Asbestos and other natural mineral fibres (EHC 53, 1986)

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
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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.

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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,
France^b

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;

(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 minerals^a
-------------------------------------------------------------------------------------------------------------
Characteristic Chrysotile Crocidolite^b Amosite^c Antho- Tremolite^d Actinolite^d
phyllite^d
-------------------------------------------------------------------------------------------------------------
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
yellow^f, brown brown
pink^f

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

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

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 Crocidolite^b Amosite^c Antho- Tremolite^d Actinolite^d
phyllite^d
-------------------------------------------------------------------------------------------------------------
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 zeolites^a
------------------------------------------------------
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;

(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
line^a
-------------------------------------------------------------------------------
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
USA^b 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 contents^a
------------------------------------------------------------------
Approximate Asbestos Reference
asbestos fibre to Fig. 3
content type^b
(% 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 sepiolite^a
----------------------------------------------------------
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 USA^a
-----------------------------------------------------
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).

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, 1972-78^a
---------------------------------------------------------
Industry Number of Percentage of results^b
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 France^a
------------------------------------------------------------------
Branch Fibre concentrations (fibre/ml) Total
------------------------------------ number of
< 0.5 0.5 - 1 1 - 2 > 2 points
------------------------------------------------------------------
Asbestos cement

Numbers^b 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 Africa^a,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) 600.0 600.0^c
(2) 81.6 80.3
(3) 8.6 8.6
(4) 300.0 300.0^d
(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/litre^a
(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)
---------------------------------------------------------------------------------------------------------

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

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

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

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

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

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

Quebec

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

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 Concentration^a Counting criteria Reference
samples (fibres/litre)
---------------------------------------------------------------------------------------------------------
Canada

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

In 7 public buildings not < 4 to < 9^b 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 asbestos^a, 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 Protocol^a 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 Protocol^a 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 Protocol^a 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 Protocol^a 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 Protocol^a 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 Protocol^a 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)

---------------------------------------------------------------------------------------------------------

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
---------------------------------------------------------------------------------------------------------

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
---------------------------------------------------------------------------------------------------------

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
---------------------------------------------------------------------------------------------------------

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 ranges^a
-------------------------------------------------
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
---------------------------------------------------------------------------------------------------------

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
processes^a

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 promotor^a. 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, 1946-75^b 1.03 (9) 1.03 (15) 0.94 (13) 1 Rubino et al. (1979b)
chrysotile 1951-75^b 1.22 (224) 1.03 (209) 1.05 (317) 10 McDonald et al. (1980)

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

Male Manufacture, 1941-79^d 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, 1943-62^b 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)
1933-75^d 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 1941-79^d 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 cancer^a
---------------------------------------------------------------------------------------------------------
Location Process Fibre Slope for increased Conversion factor
type lung cancer risk^b (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.
Carolina^c (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.

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 ecological^a 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 rate^a, 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
---------------------------------------------------------------------------------------------------------

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
---------------------------------------------------------------------------------------------------------

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.

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:

I_A(d,f,a,s) = I_U(a,s) x (1 + K_L x d x f) (1)

where I_A(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. I_U denotes lung cancer incidence at the same age "a"
in an unexposed population with similar smoking habits, and K_L is a
constant, characteristic of the mineral type and distribution of
fibre dimensions of the asbestos. The relative risk, which equals
1 + K_L 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, K_L, 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) = K_M 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 K_M 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 K_M 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