INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY

    ENVIRONMENTAL HEALTH CRITERIA 53

    ASBESTOS AND OTHER NATURAL MINERAL FIBRES

    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.

        ISBN 92 4 154193 8 

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CONTENTS

ENVIRONMENTAL HEALTH CRITERIA FOR ASBESTOS AND OTHER NATURAL 
MINERAL FIBRES 

1. SUMMARY AND RECOMMENDATIONS FOR FURTHER RESEARCH    

    1.1. 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      
    1.2. Recommendations for further research   

2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, SAMPLING AND 
    ANALYSIS   

    2.1. Identity; physical and chemical properties
         of asbestos minerals   
         2.1.1. Serpentine group minerals - chrysotile  
         2.1.2. 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  
    2.2. 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)    
    2.3. 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    
                2.3.2.1  Light microscopy   
                2.3.2.2  Electron microscopy    
                2.3.2.3  Gravimetric determination  
         2.3.3. Other methods   
         2.3.4. Relationships between fibre, particle, and mass 
                concentration  

3. SOURCES OF OCCUPATIONAL AND ENVIRONMENTAL EXPOSURE      

    3.1. Natural occurrence     
    3.2. 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. Other natural mineral fibres    
         3.2.3. 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  
         3.2.4. Use of products containing asbestos 

4. TRANSPORT AND ENVIRONMENTAL FATE    

    4.1. Transport and distribution 
         4.1.1. Transport and distribution in air   
         4.1.2. Transport and distribution in water 
    4.2. 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. 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  
    6.2. 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  
         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    

                7.1.3.6  Factors modifying carcinogenicity  
    7.2. Other natural mineral fibres   
         7.2.1. Fibrous clays   
                7.2.1.1  Palygorskite  (Attapulgite)    
                7.2.1.2  Sepiolite  
         7.2.2. Wollastonite    
         7.2.3. Fibrous zeolites - erionite 
         7.2.4. Assessment  

8. 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. 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  
    9.2. Other natural mineral fibres   
    9.3. 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  
    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, 
   Italy 

Dr J. Dunnigan, L'Institut de l'Amiante, Sherbrooke, Canada 

Dr Fischer, Federal Health Office, Berlin (West) 

Dr R. Konstanty, German Trade Union Congress, Düsseldorf, Federal 
   Republic of Germany 

Mr L. Mazzuckelli, National Institute for Occupational Safety and 
   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, 
   Franceb

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
b   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 
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. Stöber 
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, Düsseldorf, 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. SONICH-
MULLIN, 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

1.1.1.  Identity; physical and chemical properties, methods
of sampling and analysis

    The commercial term asbestos refers to a group of fibrous 
serpentine and amphibole minerals that have extraordinary tensile 
strength, conduct heat poorly, and are relatively resistant to 
chemical attack.  The principal varieties of asbestos used in 
commerce are chrysotile, a serpentine mineral, and crocidolite and 
amosite, both of which are amphiboles.  Anthophyllite, tremolite, 
and actinolite asbestos are also amphiboles, but they are rare, and 
the commercial exploitation of anthophyllite 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 
sample 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 
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 µm in length with an 
aspect ratio > 3:1 and a diameter of less than 3 µm 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 less than the resolution of the light microscope are not 
included in this assay).  Fibres with diameters smaller than 
approximately 0.25 µm 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 
equipment 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. 

1.1.2.  Sources of occupational and environmental exposure

    Asbestos is widely distributed in the earth's crust. 
Chrysotile, 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).  Chrysotile 
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 
industrial 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 
materials. 

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 µm 
in length) 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 higher.  
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 106 
fibres/litre (all fibre lengths). 

1.1.4.  Toxicological effects on animals

    Fibrosis 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 
asbestos 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 
following inhalation of attapulgite and sepiolite; a remarkably 
high incidence of mesotheliomas occurred in rats following 
inhalation of erionite.  Long-fibred attapulgite induced 
mesotheliomas following intrapleural and intraperitoneal 
administration.  Wollastonite also induced mesothelioma after 
intrapleural administration.  Erionite induced extremely high 
incidences of mesotheliomas following inhalation exposure and 
intrapleural 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 µm and less than 1.5 µm 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 
less 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 and 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 
mesothelioma 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-malignant thickening of the visceral pleura is frequently 
associated 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 
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 lung 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 
qualitative 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 undetectably 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. 

    (d) 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 
        general environment.  The only exception is erionite for 
        which a high incidence of mesothelioma in a local 
        population has been associated with exposure. 

1.2.  Recommendations for Further Research

    The molecular and cellular mechanisms associated with both the 
fibrogenic 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; 

    (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 

    (g) improvement and international standardization of methods of 
        monitoring exposure to asbestos and other fibrous 
        materials. 

2.  IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, SAMPLING AND ANALYSIS

2.1.  Identity; Physical and Chemical Properties of Asbestos Minerals

    Asbestos 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 
vary significantly, but tend to be in the millimeter range.  This 
has given rise to a technical grading based on fibre bundles, 
lengths, 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 
crocidolite 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 
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 & Nolan, 1985). 

    Two basic mineral groups, serpentine and amphibole, contain 
important asbestos minerals including the 6 minerals of special 
interest listed 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 - chrysotile

    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 
hollow tube.  These tubes form the composite fibre bundle of 
chrysotile. 

Table 1.  Physical and chemical properties of common asbestos mineralsa
-------------------------------------------------------------------------------------------------------------
Characteristic    Chrysotile     Crocidoliteb      Amositec       Antho-        Tremolited     Actinolited
                                                                  phyllited       
-------------------------------------------------------------------------------------------------------------
Theoretical       Mg3            Na2FeII3FeIII2    (Fe, Mg)7      (Mg, Fe)7     Ca2Mg5         Ca2(Mg, Fe)5
formula           (Si2O5)(OH)    (Si8O22)(OH)2     (Si8O22)(OH)2  (Si8O22)(OH)2 (Si8O22)(OH)2  (Si8O22)(OH)2
-------------------------------------------------------------------------------------------------------------
 Chemical analysis
(range of major consitutents (%))

SiO2              38 - 42        49 - 56           49 - 52        53 - 60       55 - 60        51 - 56

Al2O3             (0 - 2)e       (0 - 1)           (0 - 1)        (0 - 3)       (0 - 3)        (0 - 3)

Fe2O3             (0 - 5)        13 - 18           (0 - 5)        (0 - 5)       (0 - 5)        (0 - 5)

FeO               (0 - 3)        3 - 21            35 - 40        3 - 20        (0 - 5)        5 - 15

MgO               38 - 42        (0 - 13)          5 - 7          17 - 31       20 - 25        12 - 20

CaO               (0 - 2)        (0 - 2)           (0 - 2)        (0 - 3)       10 - 15        10 - 13

Na2O              (0 - 1)        4 - 8             (0 - 1)        (0 - 1)       (0 - 2)        (0 - 2)

N2O+              11.5 - 13      1.7 - 2.8         1.8 - 2.4      1.5 - 3.0     1.5 - 2.5      1.8 - 2.3
-------------------------------------------------------------------------------------------------------------
Colour            usually white  blue              light grey     white to      white to       pale to
                  to pale green                    to pale        grey pale     grey           dark green
                  yellowf,                         brown          brown
                  pinkf

Decomposition     450 - 700      400 - 600         600 - 800      600 - 850     950 - 1040     620 - 960
temperatureg (°C)

Fusion            1500           1200              1400           1450          1315           1400
temperature of 
residual
material (°C)
-------------------------------------------------------------------------------------------------------------

Table 1 (contd).
-------------------------------------------------------------------------------------------------------------
Characteristic    Chrysotile     Crocidoliteb      Amositec       Antho-        Tremolited     Actinolited
                                                                  phyllited       
-------------------------------------------------------------------------------------------------------------
Density (g/cm3)   2.55           3.3 - 3.4         3.4 - 3.5      2.85 - 3.1    2.9 - 3.1      3.0 - 3.2

Resistance        undergoes      good              attacked       very good     very good      attacked
to acids          fairly rapid                     slowly                                      slowly
                  attack

Resistance        very good      good              good           very good     good           good
to alkalis
-------------------------------------------------------------------------------------------------------------
 Mechanical properties of fibre as
 taken from rock samples

Tensile strength  31             35                17             (< 7)         5              5
(103 kg/cm2)

(Average)         (440)          (495)             (250)          (< 100)       (< 70)         (< 70)
(103 psi)

Young's modulus   1620           1860              1620           -             -              -
(103 kg/cm2)

(Average)         (23)           (27)              (23)
(104 psi)
-------------------------------------------------------------------------------------------------------------
Texture           usually        flexible to       usually        usually       usually
                  flexible,      brittle and       brittle        brittle       brittle
                  silky, and     tough
                  tough
-------------------------------------------------------------------------------------------------------------

Table 1 (contd).
-------------------------------------------------------------------------------------------------------------
Characteristic    Chrysotile     Crocidoliteb      Amositec       Antho-        Tremolited     Actinolited
                                                                  phyllited       
-------------------------------------------------------------------------------------------------------------
Main producing    Canada,        South Africa      South Africa   Mozambique    Italy
countries         China,                                          USA           USA
                  Italy, 
                  South Africa, 
                  Swaziland, 
                  USA,
                  USSR, 
                  Zimbabwe
-------------------------------------------------------------------------------------------------------------
a  From: CEC (1977).
b  Mineralogical name of crocidolite is riebeckite.
c  Mineralogical name of amosite is grunerite.
d  Anthophyllite asbestos is the proper term, as with tremolite and actinolite.
e  Bracketed figures denote common elemental substitution found in asbestos minerals.
f  From serpentinized dolomite deposits.
g  Dehydroxylation or dehydrogenation accompanied by disruption of crystal lattice and major loss of 
   strength.
h  Commercial exploitation of anthophyllite discontinued.
    The chemical composition is uniform in contrast to that of the 
amphibole asbestos varieties.  Some trace oxides (Table 1) are 
always present as a result of contamination during the formation of 
the mineral in the host rock.  Some of these trace elements may be 
structurally accommodated within the tetrahedral site of the silica 
layer (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 chrysotile (Harington, 1962). 

    Chrysotile 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 matter.  Chrysotile 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 chrysotile are shown 
in Table 1. 

    Exposure to acid results in the liberation of magnesium ions 
and the formation of a siliceous residue.  Chrysotile fibres are 
almost completely destroyed within 1 h when placed in 1 N 
hydrochloric acid at 95 °C (Speil & Leineweber, 1969).  Chrysotile 
is highly susceptible to acid attack, yet is more resistant to 
attack by sodium hydroxide than any of the amphibole fibres. 

    Chrysotile dehydroxylates partially and gradually; 
dehydroxylation mainly occurs at approximately 600 - 650 °C 
followed by recrystallization to fosterite and silica at about 810 
- 820 °C. 

2.1.2.  Amphibole group minerals

    The amphibole minerals are double chains of silica tetrahedra, 
cross-linked with bridging cations.  The hollow central core 
typical for chrysotile is lacking. 

    Magnesium, iron, calcium, and sodium have been reported to be 
the principal cations in the amphibole structure (Speil & 
Leineweber, 1969).  Some physical properties are summarized in 
Table 1. 

    The amphibole structure allows great latitude in cation 
replacement, 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 
matter of convenience (Table 1). 

    Whereas the comminution of chrysotile 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). 

    These 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 
(Harlow et al., 1985).  In a crystallographic study of amosite 
asbestos and its physically-different counterpart, grunerite, size 
distributions were different when they were comminuted in an 
identical manner.  This factor controls both quantity and quality 
of dose (Harlow et al., 1985). 

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 Mg2+ 
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 chrysotile.  In comparison with other amphiboles or chrysotile, 
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 
flexibility, fair spinnability, and a texture ranging from soft to 
harsh.  Unlike chrysotile, 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 (Grunerite asbestos)

    The characteristics of amosite are given in Table 1.  The Fe2+ 
to Mg2+ ratio varies, but is usually about 5.5:1.5.  Amosite fibrils 
are 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 iron-
substituted 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 chrysotile and talc deposits.  Tremolite asbestos fibrils 
range in size but may approach the dimensions of fibrils of 
crocidolite 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 
fibrous form.  Some enter the environment through human activities 
and others through natural erosion processes.  These have become 
increasingly 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 
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 
aluminium 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 part of them are fibrous, including erionite,
mesolite, mordenite, natrolites, scolecite and thomsonite (Table 2) (Wright
et al.,1983;Gottardi & Galli, 1985). 

    Erionite fibres are similar in dimension to asbestos fibres, 
though they are probably shorter in length on average (Suzuki, 
1982; Wright et al., 1983). 

Table 2.  Typical formulae of some fibrous zeolitesa
------------------------------------------------------
Erionite          (Na2K2CaMg)4.5(Al9Si27O72) x 27 H2O

Mesolite          Na2Ca2Al6Si9O30 x 8H2O

Mordenite         (Ca,Na2,K2)Al2Si10O24 x 7(H2O)

Natrolite         Na2Al2Si3O10 x 2H2O

Paranatrolite     Na2Al2Si3O10 x 3H2O

Tetranatrolite    Na2Al2Si3O10 x 2H2O

Scolecite         CaAl2Si3O10 x 3H2O

Thomsonite        NaCa2Al5Si5O20 x 6H2O

------------------------------------------------------
a   From: Mumpton (1979).

2.2.2.  Other fibrous silicates (attapulgite, sepiolite, and
wollastonite)

    The chemical composition of these minerals is:

palygorskite (attapulgite):
    Mg5Si8O20(OH)2(H2O)4 x 4H2O (Barrer, 1978);

sepiolite:
    Mg8Si12O30(OH)4(H2O)4 x 8H2O (Barrer, 1978);

wollastonite:
    CaSiO3 (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). 

    Wollastonite has received considerable attention as a possible 
substitute for asbestos.  The basic structure of this mineral is an 
infinite silicon oxygen chain (SiO3).  Calcium cations link the 
infinite chains together (Leineweber, 1980).  The properties of 
wollastonite 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 biological effects

    For respirability, the most important single property of both 
asbestos and other fibrous minerals appears to be fibre diameter.  
The smaller the fibre diameter, the greater the particle number per 
unit mass 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). 

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 
Association, 1982, 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 
1:103 to 1:107 (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 inspirability 
and respirability (Fig. 1). 

    The upper limit of the geometric diameter of respirable 
asbestos fibres is 3 µm, obtained from the cut-off of the alveolar 
fraction of spherical particles (aerodynamic diameter of 10 µm; 
specific gravity 1 g/cm3) (Fig. 1) and the average specific gravity 
of asbestos (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). 

    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., mg/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). 

    When fibre number concentrations are determined by optical 
microscopy, particles having a diameter of less than 3 µm, a 
length-to-diameter ratio greater than 3:1, and a length greater 
than 5 µm 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; Rajhans & 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 
procedures. 

    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. 

    Basically, the same principles should be applied in collecting 
samples 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 
points, duration of sampling, etc.) varies from that in the 
occupational environment (VDI, 1984). 

    The same principles should also be applied in the collection of 
samples at the work-place to determine mass concentrations (mg/m3) 
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 
be analysed is initially treated with ozone and ultraviolet 
radiation to oxidize suspended organic material.  A capillary pore 
polycarbonate filter (0.1 µm pore size) is then used to filter the 
water sample.  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 yet 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 (Langer et al., 1973; Gaudichet et al., 
1980; Pooley & 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., 
ashing 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 
procedure 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 
(Rooker et al., 1982; Walton, 1982; ILO, 1984; Taylor et al., 
1984). 

    Mineral fibres down to about 0.25 µm in diameter (lower for 
amphiboles than for chrysotile) are visible and countable by this 
method.  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 
this 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 samples.  In principle, such 
evaluations can be conducted using image analysing systems (Dixon & 
Taylor, 1979) or magnetic alignment combined with scattered light 
measurements (Gale & Timbrell, 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 in the work-place. 

2.3.2.2  Electron 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 
smaller than those found in the work-place environment.  Thus, an 
electron microscopic technique is preferred for the analysis of 
these filter samples.  For example, scanning electron microscopy 
(SEM), 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 (Clark, 1982; Lee et al., 1982; Steel et 
al., 1982). 

    In order to establish a correlation with the results obtained 
by phase contrast microscopy, the results of any fibre count 

(aspect ratio > 3:1) must contain the following size fraction: 

    -   fibres greater in length than 5 µm with diameters
        between 0.25 µm and 3 µm, 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 µm with diameters of
        less than 0.25 µm; and

    -   fibres shorter in length than 5 µm with diameters
        greater than and/or smaller than 0.25 µm.

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 
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 µm 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 µm, 
when equipped with an energy dispersive X-ray spectrometry system 
(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 µm, 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 µm.  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). 

2.3.2.3  Gravimetric determination

    Various generally-known methods are available for the 
gravimetric evaluation of filter samples (mg/m3) from the work-
place 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 X-
ray 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 Royco 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. 

    The advantages of these instruments are:

    (a) immediate location of dust sources;

    (b) instant determination of the efficiency of
        dust-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 
monitoring, 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 asbestos 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, 
1975; 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/cm3/mppcf) for various 
industrial settings varied only between 3 and 8, there were large
variations within each industry; for example, in the textile 
industry, the experimentally-determined ratio varied from 1.2 to 
11.6 and, in mines, between 0.5 and 47.4 (Robock, 1984). 
Table 3.  The numbers of fibres per ng for different size categories
(cylindrical fibre shape, density 2.5); diameter/length ratios in the second 
linea
-------------------------------------------------------------------------------
Diameter                      Length (µm)                                     
(µm)     0.625     1.25      2.5      5         10       20      40      80
-------------------------------------------------------------------------------
0.031    819 200   409 600   204 800  102 400
         1:20      1:40      1:80     1:160

0.0625   204 800   102 400   51 000   25 600    12 800
         1:10      1:20      1:40     1:80      1:160

0.125    51 200    25 600    12 800   6400      3200     1600
         1:5       1:10      1:20     1:40      1:80     1:160

0.25     12 800    6400      3200     1600      800      400     200
         1:2.5     1.5       1.10     1:20      1:40     1:80    1:160

0.5                1600      800      400       200      100     50      25
                   1:2.5     1:5      1:10      1:20     1:40    1:80    1:160

1.0                          200      100       50       25      12.5    6.25
                             1:2.5    1:5       1:10     1:20    1:40    1:80

2.0                                   25        12.5     6.25    3.2     1.6
                                      1:2.5     1:5      1:10    1:20    1.40
-------------------------------------------------------------------------------
a   From: Pott (1978).
3.  SOURCES OF OCCUPATIONAL AND ENVIRONMENTAL EXPOSURE

    Once liberated into the environment, asbestos persists for an 
unknown length 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 asbestos-
containing products.  Fibres can also be released through the 
weathering 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.  Chrysotile, 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 formations 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 chrysotile 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 chrysotile existed long before it was used 
commercially on a large scale.  The earliest dating in the ice 
cores showed the presence of chrysotile in 1750 (Bowes et al., 
1977). 

    There are also some data on levels of asbestos in water 
supplies due mainly to erosion from natural sources (e.g., 
drinking-water in areas such as  San Francisco, California; 
Sherbrooke, Quebec; and Seattle, Washington). 

    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 indicator of exposure to other natural mineral fibres 
(e.g., anthophyllite, 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; Spurny 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 resulting 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 
manufactured such as brake shoes, thermal insulation, floor tiles, 
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 manipulations), 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)a
---------------------------------------------------------------------------
Country             1979       1980       1981       1982       1983
---------------------------------------------------------------------------
Afghanistan         4000
Argentina           1371       1261       1280       1218       1350
Australia
  Chrysotile        79 721     92 418     45 494     18 587     20 000
Brazil              138 457    170 403    138 417    145 998    158 855
Bulgaria            600        700        400        600        700
Canada
  Chrysotile        1 492 719  1 323 053  1 121 845  834 249    820 000
China               140 000    131 700    106 000    110 000    110 000
---------------------------------------------------------------------------

Table 4 (contd.)
---------------------------------------------------------------------------
Country             1979       1980       1981       1982       1983
---------------------------------------------------------------------------
Cyprus
  Chrysotile        35 472     35 535     24 703     18 997     17 288
Czechoslovakia      564        617        388        342        325
Egypt               238        316        325        310        325
India
  Amphibole         32 094     33 716     27 521     19 997     17 288
Italy               143 931    157 794    137 000    116 410    139 054
Japan
  Chrysotile        3362       3897       3950       4135       4000
Korea, Republic of  14 804     9854       14 084     15 933     12 506
Mozambique          789        800        800        800        800
South Africa
  Amosite           39 058     51 646     56 834     43 457     40 656
  Crocidolite       118 301    119 148    102 337    87 263     87 439
  Chrysotile        91 828     106 940    76 772     81 140     93 016
Swaziland
  Chrysotile        34 294     32 833     35 264     30 145     28 287
Taiwan              2957       683        2317       2392       2819
Turkey              38 967     8882       2833       23 283     22 596
USAb                93 354     80 079     75 618     63 515     69 906
USSR                2 020 000  2 070 000  1 105 000  2 180 000  2 250 000
Yugoslavia          9959       10 468     12 206     10 748     9663
Zimbabwe
  Chrysotile        259 891    250 949    247 503    197 682    153 221

World Total         4 800 000  4 700 000  4 300 000  4 000 000  4 100 000
---------------------------------------------------------------------------
a   From: BGS (1983).
b   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. 

