Man-made mineral fibres (EHC 77, 1988)

INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY

ENVIRONMENTAL HEALTH CRITERIA 77

MAN-MADE 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, 1988

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CONTENTS

ENVIRONMENTAL HEALTH CRITERIA FOR MAN-MADE MINERAL FIBRES

1. SUMMARY

1.1. Identity, terminology, physical and chemical
properties, analytical methods
1.2. Sources of human and environmental exposure
1.3. Environmental transport, distribution, and transformation
1.4. Environmental concentrations and human exposure
1.5. Deposition, clearance, retention, durability, and translocation
1.6. Effects on experimental animals and in vitro test systems
1.7. Effects on man
1.8. Evaluation of human health risks
1.8.1. Occupationally exposed populations
1.8.2. General population

2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, ANALYTICAL METHODS

2.1. Identity, terminology, physical and chemical properties
2.2. Production methods
2.2.1. General
2.2.2. Historical
2.3. Analytical methods
2.3.1. Air
2.3.2. Biological materials

3. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

3.1. Production
3.2. Uses
3.3. Emissions into the environment

4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION

5. ENVIRONMENTAL CONCENTRATIONS AND HUMAN EXPOSURE

5.1. Environmental concentrations
5.1.1. Air
5.1.1.1 Occupational environment
5.1.1.2 Ambient air
5.1.1.3 Indoor air
5.1.2. Water supplies
5.2. Historical exposure levels
5.3. Exposure to other substances

6. DEPOSITION, CLEARANCE, RETENTION, DURABILITY, AND TRANSLOCATION

6.1. Studies on experimental animals
6.2. Solubility studies

7. EFFECTS ON EXPERIMENTAL ANIMALS AND IN VITRO TEST SYSTEMS

7.1. Experimental animals
7.1.1. Inhalation
7.1.1.1 Fibrosis
7.1.1.2 Carcinogenicity
7.1.2. Intratracheal injection
7.1.3. Intrapleural, intrathoracic, and
intraperitoneal administration
7.2. In vitro studies
7.3. Mechanisms of toxicity - mode of action

8. EFFECTS ON MAN

8.1. Occupationally exposed populations
8.1.1. Non-malignant dermal and ocular effects
8.1.2. Non-malignant respiratory disease
8.1.2.1 Cross-sectional studies
8.1.2.2 Historical prospective studies
8.1.3. Carcinogenicity
8.1.3.1 Glass wool
8.1.3.2 Rock wool and slag wool
8.1.3.3 Glass filament
8.1.3.4 Mixed exposures
8.1.3.5 Refractory fibres
8.2. General population

9. EVALUATION OF HUMAN HEALTH RISKS

9.1. Occupationally exposed populations
9.2. General population

10. RECOMMENDATIONS

10.1. Further research needs
10.1.1. Analytical methods
10.1.2. Environmental exposure levels
10.1.3. Studies on animals
10.1.4. Studies on man
10.2. Other recommendations
10.2.1. Classification of MMMF products

REFERENCES

WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR MAN-MADE
MINERAL FIBRES

Members

Dr B. Bellmann, Fraunhofer Institute for Toxicology and Aerosol
Research, Hanover, Federal Republic of Germany
Dr J.M.G. Davis, Institute of Occupational Medicine, Edinburgh,
United Kingdoma
Dr J. Dodgson, Environmental Branch, Institute of Occupational
Medicine, Edinburgh, United Kingdom
Professor L.T. Elovskaya, Institute of Industrial Hygiene and
Occupational Diseases, Moscow, USSR (Vice-Chairman)
Professor M.J. Gardner, Medical Research Council, Environmental
Epidemiology Unit, Southampton General Hospital,
Southampton, United Kingdom (Chairman)
Dr M. Jacobsen, Institute of Occupational Medicine, Edinburgh,
United Kingdom
Professor M. Kido, Pulmonary Division, University of Occupa-
tional and Environmental Health, Fukuoka, Kitakyushu, Japan
Dr M. Kuschner, School of Medicine, State University of New
York, Stonybrook, New York, USA^a
Dr K. Linnainmaa, Department of Industrial Hygiene and Toxico-
logy, Institute of Occupational Health, Helsinki, Finland
Dr E.E. McConnell, Toxicology Research and Testing Program,
National Institute of Environmental Health Sciences,
Research Triangle Park, North Carolina, USA (Rapporteur)
Dr J.C. McDonald, Dust Disease Research Unit, School of Occupa-
tional Health, McGill University, Montreal, Quebec,
Canada^a
Dr A. Marconi, Laboratory of Environmental Hygiene, High Insti-
tute of Health, Rome - Nomentana, Italy
Mr I. Ohberg, Rockwool AB, Skövde, Sweden
Dr F. Pott, Medical Insitute for Environmental Hygiene of the
University of Dusseldorf, Dusseldorf, Federal Republic of
Germany^a
Dr T. Schneider, Department of Occupational Hygiene, Danish
National Institute of Occupational Health, Hellerup,
Denmark
Dr J.C. Wagner, Medical Research Council, Llandough Hospital,
Penarth, United Kingdom^a

Representatives from Other Organizations

Dr A. Berlin, Health and Safety Directorate, Commission of the
European Communities, Luxembourg^b
Ms E. Krug, Health and Safety Directorate, Commission of the
European Communities, Luxembourg
Dr R. Murray (International Commission on Occupational Health),
London School of Hygiene, London, United Kingdom^b

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^a Invited but unable to attend.
^b Present for part of the meeting only.

Observers

Dr R. Anderson (Thermal Insulation Manufacturers Association),
Manville Corporation, Denver, Colorado
Dr D.M. Bernstein, Geneva Facility, Research & Consulting
Company AG, Geneva, Switzerland
Dr J.W. Hill (Joint European Medical Research Board), Pilkington
Insulation, Ltd., St Helens, Burton-in-Kendal, Cumbria,
United Kingdom
Dr O. Kamstrup (Joint European Medical Research Board), Rockwool
A/S, Hedehusene, Denmark
Dr J.L. Konzen (Thermal Insulation Manufacturers Association),
Medical and Health Affairs, Owens-Corning Fiberglass
Corporation, Toledo, Ohio, USA
Dr W.L. Pearson (Canadian Man-Made Mineral Fibre Industry),
Fiberglas Canada Inc., Willowdale, Ontario, Canada
Dr G.H. Pigott (European Chemical Industry Ecology and Toxico-
logy Centre), ICI Central Toxicology Laboratory, Alderley
Park, Macclesfield, Cheshire, United Kingdom

Secretariat

Dr F. Valic, IPCS Consultant, World Health Organization, Geneva,
Switzerland (Secretary) ^a
Ms B. Goelzer, Office of Occupational Health, World Health
Organization, Geneva, Switzerland
Dr M. Greenberg, Department of Health and Social Security,
London, United Kingdom
Ms M.E. Meek, Bureau of Chemical Hazards, Environmental Health
Centre, Health Protection Branch, Health and Welfare Canada,
Tunney's Pasture, Ottawa, Ontario, Canada (Temporary
Adviser)
Dr L. Simonato, Unit of Analytical Epidemiology, International
Agency for Research on Cancer, Lyons, France

-------------------------------------------------------------------------
^a Head, Department of Occupational Health, Andrija Stampar
School of Public Health, Zagreb, Yugoslavia.

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 MAN-MADE MINERAL FIBRES

A WHO Task Group on Environmental Health Criteria for Man-
made Mineral Fibres met at the Monitoring and Assessment
Research Centre, London, on 14-18 September 1987.

Dr B. Bennett, who opened the meeting, welcomed the
participants on behalf of the host institution. Dr M. Greenberg
greeted the participants on behalf the government, and Dr F.
Valic welcomed them on behalf of the heads of the three IPCS co-
sponsoring organizations (UNEP/ILO/WHO). The Task Group
reviewed and revised the draft criteria document and made an
evaluation of the health risks of exposure to man-made mineral
fibres.

The drafts of this document were prepared by MS M.E. MEEK of
the Environmental Health Directorate, Health and Welfare
Canada, Ottawa.

The efforts of all who helped in the preparation and
finalization of the document are gratefully acknowledged.

* * *

Partial financial support for the publication of this
criteria document was kindly provided by the United States
Department of Health and Human Services, through a contract from
the National Institute of Environmental Health Sciences,
Research Triangle Park, North Carolina, USA - a WHO
Collaborating Centre for Environmental Health Effects.

