St SMITH, M.N. (1965) Rape ti atior. of colonic mucosa by asbestos particles. An e1ectrot microscopic study in rats fed asbestos dust. Lab. .Fnyest. , 14: 2029- 2033 . WH;t.E,. R. & KUHN, C.(1980) Effects of phagocytosis of "pip.era.l... du.s.p on elastase secretion by alveolar and peritoneal t x -.cO. live mac r opha-g e . Ar ch. Environ. Health,__35 : 106 -109 . WHITWEUU, F., SCOTT, J. GRINSHOW^__M. (1977) Relat ionship http:/nvww. inchem.org/documents/ehc/ehc/ehc53.htm Page 128 of 129 11/7/2001 Asbestos and other natural mineral fibres (EHC 53, 1986) between occupations and asbestos-ibre content of the lungs in ,Pa>_ient_s_with p _1 eural_ mesothelioma, lung cancer and other diseases. .. Thorax, .32 : .377 386.. WHO vi 38.4 Evaluation of exposure_to airborne paz'ticles in the work environment, Geneva^ World Health Organization (WHO Offset Purl : -it ion No . 30. . WITCH, C.T. .13"77; Cancer mortality in relation to asbestos in municipal water supplies. Arch. Environ. Health, 32: 185. O.T , MAO, V., TOFT, P_._, & MERANGER. J.C. (1981) Cancer_.morta 1 i.t y_ and .drinking-water quality in selected Canadian runi cipalit_i.es.__ In Proceedings of the Workshop on the Compatibility of Gr_e_at Lakes Basin Cancer Recfistries, Windsor, International Joint Commission, . pp . 41.-. 5 7_._ WIGNALL, B.K. & FOX, A.J. (1982) Mortality of female uas- mask assemblers. Br. J. Ind. Med., 39: 34 -38. WRIGHT, W. W.^, ROM, W.N.. & MOATMED. F. (1983) Characterization of zeolite fiber sizes using scanning electron microscopy. Arch. Environ. Health, 38: 99-103. WYLLIE, D.M. (1973) 175- 178 , Asbestos filter sheets. Filtr. Sep., X0: ZOLOV, C., 3QURILK0V, T., & BABADJOV, L. '1967' Pleural asbestosis in agricultural workers.. Environ. Res. , 1: 287. _____ SeeAlso :. Page 129 of 129 http://www.inchem.org/documents/ehc/ehc/ehc53.htm 11/7/2001