3.2.1.3  Uses

    Asbestos has been used in thousands of applications (Shride, 
1973).  The way 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 tiles 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 with 
those of asbestos. 

    (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. 

Table 5.  Asbestos products and asbestos contentsa
------------------------------------------------------------------
                          Approximate   Asbestos    Reference 
                          asbestos      fibre       to Fig. 3
                          content       typeb
                          (% weight)
------------------------------------------------------------------
1.  Asbestos-cement       10 - 15       C, A, Cr    II-6
    building products

2.  Asbestos-cement       12 - 15       C, Cr, A    II-6
    pressure, sewage,
    and drainage pipes

3.  Fire-resistant        25 - 40       A, C        II-6, II-5
    insulation boards

4.  Insulation products   12 - 100      A, C, Cr    I-1, I-2, I-3,
    including spray                                 I-4, II-5

5.  Jointings and         25 - 85       C, Cr       II-8, III-18
    packings

6.  Friction materials    15 - 70       C           II-10

7.  Textile products      65 - 100      C, Cr       III
    not included in (6)

8.  Floor tiles and       5 - 7.5       C           II-9
    sheets

9.  Moulded plastics      55 - 70       C, Cr       II-9, II-10
    and battery boxes

10. Fillers and rein-     25 - 98       C, Cr       II-7, II-11
    forcements and
    products made
    thereof (felts,
    millboard, paper,
    filter pads for
    wines and beers,
    underseals, mastics,
    adhesives, coatings,
    etc.
------------------------------------------------------------------
a   From: CEC (1977).
b   A = amosite (not used in all countries); C = chrysotile; 
    Cr = crocidolite (not used in all countries).

    (b)   Palygorskite (attapulgite)

    Available data on the production of attapulgite in various 
countries are presented in Table 6. 

Table 6.  World production of attapulgite and sepiolitea
----------------------------------------------------------
Country      Annual production of    Annual production of
             attapulgite (tonnes)    sepiolite (tonnes)
----------------------------------------------------------
France       unknown                 2500

India        10 000

Senegal      16 700

Spain        50 000                  236 000

USA          700 000
----------------------------------------------------------
a   Modified from: Bignon et al. (1980).

    The USA is the biggest producer and consumer of attapulgite; 
consumption currently exceeds 700 000 tonnes and is almost triple 
that 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, 
1982).  Similar data for other countries are not available. 

Table 7.  Uses of attapulgite in the USAa
-----------------------------------------------------
Use                                 1981 consumption 
                                    (1000 tonnes)
-----------------------------------------------------
Drilling mud                        173.5
Fertilizers                         50.2
Filtering (oil and grease)          18.7
Oil and grease adsorbents           178.2
Pesticides and related products     106.5
Pet waste adsorbent                 105.8
Medical, pharmaceutical,            0.06
 cosmetic ingredients
Other uses                          79.5

Total                               712.46
-----------------------------------------------------
a   From: US Bureau of Mines (1982).

    In France, attapulgite 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 attapulgite 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 attapulgite could be released 
into the air.  Attapulgite has also been found in water supplies 
(Millette et al., 1979b). 

    (c)   Sepiolite

    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 für Arbeitssicherheit, 1985), 
which have reduced airborne levels in the immediate vicinity by 1 - 
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

    Products 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 
substantially 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 may approach or exceed current occupational exposure 
limits) (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 
distributed via air and water. 

4.1.1  Transport and distribution in air

    Airborne mineral 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 µm and, therefore, their sedimentation velocities are very 
low.  Measurements concerning 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). 

    Calculations 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 chrysotile 
fibres present in tap-water in San Francisco, California, were 
actually 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, chrysotile, and to a lesser extent amphibole, asbestos 
fibres are capable of chemical alteration in aqueous media.  The 
magnesium hydroxide content of chrysotile 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: chrysotile > amosite > 
actinolite > crocidolite > anthophyllite > tremolite (US 
NRC/NAS, 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 
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/m3.  For concentrations in ambient 
air, fibre/litre, fibre/m3, and ng/m3 are commonly used.  Fibre 
concentrations in biological materials are usually expressed in 
fibre/g or in µg/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 
exposure measurements made during various operations involving the 
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) of 
the currently-used Membrane Filter Method, compared with the 
sensitivity of previously-used methods for the determination of 
airborne asbestos. 

    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, 1972-78a
---------------------------------------------------------
Industry             Number of   Percentage of resultsb      
                     results    < 0.5   < 1.0     < 2.0
                                      (fibres/ml)
---------------------------------------------------------
Asbestos cement      845        86.5    95.0      98.5
Millboard/paper      135        87.0    98.2      99.6
Friction materials   900        71.0    85.5      95.0
Textiles             1304       58.5    80.7      95.0
Insulation board     545        54.0    72.5      88.6
---------------------------------------------------------
a   From: Health and Safety Commission (1979).
b   4-h samples.

Table 9.  Asbestos fibre concentrations in 1984 in various 
branches of the asbestos industry in Francea
------------------------------------------------------------------
Branch           Fibre concentrations (fibre/ml)        Total
                 ------------------------------------   number of 
                 < 0.5    0.5 - 1    1 - 2     > 2      points
------------------------------------------------------------------
 Asbestos cement

   Numbersb      261      11         6        1         279
   Percentage    93.5     3.9        2.1      0.3

 Friction materials

   Numbers       249      84         55       8         396
   Percentage    62.8     21.2       13.8     2.0

 Textile

   Numbers       81       25         17       1         124
   Percentage    65.3     20.1       13.7     0.8

 Others

   Numbers       41       14         0        1         56
   Percentage    73.2     25.0       0        1.7
------------------------------------------------------------------
 Total

   Numbers       632      134        78       11        855
   Percentage    73.9     15.6       9.1      1.2
------------------------------------------------------------------
a   From: AFA (1985).
b   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 
elevated airborne levels have been measured during the manipulation 
of these materials (e.g., home construction and renovation by the 
homeowner). 

    In this and the following section, only data obtained by 
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 included. 

    Asbestos levels in the air of mining towns in Quebec have been 
determined recently by transmission electron microscopy using 
direct transfer sample preparation techniques.  Samples were 
collected in June 1983 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 
fibres/litre (total) and 7.8 fibres/litre (> 5 µm).  Mean values 
for each of the sites sampled ranged up to 97.5 fibres/litre 
(total) and 20.6 fibres/litre (> 5 µm).  For the control 
community, the mean values were lower - 14.7 fibres/litre (total) 
and 0.7 fibres/litre (> 5 µm) (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, 
1984).  Total inorganic fibre and asbestos fibre concentrations, 
using the counting criteria used in the Membrane Filter Method 
(> 5 µm in length; < 3 µm 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 (Felbermayer & 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 (Vöcklabruck), the mean concentration was 
0.5 fibres/litre (range 0 - 2.2 fibres/litre). 

Table 10.  Fibre concentrations in mining areas of Canada
and South Africaa,b
------------------------------------------------------------
Area                Locations  Concentration (fibres/litre, 
                               longer than 5 µm)          
                               Total inorganic    Asbestos
------------------------------------------------------------
 Canada (Quebec area)
   Residential      (1)        3.2                1.8
   areas near       (2)        3.1                0.9
   asbestos mines   (3)        0.9                0.2

 South Africa
   Downwind mill    (1)        600.0              600.0c
                    (2)        81.6               80.3
                    (3)        8.6                8.6
                    (4)        300.0              300.0d
                    (5)        10.6               9.3
                    (6)        4.9                2.4

   Residences of    (1)        6.3                6.0
   asbestos mine    (2)        7.4                7.1
   workers          (3)        2.7                2.0
                    (4)        11.0               11.0
                    (5)        3.2                3.2
                    (6)        8.1                7.3
------------------------------------------------------------

Table 10 (contd.)
------------------------------------------------------------
Area                Locations  Concentration (fibres/litre, 
                               longer than 5 µm)          
                               Total inorganic    Asbestos
------------------------------------------------------------
   Residential      (1)        1.0                0.8
   areas near       (2)        0.6                0.3
   asbestos mines   (3)        1.1                0.7
                    (4)        0.4                0.2
                    (5)        0.8                0.2
                    (6)        0.8                0.5

   Near a magnesium            1.5                0.1
   mine

   Near an iron                1.5                0.3
   ore mine
------------------------------------------------------------
a   From: Robock et al. (1984) and Selles et al. (1984).
b   Practical limits of error, 95% (Poisson's distribution), 
    for the calculated concentrations of fibres/litre depend 
    on the number of fibres found in 1 mm2 of the total 
    filter surface; 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/litre).
c   Unprotected tailing dump.
d   Truck loaded with soil.

    In general, the data indicate that levels of airborne asbestos 
fibres (> 5 µm in length) in residential areas in the vicinity of 
industrial 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, 
were 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 µm) at remote locations are generally less than 1 
fibre/litre.  Levels in urban air generally range from < 1 up to 
10 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 
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 drinking-
water containing asbestos fibre levels of less than 1 x 106/litrea 
(Millette et al., 1980).  In some areas, however, levels of between 
1 and 100 x 106 fibres/litre were recorded and levels as high as 
600 x 106 fibres/litre were reported for one water supply 
contaminated with amphibole fibres from the processing of iron ore. 

    A nation-wide survey of asbestos levels in drinking-water from 
71 locations across Canada (serving 55% of the population) was the 
basis for an estimation that 5% of the population receives water 
containing levels higher than 10 x 106 fibres/litre, about 0.6% 
receives water having more than 100 x 106 fibres/litre (Canada, 
Environmental Health Directorate, 1979). Levels as high as 100 x 
106 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 106 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 µm 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 
conventional treatment processes involving chemical coagulation 
followed by filtration effectively reduce levels in drinking-water 
supplies. 

Table 11.  Fibre concentrations in outdoor air
---------------------------------------------------------------------------------------------------------
Area                    Concentration (fibres/litre)a         Counting criteria      Reference
                      Total            Asbestos             
                      inorganic        Total        > 5 µm
---------------------------------------------------------------------------------------------------------
AUSTRIA
   Leoben
  (heavy traffic)     7.0                           4.6       length: > 5 µm         Felbermayer (1983)
                                                              diameter: 0.2 - 3 µm
                                                              (SEM)

   Schalchham
  (low traffic)       1.7                           0.1       length: > 5 µm         Felbermayer (1983)
                                                              diameter: 0.2 - 3 µm
                                                              (SEM)

  Village with        4.6                           < 0.1     length: > 5 µm         Felbermayer (1983)
  asbestos-cement                                             diameter: 0.2 - 3 µm
  roofing                                                     (SEM)

  Village without     4.3                           < 0.1     length: > 5 µm         Felbermayer (1983)
  asbestos-cement                                             diameter: 0.2 - 3 µm
  roofing                                                     (SEM)

  Remote rural        1.4                           < 0.1     length: > 5 µm         Felbermayer (1983)
  areas                                                       diameter: 0.2 - 3 µm
                                                              (SEM)
---------------------------------------------------------------------------------------------------------

Table 11.  (contd.)
---------------------------------------------------------------------------------------------------------
Area                    Concentration (fibres/litre)a         Counting criteria      Reference
                      Total             Asbestos           
                      inorganic        Total        > 5 µm
---------------------------------------------------------------------------------------------------------
CANADA
   Ontario
    Metropolitan                                    < 2 - 9   length: > 5 µm         Chatfield (1983)
    Toronto                                                   diameter: all
                                                              (TEM)

    Southern                                        < 2 - 4   length: > 5 µm         Chatfield (1983)
    Ontario                                                   diameter: all
                                                              (TEM)

    Toronto                                         0 - 13b   length: > 5 µm         Chatfield (1983)
    (busy                                                     diameter: all
    intersection)                                             (TEM)

    Mississauga                                     0 - 11b   length: > 5 µm         Chatfield (1983)
                                                              diameter: all
                                                              (TEM)

    Oakville                                        0 - 8b    length: > 5 µm         Chatfield (1983)
                                                              diameter: all
                                                              (TEM)

    Bracebridge                                     0 - 2b    length: > 5 µm         Chatfield (1983)
    (remote rural                                             diameter: all
    location)                                                 (TEM)

    Peterborough                                    0 - 4b    length: > 5 µm         Chatfield (1983)
                                                              diameter: all
                                                              (TEM)

   Quebec

    Sherbrooke                                      0.7       length: > 5 µm         Lebel (1984)
                                                              diameter: all
                                                              (TEM)
---------------------------------------------------------------------------------------------------------

Table 11.  (contd.)
---------------------------------------------------------------------------------------------------------
Area                    Concentration (fibres/litre)a         Counting criteria      Reference
                      Total            Asbestos            
                      inorganic        Total        > 5 µm
---------------------------------------------------------------------------------------------------------
GERMANY, FEDERAL REPUBLIC OF
   Wanne-Eickel          ----           ----     
    300 m downwind    90.0 |           | 10         2.0       length: > 5 µm         Marfels et al. 
    from asbestos-         |           |                      diameter: 0.2 - 3 µm   (1984a)
    cement plant           |           |                      (SEM)
                           |           |               
    700 m downwind    70.0 |           | 4          0.8       length: > 5 µm         Marfels et al. 
    from asbestos-         |           |                      diameter: 0.2 - 3 µm   (1984a)
    cement plant           |           |                      (SEM)
    1000 m downwind   60.0 |           | 4          0.6       length: > 5 µm         Marfels et al. 
    from asbestos-         |           |                      diameter: 0.2 - 3 µm   (1984a)
    cement plant           |           |                      (SEM)
                           |           |               
   Dortmund                 | all       |                                
    dwelling          30.0 | lengths   | 3          0.2       length: > 5 µm         Marfels et al. 
    area                   >           <                      diameter: 0.2 - 3 µm    (1984a)
                           | all       |                      (SEM)
                           | diameters |                            
    crossing          60.0 |           | 8          0.9       length: > 5 µm         Marfels et al. 
    with heavy             |           |                      diameter: 0.2 - 3 µm   (1984b)
    traffic                |           |                      (SEM)
                           |           |                
   Gelsenkirchen       50.0 |           | 10         5.0       calculated             Friedrichs (1983)
                           |           |                      length: > 5 µm
                           |           |                      diameter: 0.2 - 3 µm
                           |           |                      (SEM)
                           |           |      
   Düsseldorf          20.0 |           | 6          1.0       calculated             Friedrichs (1983)
                           |           |                      length: > 5 µm
                           |           |                      diameter: 0.2 - 3 µm
                        ----           ----                   (SEM)
---------------------------------------------------------------------------------------------------------

Table 11.  (contd.)
---------------------------------------------------------------------------------------------------------
Area                    Concentration (fibres/litre)a         Counting criteria      Reference
                      Total            Asbestos             
                      inorganic        Total        > 5 µm
---------------------------------------------------------------------------------------------------------
SOUTH AFRICA
   Johannesburg
  (centre/traffic)    3.2                           0.2       length: > 5 µm         Selles et al. (1984)
                                                              diameter: 0.2 - 3 µm
                                                              (SEM)
   Langa
  (asbestos-cement    1.7                           0.2       length: > 5 µm         Selles et al. (1984)
  application)                                                diameter: 0.2 - 3 µm
                                                              (SEM)

   Soweto
  (asbestos-cement    1.4                           0.2       length: > 5 µm         Selles et al. (1984)
  application)                                                diameter: 0.2 - 3 µm
                                                              (SEM)

   Frankfort
  (rural)             0.2                           < 0.1     length: > 5 µm         Selles et al. (1984)
                                                              diameter: 0.2 - 3 µm
                                                              (SEM)

   at Cape Point
  (reference)         < 0.1                         < 0.1     length: > 5 µm         Selles et al. (1984)
                                                              diameter: 0.2 - 3 µm
                                                              (SEM)

USA
   California
                                       
    Upwind of                          < 0.2 - 11             length: all            John et al.
    an asbestos                                               diameter: all          (1976)
    plant
---------------------------------------------------------------------------------------------------------
a   Practical limits of error, 95% (Poisson's distribution), for the calculated concentrations of 
    fibres/litre depend on the number of fibres found in 1 mm2 of the total filter surface; 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/litre.
b   95% confidence limits.

Table 12.  Levels of asbestos fibre concentrations in indoor air
---------------------------------------------------------------------------------------------------------
Area                      Number of   Concentrationa   Counting criteria     Reference
                          samples     (fibres/litre)           
---------------------------------------------------------------------------------------------------------
 Canada

  In 3 public buildings   not         < 2b             length: > 5 µm        Chatfield (1983)
  with amosite-           applicable                   diameter: all
  containing insulation

  In 7 public buildings   not         < 4 to < 9b      length: > 5 µm       Chatfield (1983)
  with chrysotile-        applicable                   diameter: all
  containing insulation

  In 19 public buildings  14          0 to 0.3         length: > 5 µm        Pinchin (1982)
  with asbestos-                                       diameter: all
  containing insulation

 Germany, Federal Republic of

  Sporting halls          45          0.1 to 1.1       length: > 5 µm        Institute for Applied
  (sprayed                                             diameter: 0.2 - 3 µm  Fibrous Dust Research
  crocidolite                                                                (1984)

  Schools (sprayed        5           0.1 to 11.0      length: > 5 µm        Institute for Applied
  crocidolite)                                         diameter: 0.2 - 3 µm  Fibrous Dust Research
                                                                             (1984)
  Public buildings        5           0.1 to 0.2       length: > 5 µm        Institute for Applied
  (asbestos-cement                                     diameter: 0.2 - 3 µm  Fibrous Dust Research
  air ducts)                                                                 (1984)

  Public buildings        3           0.1 to 0.2       length: > 5 µm        Institute for Applied
  (asbestos-cement                                     diameter: 0.2 - 3 µm  Fibrous Dust Research
  sheets)                                                                    (1984)

  Public buildings                    1.0 to 10.0      length: > 5 µm        Lohrer (1983)
  (sprayed asbestos)                                   diameter: 0.2 - 3 µm

  Homes (electrical                   0.1 to 6.0       length: > 5 µm        Lohrer (1983)
  storage heaters)                                     diameter: 0.2 - 3 µm
---------------------------------------------------------------------------------------------------------
a   Practical limits of error, 95% (Poisson's distribution), for the calculated concentrations of 
    fibres/litre depend on the number of fibres found in 1 mm2 of the total filter surface and for 0.1 
    fibre/litre (range 0.002 - 0.6 fibres/litre) and for 1 fibre/litre (range 0.5 - 1.8 fibres/litre).
b   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 
(Eisenberg, 1974).  Asbestos may also be introduced into foods from 
impure mineral silicates, such as talc, soapstone, or pyrophyllite, 
used as carriers for spray pesticides (Kay, 1974). 

    Asbestos fibres have been detected in beverages.  
Concentrations of 0.151 x 106 fibres/litre have been found in some 
English beers (Biles & Emerson, 1968), and concentrations of 4.3 - 
6.6 x 106 fibres/litre have been recorded in Canadian beers 
(Cunningham & Pontefract, 1971); levels between 1.7 and 12.2 x 106 
fibres/litre have been found in soft drinks.  It has been suggested 
that asbestos filters used for the clarification of beverages and 
other liquids 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 lung model that 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. 

6.1.1  Asbestos

6.1.1.1  Fibre deposition

    (a)   Models

    There are five mechanisms of deposition of particles in the 
respiratory tract (i.e., inertial impaction, sedimentation, 
interception, diffusion, and electrostatic precipitation). 