1. SUMMARY

1.1. Identity, Terminology, Physical and Chemical Properties,
Analytical Methods

Man-made mineral fibres (MMMF), most of which are referred
to as man-made vitreous fibres (MMVF), are amorphous silicates
manufactured from glass, rock, or other minerals, which can be
classified into four broad groups: continuous filament,
insulation wool (including rock/slag wool, and glass wool),
refractory (including ceramic fibre), and special purpose
fibres. Nominal fibre diameters for these groups are 6 - 15 µm
(continuous filament), 2 - 9 µm (insulation wools, excluding
refractory fibre), 1.2 - 3.5 µm (refractory fibre), and 0.1 -
3 µm (special purpose fibres), respectively. Continuous
filament and special purpose fibres are made exclusively from
glass, whereas insulation wools can also be made from rock or
slag (rock wool or slag wool, also referred to as mineral wool
in the USA). Refractory fibres are a large group of amorphous
or crystalline synthetic mineral fibres that are highly
resistant to heat. They are produced from kaolin clay, from the
oxides of aluminium, silicon, or other metals, or, less
commonly, from non-oxide materials, such as silicon carbide or
nitride. MMMF usually contain a binder and mineral oil as a
dust suppressant.

MMMF do not split longitudinally into fibrils of smaller
diameter, but may break transversely into shorter segments. The
chemical composition of the various MMMF largely determines
their chemical resistance and solubility in various solutions,
whereas thermal conductivity is also determined by fibre
diameter, finer fibres giving lower thermal conductivity.

Analyses for MMMF have been restricted largely to the
measurement of total airborne mass concentrations or, more
recently (since the early 1970s), to the determination of
airborne fibre levels by phase contrast optical microscopy
(PCOM). A WHO reference method for monitoring fibre levels by
PCOM has been used fairly widely since the early 1980s.
Scanning and transmission electron microscopy offer improved
resolution and fibre identification in the determination of
MMMF. WHO has also developed reference methods to compare and
standardize assessments of MMMF by scanning electron microscopy,
but the use of these techniques needs to be extended
internationally.

1.2. Sources of Human and Environmental Exposure

The global production of man-made mineral fibres has been
estimated to be 4.5 million tonnes in 1973 and 6 million tonnes
in 1985. Fibrous glass accounts for approximately 80% of MMMF
production in the USA, 80% of which is glass wool, mainly used
in acoustic or thermal insulation. Textile grades (5 - 10% of
fibrous glass production) are used principally for the
reinforcement of resinous materials and in textiles, such as

draperies. Less than 1% of the production of glass fibre is in
the form of fine fibres used in speciality applications, such as
high efficiency filter paper and insulation for aircraft.
Mineral wool (rock wool/slag wool), which accounts for
approximately 10 - 15% of MMMF production in the USA, is used
mainly in acoustic and thermal insulation. In Europe, glass
wool and rock wool are produced in approximately equal volumes
and are also used for thermal and acoustic insulation.
Refractory fibres (1 - 2% of all MMMF) are used for high-
temperature applications.

There are few quantitative data on emissions of MMMF from
manufacturing facilities. Fibre levels in emissions from
fibrous glass plants have been reported to be of the order of
0.01 fibres/cm³. Although quantitative data are not available,
it is likely that the emission of MMMF following the
installation or disturbance of insulation is the main source of
exposure of the general population.

1.3. Environmental Transport, Distribution, and Transformation

Because of the lack of data, only general conclusions on the
transport, distribution, and transformation of MMMF in the
general environment can be drawn, based on consideration of
their physical and chemical properties and of related
information concerning the behaviour of natural mineral fibres
in ambient air and water. MMMF in ambient air are, on average,
shorter and thinner than those in the occupational environment
(because of sedimentation of larger diameter fibres and also
transverse breakage). In general, most MMMF are more water
soluble than naturally occurring asbestiform minerals and are
likely to be less persistent in water supplies. They are
removed from air by mechanical forces, sedimentation, or thermal
destruction, and from water by dissolution and deposition in
sediments.

1.4. Environmental Concentrations and Human Exposure

As a general rule, levels of MMMF in the occupational
environment have been determined by phase contrast optical
microscopy. Average concentrations during the current
manufacture of fibrous glass insulation range from 0.01 to
0.05 fibres/cm³. Levels in continuous fibre plants are an
order of magnitude lower, and concentrations in mineral wool
plants, in the USA, range up to an order of magnitude higher
(0.032 - 0.72 fibres/cm³) than those in glass wool production.
Under similar plant conditions, mean levels of ceramic fibres
are about 4 times higher than those for mineral wool fibres
(0.0082 - 7.6 fibres/cm³). Average concentrations in speciality
fine-fibre plants range from 1 to 2 fibres/cm³ and levels are
highest in microfibre production facilities (1 - 50
fibres/cm³).

In Europe, exposure in MMMF production can be divided
historical into early, intermediate, and late technological
phases. Whereas the order of magnitude of fibre concentrations
in glass wool plants in the early phase is estimated to have
been similar to that of current concentrations, concentrations
in rock wool and slag wool plants during the early technological
phase could have been one or two orders of magnitude higher than
those in the late phase. The presence of other contaminants,
such as polycyclic aromatic hydrocarbons, arsenic, and asbestos,
in the early slag wool production industry has also been
reported.

In general, airborne fibre concentrations during the
installation of products containing MMMF are comparable to, or
less than, levels found in production (< 1 fibre/ml).
Exceptions occur during blowing or spraying operations conducted
in confined spaces, such as during the insulation of aircraft or
attics, when mean levels of fibrous glass and mineral wool have
ranged up to 1.8 fibres/cm³ and 4.2 fibres/cm³, respectively.
Mean concentrations during installation of loose fill in
confined spaces have ranged up to 8.2 fibres/cm³.

Some data are available on the levels of MMMF in ambient and
indoor air. Concentrations ranging from 4 x 10^-5 to 1.7 x 10^-3
fibres/cm³, measured by TEM, have been found in ambient air.
Mean values ranging from 5 x 10^-5 to, typically, around 10^-4
fibres/cm³, but occasionally over 10^-3 fibres/cm³, occur in the
air of public buildings.

1.5. Deposition, Clearance, Retention, Durability,
and Translocation

Alveolar deposition of MMMF is governed principally by size.
For fibres of constant diameter, alveolar deposition decreases
with increasing length. On the basis of available data, it has
been suggested that there is a rapid decrease in the
respirability of fibres > 1 µm in diameter in the rat compared
with a suggested upper limit in man of ~ 3.5 µm (5 µm by mouth
breathing).

Short MMMF (<5 µm in length) are efficiently cleared by
alveolar macrophages, whereas this form of clearance appears to
be much less effective for fibres greater than about 10 µm in
length. At present, it is difficult to draw definite
conclusions concerning the relative durability of man-made and
naturally-occurring mineral fibres in vivo. In addition, there
are fibres within each of these classes of MMMF that may behave
differently from the class as a whole. For instance, longer
fibres and fibres of fine diameter dissolve more rapidly in lung
tissue than shorter or coarse ones of the same type.

The few available data indicate that translocation of the
fibres to other organs and tissues is limited. Fibre
concentrations in the tracheobronchial lymph nodes of rats
exposed to glass wool and rock wool for 1 year were low,
compared with those of glass microfibres. Levels of all fibre

types in the diaphragm were essentially zero. The trans-
migration of fibres appears to be influenced by fibre size and
durability, short fibres being present in higher numbers in
other tissues than long ones.

1.6. Effects on Experimental Animals and In Vitro Test Systems

In the majority of the inhalation studies conducted to date,
there has been little or no evidence of fibrosis of the lungs in
a range of animal species exposed to glass fibre concentrations
of various types of MMMF up to 100 mg/m³, for periods ranging
from 2 days to 24 months. In most studies, the tissue response
was confined to accumulation of pulmonary macrophages, many of
which contained the fibres. In all cases, the severity of the
tissue reaction in animals exposed to glass fibre and, in one
study, glass wool, was much less than that for equal masses of
chrysotile or crocidolite asbestos. Moreover, in contrast to
asbestos, fibrosis did not progress following cessation of
exposure. However, the number of asbestos fibres reaching the
lung may have been greater than those for fibrous glass and
glass wool.

A statistically significant increase in lung tumours has not
been found in animals exposed to glass fibres (including glass
microfibres) or rock wool in inhalation studies conducted to
date. However, in several of the relevant studies, an increase
in lung tumours that was not statistically significant was found
in exposed animals. In all of the carcinogenicity bioassays
conducted to date, similar mass concentrations of chrysotile
asbestos have clearly induced lung tumours, whereas crocidolite
asbestos has induced few or no tumours. However, available data
are insufficient to draw conclusions concerning the relative
potency of various fibres types, because the true exposure
(number of respirable fibres) was not characterized in most of
these studies.

Inhalation or intrapleural injection of aluminium oxide
refractory fibre containing about 4% silica caused minimal
pulmonary reactions in rats and no pulmonary neoplasms were
induced. On the other hand, the incidence of interstitial
fibrosis and pulmonary neoplasms following the inhalation of
fibrous ceramic aluminium silicate glass was similar to that for
chrysotile-exposed animals; however, half of the induced tumours
were not typical of those observed in animals exposed to
asbestos.