    Sedimentation is determined principally by the aerodynamic 
diameter 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 µm 
diameter would have approximately the same settling velocity as a 
10 µm sphere with a density = 1.0 g/m3 (Timbrell, 1982) and thus, 

it is generally agreed that all asbestos fibres with a diameter 
greater than 3 µm 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 
Stöber 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 
probability 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 µm 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 asbestosa, there was about 5 times more 
bronchial airway deposition for the "curly" chrysotile 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 
aligned 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 chrysotile asbestos in the peripheral lung 
airways of rats exposed for 1 h to 4.3 mg respirable chrysotile/m3 
was 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 
after 5 h, the patterns were similar, but the concentrations were 
reduced. 

6.1.1.2  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 primarily 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 µm), 
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 for 
    experimental use under the auspices of the Union Internationale 
    Contre le Cancer. 

dimensions.  Unlike amphibole fibres which are less soluble in lung 
fluids, chrysotile fibres undergo partial dissolution within the 
lungs after fibrillation (i.e., fibre splitting along the fibre 
length).  Predominant changes in the fibre, with time, include a 
decrease in magnesium, and an increase in iron content (Langer et 
al., 1970, 1972).  Mg2+ contributes to both the structural 
integrity and the positive charge of the fibre.  The process of 
leaching can cause fragmentation and more rapid disappearance of 
chrysotile from the lung compared with that of amphibole types of 
asbestos (Morris et al., 1967). 

    The results of 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 mg/m3 of respirable dust, the 
clearance patterns for chrysotile, amosite, and crocidolite could 
each be described by single exponential functions.  However, the 
rate of clearance for chrysotile was higher by a factor of 3 than 
that for amosite and crocidolite.  In addition, the retention of 
chrysotile, 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 (6 - 12 months), the lung burden of chrysotile reached a 
plateau, whereas a continued increase was observed for the 
amphiboles.  This difference was attributed to the enhanced 
clearance rate of chrysotile (Fig. 6). 

    In a study on rats conducted by Middleton et al. (1979), the 
retention of chrysotile was approximately one quarter that of the 
amphiboles and appeared to be related to the airborne asbestos 
level during dusting; at higher airborne levels (1.3 - 9.4 ng/m3), 
the retention of chrysotile was lower than of the amphiboles. 

    Muhle et al. (1983) investigated the effects of cigarette smoke 
on the retention of UICC chrysotile (type A) and UICC crocidolite 
in rats.  Results 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 chrysotile 
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 by a higher deposition rate of 
chrysotile in the upper airways compared with crocidolite and a 
decrease in deep lung clearance induced by cigarette smoke.  There 
is some evidence that tracheobronchial clearance is not influenced 
by cigarette smoke (Lippmann et al., 1980).  In man, smoking 
reduces long-term deep lung clearance (Cohen et al., 1979). 

    On the 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 of chrysotile.  Middleton et al. (1979) concluded 
that clearance could be described in terms of an exponential model, 
though somewhat modified compared with that used by Morgan et al. 
(1977a). 

    The clearance model used to describe the results of these 
short-term studies was not applicable to long-term (1-year) 
inhalation studies (Davis et al., 1978).  It was suggested, 
therefore, that the observations in long-term studies should be 
explained by an impairment of the clearance mechanism in lungs with 
high fibre burdens. 

    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 
fibre length on the retention of glass fibres in rat lungs by means 
of serial sacrifices.  The 1.5 µm diameter glass fibres were 
administered by intratracheal instillation.  The macrophage-mediated 
mechanical clearance was less effective for fibres 10 µm in length 
than for 5 µm fibres.  It was ineffective for fibres of 30 µm or 
more.  As supporting evidence, Morgan et al. (1980) cited the work 
of 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 µm. 

    Results of studies by Pooley & Clark (1980) indicated that the 
size distribution of amosite and crocidolite fibres in airborne 
samples was similar to that found in organs.  Later it was noted 
that the proportion of longer fibres of both minerals found in the 
lung was increased, probably because of the more efficient 
clearance of the shorter fibres.  It was difficult to compare the 
size distribution of airborne chrysotile with that in the lung 
because of the breakdown of chrysotile fibre aggregates and fibre 
bundles. 

    The effects of intermittent exposure to high doses of asbestos 
(defined by the author as peak) on fibre retention in the lungs of 
rats were studied by Davis et al. (1980b).  Four groups of rats 

inhaled UICC preparations of amosite or chrysotile.  Two of the 
groups were exposed respectively to the 2 asbestos types for 5 
days/week, 7 h/day, for 1 year.  The 2 other groups were treated 
with amosite and chrysotile, respectively, at 5 times the previous 
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 
chrysotile and amosite in lungs were similar regardless of whether 
"peak" (1-day/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" chrysotile group more slowly 
than that from the lungs of the "even" chrysotile 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 
potassium octatitanate (Fybex), potassium titanate (PKT), and UICC 
amosite.  The mean diameters (0.2 - 0.4 µm) and lengths (4.2 - 6.7 
µm) were nominally similar for all three types of fibre.  Numerous 
dust cells were transported to the tracheobronchial and mediastinal 
lymph nodes, where some dust cells penetrated into the blood or 
lymphatic circulation.  The dust cells migrated directly from the 
lymph nodes into adjacent mediastinal adipose tissue.  Dust-laden 
giant cells were occasionally found in the liver, and there was 
widespread migration of the fibres into other organs, without any 
significant 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 likely 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 
6.1.1.1), the examination of tissues by transmission electron 
microscopy revealed that chrysotile fibres deposited on the 
bifurcations of the alveolar ducts were taken up, at least 
partially, by type I epithelial cells 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 chrysotile is 
more likely than the amphiboles to be deposited in the upper 
airways of the respiratory tract.  In addition, chrysotile is 
cleared more efficiently from the lungs; thus, there is greater 
retention of the amphiboles.  Fibre length is an important 
determinant of clearance, with shorter fibres being cleared more 
readily, and cigarette smoking affects deep-lung but not 

tracheobronchial clearance.  There were no consistent effects on 
clearance and retention of fibres with intermittent exposure to 
high 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 & 
Graves, 1966; Bignon et al., 1970; Selikoff et al., 1972; Davis & 
Gross, 1973; Oldham, 1973).  Probably fewer than 1% of the fibres 
in the lung become coated (Gaensler & Addington, 1969).  No 
etiological significance has been attributed to the formation of 
asbestos bodies; their occurrence alone merely indicates exposure 
to asbestos and not necessarily the presence of disease (Longley, 
1969; Milne, 1971; Churg & Warnock, 1980). 

6.1.3  Content of fibres in the respiratory tract

    The mineral fibre content of organs of deceased persons who had 
been occupationally exposed to asbestos has been investigated.  
Such determinations require tissue digestion procedures that do not 
change the fibre structure, and sophisticated analysis to identify 
single submicroscopic fibres.  The reported mineral content in the 
lungs of workers exposed to fibres ranged from 1 to 10 g/kg (dry 
weight); levels in the general population are about 0.3 g/kg (dry 
weight) (Beattie & Knox, 1961). 

    No conclusions concerning the regional distribution of fibres 
in the lung can be drawn on the basis of available data (Le 
Bouffant, 1980; Sebastien et al., 1980b). 

6.2  Ingestion

    An important question in the evaluation of the possible risks 
associated with the ingestion 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 
concerning 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, 1983; Toft et al., 1984).  It is not possible to conclude 
with certainty that asbestos fibres do not cross the 
gastrointestinal wall.  However, available evidence indicates that, 
if penetration does occur, it is extremely limited.  Cook (1983) has 
suggested that 10-3 to 10-7 of ingested fibres penetrate the gut 
wall. 

    There is no available information on the bioaccumulation/ 
retention of ingested asbestos fibres.  Simulated gastric juice has 
been shown to alter the physical and chemical properties of 
chrysotile fibres and, to a lesser extent, crocidolite fibres 
(Seshan, 1983).  Available data concerning the possible elimination 
of asbestos in the urine of human beings are contradictory and 
inconclusive (Cook & Olson, 1979; Boatman, 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 
in epidemiological studies, but also to elucidate the mechanisms of 
toxicity, to define biologically important physical and chemical 
properties, and to develop hypotheses for further epidemiological 
study.  The results of toxicological studies on asbestos have also 
imparted information on dose-response relationships and the role 
of fibre type, size, and shape in the pathogenesis of asbestos-
related diseases.  However, conclusions concerning the importance 
of these variables are necessarily limited, because of the 
inability to adequately characterize fibre size in the administered 
material.  In the following section, the results of recent studies 
are emphasized, since experimental methods have improved 
considerably in the past few years. 

7.1.1  Fibrogenicity

7.1.1.1  Inhalation

    Data concerning the fibrogenicity of inhaled asbestos in animal 
species are presented in Table 13. 

    Fibrosis has been observed in 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 
following cessation of exposure (Wagner et al., 1974, 1980).  In 
general, it has been observed that shorter fibres are less 
fibrogenic (Davis et al., 1980a). 

    The results of the early studies regarding the relative 
fibrogenicity of various fibre types are confusing and 
contradictory mainly because, usually, only the airborne mass 
concentrations 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 - fibrogenicity
---------------------------------------------------------------------------------------------------------
Species   Number              Protocola                       Results                          References
---------------------------------------------------------------------------------------------------------
Guinea-   16-24 guinea-pigs,  exposure to ~ 30 000 p/ml of    asbestos bodies present in all   Wagner
pig,      2-4 rabbits, and    chrysotile (7-10% fibres        3 species exposed to all 3       (1963a)
rabbit,   3-4 Vervet monkeys  > 10 µm), amosite, or           types; chrysotile exposure
and       in exposed groups   crocidolite from South African  caused fibrosis in guinea-pigs
Vervet                        mills for various periods of    and monkeys but not in rabbits;
monkey                        time (e.g., up to 24 months     amosite caused asbestosis in
                              for guinea-pigs exposed to      all 3 species; it is difficult
                              chrysotile; lifetime for        to draw conclusions concerning
                              rabbits and Vervet monkeys      the relative pathogenicity of
                              exposed to chrysotile, but      the different fibre types 
                              only 14 months for these        because of the various periods 
                              species when exposed to         of exposure and lack of 
                              amosite)                        characterization of fibre sizes

SPF       total of 1013       groups exposed to 9.7 -         less asbestosis for amosite      Wagner et
Wistar    rats; group         14.7 mg/m3 of UICC amosite,     than for the other dusts;        al. (1974)
rat       sizes of 19-58      anthophyllite, crocidolite,     progression of asbestosis
                              chrysotile (Canadian), or       following cessation of
                              chrysotile (Rhodesian) for      exposure for all dusts
                              periods of 1 day, 3, 6, 12,     
                              or 24 months                    

SPF       groups of 48        study designed so that both     chysotile caused far more        Davis et
white     animals             mass and fibre number could     fibrosis than either amphibole,  al. (1978)
Wistar                        be examined; 5 groups exposed   even when the fibre numbers
rat of                        to 10 mg/m3 UICC chrysotile,    were similar
the Han                       crocidolite, or amosite (550    
strain                        fibres/ml amosite > 5 µm;       
                              390 fibres/ml chrysotile        
                              > 5 µm or 430 fibres/ml         
                              crocidolite > 5 µm) for         
                              12 months                       
---------------------------------------------------------------------------------------------------------

Table 13.  (contd.)
---------------------------------------------------------------------------------------------------------
Species   Number              Protocola                       Results                          References
---------------------------------------------------------------------------------------------------------
Male      total of 96         two groups exposed for          slight pulmonary fibrosis        Wehner
Syrian    exposed and 96      3 h/day, 5 days/week to         only in the 15-month exposure    et al.
golden    control animals     either 1 µg/litre (5-13         group; higher incidence and      (1979)
hamster                       fibres/ml, > 5 µm) or           severity with increased dose
                              10 µg/litre (30-118             after 5-month exposure to 10
                              fibres/ml, > 5 µm) A/C          µg/litre dose; increased
                              aerosol (chrysotile content     incidence of slight emphysema
                              10.5%) for up to 15 months      after exposure to the
                                                              10 µg/litre dose for 6 months -
                                                              after 15 months, no difference
                                                              between exposed and control
                                                              groups; authors suggested that
                                                              the minimal response might be
                                                              due to changes during processing
                                                              of the fibres that decreased
                                                              the toxicity

Rat       groups sizes of     designed to compare the         factory amosite more fibrogenic  Davis
(strain   of 48 animals       pathological effects of         than UICC sample                 et al.
not spe-                      exposure to UICC samples                                         (1980a)
cified)                       with those of factory samples;  
                              4 groups exposed to UICC        
                              amosite, UICC chrysotile,       
                              factory amosite, or factory     
                              chrysotile at 10 mg/m3 for      
                              12 months; animals permitted    
                              to complete life span           
---------------------------------------------------------------------------------------------------------

Table 13.  (contd.)
---------------------------------------------------------------------------------------------------------
Species   Number              Protocola                       Results                          References
---------------------------------------------------------------------------------------------------------
SPF       group sizes of 48   study designed to compare the   levels of peribronchial          Davis
Wistar    animals             pathological effects of peak    fibrosis generally lower for     et al.
rat                           dosing to those of even         "peak" dosing groups than for    (1980b)
of the                        dosing; 2 groups exposed        "even" dosing groups; levels
AF/HAN                        to either UICC amosite at       of interstitial fibrosis
strain                        10 mg/m3 or UICC chrysotile at  slightly higher following
                              2 mg/m3, 7 h per day, 5 days    "peak" dosing
                              per day, 5 days per week for    
                              1 year and 2 groups exposed     
                              to either amosite at 50 mg/m3   
                              or chrysotile at 10 mg/m3,      
                              1 day each week, for 1 year     

Caesar-   group sizes of      exposure for periods of 3, 6,   progression of fibrosis after    Wagner et
ian-      24 (6 and 12        or 12 months to SFA chrysotile  end of exposure for groups       al. (1980)
derived   months exposure)    (430 fibres/ml > 5 µm), Grade   inhaling all types for 6 or
Wistar    and 48 (3 months    7 chrysotile (1020 fibres/ml    12 months; UICC produced at
rat       exposure)           > 5 µm) or UICC chrysotile      least as much fibrosis as other
                              (3150 fibres/ml > 5 µm)         2 samples in all 6 groups
                              at 10.8 mg/m3                   
---------------------------------------------------------------------------------------------------------
a Unless otherwise specified, exposures were for 6 - 8 h/day, 5 days/week.
    However, in an inhalation study by Davis et al. (1978), 
chrysotile caused more lung fibrosis in rats than either 
crocidolite or amosite, even when the fibre numbers (length > 
5 µm) in the dust clouds were similar.  The authors suggested that 
the greater fibrogenicity of chrysotile might be related to the 
fact that chrysotile clouds contained many more fibres over 20 µm 
long.  The observation that shorter fibres are less fibrogenic was 
confirmed in a study by the same group, in which rats were exposed 
for 12 months to 10 mg/m3 of either short-fibred (1% > 5 µm) or 
long-fibred (30% > 5 µm) amosite (Bolton et al., 1983a). 

7.1.1.2  Intrapleural and intraperitoneal injection

    Fibrosis has also been observed following intrapleural (Smith 
et al., 1965; Burger & Engelbrecht, 1970; Davis, 1970, 1971, 1972) 
and intraperitoneal injection (Jagatic et al., 1967; Shin & 
Firminger, 1973; Engelbrecht & Burger, 1975) of asbestos.  The 
results of these studies have confirmed that short fibres are less 
fibrogenic (Burger & Engelbrecht, 1970; Davis, 1972). 

7.1.1.3  Ingestion

    Several studies of the effects of ingested asbestos on 
proliferation and other biochemical variables in the epithelial 
cells of the gastrointestinal tract have been conducted (Amacher et 
al., 1974; Epstein & Varnes, 1976; Jacobs et al., 1977).  Although 
some changes (e.g., an increase in incorporation of tritiated 
thymidine) have been noted in some studies at various times 
following 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) 
observed light and electron microscopic evidence of cellular damage 
in the intestinal mucosa of rats fed 0.5 or 50 mg of chrysotile per 
day, 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 
Wistar rats that had consumed 100 mg UICC amosite, daily, for 5 
days (Meek & Grasso, 1983). 

7.1.2  Carcinogenicity

7.1.2.1  Inhalation

    Exposure conditions in inhalation studies approach more closely 
the circumstances of human exposure to asbestos and are of most 
relevance for the assessment of human health risks.  The results of 
the most significant inhalation carcinogenicity 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 
increased incidence of bronchial carcinomas and pleural 
mesotheliomas has been observed only in the rat. 

    In an extensive and well conducted and controlled series of 
studies, Wagner et al. (1974) exposed groups of Wistar SPF rats 
(n = 19 - 58) to the 5 UICC asbestos samples at concentrations 
ranging from 10 to 15 mg/m3, for periods ranging from 1 day to 24 
months (35 h/week).  Exposure had very little effect on average 
survival.  Average survival times varied from 669 to 857 days 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 appeared 
prior to 300 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 
tumours, taking survival into account, it was concluded that the 
animals with lung tumours had significantly ( P < 0.001) more 
asbestosis than those without.  Seven malignancies of the ovary and 
eight of male genito-urinary organs were observed in the exposed 
groups of approximately 700 rats.  No malignancies were observed at 
these sites in controls.  These differences were not statistically 
significant and the incidence of malignancy at other sites was 
little different from that in the controls.  No data on the 
relationship between tumour incidence at extra-pulmonary sites and 
asbestos dose were provided. 

    In a study conducted by Davis et al. (1978), rats were exposed 
to chrysotile, crocidolite, or amosite at 2.0 or 10.0 mg/m3 for 12 
months.  All malignant pulmonary tumours occurred in chrysotile-
exposed animals.  The authors suggested that the greater 
carcinogenicity of chrysotile might be related to the fact that 
chrysotile contained many more fibres over 20 µm in length.  In 
addition to the lung tumours, extrapulmonary neoplasms included a 
relatively large number of peritoneal connective tissue 
malignancies, including a leiomyofibroma on the wall of the small 
intestine.  The relationship between these tumours and exposure to 
asbestos is uncertain, however. 

    In a recent study, inhalation of short-fibred amosite (1% > 
5 µm) at 10 mg/m3 did not produce fibrosis or pulmonary tumours in 
Wistar rats (n = 48).  In contrast, there was extensive fibrosis 
and over 30% incidence of tumours in a group similarly exposed to 
long-fibred amosite (30% > 5 µm; 11% > 10 µm) (Davis et al., in 
press). 