There has been some evidence of fibrosis in various species,
following intratracheal administration of glass fibres.
However, in most cases, the tissue response has been confined to
an inflammatory reaction. An increased incidence of lung
tumours has been reported following intratracheal administration
of glass microfibres to 2 species in the same laboratory, but
these results have not been confirmed by other investigators.

Studies involving intrapleural or intraperitoneal admini-
stration of MMMF to animals have provided information on the
importance of fibre size and in vivo durability in the induction
of fibrosis and neoplasia. The probability of the development
of mesotheliomas following intrapleural and intraperitoneal
administration of these dusts was best correlated with the num-
ber of fibres with diameters of less than 0.25 µm and lengths
greater than 8 µm; however, probabilities were also relatively
high for fibres with diameters of less than 1.5 µm and lengths
greater than 4 µm. A model in which the carcinogenic potency
of fibres is considered to be a continuous function of length
and diameter and also of stability has been proposed. Asbestos
has been more potent than equal masses of glass fibre in
inducing tumours following intrapleural administration. However,
certain types of ceramic fibres were as potent as equal masses
of crocidolite asbestos in inducing mesotheliomas after intra-
peritoneal injection. A similar tumour response was observed
after intraperitoneal injection of a comparable number of
actinolite asbestos fibres longer than 5 µm, basalt wool, and
ceramic wool. Again, individual fibre characteristics are the
important criteria for studies using this route of exposure.

In in vitro assays, cytotoxicity and cell transformation
have also been a function of fibre size distribution, long
(generally > 10 µm), narrow (generally < 1 µm) fibres being
the most toxic. In general, "coarse" (> 5 µm diameter) fibrous
glass (e.g., JM 110) has been less cytotoxic in most assays
than chrysotile or crocidolite asbestos. The cytotoxicity of a
single type of ceramic fibre was also low. However, the
cytotoxicity or transforming potential of fine glass (e.g., JM
100) has approached that of these types of asbestos. With
respect to genotoxicity, glass fibres have not induced point
mutations in bacterial assays. Glass fibres have been reported
to induce delayed mitosis, numerical and structural chromosomal
alterations, but not sister chromatid exchanges in mammalian
cells in vitro. Only a few in vitro studies on MMMF other than
glass fibres are available.

The effects of fibre coating on the toxicity of MMMF have
been examined, to a limited extent, in inhalation and in vitro
studies. However, the available data are both limited and
contradictory and no firm conclusions can be drawn at this time.
Effects of combined exposure to MMMF and other pollutants have
been examined in inhalation and intraperitoneal injection
studies. Concomitant exposure to airborne glass fibres enhanced
the toxic effects of styrene in mice, and the incidence of lung
cancer in rats exposed by inhalation to radon was increased by
concomitant intrapleural injection of glass fibres. In
contrast, the carcinogenic potency of glass fibres following
intraperitoneal administration was reduced by pre-treatment with
hydrochloric acid (HCl).

1.7. Effects on Man

Fibrous glass and rock wool fibres (mainly those greater
than 4.5 - 5 µm in diameter) cause mechanical irritation of the

skin, characterized by a fine, punctate, itching erythema, which
often disappears with continued exposure. However, few reliable
data are available concerning the prevalence of dermatitis in
workers exposed to MMMF. In several early case reports and in a
more recent limited cross-sectional study, eye irritation was
also associated with exposure to MMMF in the work-place.

In reports that appeared in the early literature, several
cases of acute irritation of the upper respiratory tract and
more serious pulmonary diseases, such as bronchiectasis,
pneumonia, chronic bronchitis, and asthma, were attributed to
occupational exposure to MMMF. However, it is likely that
exposure to MMMF was incidental rather than causal in most of
these cases, since the reported conditions have not been
observed consistently in more recently conducted epidemiological
studies.

Some cross-sectional epidemiological studies suggest that
there may be MMMF exposure-related effects on respiratory
function; others do not. In a large, well-conducted study,
there was an increase in the prevalence of low profusion small
shadowing on the chest radiographs of cigarette smokers with
increasing length of employment in MMMF manufacturing. However,
no consistent pattern of MMMF-related non-malignant effects on
the respiratory system has emerged, to date, from cross-
sectional surveys.

There has been little evidence of excess mortality from non-
malignant respiratory disease (NMRD) in MMMF workers in
analytical epidemiological studies that have been conducted to
date, including the two largest investigations conducted in
Europe and the USA. There were no statistically significant
increases in NMRD mortality in any sector of the industry in
comparison with local rates in the US study, though a
statistically significant excess was reported for glass wool
workers in comparison with national rates. In the European
study, there were no excesses of NMRD mortality. The mortality
rates were not related either to time since first exposure or to
duration or intensity of exposure.

There has not been any evidence, in studies conducted to
date, that pleural or peritoneal mesotheliomas are associated
with occupational exposure to MMMF.

An excess of mortality due to lung cancer has been observed
in the large epidemiological studies on rock wool/slag wool
production workers conducted in Europe and the USA, but not in
studies on glass wool or continuous filament workers. The
excess of lung cancer mortality and/or incidence in the rock
wool/slag wool production industry was apparent when either
local or national rates were used for comparison (both
statistically significant in the US study and not statistically
significant in the European study). There was a relationship
(not statistically significant) with time from first exposure,
in the European study, but not in the US study. No

relationships with duration of employment or estimated
cumulative exposure to fibres were observed. In the European
study, a statistically significant excess of lung cancer was
found in workers in the "early technological phase", during
which airborne fibre levels were estimated to have been higher
than in later production phases. A statistically significant
increase in lung cancer mortality in the European study, 20
years after first exposure, appeared to be associated with the
use of slag, but there was a large overlap between the use of
slag and the early technological phase. Neither the use of
bitumen and pitch nor the presence of asbestos in some products
accounted for the observed lung cancer excess. In the European
study, there was no excess lung cancer mortality in rock
wool/slag wool production workers employed in the "late
technological phase", when concentrations of fibres were thought
to be lower after the full introduction of dust suppressing
agents.

For glass wool production workers, there were no excesses of
lung cancer mortality compared with local rates in either the
large European or US cohorts, but there were statistically
significant increases compared with national rates. In both
investigations, mortality from respiratory cancer showed an
increase with time from first exposure that was not statist-
ically significant. However, it was not related to duration of
employment or estimated cumulative fibre exposure in the US
study, or to different technological phases in the European
study. The SMR for respiratory cancer, in workers who had been
exposed in the manufacture of small diameter (<3 µm) glass
wool fibres in the US cohort, was elevated compared with that in
those who had never been exposed in this production sector. The
excess in these workers was related to time from first exposure,
but neither the overall increase nor the time trends were
statistically significant. A statistically significant large
excess of lung cancer, observed in a smaller Canadian cohort of
glass wool production workers, was not related to time since
first exposure or duration of employment.

There has not been an increase in lung cancer mortality or
incidence in continuous filament production workers in studies
conducted to date.

There have been some suggestions of excesses of cancer at
sites other than the lung (e.g., pharynx and buccal cavity,
larynx, and bladder) in studies on MMMF production workers.
However, in most cases, excesses of cancer of these sites, which
were not observed consistently, were small, and were not related
to the time since first exposure or duration of employment.
Moreover, confounding factors in the etiology of some of the
cancers (e.g., alcohol consumption) have not been taken into
account in studies conducted to date.

No epidemiological data are available on cancer mortality or
incidence in refractory fibre workers.

There have been isolated case reports of respiratory
symptoms and dermatitis associated with exposure to MMMF in the
home and office environments. However, available epidemiological
data are insufficient to draw conclusions in this regard.

1.8. Evaluation of Human Health Risks

1.8.1. Occupationally exposed populations

Data available are insufficient to derive an exposure-
response relationship for dermatitis and eye irritation in
workers exposed to MMMF. In addition, although there has been
some evidence of non-neoplastic respiratory effects in MMMF-
exposed workers, no consistent pattern has emerged and it is not
possible, therefore, to draw conclusions concerning the nature
and extent of the hazard in this regard.

Although there is no evidence that pleural or peritoneal
mesotheliomas have been associated with occupational exposure in
the production of various MMMF, there have been indications of
increases in lung cancer from the principal epidemiological
studies, mainly in workers in the rock wool/slag wool sector
employed in an early production phase. Although it is possible
that other factors may have contributed to this excess, possible
contaminants and potential confounding factors examined to date
have not explained the excess lung cancer rate. Moreover,
available data are consistent with the hypothesis that it is the
airborne fibre concentrations that are the most important
determinant of lung cancer risk.

In general, airborne MMMF fibre concentrations present in
work-places with modern control technology are low. However,
mean elevated levels within the same order as those estimated to
have been present in the early production phase have been
measured in several segments of the production and application
industry (e.g., ceramic fibre and small diameter glass wool
production and spraying of insulation wool in confined places).
The lung cancer risk for the small number of workers employed in
these sectors could potentially be elevated if protective
equipment is not used.

1.8.2. General population

On the basis of available data, it is not possible to
estimate quantitatively the risks associated with exposure of
the general population to MMMF in the environment. However,
levels of MMMF in the typical general and indoor environments
measured to date are much lower (by some orders of magnitude)
than some occupational exposures in the past associated with
raised lung cancer risks. Thus, the overall picture indicates
that the possible risk for the general population is very low,
if there is any at all, and should not be a cause for any
concern if current low exposures continue.

2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, ANALYTICAL METHODS

2.1. Identity, Terminology, Physical and Chemical Properties

The man-made mineral fibres (MMMF), discussed in this
document, will be restricted largely to a subset known as man-
made vitreous fibres (MMVF), which are fibres manufactured from
glass, natural rock, or other minerals. They are classified
according to their source material. Slag wool, rock wool, and
glass wool or filaments are produced from slag, natural rock,
and glass, respectively (Ottery et al., 1984). Refractory
fibres, including ceramic fibres, which are also discussed in
this report, comprise a large group of amorphous or partially
crystalline synthetic mineral fibres that are highly refractory.
They are produced from kaolin clay or the oxides of alumina,
silicon, or other metals, or, less commonly, from non-oxide
materials, such as silicon carbide, silicon nitride, or boron
nitride.

In North America, slag wool and rock wool are often referred
to as "mineral wool"; in Europe and Asia, the term "mineral
wool" also includes glass wool. A "wool" is an entangled mass
of fibres in contrast to the more ordered fibres in continuous
filament (textile) glass.

While naturally occurring fibres are crystalline in
structure, most man-made mineral fibres are amorphous
silicates.^a The amorphous networks of MMMF are composed of
oxides of silica, boron, and aluminium, oxides of the alkaline
earth and alkali metals, oxides of bivalent iron and manganese,
or amphoteric oxides (e.g., Al₂O₃, Fe₂O₃) (Klingholz, 1977).
The chemical compositions of various types of MMMF are presented
in Fig. 1 and Tables 1 and 2. Common trade names are given in
Table 3 and codes for fibres commonly used in studies of
biological effects are included in Table 4. The terminology
currently used is not consistent or well defined. Categories
and materials are named with reference to use, structure, raw
material, or process. The distinctions are not always clear,
and categories may overlap.

MMMF products usually contain a binder and an oil for dust
suppression. Textile fibre may contain a sizing agent for
lubrication. Some special fibres contain a surfactant for
improving dispersion. MMMF may be produced with only an oil as
a dust suppressant. Special purpose fibres may be produced
without any additives (Hill, 1977). Some chemicals used in
binders are presented in Table 5.

----------------------------------------------------------------
^a Most ceramic (aluminosilicate) fibres have an amorphous
structure when they are produced, but some conversion to
crystalline material (cristobalite, mullite) can occur at high
temperature (> 1000 °C) (Vine et al., 1983; Gantner, 1986;
Khorami et al., 1986; Strübel et al., 1986).

Table 1. Examples of the composition of continuous glass
filament, glass wool, rock wool, and slag wool (% by weight)
-------------------------------------------------------------
Component Continuous Glass wool^b Rock wool^c Slag wool^c
glass
filament^a
-------------------------------------------------------------
SiO₂ 52 - 56 63 47 - 53 40 - 45
CaO 16 - 25 7 16 - 30 10 - 38
Al₂O₃ 12 - 16 (+Fe₂O₃) 6 6 - 13 11.5 - 13.5
B₂O₃ 8 - 13 6 - -
MgO 0 - 6 3 - -
Na₂O 0 - 3 14 2.3 - 2.5 1.4 - 2.5
K₂O 0 - 3 1 1 - 1.6 0.3 - 1.4
TiO₂ 0 - 0.4 - 0.5 - 1.5 0.4 - 2
Fe₂O₃ 0.05 - 0.4 - 0.5 - 1.5 8.2
F₂ - 0.7 - -
-------------------------------------------------------------
^a From: Klingholz (1977).
^b From: Mohr & Rowe (1978).
^c From: IARC (in press).

Table 2. Composition of some commercial ceramic fibres^a (% by weight)
------------------------------------------------------------------------------------
Component Fiber- Fiber- Fiber- Fiber- Alumina Zirconia Fireline Nextel^R
frax^R frax^R max^Tm frax^R bulk bulk ceramic ceramic
bulk long bulk HSA (SAFFIL^R) fibre 312
staple
------------------------------------------------------------------------------------
Al₂O₃ 49.2 44 72 43.4 95 - 95-97.25 62
SiO₂ 50.5 51 27 53.9 5 < 0.3 95-97.25 24
ZrO₂ - 5 0 0 0 92 - -
Fe₂O₃ 0.06 0 0.02 0.8 - - 0.97-0.53 -
TiO₂ 0.02 0 0.001 1.6 - - 1.27-0.70 -
K₂O 0.03 - - 0.1 - - - -
Na₂O 0.20 - 0.10 0.1 - - 0.15-0.08 -
CaO - - 0.05 - - - 0.07-0.04 -
MgO - - 0.05 - - - trace -
Y₂O₃ - - - - - 8 - -
B₂O₃ - - - - - - 0.06-0.03 14
Leachable < 10 < 10 11 < 10 - - - -
chlorides ppm ppm ppm ppm
Organics - - - - - - 2.47-1.36 -
------------------------------------------------------------------------------------
^a From: IARC (in press).

Unlike some natural fibres, MMMF do not split longitudinally
into fibrils of smaller diameter, though they may break
transversely into shorter fragments. Consequently, the
diameters of fibres to which workers may be exposed will depend
on the diameter as manufactured, but the length of such fibres
will vary according to the extent to which they have been broken
subsequently (HSC, 1979).

A particle of any shape, density, and size has a defined
settling speed in air. The diameter of a sphere with density
1 g/cm³ and having the same settling speed as the particle in
question will be its aerodynamic diameter (D_ae). For MMMF, the
D_ae is roughly 3 times the geometric diameter, with only a small
dependence on fibre length.

2.2. Production Methods

2.2.1. General

The methods of production of various MMMF are presented in
Fig. 2. Man-made mineral fibres are produced from a liquid melt
of the starting material (e.g., slag, natural rock, glass,
clays) at temperatures of 1000 - 1500 °C. Three basic
fiberizing methods, which vary from plant to plant and which
have changed with technological advances, are used: mechanical
drawing, blowing with hot gases, and centrifuging. Combinations
of these methods (e.g., drawing/blowing, blowing/blowing,
centrifuging/blowing) are sometimes used (Klingholz, 1977).

MMMF are manufactured to nominal diameters^a and fall into
four broad groups (Fig. 2): continuous filaments, insulation
wools, refractory fibres, and special purpose fibres (Hill,
1977; Ottery et al., 1984). Continuous filaments, used in tex-
tiles and for reinforcing plastics, are produced by the drawing
process and individual fibre diameters (6 - 15 µm) are closely
distributed around the median value. Few are respirable. The
nominal diameter of insulation wools, which are produced largely
by centrifuging or blowing or a combination of both, is about 4
or 5 µm.^b The production method gives a much wider distribu-
tion around the nominal diameter, with a high proportion of
respirable fibres. For special applications, such as hearing
protection, the nominal diameter may be as low as 1 - 2 µm.
Special fibres, which account for only about 1% of world
production, are used in special applications, such as high-
efficiency filter papers (Hill, 1977) and insulation for
aircraft and space vehicles (Kilburn, 1982). The diameters of
the majority of these fibres are less than 1 µm. Continuous
filaments and special purpose submicron-range fibres are made
exclusively from glass, whereas insulation wools can also be
manufactured from rock or slag.

----------------------------------------------------------------
^a The nominal diameter is the median length-weighted diameter.
All fibres in the sample are joined together in order of
increasing diameter; the diameter halfway along this long
fibre is then the nominal diameter.
^b Some glass fibre insulation wool with a nominal fibre dia-
meter of about 2 µm is now being produced in North
America.

Table 3. Synonyms and trade names of MMMF products^a
------------------------------------------------------------------------
Term/Name Category Remarks
------------------------------------------------------------------------
TEL GW
Fibreglass insulation GW Fiberglas^R is a trade name
Boron silicate glass GW Most glass wools are of boro-
fibre silicate type
Saint Gobain GW Major insulation producer
(TEL process)
GF/D Whatman filter GF Filters made from glass fibres
GF/C microfilter GF Filters made from glass fibres
Rock wool RW Rockwool^R is a trade name
Pyrex glass fibres GF Pyrex^R is a glass with high
chemical resistance
Basalt wool RW
Mineral wool
Man-made mineral Slag or rock wool (USA)
insulation fibres Glass, slag, or rock wool (Europe)
Insulation wool
Refractory fibres CF
Fibrous ceramic aluminium CF
silicate glass
Saffil^R alumina oxide (4% silica)^b
Fiberfrax^R CF
Ceramic wool CF
Owens-Corning Beta^R GF
Calcium silicate CF
Calcium-alumino-silicate CF
Refractory ceramic fibre CF
Alumina and zirconia fibre CF
Zirconia CF
Fireline ceramic CF
Nextel^R ceramic fibre CF
Fibermak^TM
------------------------------------------------------------------------
^a Only synonyms and trade names used in this document are listed.
^b Microcrystalline.