Table 14.  Inhalation studies - carcinogenicity
---------------------------------------------------------------------------------------------------------
Species     Number           Protocola                      Results                         Reference
---------------------------------------------------------------------------------------------------------
rat,        12 (controls);   exposure to chrysotile,        increased lung tumour           Reeves et al.
rabbit,     20-69 (exposed)  crocidolite, or amosite for    incidence in rats (7-9% in      (1974)
guinea-pig,                  4 h/day, 4 days/week, for      those with adequate survival
gerbil,                      2 years; mean concentration    record)
mouse                        = 50 mg/m3; light microscopic  
                             fibre count of chrysotile: 54  
                             fibres/ml; amosite:            
                             864 fibres/ml, crocidolite:    
                             1105 fibres/ml                 

SPF         total of 1013    groups exposed to UICC         higher incidence of tumours     Wagner et al.
Wistar      rats; group      amosite, anthophyllite,        with 12 months exposure than    (1974)
rat         sizes of 19-58   crocidolite, chrysotile        with 6 months, but little
                             (Canadian), or chrysotile      difference following 12 and 24
                             (Rhodesian), at 9.7 - 14.7     months exposure; of 20 tumours
                             mg/m3, for periods of 1 day,   which metastasized, 16 were in
                             3, 5, 6, 12, or 24 months,     chrysotile-exposed groups, 3 in
                             for 35 h/week                  crocidolite-exposed groups and
                                                            1 in anthophyllite-exposed
                                                            groups; of 11 mesotheliomas, 4
                                                            occurred following exposure to
                                                            crocidolite and 4 following
                                                            exposure to Canadian chrysotile;
                                                            2 mesotheliomas occurred
                                                            following 1-day exposures;
                                                            positive association between
                                                            the incidence of asbestosis and
                                                            lung cancer; no association
                                                            between exposure and
                                                            gastrointestinal cancer
                                                            incidence
---------------------------------------------------------------------------------------------------------

Table 14 (contd.)
---------------------------------------------------------------------------------------------------------
Species     Number           Protocola                      Results                         Reference
---------------------------------------------------------------------------------------------------------
Syrian      102 animals      animals exposed to UICC        10 out of 12 lung adenomas      Wehner et al.
golden      per group        Canadian chrysotile at 23      found in 510 hamsters,          (1975, 1979);
hamster                      µg/litre for 7 h/day,          occurred among the 102 animals  Wehner (1980)
                             5 days/week, for 11 months;    in the asbestos-exposed
                             half of animals also exposed   groups, indicating an early
                             for 10 min 3 times a day to    neoplastic response; incidence
                             cigarette smoke for duration   of laryngeal lesions and
                             of their life span; one        malignant tumours significantly
                             control group exposed to       lower in asbestos + smoke-
                             smoke + sham dust, one         exposed group than in smoke-
                             exposed to sham smoke          exposed control group, probably
                             + sham dust                    due to significantly shorter
                                                            life span in asbestos-exposed
                                                            animals

SPF white   group size = 48  experiment designed so that    all malignant pulmonary         Davis et al.
Wistar rat                   both mass and fibre number     neoplasms occurred in           (1978)
of the Han                   could be examined; 5 groups    chrysotile-exposed animals;
strain                       exposed to UICC chrysotile,    the authors suggested that
                             crocidolite, or amosite at 2   the greater pathogenicity of
                             or 10 mg/m3 (550 amosite       chrysotile might be due to
                             fibres/ml > 5 µm; 390          greater number of fibres
                             chrysotile fibres/ml           > 20 µm in length
                             > 5 µm or 430 crocidolite      
                             fibres/ml > 5 µm)              
---------------------------------------------------------------------------------------------------------

Table 14.  (contd.)
---------------------------------------------------------------------------------------------------------
Species     Number           Protocola                      Results                         Reference
---------------------------------------------------------------------------------------------------------
rat         group size = 48  designed to compare the        factory chrysotile produced     Davis et al.
(strain                      pathological effects of        similar levels of lung          (1980a)
not spe-                     exposure to UICC samples       pathology to those produced by
cified)                      with those of factory          UICC sample except that a
                             samples; 4 groups exposed to   slightly smaller number of
                             UICC amosite, UICC chrysotile,  bronchial carcinomas was
                             factory amosite, or factory    produced by the factory dust;
                             chyrsotile at 10 mg/m3 for 12  little carcinogenicity with
                             months; animals permitted to   both amosite samples; based on
                             complete life span             the analysis of fibre sizes in
                                                            each of the samples, authors
                                                            concluded that "while fibro-
                                                            genicity and carcinogenicity
                                                            both depend upon the presence
                                                            of relatively long fibres in
                                                            dust clouds, different lengths
                                                            are involved in each process
                                                            and tumour production requires
                                                            the largest fibres"

SPF Wistar  group size =     study designed to compare the  no differences in the           Davis et al.
rat,        48               pathological effects of "peak" incidence of pulmonary          (1980b)
AF/HAN                       dosing with those of "even"    neoplasms between "peak" dosing
strain                       dosing; 2 groups exposed to    groups and "even" dosing groups;
                             UICC amosite at 10 mg/m3 or    the authors concluded that no
                             UICC chrysotile at 2 mg/m3,    indication that short periods
                             7 h/day, 5 days/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
                             chrysotile at 10 mg/m3         than would be indicated by the
                             1 day/week for 1 year          raised overall dust counts for
                                                            the day in question (there were,
                                                            however, 2 bronchial carcinomas
                                                            in the "peak" dosing amosite
                                                            group and none in the "even"
                                                            dosing group)
                                                            
---------------------------------------------------------------------------------------------------------

Table 14.  (contd.)
---------------------------------------------------------------------------------------------------------
Species     Number           Protocola                      Results                         Reference
---------------------------------------------------------------------------------------------------------

Barrier-    group sizes =    exposure for periods of        tumour yield significantly      Wagner et al.
protected   24 (6 and 12     either 3, 6, or 12 months to   greater with UICC chrysotile    (1980)
Caesarian-  months exposure) SFA chrysotile (430            than with Grade 7
derived     and 48 (3        fibres/ml > 5 µm) or UICC      
Wistar rat  months exposure) chrysotile (3150 fibres/ml     
                             > 5 µm) at 10.8 mg/m3          
---------------------------------------------------------------------------------------------------------
a Unless otherwise specified, exposures were for 6 - 8 h/day, 5 days/week.
    The results of inhalation studies impart some useful 
information concerning dose-response relationships and the 
carcinogenic potential of asbestos of various types and fibre 
sizes.  An approximately linear relationship between the incidence 
of lung cancer and dose has been found in several studies (Wagner 
et al., 1974, 1980; Davis et al., 1978) and, although insufficient 
numbers of mesotheliomas have been produced in inhalation studies 
to draw definitive conclusions, it has been noted that most have 
been found in animals that received a high total dose of asbestos 
(Davis, 1979).  However, the incidence following a short period of 
exposure (i.e., 1 day) has been greater than would be expected on 
the basis of a linear hypothesis for the dose-response relationship 
(Wagner et al., 1974).  It is also of interest to note that in two 
studies (Davis et al., 1978; Wagner et al., 1980), all of the 
mesotheliomas observed (3) occurred in the groups 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 
intratracheal injection and therefore it is difficult to 
extrapolate the results directly to man.  In addition, the greater 
incidence of infection following exposure by this route often 
complicates the interpretation of the results.  However, the 
results of such investigations have confirmed the observations in 
inhalation studies.  Furthermore, significantly-increased incidences 
of both mesothelioma and lung cancer have been observed in dogs 
concomitantly exposed to cigarette smoke (inhalation) and asbestos 
(intratracheally) (Humphrey et al., 1981). 

7.1.2.3  Direct administration into body cavities

    Wagner (1962) first reported that "it is possible to produce 
tumours which appear to be arising from the mesothelial cells of 
the pleura by 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 these studies are summarized in chronological order in 
Table 15. 

Table 15.  Intrapleural and intraperitoneal administration studies
---------------------------------------------------------------------------------------------------------
Species     Number           Protocol                       Results                         Reference
---------------------------------------------------------------------------------------------------------
Wistar      11 groups; 10    intrapleural injection of      30 months after exposure,       Wagner (1962)
rat         animals/group    50 mg of 3 samples of          pleural mesotheliomas in 2
                             crocidolite from South         crocidolite-treated rats, 1
                             African mines, 3 samples       chrysotile-treated rat, and
                             from mills in the same region, 1 rat receiving pure silica;
                             2 samples of chrysotile from   authors concluded "it is
                             mines, 1 sample of amosite,    possible to produce tumours
                             99.9% pure silica dust or      which appear to be arising
                             pure carbon black              from the mesothelial cells of
                                                            the pleura by inoculating
                                                            certain dusts into the          
                                                            pleural cavities of rats"       

Syrian      15 animals/      intrapleural injection of      granulomatous inflammation      Smith et al.
Golden      exposed group;   25 mg of soft chrysotile       and fibrosis in hamsters        (1965)
hamster     15 untreated     (average fibre length 67 µm),  receiving all 3 types; 5
            controls         harsh chrysotile (36 µm) and   tumours, possibly
                             amosite (18 µm); also soft     mesotheliomas; 2 in harsh
                             chrysotile in diet (10 g/kg)   chrysotile-treated hamsters
                             (10 g/kg) of chrysotile-       and 3 in amosite-treated
                             treated animals; amosite       hamsters
                             (10 g/kg) in diet of amosite-                                  
                             treated animals                                                

SPF Wistar  48 males, 48     intrapleural injection of      appreciable proportion of       Wagner & 
rat and     females/exposed  20 mg of Transvaal amosite     animals treated with all types  Berry (1969)
"standard"  group            (91% < 5 µm in length)         of asbestos developed a
rat                          superfine grade of Canadian    mesothelioma; large number of
                             chrysotile (92% < 5 µm),       tumours found in animals
                             North West Cape crocidolite    receiving crocidolite (SPF:
                             (70% < 5 µm); extracted        55/94, standard: 62/91); fewer
                             crocidolite (86% < 5 µm),      tumours in amosite-treated
                             silica or saline               group (SPF: 38/96, standard:
                                                            26/84) and period between 
                                                            inoculation and development 
---------------------------------------------------------------------------------------------------------

Table 15.  (contd.)
---------------------------------------------------------------------------------------------------------
Species     Number           Protocol                       Results                         Reference
---------------------------------------------------------------------------------------------------------
SPF Wistar                                                  of mesothelioma much longer  
rat and                                                     than with the other 2 types; 
"standard"                                                  authors note "the high
rat (contd.)                                                incidence of these neoplasms
                                                            following the inoculation of    
                                                            chrysotile was unexpected"       
                                                            (SPF: 61/96, standard: 62/90)   

Female      1200             40 mg of 17 materials applied  amosite,chrysotile, and 4       Stanton & 
pathogen-                    on a fibrous glass vehicle     different types of crocidolite  Wrench (1972)
free                         to the pleura including 3      produced equally high incidence
Osborne-                     types of asbestos in 7         (58-75%) of mesotheliomas;
Mendel                       forms, 6 types of fibrous      hand-milled crocidolite not
rat                          glass, 2 types of silica,      exposed to extraneous oils or
                             etc; 2-year observation        metallic mining yielded dose-
                             period                         related tumour responses
                                                            comparable with those of a
                                                            standard reference milled
                                                            crocidolite; standard crocidolite
                                                            caused fewer tumours (20-32%)
                                                            when reduced to submicroscopic
                                                            fibrils; pulverized fragments
                                                            of mill and nickel metal and
                                                            fibrous glass vehicle alone did
                                                            not induce tumours; 2 forms
                                                            of fine fibre-glass milled to
                                                            approach length of asbestos fibre
                                                            produced moderately high
                                                            incidence (12-18%); authors     
                                                            concluded "the simplest         
                                                            incriminating feature for both  
                                                            carcinogenicity and fibrogenicity                 
                                                            seems to be a durable fibrous shape,              
                                                            perhaps in a narrow range of size"                
---------------------------------------------------------------------------------------------------------

Table 15.  (contd.)
---------------------------------------------------------------------------------------------------------
Species     Number           Protocol                       Results                         Reference
---------------------------------------------------------------------------------------------------------
SPF Wistar  12 - 36          intrapleural injections of     the risk of developing a        Wagner et al.
rat                          0.5, 1, 2, 4, or 8 mg of SFA   mesothelioma at a given time    (1973)
                             chrysotile and crocidolite     after injection was
                             (from Northeast Cape mine);    proportional to dose for both
                             intrapleural injection of      SFA chrysotile and crocidolite;
                             20 mg of Canadian chrysotile   of the UICC standard reference
                             samples, SFA chrysotile, or    samples, crocidolite was the 
                             saline (control); intrapleural most carcinogenic and removal 
                             injection of 20 mg of the 5    of oils by benzene extraction
                             UICC samples, brucite or       did not alter the 
                             barium sulfate; intrapleural   carcinogenicity of these  
                             injections of ceramic fibre,   samples; results were 
                             fibre glass, glass powder,     consistent with the hypothesis 
                             aluminium oxide, and 2         that finer fibres are more 
                             samples of SFA chrysotile      carcinogenic                                

Rat                          3 intrapleural injections of   mesotheliomas in 46% of the     Shabad et al.
(strain                      20 mg of chrysotile from       exposed rats                    (1974)
not                          filters at 2 USSR mines        
specified)                   (99% fibres < 5 µm in          
                             length)                                                        

Osborne-    30 in each       pleural implantation on a      fibres < 1.5 µm in diameter     Stanton et 
Mendel      exposed group    fibrous glass vehicle of       and > 8 µm in length yielded    al. (1977)
rat                          40 mg of 17 samples of         highest probability of pleural
                             fibrous materials of diverse   mesotheliomas
                             types or dimensional           
                             distribution                                                   
---------------------------------------------------------------------------------------------------------

Table 15.  (contd.)
---------------------------------------------------------------------------------------------------------
Species     Number           Protocol                       Results                         Reference
---------------------------------------------------------------------------------------------------------
Osborne-    30 - 50 in each  pleural implantation on a      percentage probability of       Stanton & 
Mendel      exposed group    fibrous glass vehicle of       pleural mesotheliomas ranged    Layard (1978)
rat                          40 mg of 37 samples, which     from 0 to 100%, lesions in
                             were variations of 7 fibrous   groups with low probability of
                             materials; fibre-size          tumours were highly cellular
                             distributions similar to       and fibres were completely
                             asbestos                       contained within macrophages;
                                                            lesions in high tumour 
                                                            probability groups were 
                                                            relatively acellular with an 
                                                            abundance of collagen and free, 
                                                            long fibres in interstitial                 
                                                            tissue                          

Wistar      total of 1086    intraperitoneal injection      fibrous dusts (except soluble   Pott et al.
rat                          of 9 fibrous dusts             gypsum fibres) induced          (1976a)
                             (chrysotile, milled            malignant tumours of the
                             chrysotile, crocidolite,       peritoneum (6 mg chrysotile-77%;
                             palygorskite, nemalite,        2 mg crocidolite-39%; 2 mg glass
                             gypsum, 3 types of glass       fibres JM 104-27%); clear dose-
                             fibres) and 8 granular dusts;  response relationships for  
                             injected doses between         chrysotile and 2 types of glass 
                             2 and 100 mg; observation      fibres; reduction in 
                             period 30 months               carcinogenicity of chrysotile 
                                                            after milling to very short 
                                                            fibres; carcinogenicity
                                                            greatest for fibres with
                                                            length > 3 µm and diameter 
                                                            < 1 µm; durability of fibres 
                                                            also important               
---------------------------------------------------------------------------------------------------------

Table 15.  (contd.)
---------------------------------------------------------------------------------------------------------
Species     Number           Protocol                       Results                         Reference
---------------------------------------------------------------------------------------------------------
Rat          8               inhalation of 3000 WLM radon   all animals developed lung      Lafuma et al.
                             222 over one month and         tumours including 7             (1980)
                             intrapleural injection of      mesotheliomas, authors
                             2 mg chrysotile after 71 days  concluded "synergistic
                                                            effect obvious"                 

            10               whole body irradiation - 230   extrapulmonary tumours in
                             rads for 1 day and             irradiated controls and in rats
                             intrapleural injection of      receiving asbestos orally and
                             2 mg chrysotile after 125      by intrapleural injection; no
                             days or 150 rads and 1%        specific localization in
                             chrysotile in diet for 6       asbestos exposed animals
                             months after 35 days                                           

Barrier-    48/exposed       intrapleural injection of      allowing for different          Wagner et al.
protected   group; 48        20 mg of SFA, UICC Canadian    survival times, SFA was about   (1980)
Caeserian-  in control       or Grade 7 chrysotile          twice as carcinogenic as
derived     group                                           Grade 7, which was 3 times as
Wistar                                                      carcinogenic as UICC sample;
rat                                                         results not well correlated 
                                                            with results of an inhalation 
                                                            study with these materials            

SPF male    16 in HCl-       intrapleural injection of      in life-time observation        Monchaux et 
Sprague     treated          20 mg untreated UICC           period, a total of 68           al. (1981)
Dawley      chrysotile-      chrysotile A or 4 samples      pleural mesotheliomas, 1 lung
rat         exposed group;   leached to various extents     cancer, and 9 peritoneal
            > 32 in all      (10 - 90% Mg removed) by       mesotheliomas in the total
            other exposed    oxalic acid or HCl; also       of 304 animals; proportion of
            groups; 32       crocidolite or glass fibre     cancer lower than expected
            control                                         because of early deaths from
            animals                                         infection; carcinogenicity 
                                                            of chrysotile with 44% Mg 
                                                            removed; authors concluded
                                                            "size is not the only factor 
                                                            involved in the induction of 
                                                            pleural cancers by mineral   
                                                            fibres"                         
---------------------------------------------------------------------------------------------------------

Table 15.  (contd.)
---------------------------------------------------------------------------------------------------------
Species     Number           Protocol                       Results                         Reference
---------------------------------------------------------------------------------------------------------
NEDH rat    --               intrapleural, intraperitoneal, a significant incidence         Warren et al.
                             and intratracheal              (3.8%) of mesotheliomas in      (1981)
                             administration of 2 mg         159 rats treated with asbestos
                             of UICC Canadian or            alone; this incidence 
                             Rhodesian chrysotile,          increased to 11.8% in animals
                             with or without ancillary      also receiving radiation
                             radiation treatment (1000      treatment (borderline
                             rads-whole body) or            statistical significance) and
                             injection of 1 mg 3-MC         25.5% in animals also
                                                            administered 3-MC (significant
                                                            increase); early tissue
                                                            responses were similar to
                                                            asbestos reactions without      
                                                            specific pathological changes
                                                            attributable to radiation or    
                                                            3-MC                            

Female      3 groups, 20     intraperitoneal injection of   life-time observation; 8        Kolev (1982)
Wistar      animals/group    50 mg milled UICC crocidolite  mesotheliomas (40%) in
rat                          (fibre lengths 3 - 5 µm),      amorphous crocidolite-exposed
                             amorphous UICC crocidolite,    group; 3 mesotheliomas (15%)
                             or saline                      in fibrous crocidolite-exposed
                                                            group and none in saline 
                                                            group; statistically 
                                                            significant difference; author 
                                                            questioned the fibrous 
                                                            structure of asbestos as the 
                                                            predominant cause of peritoneal
                                                            mesothelioma and suggested that
                                                            submicroscopic particles might  
                                                            be important in induction of    
                                                            tumours                         
---------------------------------------------------------------------------------------------------------

Table 15.  (contd.)
---------------------------------------------------------------------------------------------------------
Species     Number           Protocol                       Results                         Reference
---------------------------------------------------------------------------------------------------------
AF/HAN      7 groups, 32     intraperitoneal injection of   production of mesothelial       Bolton et al.
Wistar      animals/group    25 mg of 5 samples of UICC     tumours in 94 - 100% of the     (1982b)
rat                          chrysotile and factory         animals in 6 groups; chrysotile
                             amosite collected from         more carcinogenic than amosite;
                             airborne asbestos clouds       heated chrysotile (850 °C) least
                             of inhalation study            carcinogenic; some correlation
                                                            between carcinogenicity and
                                                            fibre length; good correlation
                                                            between carcinogenicity and     
                                                             in vitro cytotoxicity           

AF/HAN      17 groups;       intraperitoneal injection of   mesothelial tumours in 0 - 96%  Bolton et al.
SPF Wistar  19-48 animals    0.01 - 25 mg elutriated UICC   of animals; graded dose         (1983b)
            per group        chrysotile and crocidolite     response for both chrysotile
                                                            and crocidolite; for a given
                                                            dose, more tumours in
                                                            chrysotile 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 inhalation 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 asbestos-
associated 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 fibrogenicity 
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 µm and less than 1.5 
µm in diameter (Wagner et al., 1973; Stanton et al., 1977). 

    In an extensive study, Stanton et al. (1981) implanted 72 dusts 
containing fibres of various sizes in the pleura of Osborne-Mendel 
rats.  The correlation coefficients for the logit of tumour 
probability with the common logarithm of number of particles per 
microgram in different dimensional ranges are presented in Table 
16.  The probability of the development of pleural mesotheliomas 
was highest for fibres with a diameter of less than 0.25 µm and 
lengths greater than 8 µm.  However, probabilities were also 
"relatively" high for fibres in other size categories (i.e., with 
diameters of up to 1.5 µm and lengths greater than 4 µm).  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 diameter           Fibre length (µm)       
(µm)            (< 4)      (> 4 - 8)     (> 8)
-------------------------------------------------
> 4             -          -0.28          -0.30

> 1.5 - 4       -0.45      -0.24          0.13

> 0.25 - 1.5    0.01       0.45           0.68

< 0.25          0.20       0.63           0.80
-------------------------------------------------
a  From: Stanton et al. (1981).