GW = glass wool.
GF = glass fibre other than wool.
RW = rock wool.
SW = slag wool.
CF = ceramic fibre.

Table 4. Codes for Manville glass fibres mentioned in
this document^a
---------------------------------------------------------
Designation Range of nominal Glass type^b
diameters (µm)
---------------------------------------------------------
Code: JM 80 .24 - .28 475
JM 100 .28 - .38 475
JM 102 .35 - .42 475
JM 104 .43 - .53 475, E
JM 106 .54 - .68 475, E
JM 110 1.9 - 3 475
---------------------------------------------------------
^a Current data. Specifications have changed over time.
^b 475: General purpose borosilicate.
E: Electrical grade, alkali-free borosilicate.

Table 5. Chemicals used in
binders for MMMF^a
-------------------------------
Phenol formaldehyde resin
Urea formaldehyde resin
Melamine formaldehyde resin
Polyvinyl acetate
Vinsol resin
Urea
Silicones
Dyes
Ammonium sulfate
Ammonium hydroxide
Starch
Carbon pigment
Epoxy resins
Pseudo-epoxy resins
Bitumens
-------------------------------
^a From: Hill (1977) and WHO (1983a).

Available data on the physical and chemical properties of
some MMMF are presented in Table 6. The chemical composition of
the various MMMF determines their chemical resistance (the sum
of the acidic oxides divided by the sum of the amphoteric and
basic oxides measured in molar units). Typical values are
0.50 - 0.65 for slag wool, 0.80 - 1.10 for rock wool, and
1.55 - 2.50 for glass wool (Klingholz, 1977). The solubility of
MMMF in aqueous and physiological solutions varies considerably,
according to their chemical composition and fibre size
distribution. Solubility increases with increasing alkali
content for a given composition of other elements, and fine
fibres degrade more rapidly than coarse ones in vitro (Spurny et
al., 1983). Thermal conductivity is mainly a function of fibre
diameter and bulk density, with finer fibres having a lower
thermal conductivity.

Table 6. Physical and chemical properties of some MMMF
--------------------------------------------------------------------------------------------------------
MMMF Fibre size Fibre sur- Melting Density Refractive Physical
distribution^a face area^b point^b,c (g/cm³) index^a state^b
(µm) (m²/g) (°C)
--------------------------------------------------------------------------------------------------------

Glass filament range of fibre - - 2.596^a 1.548
diameters: 6 - 9.5

Glass wool range of fibre - - 2.605^a 1.549
(coarse) diameters: 7.5 - 15

Glass wool range of fibre - -
diameters:
- micro glass fibres 0.75 - 2 2.568^a 1.537
- special purpose 0.25 - 0.75
glass fibres

Ceramic mean fibre dia- 0.5 1790 2.73^b - white fibre
(Fiberfrax^R bulk) meters: 2 - 3;
mean fibre length:
< 102 mm

Ceramic (Fiber- mean fibre dia- - 1790 2.62^b - white fibre
frax^R long staple) meters: 5 and 13;
mean fibre length:
< 254 mm

Ceramic mean fibre dia- 7.65 1870 3^b - white, mullite,
(Fibermax^TM bulk) meters: 2 - 3.5 polycrystalline

Ceramic mean fibre dia- 2.5 1790 2.7^b - white to light
(Fiberfrax^R HSA) meters: 1.2; grey
mean fibre length:
3 mm

Ceramic mean fibre dia- - 2040 3^b - white
(SAFFIL^R - alumina meters: 3; mean
bulk) fibre length:
3 mm

Table 6. (contd.)
--------------------------------------------------------------------------------------------------------
MMMF Fibre size Fibre sur- Melting Density Refractive Physical
distribution^a face area^b point^b,c (g/cm³) index^a state^b
(µm) (m²/g) (°C)
--------------------------------------------------------------------------------------------------------

Ceramic mean fibre dia- - 2600 0.24-0.64^b - white
(zirconian bulk) meters: 3 - 6;
mean fibre length:
< 1.5 mm

Fireline ceramic - - 1700 - - white to cream
colour

Ceramic mean fibre dia- < 1 1700 > 2.7^b - white, smooth,
(Nextel^R fibre meters: 8 - 12; transparent,
312 filament) mean fibre length: continuous poly-
continuous crystalline
metal oxide
--------------------------------------------------------------------------------------------------------
^a From: NIOSH (1977).
^b From: IARC (in press).
^c Vitreous fibres have no precies melting point.
2.2.2. Historical

Production conditions in early mineral wool plants were
usually very primitive, particularly those operating before
1950. Many different raw materials were used, especially in the
slag wool industry. In addition to foundry and steel slags,
chrome, lead, and copper slags were also used. The glass wool
industry, being based on an already existing raw material and
melting technology, was technologically more advanced and stable
(Ohberg, in press).

The production environment during these early operations was
poorly controlled and could occasionally be heavily polluted.

Some plants started in a batch operation mode and operated
this way for a period that varied between plants. Subsequently,
production methods changed to continuous operating procedures
(Cherrie & Dodgson, 1986; Ohberg, in press). Oil was not usually
used as a dust suppressant during these early operations.

In a historical environmental investigation (Cherrie &
Dodgson, 1986), conducted as part of the large European
epidemiological study (Simonato et al., 1986a, in press), the
absence of oil and or the use of batch production was defined as
the early technological phase. The introduction of dust-
suppressing agents and implementation of continuous production
procedures constituted the late phase. Between the early and
late phases, in most production facilities, there was a
transition period called the intermediate phase.

Methods of product manufacture and manipulation were
principally manual, the products were very simple, and
production rates were low in the early phase. Later, the
diversity and complexity of the products increased as well as
the production rate. The degree of mechanization was also
increased (i.e., introduction of saws, cutters, conveyors,
etc.), with a corresponding gradual reduction of manual handling
(Cherrie et al., in press; Dodgson et al., in press; Ohberg, in
press).

2.3. Analytical Methods

2.3.1. Air

The methods currently used for the collection, quantifica-
tion, and identification of airborne fibrous particulates in the
occupational and general environments are summarized in
Table 7. The detection limits shown in Table 7 are optimal
values. Rather higher detection limits are achieved in routine
practice; namely, 0.25 µm for PCOM, 0.05 µm for SEM, and
0.005 µm for TEM.

Table 7. Measurement of MMMF
--------------------------------------------------------------------------------------------------------
Measure- Sampling Quantification Identif- Detect- Comments Reference
ment ication tion
limit
(µm)
--------------------------------------------------------------------------------------------------------
Mass glass wool or gravimetric biologically WHO (1981)
cellulose (analytical relevant
ester balance) fraction not
membrane determined
filters;
pore size
0.6 - 1.5 µm

Fibre cellulose ester phase contrast morphology 2 x 10^-1 fibres with WHO (1981, 1985);
number membrane optical diameter Chatfield (1983)
filters; microscopy < 0.2 µm not
pore size (PCOM) detected; not
0.5 - 1.5 µm possible to
distinguish
MMMF from
other fibres

Fibre membrane or scanning morphology; 5 x 10^-4 improved Burdett & Rood
number Nuclepore electron chemical resolution (1983); Chatfield
polycarbonate microscopy composition and fibre (1983)
filters (SEM) by EDXA^a identification

Fibre membrane or transmission morphology; 2 x 10^-5 best resolution Chatfield (1983)
number Nuclepore electron chemical and fibre
filters microscopy composition identification;
(TEM) by EDXA; sample
crystalline preparation
structure not standardized
by SAED^b
--------------------------------------------------------------------------------------------------------
^a EDXA = Energy dispersive X-ray analysis.
^b SAED = Selected area electron diffraction.
For MMMF, analyses have been restricted largely to the
measurement of total airborne mass concentration or, more
recently, to the determination of airborne fibre number
concentrations by phase contrast optical microscopy (PCOM). The
method for sampling personal exposure levels involves drawing a
measured volume of air through a filter mounted in a holder that
is located in the breathing zone of the subject. Static
sampling methods are not recommended for measuring personal
exposures. When measuring mass concentrations of MMMF, either
cellulose ester membrane or glass fibre filters can be used.
The filters are stabilized in air and weighed against control
filters, both before and after sampling, to permit correction of
weight changes caused by varying humidity. Only cellulose ester
filters are used for assessing fibre number concentrations. In
this case, the filter is made optically transparent with one of
several clearing agents (e.g., triacetin, acetone, or ethylene
glycol monomethyl ether) and the fibres present within random
areas are counted and classified using PCOM. For this purpose,
a fibre is defined as a particle having a length to diameter
ratio (aspect ratio) > 3 and a length > 5 µm. Respirable
fibres are those with diameters < 3 µm. Fibres with diameters
exceeding 3 µm are termed non-respirable fibres.