    In an extensive series of studies involving intraperitoneal 
administration, Pott & Friedrichs (1972) and Pott et al. (1976a) 
induced peritoneal mesotheliomas in Wistar rats injected with 
different varieties of asbestos, fine glass fibres, and nemalite 
(magnesium hydroxide).  Few or no tumours developed following 

administration of several amorphous dusts that were chemically 
similar to one of the forms of asbestos.  Very few tumours developed 
following administration of 100 mg of UICC chrysotile fibres 
shortened by ball-milling for 4 h, compared with 6.25 mg of the 
original sample.  The results of further studies confirmed that 
tumour incidence for relatively low doses (0.5 - 2 mg) of dust 
samples with a sufficient number of durable long and thin fibres 
was high.  Tumour incidence for unstable, long, thin fibres (e.g., 
leached 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 µm in length, have the same 
carcinogenic potency as 4 fibres, 5 µm in length, or 1 fibre, 20 µm 
in length (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 
results of these studies, it has been concluded that the physical 
and chemical constitution of fibres influences the carcinogenic 
potential insofar as it determines the stability in the body. 

    These observations concerning the importance of fibre size and 
shape in tumour induction have given rise to speculation that 
mesotheliomas may be caused by physical irritation caused by fibres 
that are carried to the pleural surface by both lymphatic transport 
within macrophages or by direct penetration of free fibres (Davis, 
1981; Craighead & Mossman, 1982).  A great deal of attention has 
been focused on this "carcinogenic subset" of fibres.  However, 
there are still several unanswered questions concerning the 
relative importance of fibres with dimensions in the critical range 
for mesothelioma induction (Harington, 1981). 

    Acid leaching of chrysotile significantly decreased the 
carcinogenic 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). 

    Results of studies involving intrapleural or intraperitoneal 
injection, or implantation have also imparted some information on 
dose-response relationships, the relative potency of various fibre 
types, and the time course of the development of asbestos-related 
disease.  There was evidence of a dose-response relationship for 
malignant tumour incidence following exposure to both chrysotile 
and crocidolite, in several of the studies (Wagner et al., 1973; 
Smith & Hubert, 1974; Bolton et al., 1983b).  Fig. 8 shows the 
regression line for dose-response relationships after 
intraperitoneal injection of chrysotile, crocidolite, and glass 
fibres (Johns-Manville 104), derived from the results of Pott et 
al. (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 of malignant neoplasms than an equal mass of chrysotile 
(Gross & Harley, 1973; Wagner et al., 1973; Engelbrecht & Burger, 
1975; Monchaux 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, 
chrysotile was found more potent in inducing mesotheliomas than an 
equal mass of crocidolite (Bolton et al., 1983b) or amosite (Bolton 
et al., 1982b).  The distribution of fibre sizes was not well 
characterized in 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%) 
in 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 & Wagner (1976) injected 
doses of equal 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 
mesotheliomas; 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 of malignant tumours induced by the intrapleural and 
intraperitoneal inoculation of animals (Harington, 1981).  In 
addition, aerodynamic 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 
implantation 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 µm) are 
more effectively cleared from the lungs by macrophages than long 
fibres, which cannot be phagocytosed by single cells (Harington, 
1981).  However, the need for caution in the extrapolation of the 
results 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., 
1980).  The authors suggested that problems of aggregation of 
fibres, in the suspension prepared for intrapleural injection, 
might have resulted in different size distributions. 

7.1.2.4  Ingestion

    Studies on the effects of ingested asbestos on animal species 
have been reviewed (Toft et al., 1984), and the results of the most 
recent and extensive of these studies are presented in Table 17. 

    On the basis of their review, Toft et al. (1984) concluded that 
there was no conclusive evidence from the toxicological studies 
conducted to date, that ingested asbestos is carcinogenic.  The 
results of early studies were inconclusive because of shortcomings 
in study design; many of the investigations were conducted for 
relatively short periods of time with insufficient numbers of test 
and 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 the 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 
lifetime asbestos feeding studies in the same laboratory (US NTP, 
1985).  However, the increase was not statistically-significant in 
comparison with concurrent controls and was limited to one sex.  In 
addition, the study was not designed to investigate exposure-
response relationships.  It is of interest to note that no 
increase in tumour incidence was observed following administration 
of short-range chrysotile, which was composed of size ranges more 
similar to those found in drinking-water. 

    Some of the toxicological studies on ingested asbestos that 
have been conducted recently by various investigators have been 
very extensive (Donham et al., 1980; McConnell, 1982a,b).  However, 
there have been several criticisms concerning the suitability with 
respect to extrapolation to man of the vehicles in which asbestos 
has been administered, the fibre size of the administered 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 
participate in the fibrogenic reaction, and (d) pulmonary 
epithelial cells, which can also undergo malignant transformation.  
These cells, proliferating cell lines, and erythrocytes have been 
used  in vitro studies. 

    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.  
Prediction 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 
selection of materials to be tested  in vivo.  The tests are also of 
use in the study of mechanisms. 

Table 17.  Toxicological studies - ingested asbestos
---------------------------------------------------------------------------------------------------------
Species        Number of    Protocol                   Results                              Reference
               test animals
---------------------------------------------------------------------------------------------------------
Syrian Golden  60           0.5 mg amosite/litre       no tumours                           Smith et al.
hamster                     drinking-water over the                                         (1980)
                            lifetime

               60           5 mg amosite/litre         3 malignant tumours including
                            drinking-water             a peritoneal mesothelioma, 2
                                                       early squamous cell carcinomas
                                                       of the forestomach

               60           50 mg amosite/litre in     1 malignant tumour; authors          
                            drinking-water over the    concluded "tumours not treatment-
                            lifetime                   related"

Male Wistar    25           250 mg amosite per week    1 malignant tumour in gastric        Bolton et al.
rat                         in dietary margarine       muscle layer                         (1982a)
                            supplement, for periods
                            up to 25 months

               25           250 mg chrysotile per      1 pleural histiocytic tumour;
                            week in dietary margarine  significant increase in      
                            supplement, for periods    incidence of benign tumours in
                            up to 25 months            tissues 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

               25           250 mg crocidolite per     no 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                   Results                              Reference
               test animals
---------------------------------------------------------------------------------------------------------
F 344 rat      500          10% chrysotile in the      5 tumours including 1 mesothelioma;  Donham et al.
                            diet over the lifetime     incidence not statistically          (1980)
                                                       significantly greater than in
                                                       control group

Syrian golden  250 males    1% amosite in the diet     no adverse effects on body weight    McConnell
hamster        250 females  fed to nursing mothers     gain and survival; no                (1982a)
                            and over the lifetime of   statistically-significant increase
                            the pups                   in tumour incidence

               250 males    1% short-range chrysotile  significant increase in adrenal      McConnell
               250 females  (98% < 10 µm in            cortical adenomas in males; not      (1982b)
                            length) in the diet fed to considered to be treatment-
                            nursing mothers and over   related
                            the lifetime of the pups

               250 males    1% intermediate range      significant increase in adrenal
               250 females  chrysotile (65% > 10 µm    cortical adenomas in males and
                            in length) in the diet     females; not considered to be
                            fed to nursing mothers     treatment-related
                            and over the lifetime of
                            the pups

F 344 rat      250 males    1% tremolite in the diet   no overt toxicity and no adverse     McConnell
               250 females  fed to the dams and over   effects on survival rate; no         et al.
                            the lifetime of the pups   statistically-significant increase   (1983)
                                                       in tumour incidence
---------------------------------------------------------------------------------------------------------

Table 17. (contd.)
---------------------------------------------------------------------------------------------------------
Species        Number of    Protocol                   Results                              Reference
               test animals
---------------------------------------------------------------------------------------------------------
F 344 rat      250 females  1% amosite in the diet     no overt toxicity and no adverse     McConnell
               250 males    fed to the dams and over   effects on survival rate; no         et al.
                            the lifetime of the pups   statistically-significant increase   (1983)
                                                       in tumour incidence in the gastro-
                                                       intestinal tract; the biological
                                                       significance of increases in
                                                       the rates of C-cell carcinomas of
                                                       the thyroid and monocytic leukaemia
                                                       in male rats is questionable

F 344 rat      250 males    1% short-range chrysotile  no overt toxicity and no adverse     US NTP
               250 females  (98% < 10 µm in length     effects on survival rate; no         (1985)
                            in the diet fed to         significant increase in tumour
                            nursing mothers and        incidence
                            over the lifetime of
                            the pups

               250 females  1% intermediate range      no overt toxicity and no adverse
               250 males    chrysotile (65% > 10       effects on survival rate;
                            µm in length) in the       increase in benign epithelial
                            diet fed to nursing        neoplasms in large intestine
                            mothers and over the       of males; insignificant when
                            lifetime of the pups       compared with concurrent controls
                                                       (88), but significant when
                                                       compared with pooled controls (524)
---------------------------------------------------------------------------------------------------------
    Reviews have been made by Harington et al. (1975), Beck (1980), 
and Gormley et al. (1980), and, more recently, these assays have 
received particular attention (Schluchsee Meeting, 1985). 

7.1.3.1  Haemolysis

    Although haemolysis alone is not a good predictor of  in vivo 
pathogenesis (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).  Chrysotile induces haemolysis more rapidly than 
the amphiboles (Schnitzer & Pundsack, 1970; Harington et al., 
1975).  Haemolysis by chrysotile fibres may be related to the 
adsorption of the red blood cell membranes on the fibres and not to 
an interaction 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 by 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 
(Allison, 1973).  The effects are more marked with chrysotile than 
with amphibole fibres (Harington et al., 1975). 

    Allison (1973) investigated the limits of the size of fibres 
that can be ingested by phagocytosis.  Irrespective of the type of 
asbestos, short fibres (< 5 µm) were readily and completely taken 
up by phagocytosis, whereas long fibres (> 25 µm) were not.  The 
cells attached to, or enveloped the ends of, the latter, but 
portions remained outside the cells.  The long fibres caused 
localized damage to the cell membrane while they were being 
phagocytosed; in addition, energy metabolism was increased (Beck et 
al., 1971).  Obviously, fibres with a length that exceeds the cell 
diameter remain partially extracellular. 

    In macrophages and in macrophage-like cells (P 388 D1), long 
asbestos fibres caused increased permeability to two lysosomal 
enzymes (beta-glucuronidase, beta-galactosidase) and to the cytoplasmic 
enzyme lactic acid dehydrogenase (Beck et al., 1972; Davies, 1980).  
This enzyme release is coupled with an increase in permeability to 
extracellular dyes, and often occurs in the absence of cell death. 
Asbestos fibres interfere with the normal digestion of secondary 
lysosomes, resulting, in some cases, in accumulation of acid 
hydrolases.  After 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 
counterbalanced by antiproteases, lung tissue damage can occur. 

7.1.3.3  Fibroblasts

    Beck et al. (1971) reported that long fibres of chrysotile were 
not completely phagocytosed by proliferating mouse fibroblasts, 
type L 929. 

    In lung fibroblast cultures, chrysotile has been shown to be 
highly cytotoxic when first added and to induce biochemical and 
morphological alterations (Richards & Jacoby, 1976).  It has also 
been shown that, if lung fibroblast-like cells are continuously 
exposed to small quantities of chrysotile, their ability to 
synthesize collagen is increased (Hext et al., 1977).  Fibroblasts 
undergo a maturation process leading to rapid cellular aging. 

7.1.3.4  Cell-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 & Seabright 
(1975) and Huang (1979).  In Huang's study, it was reported that 
amosite, crocidolite, and chrysotile were weakly mutagenic.  At 10 
and 100 µg fibre/ml, chrysotile completely inhibited cell growth 
(Livingston et al., 1980); cells exposed to amosite and crocidolite 
proliferated only at the lower concentration.  Crocidolite 
significantly elevated the sister chromatid exchange rate and 
larger (> 5 µm) chromosomes were most sensitive.  The chromosomal 
aberrations found in Chinese hamster cells by Sincock et al. (1982) 
could not be detected in primary human fibroblast or in human 
lymphoblastoid cell lines. 

    In tracheal epithelial cells, chrysotile and crocidolite did 
not cause breakage of DNA (Mossman et al., 1983).  Hahon & Eckert 
(1976) 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, 
pleural mesothelial cells, and other cell-lines see Beck (1980). 

7.1.3.5  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 
fibroblast-stimulating factor (Heppleston & Styles, 1967).  The 
incomplete phagocytosis of asbestos fibres may induce the same 
process (Beck et al., 1972).  There is some evidence that the 

immune system is stimulated by the effects of mineral dusts on the 
macrophages (Pernis & Vigliani, 1982); the authors supposed that 
this process was mediated by the production of interleukin-1, 
which also stimulates fibroblasts.  However, Miller et al. (1978) 
concluded from their studies that quartz and crocidolite had quite 
different biological effects on the macrophages and that the 
development of pulmonary fibrosis might, to some extent, be caused 
by different mechanisms in each instance. 

Table 18.  Some possible mechanisms of 
action of asbestiform fibres in the 
development of fibrosis (F), mesothelioma 
(M), and lung cancer (C)
--------------------------------------------
Mechanism or possible              Disease
important effects
--------------------------------------------
Incomplete phagocytosis,
release of enzymes, and            F, C, M
free radicals

Effects on the immune system       F, C, M

Effects on cell differentiation    F, C, M

Alteration in cell proliferation   F, C, M
processesa

Interaction with DNA               C, M

Adsorption and transfer of         C
polycyclic aromatic hydrocarbons
--------------------------------------------
a   Increase not only in cell proliferation 
    but effects on intracellular processes, 
    such as DNA or protein synthesis.

    The release of oxygen-free radicals after incomplete 
phagocytosis of fibres may cause peroxidation of membranes and 
damage to macromolecules (Mossman & Landesman, 1983).  This could 
be a possible mechanism of the induction of asbestos-related 
diseases. 

     Carcinogenic potential

    The mechanisms of carcinogenesis of asbestos are not well 
understood.  However, several hypotheses have been proposed, and 
these will be discussed briefly in the light of the experimental 
findings just 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 
(genotoxicity).  Fewer data are available concerning the 
genotoxicity of the other asbestiform mineral fibres; however, 

erionite 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 
separately. 

    (a)   Mesothelioma

    It has been hypothesized that asbestos initiates mesotheliomas, 
since there is no evidence from experimental studies that asbestos 
or any other natural mineral fibres promote mesotheliomas initiated 
by other agents.  Furthermore, there is no association between 
smoking and mesothelioma incidence in asbestos workers (US NRC/NAS, 
1984).  This hypothesis is strengthened by the observation of 
chronic preneoplastic reactions of mesothelial cells following the 
intrapleural or intraperitoneal 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 
µm), and thinner (< 1 µm) fibres of various minerals induce high 
mesothelioma 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 
(splitting, solubility, disintegration), and migration activity 
account for the variations observed in mesothelioma incidence in 
animals. 

    (b)   Lung cancer

    In the case of bronchogenic cancer, there is evidence that 
factors other than fibre size, such as adsorbed environmental 
pollutants (polycyclic aromatic hydrocarbons, etc), and tobacco 
smoke, can contribute to the total carcinogenic potential of 
mineral fibres. 

    Therefore, the extent to which results regarding the 
quantitative relationships obtained in the intrapleural and 
intraperitoneal 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 
inhalation and intrapleural injection in rats.  However, there is 
some evidence from inhalation studies that longer fibres are more 
carcinogenic.  Some authors see similarities between asbestos and 
promotors such as phorbol ester (Topping & Nettesheim, 1980; 
Craighead & Mossman, 1982). 
---------------------------------------------------------------------
a   For the purposes of this document, a promotor is defined as an 
    agent that increases the tumourigenic 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 
tumours by asbestos fibres is the adsorption and transfer of 
polycyclic aromatic hydrocarbons into cells ("carrier hypothesis"). 

    Equal milligram amounts of crocidolite asbestos, carbon, 
hematite, and kaolin have been compared for their ability to bind 
and release the radiolabelled polycyclic aromatic hydrocarbon and 
3-methylcholanthrene (3MC), into culture medium (Mossman & 
Craighead, 1982).  Asbestos did not adsorb more 3MC or release 
greater amounts of the hydrocarbon than the other materials. 

    The results of Bogovski et al. (1982) showed low lung-tumour 
rates in rats after intratracheal instillations of either 
benzo( a )pyrene or chrysotile, alone (6.1% after 5 x 5 mg 
benzo( a )pyrene, 3.7% after 5 x 1 mg chrysotile, 2.6% in the 
control group).  The instillation of a mixture of the 2 substances 
yielded 40% lung tumours, and the addition of phenol (1% in 
polyglycin), 78.9% lung tumours.  However, the tumour yield 
following exposure to a mixture of chrysotile and benzo( a )pyrene 
was lower in the studies of Smith et al. (1970) on hamsters and of 
Pylev (1972) on rats.  After intraperitoneal or intrapleural 
injections, the chrysotile-induced tumour rate was not augmented 
by benzo( a )pyrene (Pott et al., 1972; Pylev, 1980). 

    A syncarcinogenicity in man of polycyclic aromatic hydrocarbons 
and chrysotile was proposed when organic substances containing 
benzo( a )pyrene were found in chrysotile (Harington, 1962; Pylev & 
Shabad, 1973).  However, the amounts were very low (2 - 240 µg 
benzo( a )pyrene per kg chrysotile).  The doses of benzo( a )pyrene 
given in the studies of Bogovski et al. (1982) were 107 to 109 
times higher than would be received if administering equal amounts 
of natural chrysotile.  Thus, it appears very dubious that 
contamination with polycyclic aromatic hydrocarbons enhances the 
carcinogenicity of asbestos significantly.  Lakowicz & Bevan (1980) 
reported that the adsorption of benzo( a )pyrene on chrysotile and 
anthophyllite greatly enhanced their rates of uptake in the liver 
microsomes, compared with a microcrystalline dispersion of benzo( a )
pyrene.  Crocidolite, from which the natural organic substances had 
been removed by extraction, produced a tumour incidence after 
intrapleural administration in rats similar to that produced by 
untreated samples (Wagner & Berry, 1969; Stanton & Wrench, 1972).  
Therefore, available data do not provide conclusive support for the 
"carrier hypothesis". 

7.2  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 preliminary  in vitro studies have been conducted with some 
of the 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 
 vitro.  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 
take into 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. 

    Exposure conditions in inhalation studies approach most closely 
the circumstances of human exposure to natural mineral fibres and 
are most relevant for the assessment of health risks to man.  
However, only two such studies involving exposure to natural 
mineral fibres other than asbestos (erionite, attapulgite, and 
sepiolite) have been conducted to date. 

    Interpretation 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,
wollastonite, and erionite.