Sampling strategies should be well-designed, based on
careful consideration of "how", "where", "when", and "for how
long" to sample, as well as "how many samples" to collect to
ensure that the results are comparable. Sampling strategies
will vary depending on the reason for sampling, e.g.,
epidemiology, dust control, etc. Sampling strategy has been
discussed in the literature (NIOSH, 1977; Valic, 1983; WHO,
1984).

Although the basic methods for the determination of total
airborne mass and fibre number concentrations in most countries
are similar, differences in the sampling procedure, the filter
size and type, the clearing agent, and the microscope used, and,
particularly, statistical and subjective errors in counting,
contribute to variations in results. In order that results from
different countries should be more comparable, a reference
method for monitoring MMMF at the work-place based on PCOM was
proposed by WHO in 1981 and has been widely used in a slightly
modified form (WHO, 1985) since that time. The results of
recent slide exchanges among participating laboratories have
shown a maximum systematic counting difference of about 1.8
times for this method (Crawford et al., in press).

Rendall & Schoeman (1985) reported that the contrast of the
phase image for the counting of glass fibres was improved by the
low-temperature ashing of the membrane filter attached to glass
slides by acetone vapours followed by microscopic examination
using simple Köhler illumination. Automatic counting methods
are currently being developed and may in future provide greater
consistency in results (Burdett et al., 1984).

The improved resolution of electron microscopy and the
identification capacity, particularly of the analytical
transmission electron microscope (TEM with selected area
electron diffraction (SAED) and energy dispersive X-ray analysis
(EDXA)), make these methods more suitable for analysis of fibres
in the general environment, where MMMF may constitute only a
small fraction of the airborne fibrous material. However, to
date, use of these methods for the determination of MMMF has
been restricted largely to the characterization of fibre sizes
airborne in the occupational environment.

In analysing by SEM, the fibres collected on polycarbonate
filters can be directly examined. This avoids the need to use
transfer techniques that may affect the fibre size distribution.
WHO has developed a reference method for SEM, principally to
characterize fibre size (WHO, 1985). Using the same sampling
method as for the PCOM method, samples are collected on a
polycarbonate (Nuclepore) or PVC-copolymer membrane filter
(Gelman DM 800) and observed at a magnification of 5000 times.
Fibre lengths and diameters are measured from optically enlarged
images of photomicrographs.

In the past, methods of sample preparation for TEM have
varied considerably, making comparison of values obtained by
different investigators difficult. At present, direct transfer
preparation techniques involving carbon coating of particles on
the surface of a polycarbonate or membrane filter and indirect
sample preparation methods, in which attempts have been made to
retain the fibre size distribution, are the most widely accepted
for analysis of fibres in air and water (Toft & Meek, 1986).

The size distribution of "superfine" MMMF has been
successfully measured by a direct transfer sampling method on a
membrane filter, subsequent analysis by analytical TEM, and
fibre measurement by an image analysis system (Rood & Streeter,
1985). On the basis of their results, the authors concluded
that a substantial proportion of the fibres would not have been
detected by PCOM or SEM, even fibres longer than 5 µm.

2.3.2. Biological materials

Several techniques have been developed for the recovery and
determination of mineral fibres in biological tissues. Fibres
are commonly separated from tissue samples by digestion (e.g.,
by sodium hypochlorite or potassium hydroxide) or ashing (both
low and high temperature) and identified subsequently by light
or electron microscopy. Methods for sampling, analysis, and
identification of mineral fibres in lung tissues have been
reviewed recently by Davis et al. (1986).

To date, methods for the sampling and analysis of tissues
for fibrous particles have not been standardized and it is
difficult to compare the results of various investigators.
Moreover, available data indicate that common methods of tissue
separation, such as tissue digestion with sodium hypochlorite or

potassium hydroxide, cause substantial losses of MMMF (Johnson
et al., 1984b). Thus, data on levels of MMMF in biological
tissues should be cautiously interpreted.

A method for the sampling and determination of fibres in the
eyes of workers handling MMMF has been described by Schneider &
Stokholm (1981). Mucous threads and dried mucous, stained with
alcian blue, were removed from the eye, placed on a slide,
ashed in a low-temperature asher, and examined for non-
respirable fibre content by optical microscopy. The authors
reported a good correlation, among 15 samples, between fibre
levels in the eyes and total dust exposure or total non-
respirable fibre exposure. Levels were not correlated with
airborne respirable fibre concentrations.

3. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

3.1. Production

Few recent quantitative data are available concerning the
global production of MMMF. As illustrated in Table 8, this
value was reported to be 4.5 million tonnes in 1973 (WHO, 1983a;
Järvholm, 1984). In 1976, the value of the production of MMMF
was estimated to be greater than 1 billion US dollars (Corn,
1979).

Table 8. Estimated world production of MMMF materials
in 1973^a
---------------------------------------------------------
Area Insulation Textile Total
materials materials
1000 % 1000 % 1000 %
tonnes tonnes tonnes
---------------------------------------------------------
America

Central/South 120 3 20 2 140 3
North America 1600 43 400 46 2000 43

Australia 30 1 - - - -

Europe

Eastern 600 16 85 10 685 15
Western 1200 32 260 30 1460 32

Japan 200 5 100 12 300 7

World 3750 100 865 100 4585 100
---------------------------------------------------------
^a From: WHO (1983a).

It has been estimated that, in 1985, total world production
of MMMF was between 6 and 6.5 million tonnes, of which
insulation wools accounted for approximately 5 million tonnes
and textile grades for 1 - 1.5 million tonnes (EURIMA, 1987)^a.

Estimated annual production of fibrous glass in the USA in
the late 1970s was 370 000 tonnes for textile fibres and
1 200 000 tonnes for glass wool. Total annual production in the
USA has been estimated to be 200 000 tonnes for mineral wool
(slag and rock wool) and 21 000 tonnes for ceramic fibre (NRC,
1984). In the United Kingdom, production of wool materials rose
from 3500 tonnes in 1937 to 130 000 tonnes in 1977 (WHO, 1983a).

--------------------------------------------------------------------------
^a Information provided by the European Insulation Manufacturers
Association, Luxembourg.

3.2. Uses

The main uses of MMMF are presented in Fig. 3. Fibrous
glass accounts for approximately 80% of MMMF production in the
USA, with 80% of this being wool fibres used mainly in thermal
or acoustic insulation (Kirk-Othmer, 1980). Insulation wools
are usually compressed into "bats", "boards", "blankets",
"sheets" etc. or bagged as loose wool for blowing or pouring
into structural spaces. Some products are sewn or glued on to
asphalt paper, aluminium foil, etc. Textile grades, which
account for 5 - 10% (or greater) of all fibrous glass, are used
extensively in reinforcing resinous materials (e.g., automobile
bodies or boat hulls), paper and rubber products, in textiles,
such as draperies, and in electrical insulation and cording.
Less than 1% of the production of glass fibre is in the form of
fine fibres (fibre diameters < 1 µm), which are used in
specialty applications such as high efficiency filter papers and
insulation for aircraft and space vehicles.

Rock wool and slag wool, which account for approximately
10 - 15% of MMMF production in the USA, are used mainly as
acoustic or thermal insulation for industrial buildings or
processes. In Europe, where the production volumes of glass
wool and rock wool are similar, rock wool and slag wool are also
used extensively for domestic insulation.

Ceramic fibres (1 - 2% of all MMMF) are used mainly for
high-temperature insulation, e.g., thermal blankets for
industrial furnaces. Smaller quantities are used for expansion
joint filling.

3.3. Emissions into the Environment

Data on emissions of MMMF from manufacturing facilities are
limited. Fibre levels in emissions from fibrous glass and
mineral wool plants in the Federal Republic of Germany,
determined by SEM, were of the order of 10^-2 fibres/cm³
(Tiesler, 1982). On the basis of these data, it was estimated
that the total fibrous dust emissions from MMMF plants in this
country were about 1.8 tonnes/year. Emissions of respirable
fibres (defined by the investigators as fibres with lengths
exceeding 10 µm and diameters of less than 1 µm) were
estimated to be 80 kg/year.

It seems likely that the main source of emissions of MMMF
(mainly glass fibres) in indoor air is insulation in public
buildings or homes. Although quantitative data are not
available, emissions are probably highest shortly after
installation or following disturbance of the insulation (NRC,
1984).

4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION

The transport, distribution, and transformation of MMMF in
the general environment have not been specifically studied.
However, some general conclusions can be drawn, on the basis of
the physical and chemical properties of MMMF and information
concerning the behaviour of natural mineral fibres in the
ambient air and water.