Table 19.   In vivo  studies - natural mineral fibres other than asbestos
---------------------------------------------------------------------------------------------------------
Fibre type    Source and fibre     Protocol           Number Species  Results                   Reference
              size distribution
---------------------------------------------------------------------------------------------------------
Palygorskite  Spanish; fibre size  inhalation of      40     F 344    fibrosis grade at 3       Wagner
(Attapulgite) distribution not     10 mg/m3 for 12           rat      months: 3.3 (control:     (1982)
              reported             months; 4 animals                  1.1), 6 months: 2.6
                                   sacrificed at 3,                   (control: 1.0), and
                                   6, and 12 months                   12 months: 3.5 
                                                                      control: 1.1)
                                                          
Attapulgite   Spanish; fibre size  intrapleural       40     F 344    10 mesotheliomas; 16      Wagner
              distribution not     inoculation of            rat      survivors at unspecified  (1982)
              reported (without    unspecified dose;                  time period following
              ultrasonication)     animals observed                   administration
                                   for life span                      
                                                          
Attapulgite   Spanish; fibre size  intrapleural       40     F 344    5 mesotheliomas           Wagner
              distribution not     inoculation of            rats     (chrysotile B: 9          (1982)
              reported (with       unspecified dose;                  mesotheliomas), 22      
              ultrasonification)   animals observed                   survivors (chrysotile B:
                                   for life span                      19 survivors) at
                                                                      unspecified time period
                                                                      following administration

Attapulgite   two samples from     intrapleural       30-50  Osborne- tumour incidence 2/29     Stanton
              Attapulgus, Georgia; implantation of           Mendel   (7%) for both samples     et al.
              purity > 90%         40 mg; animals            rat                                (1981)
              "composed entirely   observed for 2
              of short fibres      years
              of consistently      
              small diameter"      

Attapulgite   source not reported; intraperitoneal    33-34  Wistar   76.5% of animals          Pott
              fibre length < 5     injection -               rat      developed tumours         et al.
              µm 70%               3 x 25 mg; animals                 chrysotile A - 54.5%);    (1976a)
                                   observed for                       mesotheliomas in 70.6%
                                   life span                          (chrysotile A - 48.5%
                                                                      mesotheliomas);
                                                                      first tumour - 257 days
                                                                      (chrysotile A - 323 
                                                                      days) after injection
---------------------------------------------------------------------------------------------------------

Table 19.  (contd.)
---------------------------------------------------------------------------------------------------------
Fibre type    Source and fibre     Protocol           Number Species  Results                   Reference
              size distribution
---------------------------------------------------------------------------------------------------------
Sepiolite     Spanish; fibre size  inhalation of      40     F 344    fibrosis grade at 3       Wagner
              distribution not     10 mg/m3 for 12           rat      months: 3.1 (control:     (1982)
              reported             months; 4 animals                  1.1), 6 months: 3.1
                                   sacrificed at 3,                   (control: 1.0), and
                                   6, and 12 months                   12 months: 3.2 
                                                                      (control: 1.1)

Sepiolite     Spanish; fibre size  intrapleural       40     F 344    0 mesotheliomas; 19       Wagner
              distribution not     inoculation of            rats     survivors at unspecified  (1982)
              reported (without    unspecified dose;                  time period following
              ultrasonification)   animals observed                   administration
                                   for life span                      

Wollastonite  4 samples from       intrapleural       30-50  Osborne- tumour incidence 5/20     Stanton
              Canadian mine; only  implantation of           Mendel   (25%), 3/21 (14.3%),      et al.
              one sample           40 mg; animals            rats     2/25 (8%), 0/24           (1981)
              completely fibrous;  observed for 2                     
              fibres "relatively   years                              
              large"                                                  

Erionite      New Zealand -        inhalation of      40     F 344    no mesotheliomas in       Wagner
              frequency of fibres  10 mg/m3 for 1            rat      the animals not           (1982)
              < 0.5 µm in          year; 4 animals                    sacrificed 8 months
              diameter and > 4     sacrificed at 3,                   after exposure
              µm in length = 1.9%  6, and 12 months                   

Erionite      Oregon - frequency   inhalation of      40     F 344    mesotheliomas in 27       Wagner
              of fibres < 0.4      10 mg/m3 7 h/day,         rat      (96.4%) of the 28         et al.
              µm in diameter       5 days per week,                   animals not sacrificed    (1985)
              and > 5 µm in        for 1 year; 4                      12 months after 
              length = 13.3%       animals sacrificed                 exposure; mean survival 
                                   at 3, 6, and 12                    time 580 days
                                   months                             
---------------------------------------------------------------------------------------------------------

Table 19.  (contd.)
---------------------------------------------------------------------------------------------------------
Fibre type    Source and fibre     Protocol           Number Species  Results                   Reference
              size distribution
---------------------------------------------------------------------------------------------------------
Erionite      New Zealand -        intrapleural       40     F 344    6 mesotheliomas; 20       Wagner
              frequency of fibres  inoculation of            rat      survivors at unspecified  (1982)
              <0.5 µm in           20 mg; animals                     time period following
              diameter and > 4     observed for life                  administration
              µm in length = 1.9%  span

Erionite      Oregon - frequency   intrapleural       40     F 344    40 mesotheliomas (100%);  Wagner
              of fibres < 0.5      inoculation of            rat      mean survival time        et al.
              µm in diameter and   20 mg; animals                     390 days                  (1985)
              > 4 µm in length     observed for life
              = 9.5%               span

Erionite      Karain - frequency   intrapleural       40     F 344    38 mesotheliomas (95%)    Wagner
              of fibres < 0.5      inoculation of            rat      mean survival time        et al.
              µm in diameter       20 mg; animals                     435 days                  (1985)
              and > 4 µm in        observed for life
              length = 2.9%        span

Erionite      "sedimentary         intrapleural       40     Sprague- incidence of mesothel-    Maltoni
              erionite" source     injection of              Dawley   iomas after 67 weeks -    et al.
              and fibre size       25 mg; animals            rat      52.5% (UICC Canadian      (1982a,b)
              distribution not     observed for life                  chrysotile: 0% 
              reported             span                               mesotheliomas)

Erionite      source not reported; intraperitoneal    10     Swiss    malignant peritoneal      Suzuki
              average length 1 µm  injection of              albino   tumours in 6 out of 10    (1982)
              (95% < 8 µm);        10 or 30 mg;              male     (60%) 8 - 22 months
              average width 0.1    animals observed        mouse      after administration;
              µm (94.4% < 1 µm)    for life span                      malignant peritoneal
                                                                      tumours in 2 out of 4
                                                                      (50%) chrysotile-
                                                                      treated controls 
                                                                      between 9 and 16 months
---------------------------------------------------------------------------------------------------------

Table 19.  (contd.)
---------------------------------------------------------------------------------------------------------
Fibre type    Source and fibre     Protocol           Number Species  Results                   Reference
              size distribution
---------------------------------------------------------------------------------------------------------
Erionite      "sedimentary         intraperitoneal    40     Sprague  incidence of mesothel-    Maltoni
              erionite"; source    injection of              Dawley   iomas after 67 weeks -    et al.
              and fibre size       25 mg; animals            rat      2.5% (UICC Canadian       1982a,b)
              distribution not     observed for life                  chrysotile: 2.5% 
              reported             span                               mesotheliomas)

Erionite      naturally-occurring  intraperitoneal    50     BALB/c   peritoneal mesotheliomas  Suzuki &
              from Colorado, USA   injection of              mouse    in 21/42 dissected        Kohyama
                                   10 mg; animals                     animals (50%) between 7   (1984)
                                   observed for life                  and 23 months after
                                   span                               exposure

Erionite      naturally-occurring  intraperitoneal    50     BALB/c   peritoneal mesotheliomas  Suzuki &
              from Nevada, USA     injection of              mouse    in 6/18 (33%) (0.5-mg     Kohyama
                                   0.5, 2, or 10 mg;                  group), 24/44 (55%)       (1984)
                                   animals observed                   (2-mg group), and 3/10
                                   for life span                      (38%) (10-mg group)
---------------------------------------------------------------------------------------------------------

Table 20.   In vitro studies - natural mineral fibres other than asbestos
---------------------------------------------------------------------------------------------------------
Fibre type    Source and fibre                 Results                         Reference
              size distribution
---------------------------------------------------------------------------------------------------------
Attapulgite   Spanish; thinnest fibres 0.02 -  more haemolytic in human        Bignon et al. (1980)
              0.03 µm wide; mean length        red blood cells than UICC
              > 0.8 µm and aspect              chrysotile A
              ratio > 17

Attapulgite   "short-fibre"; source and        cytotoxic in mouse peritoneal   Chamberlain et al. (1982)
              distribution of sizes not        macrophages but not in A 549
              reported                         and V79-4 cells

              "long-fibre"; source and         cytotoxic in all 3 cell
              distribution of sizes not        types (see above)
              reported

Attapulgite   relatively pure sample from      minimal inhibition of           Reiss et al. (1980)
              mine in Attapulgus, Georgia;     colony-forming efficiency
              "fibres of small or smaller      of I-407 cells (16% vs 54%
              diameter range than diameter     for equal dose of amosite)
              range for chrysotile"

Attapulgite   source and fibre size            alteration in thymidine         Lemaire et al. (1982)
              distribution not reported        incorporation by lung 
                                               fibroblasts at 48 h; 63% of 
                                               that observed for chrysotile B
---------------------------------------------------------------------------------------------------------

Table 20.  (contd.)
---------------------------------------------------------------------------------------------------------
Fibre type    Source and fibre                 Results                         Reference
              size distribution
---------------------------------------------------------------------------------------------------------
Sepiolite     source not reported; "short-     not cytotoxic in mouse          Chamberlain et al. (1982)
              fibre" (90% < 0.5 µm)            peritoneal macrophages;
                                               A549 or V79-4 cells

              source not reported; "long-      cytotoxic in all 3 cell
              fibre" (90% < 3.5 µm)            types (see above)

Wollastonite  source and fibre size            no release of lysosomal         Pailes et al. (1984)
              distribution not reported        enzymes nor damage to
                                               membrane in rabbit alveolar
                                               macrophages exposed to
                                               250 µg/ml; far less
                                               cytotoxic than chrysotile

Erionite      Oregon; 6.2 x 103 fibres/µg      increase in morphological       Poole et al. (1983)
              of dust; median length           transformation and unscheduled
              1.7 µm, 4.3% > 6 µm              DNA repair synthesis
                                               in C3H10T1/2 cells and
                                               unscheduled DNA repair
                                               synthesis in A549 cells;
                                               more active than UICC
                                               chrysotile and crocidolite
---------------------------------------------------------------------------------------------------------
7.2.1  Fibrous clays

7.2.1.1  Palygorskite (Attapulgite)

    The preliminary results of an inhalation study indicate that 
the degree of fibrosis for animals sacrificed following exposure to 
Spanish attapulgite for 3, 6, or 12 months was similar to that for 
animals exposed to crocidolite (Wagner, 1982).  The fibre size 
distribution of the attapulgite and the administered dose were not 
reported in the early published account of the preliminary results 
of this study. 

    In a study involving intrapleural administration in rats 
(Wagner, 1982), Spanish attapulgite was less potent in inducing 
mesothelial tumours than equal masses of UICC chrysotile B, while, 
in another study involving intraperitoneal injection of attapulgite 
of unreported origin (Pott et al., 1976a), it was more potent than 
chrysotile A.  The fibre size distribution of the attapulgite 
samples was not specified in the first of the above two studies, 
while, in the second, 30% of fibres were more than 5 µm in length. 
In a further study, the incidence of tumours following intrapleural 
implantation of attapulgite in rats was low (7% versus 48.3% for 
UICC crocidolite); this low value was well correlated with the low 
proportion of fibres in the critical size range (< 0.25 µm in 
diameter; > 8 µm 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 
have been somewhat contradictory.  However, the fibre size 
distributions of the administered samples have not been reported in 
the published accounts of most of the studies.  Attapulgite has been 
more haemolytic in red blood cells than UICC chrysotile 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  
pathogenesis of mineral dusts.  In another assay, the alteration in 
thymidine incorporation by lung fibroblasts exposed to attapulgite 
was 63% of that observed for chrysotile B (Lemaire et al., 1982) 
and "minimal inhibition" of the colony-forming efficiency of I-407 
cells by attapulgite (16% versus 54% for an equal dose of amosite) 
has been reported (Reiss et al., 1980). 

    It has also been reported that "short-fibre" attapulgite is 
cytotoxic for mouse peritoneal macrophages but not for A549 and 
V79-4 cells, whereas "long-fibre" 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" 
attapulgite may be "fibrogenic" in  in vivo studies, whereas "long-
fibre" attapulgite may be "fibrogenic and carcinogenic".  Using 
P388D1 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 
hydrocarbons such as benzo( a )pyrene and nitrosonornicotine (Harvey 
et al., 1984). 

7.2.1.2  Sepiolite

    The preliminary results of an inhalation study indicate that 
the degree of fibrosis for animals sacrificed after exposure to 
sepiolite for 3, 6, or 12 months was similar to that for animals 
exposed to crocidolite (Wagner, 1982).  Additional details on the 
fibre size distribution of the sepiolite and on the study protocol 
were not reported in the early published account of the preliminary 
results of this study. 

    No mesothelial tumours were reported in 40 F 344 rats, at an 
unspecified period prior to study completion, following 
intrapleural administration of sepiolite (Wagner, 1982). "Short-
fibre" sepiolite was not cytotoxic in mouse peritoneal macrophages, 
A549, or V79-4 cells, whereas "long-fibre" sepiolite was cytotoxic 
in all three systems (Chamberlain et al., 1982). 

7.2.2  Wollastonite

    In studies involving the intrapleural implantation in rats of 4 
samples of wollastonite from a Canadian mine, the mesothelial 
tumour incidence varied from 0 to 25% (versus 48.3% for UICC 
crocidolite) (Stanton et al., 1981). 

    In  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 chrysotile known to be cytotoxic in this system 
(Pailes et al., 1984).  In addition, wollastonite was found to be 
far less haemolytic in red blood cells than asbestos (Hefner & 
Gehring, 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 
wollastonite shows that these natural mineral fibres induce effects 
on pulmonary macrophages that may simulate events occurring in the 
lung following dust exposure, such as impaired phagocytic capacity 
of the exposed macrophages, and serum complement activation, as 
measured by dose-related increases in pulmonary macrophage 
chemotaxis (Warheit et al., 1984). 

7.2.3  Fibrous zeolites - erionite

    In an inhalation study (Wagner et al., 1985) in which animals 
were exposed for one year to erionite from several sources, at 10 
mg/m3 7 h/day, 5 days per week, a remarkably high incidence of 
mesotheliomas (96.4%) occurred in the animals that remained 12 
months after exposure (sample from Oregon) (frequency of fibres 
< 0.4 µm in diameter and > 5 µm 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., 1974; Wagner et al., 1974; Davis et al., 1978).  
The time to development of the tumours in the Oregon erionite-
exposed 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 µm in diameter and > 4 µm in length = 
1.9%) for one year (Wagner, 1982). 

    In studies involving injection into the body cavities of 
animals, erionite has been extremely potent in the induction of 
mesothelial tumours; indeed one author reported that it is the 
"most potent known experimental carcinogenic agent for the pleural 
mesothelium" (Maltoni et al., 1982b).  For example, in a study 
involving the intrapleural administration in rats of 20 mg of 
erionite from Oregon, the mesothelial tumour incidence was 100%; 
for samples originating from Karain this value was 95% (Wagner et 
al., 1985).  The incidence of tumours after 67 weeks, in rats 
receiving an intrapleural injection of 25 mg of "sedimentary 
erionite" of unreported origin, was 52.5% (UICC Canadian chrysotile 
0%) (Maltoni et al., 1982a,b).  In the same study, the incidence of 
tumours following intraperitoneal injection of a similar amount of 
the same material was considerably less (2.5%) (UICC Canadian 
chrysotile 2.5%).  On the basis of these results, the authors 
concluded that there was a different degree of "responsiveness of 
the pleura and peritoneum to erionite and crocidolite" (crocidolite 
was more potent in inducing tumours following intraperitoneal 
administration).  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 µm; average width 0.1 µm) was administered 
intraperitoneally to mice (incidence in chrysotile-exposed animals, 
2/4, 50%) (Suzuki, 1982).  No peritoneal tumours were observed in 
male BALB/c mice that had been administered erionite by a single 
intraperitoneal injection and had died less than 7 months after 
exposure.  Between 7 and 23 months after administration, there were 
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, 24/44 (55%), and 0.5 mg Nevada erionite, 6/18 
(33%). 

    Available data also indicate that some forms of erionite are 
more toxic in  in vitro systems than crocidolite and chrysotile.  A 
sample of erionite from Oregon increased morphological 
transformation in mammalian C3H1OT1/2 cells and unscheduled DNA 
repair synthesis in A549 cells to a greater extent than UICC 
chrysotile and crocidolite (Poole et al., 1983).  The authors noted 
that fewer fibres in the sample of erionite administered were in 
the "pathogenic" size range (4.3% > 6 µm long, median length 1.7 
µm), compared with the UICC crocidolite, and suggested that there 
might be some property of erionite that makes it quantitatively 
more active. 

7.2.4  Assessment

    Although, in general, the toxicological information is not 
adequate to assess the potential risks associated with exposure to 
most of these fibrous minerals, it can be concluded, with some 
certainty, that some forms of erionite may 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 may be "the most dangerous of the natural 
fibres" (Wagner, 1982) and by another that it is the most potent 
known experimental carcinogenic agent for the pleural mesothelium 
(Maltoni et al., 1982). 

8.  EFFECTS ON MAN

8.1  Asbestos

    The epidemiological studies discussed below are categorized 
according to whether the asbestos exposure was occupational (mining 
and milling, manufacturing, or product application), para-
occupational (neighbourhood of an asbestos industrial plant, or 
home of an asbestos worker), or exposure of the general population 
(air or water). 

8.1.1  Occupational exposure

    Inhalation of asbestos dust can cause fibrosis of the lung 
(asbestosis), changes in one or both surfaces of the pleura, 
bronchial 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 in the earliest stages of the disease. 

    Under recent exposure conditions, asbestosis will rarely be 
detectable, even in its early stages, in less than 20 years from 
first exposure.  In the majority of cases, asbestosis will advance 
after cessation of exposure (Berry, 1981; Jones, R.N., et al., 
1980; Navratil, 1982), though early cases do not show any 
appreciable radiographic change over many years, provided that 
there is no further exposure (Gregor et al., 1979; Rubino et al., 
1979a; Liddell & McDonald, 1980). 

    The 1968 British Occupational Hygiene Society standard of 2 
fibres/ml for chrysotile was based on a retrospective study of a 
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 
fibre/ml years was of the order of 2% (Acheson & Gardner, 1979), 
and a recent analysis suggests that the lifelong risk of developing 
early signs of asbestosis may be even higher (Berry et al., 1979). 

    There is no substantial evidence that asbestos fibre type 
influences 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 
(McDonald, 1984). 

    As 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 North American insulation workers (Selikoff et al., 1979), 
this distinction 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 
experience is more 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 
and between countries and social classes, and expected numbers are 
therefore unreliable.  Asbestosis mortality in heavily-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 
cigarette smoking (Hammond et al., 1979).  If the risk were 
linearly related to intensity of exposure at lower levels, these 
relationships would provide a basis for estimating low-level risks 
(Peto, 1978), but this seems implausible for such a generalized 
progressive condition. 

8.1.1.2  Pleural thickening, 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 
prevalence 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., 
1972).  Pleural calcification is occasionally seen as a very late 
consequence of occupational exposure. 

8.1.1.3  Bronchial cancer

    The first reports (Gloyne, 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 
years.  The first epidemiological confirmation of this association 
was published by Doll (1955).  Since then, over 30 cohort studies 
have been carried out in industrial populations in several 
countries.  The majority have shown an excess lung cancer risk 
(McDonald, 1984), but several studies have shown no significant 
excess mortality from bronchial tumours, even though some 
mesotheliomas occurred (Rossiter & Coles, 1980; Thomas et al., 
1982; Berry & Newhouse, 1983; Ohlson & Hogstedt, 1985). 

    (a)   Type of asbestos

    It is not clear whether chrysotile, crocidolite, and amosite 
differ in their potential to cause lung cancer.  Occupational 
exposures to these fibres usually occur under different industrial 
circumstances 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., 1980); however, it is not known whether the exposure levels or 
other 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 
definitive.  Recent studies of 2 textile plants, one using 
chrysotile only (McDonald et al., 1983a), the other using a mixture 
of chrysotile and amphiboles (McDonald et al., 1983b), showed no 
difference in lung cancer risk between the two.  However, as with 
the mining studies, it is difficult to make such cross-study 
comparisons, because of possible differences in the actual exposure 
levels and other risk factors.  In gas-mask manufacture, in the 
1940s, those exposed to crocidolite had a greater excess of lung 
cancer than those using only chrysotile (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 
intensity information.  In two of these studies, both on asbestos 
cement 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 studies (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 many factors, including the 
limited exposure measurements made during the relevant time 
periods.  The estimated slopes, however, exhibit a pattern 
according to industrial process, with the lowest values reported 
for miners and friction product workers; the highest for textile 
workers, and intermediate values in other manufacturing plants. 

    The variations in these results may be related to the state and 
physical treatment of the asbestos in different situations, the 
dust clouds thus containing asbestos fibres of different physical 
dimensions.  A detailed review of other exposure-response estimates 
for lung cancer in different cohorts has recently been published by 
the US NRC/NAS (1984). 

Table 21.  Standardized mortality ratios for cancers of the lung, gastrointestinal tract,
and other sites in asbestos workers (number of deaths in parentheses)a
---------------------------------------------------------------------------------------------------------
Sex     Type of       Period of    Standardized mortality ratio for:   Number   Reference
        exposure      observation  Lung         Gastro-     Other      of     
                                   cancer       intestinal  cancer     mesothel-
                                                cancer                 iomas
---------------------------------------------------------------------------------------------------------
Male    Mining,       1946-75b     1.03 (9)     1.03 (15)   0.94 (13)  1        Rubino et al. (1979b)
        chrysotile    1951-75b     1.22 (224)   1.03 (209)  1.05 (317) 10       McDonald et al. (1980)

Male    Manufacture,  1936-77c     0.85 (28)    0.91 (18)   0.93 (26)  2        Thomas et al. (1982)
        chrysotile    1958-77b     2.00 (59)    1.46 (25)   1.28 (35)  1        McDonald et al. (1983a)
                      1958-77b,c   1.49 (84)    1.14 (59)   1.16 (70)  0        McDonald et al. (1984)
                      1953-83b,c   1.61 (113)   1.10 (47)   0.84 (48)  17       Peto et al. (in press)

Male    Manufacture,  1941-79d     1.03 (143)   0.96 (103)  0.88 (77)  8        Berry & Newhouse (1983)
        mixed         1947-80      1.96 (57)    1.11 (19)   1.00 (28)  5        Acheson et al. (1984)
                      1944-76      1.72 (44)    1.04 (31)   0.95 (89)  3        Clemmesen & Hjalgrim-
                                                                                Jensen (1981)e

Male    Manufacture,  1941-73      6.29 (84)    2.07 (26)   1.62 (42)  11       Selikoff & Hammond (1975)
        amosite

Male    Insulation,   1943-62b     7.00 (42)    2.99 (29)   1.04 (17)  7        Selikoff et al. (1964)
        mixed         1967-76      4.24 (397)   1.67 (89)   1.98 (258) 102      Selikoff et al. (1979)
                      1933-75d     2.38 (103)   1.18 (40)   1.39 (38)  46       Newhouse & Berry (1979)

Male    Shipyards     1947-78      0.84 (84)    0.83 (68)   1.11 (87)  31       Rossiter & Coles (1980)

Male    Various       -            3.07 (55)    1.05 (16)   1.29 (36)  23       Mancuso & Coulter (1963);
                                                                                Weiss (1977); Newhouse &
                                                                                Berry (1979); Finkelstein
                                                                                (1983)

Female  Manufacture,  1936-75      8.44 (27)    1.96 (20)   1.62 (33)  21       Newhouse & Berry (1979)
        mixed         1941-79d     0.53 (6)     1.06 (29)   0.85 (51)  2        Berry & Newhouse (1983)

Female  Various       -            2.06 (27)    1.28 (15)   0.99 (90)  7        Mancuso & Coulter (1963);
                                                                                Acheson et al. (1982);
                                                                                Peto et al. (in press)
---------------------------------------------------------------------------------------------------------
a  From: Doll & Peto (1985).
b  Twenty or more years after first employment.
c  Some little exposure to amphiboles.
d  Ten or more years after first employment.
e  Cases of cancer and incidence ratios, not deaths.

Table 22.  Exposure-response relationships for bronchial cancera
---------------------------------------------------------------------------------------------------------
Location        Process   Fibre       Slope for increased  Conversion factor
                          type        lung cancer riskb    (mppcf to fibre/ml)   Reference
                                      (fibres/   (mppcf    authors  other
                                      ml years)  years)
---------------------------------------------------------------------------------------------------------
 Canada

  Quebec        mining/   chrysotile  -          0.0014    1        -            McDonald et al.
                milling                                    5        -            (1980)

 USA

  Connecticut   friction  chrysotile  -          0.000     -        any          McDonald et al.
                products                                                         (1984)

  Louisiana     cement    mixed       -          0.0044    -        1            Hughes & Weill
                products                                                         (1980)

  Pennsylvania  textile   mixed       -          0.051     -        1            McDonald et al.
                                                                    3            (1983b)
                                                                    5

  South         textile   chrysotile  0.023      -         NA       NA           Dement et al.
  Carolinac                                                                      (1982)
                                      -          0.082     -        3            McDonald et al.
                                                           -        5            (1983a)
                                                 0.051     -        3
                                                 -         -        5

  area not      mixed     mixed       -          0.00658   -        1            Enterline & Henderson
  stated                                                   -        3            (1973)
                                                           -        5

 United Kingdom  

  area not      friction  chrysotile  0.00058    -         NA       NA           Berry & Newhouse
  stated        products                                                         (1983)
---------------------------------------------------------------------------------------------------------
a  Modified from: Canada, National Health and Welfare (1984); report of Committee of Experts.
b  Adjusted to relative risk or SMR = 1 at zero dose.
c  Studies in same factory.
NA = not applicable.
    (c)   Co-carcinogens

    Because of a lack of information on smoking in most cohorts, it 
has been 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 
the 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 
constant; if additive, then the risk due to asbestos exposure would 
be added arithmetically to the smoking risk). 

    A review of the available studies (Saracci, 1981) and a recent 
report based on the Canadian mining population (Liddell et al., 
1983) suggest that the joint effect of these two exposures is 
probably more than additive but not always multiplicative. 

    If asbestos acts, at least in part, as a promoter rather than 
an initiator of lung cancer, then exposures other than personal 
smoking may also be important.  In particular, passive smoking, air 
pollution, or ionizing radiation may play a role, but no human data 
are available, as yet, concerning the combined effects of these 
factors with asbestos. 

8.1.1.4  Mesothelioma

    The majority of known cases of mesothelioma arise as a result 
of occupational or para-occupational exposure to asbestos or other 
fibrous 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 
(McDonald, 1984). 

    (a)   Fibre type

    No reliable exposure-response information is available for 
mesothelioma.  The 8 studies with adequate measurements of exposure 
intensity and duration showed only a small number of cases of 
mesothelioma, and, in at least 4 of the 7 populations studied, 
exposure was to mixed fibre types.  Semi-quantitative data 
(Newhouse & 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 
(Rossiter & Coles, 1980; Peto et al., 1982; Browne, 1983a,b). 

    Definitive conclusions cannot be drawn in the absence of 
exposure-response information for individual fibre types.  However, 
available evidence suggests a substantial difference between 
chrysotile and the amphiboles (especially crocidolite) in their 
capacity to cause mesothelioma.  The evidence is summarized below. 

1.  Substantial numbers of cases have occurred in naval dockyard 
    cities where amphibole exposure, especially during World War 
    II, was probably heavy (Harries, 1968; McDonald & McDonald, 
    1978).  Of special interest is the study of Rossiter & Coles 
    (1980) 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. 

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; Langer (on the basis of tissue analysis), personal 
    communication, 1985). 

3.  Short-term exposure to pure crocidolite of workers engaged in 
    the manufacture 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 
    mesothelioma.  The same was true, but to 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 plant in which only amosite was used 
    (Seidman et al., 1979).  In contrast, very few cases have been 
    reported among chrysotile production workers in Canada, Italy, 
    South Africa, and the USSR. 

4.  Cohort studies on 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; in the other, small quantities of 
    amphibole were used, and there were 20 cases of mesothelioma.  
    In a third plant, 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, 1980). 

6.  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, 
    variations in the persistence of different fibre types in the 
    lung complicate the interpretation of the results of tissue 
    burden studies. 

7.  In a friction products plant studied by Berry & Newhouse (1983) 
    in which only chrysotile was used (except in a well-defined 
    area of one workshop, where crocidolite was processed for 9 
    years), the only excess mortality comprised 10 deaths from 
    pleural mesothelioma, 8 or perhaps 9 in men who had worked with 
    the crocidolite. 

8.  Five cases of mesothelioma were reported by Acheson et al. 
    (1982) among 219 deaths in women who had manufactured military 
    gas masks (containing crocidolite) compared with 1 case among 
    177 deaths in women manufacturing civilian masks (containing 
    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 after first employment, in a London insulation products 
    factory in which only amosite was used (Acheson et al., 1981). 

    An indication 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 mesotheliomas, greater risks were associated with crocidolite 
and possibly amosite exposures than with chrysotile exposure alone.  
Exposure to mixed fibres generally resulted in an intermediate 
risk.  Results of studies not reporting the mesothelioma site are 
consistent with these findings. 

    The reasons for the different mesothelioma risks associated 
with different fibre types could include differences in the 
physical dimensions of the fibres and the possibilities of higher 
effective doses, increased peripheral deposition, and/or longer 
tissue persistence for amphibole exposure than for chrysotile. 

    (b)   Industrial process

    Current information does not suggest an important differential 
in risk according to the industrial process. 

8.1.1.5  Other cancers

    Many cohort studies on different populations have suggested 
that cancer at sites other than the lung, pleura, and peritoneum 
has resulted from occupational exposure to asbestos.  In contrast, 
other studies have shown no excesses of cancer at other sites. 

    (a)   Gastrointestinal cancers

    In 18 out 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 confounding factors such as social 
class and geographical variations, and because of possible 
misdiagnosis.  Moreover, there is no evidence of dose-related 
effects.  Thus, a causal relationship with asbestos has not been 
established.  This subject has been reviewed recently by Acheson & 
Gardner (1983), the Ontario Royal Commission on Asbestos (1984), 
and Doll & Peto (1985). 

    (b)   Kidney cancer

    The excess of kidney cancer observed by Selikoff et al. (1979) 
has not been supported by any other study so far.  A causal 
relationship has not been established. 

    (c)   Laryngeal cancer

    Evidence concerning this cancer is conflicting.  In addition to 
the small excess noted by Selikoff et al. (1979), 2 case-control 
studies, one in Liverpool by Stell & McGill (1973), and the other 
in Toronto by Shettigara & Morgan (1975), produced evidence of 
increased risk.  On the other hand, there was no excess in Quebec 
miners and millers (McDonald et al., 1980), and the results of a 
case-control study in London by 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 
any, would be small in comparison with bronchial cancer. 

    (d)   Other sites

    Among insulation workers, 252 deaths were certified as due to 
"other cancer", but 54 of these were reclassified on review as 
mesothelioma and 28 as lung cancer (Selikoff, 1982).  Reanalysis of 
the data has suggested that a substantial part, and perhaps all, of 
the apparent excess due to other cancers can be attributed to 
misdiagnosis.  Two sites particularly liable to be certified 
incorrectly are the pancreas and liver; 16 of the 49 deaths 
certified as due to pancreatic cancer were, in fact, due to 
peritoneal mesothelioma (Selikoff & Seidmann, 1981).  There is, 
therefore, little evidence of a causal relationship between 
asbestos and cancers of these other sites. 

    There have been three studies in which there was an excess 
mortality from ovarian tumours in workers exposed to mixed fibres 
(Acheson et al., 1982; Wignall & Fox, 1982; Newhouse et al., 1980), 
but, in two other studies, no increase was found (Acheson et al., 
1982; Berry & Newhouse, 1983). 

8.1.1.6  Effects on the immune system

    Changes in immunological variables have been observed in 
patients with asbestosis 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 may effect similar changes. 

    Pernis et al. (1965) reported a significant increase in 
rheumatic factors in asbestos workers with diagnosed asbestosis.  
Increases in non-organ-specific anti-nuclear antibodies and 
rheumatoid factors have also been reported by Turner-Warwick & 
Parkes (1970), Lange et al. (1974), Kagan et al. (1977b), and 

Navratil & Jezkova (1982).  In addition, changes characteristic of 
idiopathic interstitial pulmonary fibrosis, such as increased 
levels of the immunoglobulins IgA, IgG, IgM, IgE, and complement 
components 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 
(Huuskonen et al., 1978; Lange, 1980).  A decrease in the number of 
T cells (Kang et al., 1974; Kagan et al., 1977a), defects in cell-
mediated immunity, and a deficiency of the generation of the 
migration inhibition factor (MIF) have also been shown in persons 
with asbestosis (Lange et al., 1978).  It has been suggested that 
changes in T-cell subpopulations affect immunoregulatory phenomena 
with a resulting decrease in T-cell-mediated immunity and increase 
in B-cell activity.  This could explain the known increased 
production 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 
macrophages in the etiology of this disease has been published by 
Kagan (1980). 

    The immunological status of individuals with asbestos-related 
cancers has been described in only a limited number of reports 
(Ramachander et al., 1975; Haslam et al., 1978).  These studies 
indicate that the mitogenic lymphocyte response is impaired in such 
patients. 

8.1.2  Para-occupational exposure

8.1.2.1  Neighbourhood 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 of an anthophyllite mine (Kiviluoto, 1960), and similar 
observations were made in populations living in the vicinity of an 
anthophyllite mine in Bulgaria (Zolov et al., 1967), an actinolite 
mine in Austria (Neuberger et al., 1982), and an asbestos factory 
in Czechoslovakia (Navratil & Trippe, 1972). 

    There is some evidence, mainly 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 
series.  In an early review, of 33 cases of mesothelioma in the 
Northeast Cape province of South Africa (Wagner et al., 1960), 
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 identified 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 cases 
of mesothelioma observed in the neighbourhood of shipyards were 
reviewed by Bohlig & Hain (1973), who  reported 38 cases of "non-
occupational" mesothelioma, which occurred during a 10-year period 
in residents in the vicinity of a Hamburg asbestos plant.  However, 
in a study conducted in Canada, excluding individuals with 
occupational or household exposure to asbestos, only 2 out of the 
254 (0.75%) cases of mesothelioma recorded in Quebec between 1960 
and 1978 lived within 33 km of the chrysotile mines and mills 
(McDonald, 1980).  In addition, in a systematic investigation of 
all 201 cases of mesothelioma and 19 other pleural tumours reported 
to the Connecticut Tumour Registry, between 1955 and 1977, and 604 
randomly-selected decedent controls, there was no association 
between incidence 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 1966-
67, 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 periods 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 years (Vianna 
& Polan, 1978).  In most of the studies, there were few data 
concerning the type of asbestos to which neighbourhood residents 
were exposed. 

    Four ecologicala epidemiological 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; Siemiatycki, 1983).  On the basis of the analysis of 
cancer incidence data from the Quebec Tumour Registry, the risk for 
residents 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 in males were attributed, in part, to occupational 
exposure.  There was increased risk of cancer of the pleura in both 
sexes, which decreased with increasing  distance of  residence from 
the asbestos mines.  The authors emphasized the limitations of 
their 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; Siemiatycki, 1983).  Mortality between 1966 and 1977 in 
agglomerations (several municipalities) around the asbestos-mining 
communities of Asbestos and Thetford Mines was compared with that 
of the Quebec population.  A statistically-significant 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. 

cancer among males in these agglomerations was attributed to 
occupational exposure.  A telephone survey indicated that 75% of 
the men in these communities had worked in the mines (Siemiatycki, 
1983).  For women, whose exposure had been confined to the 
environment or, in some cases, to environmental exposure and family 
contact, there were no statistically-significant excesses of 
mortality due to all causes (standard mortality ratea, SMR = 0.89), 
all cancers (SMR = 0.91), digestive cancers (SMR = 1.06), 
respiratory cancers (SMR = 1.07), or other respiratory disease (SMR 
= 0.58).  Similarly, there were no significant excesses when the 
mortality rate at age less than 45 was considered or when the 
reference population was confined to towns of similar size. 
Unfortunately, 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 of 1.1 - 1.4 for lung cancer could not be ruled 
out in such a study. 

    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 
asbestos-cement production plant, in comparison with local and 
national population statistics (community size and agricultural 
index were taken into consideration) (Neuberger et al., 1984). 

    In another ecological study conducted in the USA, in which 
there was some attempt to control for the urban effect, 
geographical 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 
variables, which are difficult to eliminate.  In addition, true 
excess cancer risk is probably underestimated in such studies, 
because of population  mobility over a latent period of several 
decades (Polissar, 1980).  Case-control and cohort studies are 
generally more powerful than ecological epidemiological studies, 
because exposure and outcome are assessed for individuals rather 
than for populations.  One relevant cohort study has been 
conducted.  Mortality data for men who lived within 0.5 miles of an 
amosite factory in Paterson, New Jersey in 1942 were compared with 
data in 5206 male residents of a similar Paterson neighbourhood 
with no asbestos plant (Hammond et al., 1979).  All men who worked 
in the factory were excluded.  Approximately 780 (44% of the 
"exposed" population) and 1735 (46% of the "unexposed" population) 
died during the 15-year period 1962-76.  With respect to total  
deaths, deaths from cancer (all sites combined), and lung cancer, 
mortality experience was slightly worse in the "unexposed" 
population during this 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 
plaques and mesothelioma may be increased in populations residing 
in the vicinity of asbestos mines or factories.  However, there is 
no evidence that the risk of lung cancer is increased in similarly-
exposed populations.  However, it should be noted that, in the past, 
airborne fibre levels near asbestos facilities were generally much 
higher than they are today.  For example, Bohlig & Hain (1973) 
mentioned that before the second World War, there was "visible 
snowfall-like air pollution" from an asbestos factory in Germany.  
It is also claimed that, 20 years ago in Quebec mining 
communities,"snow-like films of asbestos" accumulated regularly 
(Siemiatycki, 1983). 

8.1.2.2  Household exposure

    Measurements made by Nicholson et al. (1980) in the homes of 
miners and non-miners in a chrysotile-mining community in 
Newfoundland, showed that fibre concentrations were several times 
higher in the former than the latter.  Studies of both Newhouse & 
Thompson (1965) in the United Kingdom and of McDonald & McDonald 
(1980) in North America showed more cases of household exposure in 
mesothelioma patients than in controls, after exclusion of 
occupation.  Two further epidemiological surveys have specifically 
addressed the question.  Vianna & Polan (1978) studied the asbestos-
exposure history of all 52 histologically confirmed fatal cases of 
mesothelioma in females in New York State (excluding New York 
City), in 1967-77, with matched controls.  Excluding 6 cases 
exposed at work, 8 others had a husband and/or father who worked 
with 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 by Anderson et al. (1979), over 3100 household 
contacts of 1664 surviving employees of the Paterson amosite 
asbestos 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 325 controls of similar age 
distribution, were selected for radiographic and other tests.  
Small opacities and/or pleural abnormalities were observed in 35% 
of the 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 by 
consensus, it was made without knowledge of exposure category.  The 
mortality experience of this population of household contacts is 
also under study; the method has not yet been adequately described 
but at least 5 cases of mesothelioma and excess mortality from lung 
cancer have been reported. 

8.1.3  General population exposure

    (a)   Inhalation

    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 & Studeny, 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 mesothelial tumours undertaken by McDonald & McDonald 
(1980) in Canada during the period 1960-75, and in the USA in 1972.  
Systematic ascertainment through 7400 pathologists yielded 668 
cases which, with controls, were investigated primarily for 
occupational factors.  After exclusion of those with occupational, 
domestic, or mining neighbourhood exposure, the places of residence 
of women were examined for the 20 to 40-year period before death.  
Of 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 
chance, quite apart from the greater likelihood of case recognition 
in urban than rural areas and the contribution of exposure in the 
immediate neighbourhood of 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 
in a recent analytical review by 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 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 
evidence that both occupational and domestic exposure accounted for 
some cases in women, there is little room left for any material 
effect attributable to general environment exposure. 

    (b)   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 complex question, as the exposures are intermittent and the 
concentrations vary.  However, even in industrial cohorts, the 
association of asbestos exposure with alimentary cancer is 
irregular (McDonald, 1984) and not wholly convincing (Acheson & 
Gardner, 1983). 

    Ecological epidemiological 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 Bay 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 
drinking-water in the studies conducted in Canada (Wigle, 1977; 
Toft et al., 1981), Connecticut (Harrington et al., 1978; Meigs et 
al., 1980), Duluth (Mason et al., 1974; Levy et al., 1976; 
Sigurdson et al., 1981), Florida (Millette et al., 1983), and Utah 
(Sadler et al., 1981).  However, all of these studies had 
limitations (Toft et al., 1984).  The Duluth and Connecticut 
studies both had the disadvantage of relatively recent onset of 
exposure (1955 in Duluth, mostly since 1955 in 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. 

    In 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 
cancer (Kanarek et al., 1980; Conforti et al., 1981).  This study 
had 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 
population-based cancer incidence data (Toft et al., 1984).  
However, there were several confounding factors that complicate 
interpretation of the results of the San Francisco Bay area study.  
Reanalysis, taking population density into account, reduced the 
significance of the relationship observed between ingested 
asbestos and cancer in males and increased the significance of the 
association for females (Conforti, 1982).  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 
of the association that was observed in the California study 
(Tarter, 1982). 