Mineral fibres with small diameters are most likely to
remain airborne for long periods. Marconi et al. (in press) and
Riediger (1984) reported that, during operations involving the
use of mineral wool products, there is a general trend for
airborne fibres to become shorter and thinner with increasing
distance from working areas. For example, during the
installation of rock wool blankets, Marconi et al. (in press)
reported that the respirable fraction of airborne fibres in the
working areas accounts for about 67% of total airborne fibres.
At a distance of about 5 m from the working area, the respirable
fraction is about 90% of the total fibres. This is attributable
to the sedimentation of larger diameter fibres.

The solubility of MMMF in water varies considerably as a
function of their chemical composition and fibre size
distribution (section 2). Solubility increases with increasing
alkali content for a given composition of other elements, and
fibres with fine diameters degrade more rapidly than coarse ones
(Spurny et al., 1983). However, in general, MMMF are more water
soluble than naturally occurring asbestiform minerals and, thus,
most are likely to be less persistent in water supplies.

MMMF can be removed from the environment by breakage into
successively smaller fragments, thus losing their fibre
characteristics, by sedimentation and subsequent burial in
soil, or by thermal destruction (e.g., during incineration of
MMMF-containing waste). Dissolution and deposition and
subsequent burial in sediments are the most likely mechanisms of
removal from water.

5. ENVIRONMENTAL CONCENTRATIONS AND HUMAN EXPOSURE

5.1. Environmental Concentrations

5.1.1. Air

5.1.1.1. Occupational environment

(a) Production

Available data on levels of MMMF in production industries
are presented in Tables 9 and 10. Although in most of the
surveys conducted to date, both mass concentrations of
particulate matter and respirable fibre levels have been
determined, this discussion will be restricted largely to
information on fibre concentrations that appear to be most
relevant for the evaluation of potential health effects.

Comparison of data from various surveys is complicated by
lack of consistency in the classification of various operations
and job categories and by differences in sampling strategy and
fibre counting criteria. For example, a reference method for
the determination of airborne MMMF in the occupational
environment has been introduced only relatively recently (WHO,
1981, 1985); reassessment using the WHO PCOM reference method of
levels determined previously by interference microscopy resulted
in an increase in reported airborne concentrations in European
insulation plants of approximately two-fold (Cherrie et al.,
1986). However, in spite of the difficulties in comparing data,
some general conclusions concerning airborne fibre size and
concentrations in occupational environments can be drawn. Fibre
levels in plants manufacturing MMMF are substantially lower than
those measured in factories using asbestos. In addition, in
general, the measured median diameter of airborne fibres is
consistently and substantially smaller than the nominal diameter
of the fibres in the product. The median airborne fibre dia-
meters were 4 µm, 1.5 µm, and 0.2 µm for a product of nominal
fibre diameters of 14 µm, 6 µm, and 1 µm, respectively (Esmen
et al., 1979a). Esmen et al. (1979a) have shown that there is a
negative correlation (r = -0.96) between the overall process
average exposure levels (fibres/cm³) and the size of the nominal
diameter produced. A similar pattern has been observed by
Cherrie & Dodgson (1986).

Table 9. Airborne concentrations of MMMF in production industries
--------------------------------------------------------------------------------------------------------
Sampling Analysis Results Reference
Occupational group mean fibre Fibre size
concentrations in fibres/cm³ distribution
--------------------------------------------------------------------------------------------------------
After 1970: Phase % fibres with dia- Konzen
650 samples in 6 contrast meter < 3.5 µm: (1976)
wool insulation, 5 optical Glass wool plants, 0.11 - 0.16 68.9 - 87.1
continuous textile, microscopy; Continuous textile, 0.07 - 0.37 76.9 - 98.0
and 4 fibre length: Non-corrosive product, 0.12 72.3
glass-reinforced diameter Flame attenuated
plastic products > 3:1 fibre production, 0.38 89.3
plants

1975-78: Phase Estimate of exposure for various Concentration of Corn &
> 1500 personal contrast operations: fibres with dia- Sansone
8-h samples in optical meter < 1.5 µm (1974);
16 production microscopy; and length > 8 µm: Corn et
facilities (loose, length: Continuous, < 0.003 0 al. (1976);
continous, and diameter Coarse, 0.001 - 0.005 10^-5 - 10^-4 Esmen
mixed) including 5 > 3:1; Fibre glass insulation, 0.01 - 0.05 10^-3 - 10^-2 et al.
mineral wool plants length Mineral wool, 0.2 - 2 5 x 10^-2 - (1978,
in the USA > 5 µm; 5 x 10^-1 1979a);
transmission Specialty-fine, 1 - 2 0.5 - 1 Corn
electron Microfibre, 1 - 50 0.5 - 20 (1979);
microscopy Esmen
(1984)

> 950 breathing phase Continous filament glass fibres: % with diameter HSC (1979);
zone and static contrast mean < 0.02; insulation wools- < 1 µm: glass wool Head
general atmospheric optical fibre production: 0.12 - 0.89; insulation - 16%; & Wagg
> 4-h samples at 25 microscopy; production of basic fibrous mineral wool insul- (1980)
manufacturing plants length: materials (slab, board, etc): ation - 18%; glass
and construction diameter 0.02 - 0.37; conversion of basic microfibres - 60%;
sites in the > 3:1; materials to finished products ceramic fibre - 18%
United Kingdom length (e.g., pipe sections): 0.02 - 0.35;
> 5 µm; special purpose fibres: 0.8 -
diameter 3.70; ceramic fibre-manufacture
< 3 µm; 10% and conversion: 1.09 - 1.27
re-examined
by interference
microscopy for
fibre size
distribution

After 1980: phase In order of decreasing concentra- Tendency for fibre Hammad &
> 200 personal contrast tions: diameters to be Esmen
8-h samples in optical Very fine glass fibre plant: smaller than in (1984)
7 plants (2 mineral microscopy; 0.048 - 6.77 the first survey
wool, 2 ordinary length: Mineral wool plants:
glass fibre, 2 diameter 0.032 - 0.72
ordinary and fine > 3:1; Ordinary and fine glass fibre plants:
glass fibre, and length 0.014 - 2.22
1 very fine glass > 5 µm; Ordinary glass fibre plants:
fibre) in the USA transmission 0.017 - 0.062
electron
microscopy

> 300 personal and phase % with diameter Dement
stationary samples in contrast < 1 µm: (1975)
11 plants (4 large optical Large diameter glass insulation 2 - 46%
diameter insulation, microscopy: plants, 0.04 - 0.20
6 manufacturing or all visible Small diameter glass fibre 62 - 96%
using small diameter fibres; plants, 0.8 - 21.9
fibres, and 1 making electron Fibrous glass reinforced plastics < 1%
fibrous glass microscopy plant, 0.03 - 0.07
reinforced products) for a
in the USA proportion
of samples
--------------------------------------------------------------------------------------------------------

Table 9. (contd.)
--------------------------------------------------------------------------------------------------------
Sampling Analysis Results Reference
Occupational group mean fibre Fibre size
concentrations in fibres/cm³ distribution
--------------------------------------------------------------------------------------------------------
1981: unspecified phase Centrifuging/blowing: < 0.1 - 0.44 Less than 1% Riediger
number of samples contrast Centrifuging rock and slag wool: of fibres with (1984)
at 75 locations optical < 0.1 - 0.4 length > 20 µm and
in plants in microscopy: Blowing rock wool: < 0.1 - 0.5 diameter < 0.25 µm
the Federal Republic length: Cutting glass fibre filters:
of Germany diameter 0.1 - 0.2
> 3:1; Glass fibre reinforced plastics
length (grinding and cuffing): < 0.1 - 0.4
> 5 µm;
diameter
< 3 µm;
scanning
electron
microscopy
for a
proportion
of samples
(40 out of
75)

Unspecified number phase % of fibres Indulski
of static samples contrast with diameter et al.
in 3 rock wool optical < 1.5 µm: (1984)
and 1 continuous microscopy: Rock wool: 0.10 - 0.65 17 - 53.5
filament plant length: Glass fibre (continuous filament): 27
diameter 0.10 - 0.46
> 3:1;
length
> 5 µm;
diameter
< 3 µm

430 personal 8-h phase Mean concentrations ranged from Geometric mean dia- Esmen
samples in 3 ceramic contrast 0.0082 (fibre cleaning) to 7.6 meter, 0.7 + 0.2 et al.
fibre production optical (process helper); individual range, µm; ~90% < 3 µm (1979b)
and product microscopy; 0.0012 - 56 in diameter; dia-
manufacturing length: meters of airborne
plants diameter fibres from manu-
> 3:1; facturing operations
length greater than those
> 5 µm; from production
transmission zones
electron
microscopy

10 samples each phase Revised fibre concentrations Median fibre Cherrie
from 10 rock and contrast approximately twice the original lengths: rock et al.
glass wool plants optical levels; mean levels in insula- wool plants, 10 - (1986)
in Europe examined microscopy; tion wool plants < 0.1 and in 20 µm; glass wool
by Ottery et al. length: continuous filament plants < 0.01 plants, 8 - 15 µm;
(1984) plus 20 diameter median diameters:
"high" and "low" > 3:1; rock wool, 1.2 -
density samples length 2 µm; glass wool,
reassessed using > 5 µm; 0.7 - 1 µm; 20 -
WHO PCOM^a diameter 50% of fibres with
reference method < 3 µm; lengths > 8 µm and
scanning diameters < 1.5 µm
electron (% higher in glass
microscopy wool than in rock
wool plants)
--------------------------------------------------------------------------------------------------------
^a PCOM = Phase contrast optical microscopy.