Table 23.  Epidemiological studies: asbestos in drinking-water
---------------------------------------------------------------------------------------------------------
Study area   Fibre type    Population and     Study design               Results              Reference
                           exposure
---------------------------------------------------------------------------------------------------------
Duluth,      amphibole     ~100 000           ecological: comparison of  no evidence of       Levy et al.
Minnesota    (mine         exposed to 1 - 65  age-adjusted cancer        increased risk of    (1976);
             tailings)     x 106 fibres/      incidence rates (1969-74)  gastrointestinal     Sigurdson
                           litre for 15 -     in Duluth with those in    cancers due to the   et al.
                           20 years           Minneapolis and St.  Paul   presence of          (1981);
                                                                         asbestos             Sigurdson
                                                                                              (1983)

             amphibole     ~100 000 ex-       ecological: determination  no evidence of       Mason et 
             (mine         exposed to 1 - 65  of SMRs (1950-69) for      increased risk of    al. (1974)
             tailings)     x 106 fibres/      Duluth with comparison     gastrointestinal
                           litre for 15 -     population (Minnesota)     cancers due to the
                           20 years                                      presence of
                                                                         asbestos             

Connecticut  chrysotile    ~580 000           ecological: determination  authors attributed   Harrington
             (asbestos-    exposed to 1 x     of standardized cancer     largely negative     et al.
             cement pipe)  106 fibres/        incidence ratios (1935-    results to low       (1978);
                           litre for          73) from Connecticut       concentrations of    Meigs
                           ~20 years          Tumor Registry data;       asbestos fibres in   et al.
                                              towns grouped by exposure  drinking-water       (1980)
                                              to asbestos in drinking-                        
                                              water and population       
                                              density; multiple 
                                              regression analysis with 
                                              a series of independent 
                                              variables concerning 
                                              population density, 
                                              socioeconomic status, 
                                              and drinking-water 
                                              quality              
---------------------------------------------------------------------------------------------------------

Table 23.  (contd.)
---------------------------------------------------------------------------------------------------------
Study area   Fibre type    Population and     Study design               Results              Reference
                           exposure
---------------------------------------------------------------------------------------------------------
Florida      chrysotile    ~200 000           ecological: comparison     no evidence for an   Millette
(Escambia    (asbestos-    exposed to < 10    of SMRs for 7 cancer       association between  et al.
county)      cement pipe)  x 106 fibres/      sites among 3 exposure     use of A/C pipe and  (1983)
                           litre; long-       groups                     deaths due to
                           standing                                      gastrointestinal
                           contamination                                 and related cancers,
                           (~40 years)                                   limited sensitivity  
                                                                         and analysis         
                           
Quebec       chrysotile    ~30 000 ex-        ecological: comparison     no consistent,       Wigle
             (mining       exposed to ~200 x  of observed to expected    convincing           (1977)
             activities)   106 fibres/        cancer mortality (1964-    evidence of          
                           litre; long-       73), calculated on the     increased cancer     
                           standing           basis of Quebec mortality  risks attributable   
                           contamination      rates specific for sex,    to ingestion of      
                           (~80 years)        site, period, and age      drinking-water       
                                                                         contaminated by      
                                                                         asbestos             
                                                                                              
---------------------------------------------------------------------------------------------------------

Table 23.  (contd.)
---------------------------------------------------------------------------------------------------------
Study area   Fibre type    Population and     Study design               Results              Reference
                           exposure
---------------------------------------------------------------------------------------------------------
Quebec       chrysotile    ~25 000 in         ecological: comparison     no consistent,       Toft
(contd.)     (mining       Thetford Mines     of ASMRs (1966-76)         convincing evidence  et al.
             activities    and 100 000 in     for 71 municipalities      of increased         (1981);
             and natural   Sherbrooke         across Canada stratified   cancer risks         Wigle
             erosion)      exposed to ~100    by asbestos concent-       attributable to      et al.
                           x 106 fibres/      rations in drinking -      ingestion of         (1981)
                           litre; long-       water, use of              drinking-water
                           standing           chlorination; ASMRS for    contaminated by
                           contamination      Sherbrooke compared with   asbestos
                           (~80 years)        those for 7 municipalites
                                              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, drinking-water 
                                              quality, and mobility

California   chrysotile    ~3 000 000         ecological: determination  evidence of          Kanarek
(Bay Area)                 exposed to ~36     of standardized cancer     positive             et al.
                           x 106 fibres/      incidence ratios for 722   associations and     (1980);
                           litre;             census tracts (1969-74)    exposure-response    Conforti
                           longstanding       from Third National        relationships        et al.
                           contamination      Cancer Survey data;        between asbestos     (1981);
                           (~60 years)        census tracts aggregated   concentrations in    Tarter
                                              by asbestos concentration  drinking-water and   (1981)
                                              and income or education;   cancer incidence     
                                              log linear regression      
                                              analysis with 6 
                                              independent variables    
---------------------------------------------------------------------------------------------------------

Table 23.  (contd.)
---------------------------------------------------------------------------------------------------------
Study area   Fibre type    Population and     Study design               Results              Reference
                           exposure
---------------------------------------------------------------------------------------------------------
Utah         chrysotile    24 000 exposed     ecological: comparison     positive             Sadler
             (asbestos-    to unknown         of cancer incidence data   association for      et al.
             cement pipe)  concentrations     from Third National        gall bladder cancer  (1981)
                           for 20 - 30 years  Cancer Survey data for     in females and       
                                              several Utah communities   kidney cancer and    
                                                                         leukaemia in males,  
                                                                         but study did not   
                                                                         control for sex,    
                                                                         socioeconomic status,
                                                                         population density,
                                                                         and migration       

Washington   chrysotile    population of      case-control:              authors concluded    Polissar
(Puget                     Seattle, Everett,  determination of odds      that study did       et al.
 Sound)                    and Tacoma         ratios for cancer          not provide          (1982)
                           metropolitan       incidence (1974-77) and    evidence of a
                           areas exposed to   mortality (1955-75) in     cancer risk due to
                           ~200 x 106         two groups of census       the ingestion of
                           fibres/litre;      tracts aggregated          asbestos in
                           longstanding       according to asbestos      drinking-water
                           contamination      estimates of length         
                           (~60 years)        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, 
which are difficult to eliminate, and the potential to 
underestimate cancer risk due to population mobility over a latent 
period of several decades.  In the more powerful case-control study 
conducted in 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 
ingestion of asbestos in drinking-water. 

    Thus, the studies conducted to date provide little convincing 
evidence of an association between asbestos in public water 
supplies and cancer induction. 

8.2  Other Natural Mineral Fibres

    The present review of minerals that may occur in fibrous form 
will be confined to the fibrous clays, fibrous zeolites, and 
wollastonite.  Although the effects of human exposure to these 
fibres should be described in the same sequence as those for 
asbestos, it is not possible with the very scanty epidemiological 
data available.  Instead, such information, as exists, will be 
examined under 4 main mineralogical headings. 

8.2.1  Fibrous clays

8.2.1.1  Palygorskite (attapulgite)

    The biological effects of these mineral fibres were reviewed by 
Bignon et al. (1980).  They mention only a 41-year-old man with 
pulmonary fibrosis who had been exposed for 3 years in attapulgite 
mining in France, and a 60-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 
studies of attapulgite workers.  However, surveys are in progress 
in the USA. 

8.2.1.2  Sepiolite

    There appears to have been only one epidemiological survey of 
workers exposed to sepiolite, i.e., a radiographic study of 63 men 
engaged in trimming sepiolite stones in Eskisehir, Turkey, in the 
manufacture of souvenirs.  They had been employed from 1 to 30 
years (mean 11.9 years), and 10 showed radiographic evidence of 
pulmonary fibrosis.  However, more than half of those with fibrosis 
came from dusty rural regions that were rich in tremolite asbestos 
and zeolite deposits; silica and deatom particles were also present 
(Baris et al., 1980). 

8.2.2  Wollastonite

    Surveys have been made of wollastonite-mine and -mill workers 
in New York State and of workers exposed to this mineral in a 
Finnish limestone quarry.  In the American studies (Shasby et al., 
1979; Hanke et al., 1984), 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 
had a significantly greater decline in peak expiratory flow.  In 
the Finnish surveys (Huuskonen et al., 1983a,b), slight pulmonary 
fibrosis was detected radiologically in 14 men, and bilateral 
pleural changes in 13 men out of 46 exposed for 10 years or more. 
Preliminary results from a cohort study on 238 of the quarry 
workers showed no excess mortality, but the authors noted that one 
woman with 20 years exposure died from a malignant retroperitoneal 
mesenchymal tumour, 30 years after first employment. 

8.2.3  Fibrous zeolites - erionite

    The remarkable incidence of mesothelial tumours in some remote 
Anatolian villages was first reported by Baris (1975).  The results 
of intensive environmental and epidemiological studies have since 
been described (Baris et al., 1978, 1979; Lilis, 1981; Saracci et 
al., 1982; Sébastien 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 
inhabitants 5 km away, at least 27 cases occurred in the period 
1978-80 (Artvinli & Barris, 1979).  Both sexes were equally 
affected and at an appreciably younger age than is usual in 
occupational cases.  Although many questions remain unanswered, 
there appears to be little doubt that this disastrous situation was 
largely attributable to environmental exposure, from infancy, to 
fine zeolite fibres of volcanic origin, which occur in local dust 
and which have been identified in the lung tissue of patients.  The 
elemental composition of most of these fibres was consistent with 
erionite.  Little asbestos outcropping is used in this area of 
Turkey (Rohl et al., 1982). 

9.  EVALUATION OF HEALTH RISKS FOR MAN FROM EXPOSURE TO ASBESTOS 
AND OTHER NATURAL MINERAL FIBRES

9.1  Asbestos

9.1.1  General considerations

    The results of extensive epidemiological and toxicological 
studies have confirmed that health risks due to asbestos exposure 
are mainly associated with inhalation.  The risks from ingestion 
seem to be negligible, by 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 
different types, the biological effect of which is influenced by 
several 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 way they are manipulated in the various processes 
from mining to final demolition markedly influence the hazards.  
Therefore, it is not possible to make a simple risk assessment or 
derivation of dose-response curve for asbestos. 

    The principle asbestos-related hazards for man are two types of 
respiratory cancer: bronchial carcinoma and mesothelioma; the 
latter affects the pleural surfaces and may also occur in the 
peritoneum.  Both types of cancer progress rapidly and have low 
survival rates, and the detection of these health effects would be 
relatively easy, if it were not for the fact that many cases of 
bronchial cancer can, in general, be attributed to cigarette 
smoking.  At present, it is not possible to separate cases 
specifically due to smoking or to asbestos exposure.  There is 
epidemiological evidence of a more than additive effect on lung 
cancer risk with concurrent exposure to asbestos and cigarette 
smoke.  Thus, overall, smoking is a major 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 
causes 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 
it is likely that asbestosis will no longer be the cause of 

significant asbestos-related mortality.  The incidence of 
asbestosis among asbestos-exposed workers appears to be declining.  
Jacobson et al. (1984) have reported a low prevalence of detectable 
X-ray changes in asbestos workers initially employed in 1971 or 
later to fibre levels meeting current standards in 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 by the belief that there may be no 
threshold for many carcinogens below which there is no risk, but 
this "no threshold" hypothesis has not been proved in the case of 
asbestos.  It may be that the risk is epidemiologically 
undetectably low at the concentrations of airborne asbestos that 
can be measured only at the high sensitivity of electron 
microscopy. 

    The need to consider the full implications of the "no 
threshold" hypothesis for the induction of cancers by asbestos has 
led to much effort to use past experience with high-level 
occupational exposures to predict the possible hazards at much 
lower levels where no excess risks have actually been observed.  
This applies both to the occupational setting (to set occupational 
exposure limits) and to possible risks in the general environment. 

    There are two broad approaches to assessing health risks:

1.  The qualitative approach, making use of a variety of empirical 
    observations related to particular past situations. 

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

9.1.2.1  Occupational

    There are several studies concerning occupationally exposed 
groups (section 8) in which the conditions in the past have not 
caused a detectable increase in bronchial cancer and in which the 
numbers of those involved, the time since first exposure, and the 
completeness of follow-up were such that even a moderate increase 
in bronchial cancer risk should have been detected.  The experience 
in these factories suggests that it may be possible to use asbestos 
under particular circumstances with no detectable excess of 
bronchial cancer. 

    Mesotheliomas 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 chrysotile. 

9.1.2.2  Para-occupational exposure

    Mesothelioma mortality has been found to be elevated in 
populations exposed in an indirect or para-occupational manner.  
These fibre exposures originated from mining and milling 
operations, from factories releasing fibres into neighbourhoods, or 
from asbestos carried home on the clothing of workers.  However, 
levels associated with such exposures appear to be extremely 
variable, and it is not possible to derive quantitative estimates 
of risk from these data. 

    In several studies, excess risk of lung cancer from para-
occupational exposure has not been reported.  For many years, in 
the past, 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 
introduction 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, 
1977). 

9.1.2.3  General population exposure

    For the general environment, the Task Group concluded that:

    (a) the major fibre type observed in the general environment 
        is chrysotile; the average fibre concentration ranges over 
        three orders of magnitude from remote rural to large urban 
        areas; 

    (b) chrysotile fibres in the general environment are virtually 
        all less than 5 µm in length and possess diameters that 
        require electron microscopy for visualization; these fibres 
        have not been characterized in 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 
regarding the physical and chemical properties of the fibre types, 
measurements of exposure, and biological response in both human 
beings and animals.  On this basis, the Task Group emphasized 
specific principles and then commented on the most frequently cited 
assessment models. 

    (a)   Fibre type

    The Task Group believed that any risk model for mesothelioma 
must distinguish among the fibre types. 

    The human data reviewed by the Task Group indicate that the 
asbestos-related diseases observed in the work-place are a function 
of fibre type.  The amphiboles have been associated with 
asbestosis, mesothelioma, and lung cancer.  The association of 
chrysotile with the first two diseases has also been established, 
but its association with mesothelioma is less clear.  Of the total 
of 320 mesotheliomas reported for all cohort studies on asbestos-
exposed workers, only 12 occurred in workers exposed to chrysotile 
alone, though the majority of workers studied were exposed to 
chrysotile.  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 chrysotile. 

    (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 
differences in fibre size, both length and diameter, may be 
responsible for variations in lung cancer rates observed in 
different industries.  Short fibres (< 5.0 µm) appear to be less 
active biologically than long fibres (> 5.0 µm) 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 µm.  The Task Group believed that extrapolating 
disease experience in the work-place, derived on the basis of 
measurements of long fibres, to the ambient air, which contains 
mainly short fibres, introduced a major variable of unknown 
consequence. 

    Historically, work-place exposures to asbestos have been 
measured using a variety of non-specific methods.  Currently, such 
measurements are made, in most cases, by using membrane filter 
collection and subsequent analysis by phase contrast light 
microscopy.  With phase contrast light microscopy, the number of 
fibres per volume of air are determined.  However, by convention, 
only fibres > 5 µm in length, with diameters smaller than 3 µm, 
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 by 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 fibre dose.  For this last parameter, the use of cumulative 
dose may not be appropriate in calculating dose-response 
relationships. 

    (c)   Mechanism of action

    Once inhaled, chrysotile 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 
tissue is considered to be an integral part of dose.  In addition, 
asbestos may act as a promotor (section 7.1.3.5).  These factors 
have not been taken into account in models for quantitative risk 
assessment. 

9.1.3.1  Bronchial cancer

    At low levels of asbestos exposure, such as those that occur in 
the general environment, the excess cancer incidence is too low to 
be detected directly.  Efforts 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 
levels, 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 reasonably 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 
formula: 

IA(d,f,a,s) = IU(a,s) x (1 + KL x d x f)                 (1)

where IA(d,f,a,s) denotes lung cancer incidence among asbestos 
workers aged "a" who smoke "s" cigarettes per day and have been 
exposed for a total duration of "d" years at an average level of 
"f" fibre/ml.  IU denotes lung cancer incidence at the same age "a" 
in an unexposed population with similar smoking habits, and KL is a 
constant, characteristic of the mineral type and distribution of 
fibre dimensions of the asbestos.  The relative risk, which equals 
1 + KL 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 chrysotile mining and milling 

industry and fibres/ml in the textile industry, obtained using 
entirely different 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 Equation 1, KL, the "constant", represents a number of 
biologically important variables such as fibre type, size 
distribution of the airborne fibre, and the rate of lung clearance 
of 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 
absolute excess risk can be expected in the future, unless the 
asbestos dust levels are reduced. 

    The reservations concerning the reliability of the model 
indicate that it can be used to obtain only a very broad 
approximation of the lung cancer relative risk.  The different 
values of the extrapolated risk estimates (generated predicting 
excess cancers per million people in the general population) varied 
over many orders of magnitude (US NRC/NAS, 1984). 

9.1.3.2  Mesothelioma

    For both pleural and peritoneal mesothelioma, the incidence has 
been reported 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 effect of 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 
first exposure, is proportional to t4-(t-d)4, where d is duration 
of exposure (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: 

I(t,f,d) = KM x f x  (t4-(t-d)4)                        (2)

where t denotes years since first exposure, f is the level of 
exposure in fibre/ml, and d is duration of exposure in years.  The 
constant KM depends on the type of fibre and the distribution of 
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 by the formula (Equation 2) is not 
supported by all of the data available, and fibre types are not 
distinguished.  This last feature led the Task Group to the 
conclusion that the KM value, which has been generated from 
amphibole and mixed fibre data, cannot be used for chrysotile. 

    The Task Group concluded that any 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 
women 

    Because of the many sources of uncertainty and consequent error 
in risk estimation based on extrapolation, it is necessary to 
reconsider the possibility of some more direct approach.  The 
incidence of malignant mesothelioma is a relatively specific 
indicator of mineral fibre exposure.  If observed in a standardized 
manner 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 
8).  This approach was explored in recent analytical reviews by 
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 
world war.  Given the usual latency for mesothelioma of 20 - 40 
years, it might be expected to see the effects of asbestos exposure 
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 is rising steeply (up to 10% per annum), 
whereas in women, it is doubtful whether there is any increase.  
Since there is evidence that both occupational and domestic 
exposure account for some cases in women, there is little room left 
for any material effect attributable to general environmental 
exposure.  However, the sensitivity of this approach needs to be 
evaluated. 

9.1.4  Estimating the risk of gastrointestinal tract cancer

    Because 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 of laboratory 
research suggest that all mineral fibres of similar size, shape, 
and persistence, may well carry the same or greater risks for man.  

Until there is information to the contrary, it may be prudent to 
make 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. 

9.3  Conclusions

9.3.1  Asbestos

9.3.1.1  Occupational risks

    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 size, fibre dose, and industrial processing.  Adequate 
control 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 
cancer attributable to asbestos cannot be quantified reliably and 
are probably undetectably 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. 

9.3.2  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 local population has been associated with exposure. 

10.  PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES

10.1.  IARC

    The carcinogenic risk of asbestos was evaluated in detail in 
December 1976 by an International Agency for Research on Cancer 
Working Group (IARC, 1977), and this evaluation was reconsidered in 
1982 by another 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 anthophyllite and small amounts of chrysotile 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 
    asbestos factories and crocidolite mines, and in people living 
    with asbestos workers.  Cigarette smoking and occupational 
    exposure to asbestos fibres increase lung cancer incidence 
    independently; when they occur together, they act 
    multiplicatively" (IARC, 1977). 

2.  "There was sufficient evidence for carcinogenicity to animals.  
    All types of commercial asbestos fibre that have been tested 
    are carcinogenic to mice, rats, hamsters, and rabbits, 
    producing mesotheliomas and lung carcinomas after inhalation 
    exposure and after administration intrapleurally, 
    intratracheally, or intraperitoneally" (IARC, 1977). 

3.  "There was inadequate evidence for activity in short-term 
    tests.  Asbestos was not mutagenic in  Salmonella typhimurium 
    or  Escherichia coli (Chamberlain & Tarmy, 1977).  It has been 
    claimed to be weakly mugtagenic in Chinese hamster cells 
    (Huang, 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 
    cells 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 1977, a group of experts evaluated, for the Commission of 
European Communities, the public health risks of exposure to 
asbestos (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; 
        there exist indications that intermittent even short-term 
        exposure may suffice to induce a mesothelioma after a long 
        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; 

    -   there is general agreement that the risk of mesothelioma is 
        fibre related in the order crocidolite > amosite > 
        chrysotile > anthophyllite, but the magnitude of the 
        difference 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 yet whether only fibres longer than 
        5 µm carry a biological risk, whereas the general public is 
        exposed relatively much more to short fibres (< 5 µm); the 
        relationship between short and long fibres varies widely 
        with the source of the fibrous dust; and 

    -   it is not known whether some groups or members of the 
        general public have a high susceptibility. 

    From this, it can be concluded that it is impossible to come to 
a reliable quantitative assessment of the risk of malignancies for 
the general public: present evidence does not point to there being 
a threshold level 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 
achieved in the general public) where the risk is negligibly small. 
 
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    See Also:
       Toxicological Abbreviations