Table 10. Airborne gravimetric concentrations of MMMF in production industries
--------------------------------------------------------------------------------------------------------
Sampling Analysis Results Reference
Short-term samples Time-weighted
(mg/m³) average concen-
tration (mg/m³)
--------------------------------------------------------------------------------------------------------
1972; Total airborne 0.1 - 0.75 Roschin & Azova
unspecified dust in (1975)
number breathing
of samples zone
in glass
fibres plant

Mullitosilica Gravimetry, 2.6 - 10.5 (loading in equipment, 2 - 3 Skomarokhin
fibres chemistry, and cutting, and packing glass fibres) (1985)
microscopy
SiO₂:Al₂O₃ _~1.0
SiO₂ _~45.2%
Al₂O₃ _~53.1%
Fe₂O₃ - 0.09%
CaO - 0.19%
MgO - 0.34
K₂O - 0.11
Na₂O - 0.19
length: 1 - 3 µm < 2.3%
4 - 6 µm - 4.3 - 7.6%
7 - 11 µm - 7 - 11.3%
12 - 17 µm - 10.5 - 13%
18 - 25 µm - 17.3 - 20.3%
> 25 µm - 38 - 48.7%
diameter: 1 - 3 µm
--------------------------------------------------------------------------------------------------------
The average concentrations measured by PCOM during the manu-
facture of fibrous glass insulation are of the order of
0.03 fibres/cm³. Average concentrations in continuous fibre
plants are about one order of magnitude lower and concentrations
in mineral wool (rock and slag) plants in the USA range up to
one order of magnitude higher. Corresponding concentrations in
European rock wool plants are of the order of 0.1 fibres/cm³.
Under similar plant conditions, airborne fibre concentrations
are about 4 times higher in ceramic fibre production than in US
mineral wool (rock and slag) plants, and average ceramic fibre
concentrations have been reported to range from 0.0082 to 7.6
fibres/cm³ (Esmen et al., 1979b). Average airborne concentra-
tions in speciality fine fibre plants range from 1 to
2 fibres/cm³ and concentrations are highest in microfibre
production facilities (1 - 50 fibres/cm³). However, it should
be noted that individual exposure varies considerably; for
individuals in the same job classification, concentrations range
over 2 orders of magnitude (Corn, 1979).

Total dust concentrations are typically of the order of
1 mg/m³, irrespective of the fibre type manufactured (excluding
ceramic). Overall averages were 4 - 5 mg/m³ for one rock wool
and one glass wool plant where manufacturing was reported to be
heavy or very heavy (Esmen et al., 1979a). The situation in 13
European plants was similar (Cherrie et al., 1986). Averages
for 3 US ceramic fibre production plants were 6, 1.6, and
0.85 mg/m³, respectively. Results from a USSR ceramic fibre
plant are comparable (Skomarokhin, 1985).

With respect to the relationship between fibre and mass
concentrations, Ottery et al. (1984) summarized their observa-
tions as follows:

"Where fibre and mass concentrations were compared on a
plant-average basis a broad correlation was observed (in
general, those plants which are "dusty" are also the ones with
higher airborne fibre concentrations). However, this relation
was not consistent between different occupational groups, nor
was there any detectable correlation when mass and fibre
concentrations were considered on an individual basis."

This is generally consistent with the observations of other
investigators (Esmen et al., 1978; Head & Wagg, 1980).

Table 11. Airborne concentrations of MMMF in application industries
--------------------------------------------------------------------------------------------------------
Application Number of Analysis Concentration Reference
samples (fibres/cm³)
Mean (range)
--------------------------------------------------------------------------------------------------------
Denmark
Attic insulation, existing total of 200 phase contrast optical 0.89 (0.04 - 3.5) Schneider
buildings samples at microscopy; length: (1979, 1984)
24 sites diameter > 3:1; length
Insulation, new buildings > 5 µm; diameter < 0.10 (0.04 - 0.17)
3 µm; scanning elec-
Technical insulation tron microscopy 0.35 (0.03 - 1.6)

Italy
Ship insulation (rock wool
blankets)
- inside room 8 phase contrast optical 0.19 (0.05 - 0.65) Marconi
- outside room 9 microscopy; length: 0.021 (0.002 - 0.05) et al.
- installers 14 diameter > 3:1; length 0.13 (0.009 - 0.41) (1986)
- "finishing" workers 14 > 5 µm; diameter 0.12 (0.03 - 0.31)
< 3 µm
Sweden
Attic insulation, existing total of 58 phase contrast optical 1.1 (0.1 - 1.9) Hallin
buildings samples at microscopy; length: (1981);
14 sites diameter > 3:1; length Schneider
Insulation, new buildings > 5 µm; diameter < 0.57 (0.007 - 1.8) (1984)
3 µm
Technical insulation 0.37 (0.01 - 1.39)
(boilers, cisterns)

Acoustic insulation 0.15 (0.11 - 0.18)
- spraying 0.51 (0.13 - 1.1)
- hanging fabric 0.60 (0.30 - 0.76)
--------------------------------------------------------------------------------------------------------

Table 11. (contd.)
--------------------------------------------------------------------------------------------------------
Application Number Analysis Concentration Reference
of (fibres/cm³)
samples Mean (range)
--------------------------------------------------------------------------------------------------------
United Kingdom
Domestic loft insulation phase contrast optical Head & Wagg
- glass fibre blanket 12 microscopy; length: 0.70 (0.24 - 1.8) (1980)
- loose fill-mineral wool 16 diameter > 3:1; length 8.2 (0.54 - 21)
> 5 µm; diameter < 3 µm

Fire protection-structural steel
- sprayed mineral wool 22 0.77 (0.16 - 2.6)

Application in industrial products
- industrial engine exhaust
insulation (mineral wool) 15 0.085 (0.02 - 0.36)

USA
Fibrous glass duct wrapping 5 phase contrast optical 0.02 - 0.09 Fowler et
Wall and plenum insulation 5 microscopy; size cri- 0.01 - 0.47 al. (1971)
Pipe insulation 6 teria not described 0.02 - 0.09
Housing insulation 1 0.20

Acoustic ceiling installer 12 phase contrast optical 0.0028 (0 - 0.0006) Esmen et
microscopy; length: al. (1982)
Duct installation diameter > 3:1; length
- pipe covering 31 > 5 µm; diameter < 3 0.06 (0.0074 - 0.38)
- blanket insulation 8 µm; transmission 0.05 (0.025 - 0.14)
- wrap around 11 electron microscopy 0.06 (0.030 - 0.15)

Attic insulation (fibrous glass)
- roofer 6 0.31 (0.073 - 0.93)
- blower 16 1.8 (0.67 - 4.8)
- feeder 18 0.70 (0.06 - 1.5)

Attic insulation (mineral wool)
- roofer 9 0.53 (0.041 - 2.03)
- blower 23 4.2 (0.50 - 15)
- feeder 9 1.4 (0.26 - 4.4)

Installer of building 31 0.13 (0.013 - 0.41)
insulation
--------------------------------------------------------------------------------------------------------
(b) User industries

Available data on airborne fibre concentrations associated
with the installation of products containing MMMF are presented
in Table 11. Airborne concentrations during the installation of
insulation vary considerably, depending on the method of
application and the extent of confinement within the work-space.
Concentrations during installation are comparable to, or lower
than, levels found in the production of the fibrous material
(Esmen et al., 1982), with the exception of blowing or spraying
operations conducted in confined spaces, such as during the
insulation of aircraft or attics (Head & Wagg, 1980; Esmen et
al., 1982). In various surveys, mean concentrations during
the installation of fibrous glass insulation in attics have
ranged up to 1.8 fibres/cm³; mean concentrations during the
application of mineral wool insulation under similar
circumstances have been as high as 8.2 fibres/cm³. During the
installation of rock wool blankets in very confined spaces on
board ships, concentrations have been less than 0.65 fibres/cm³
(Marconi et al., in press). It should be noted that the time-
weighted average exposure of insulation workers is probably
considerably less than these mean concentrations during
application, as insulators work with MMMF materials from < 10 to
100% of their time, depending on their employment and the type
of construction site (Fowler et al., 1971). The majority of
joiners and carpenters may use from 0.5 to 15% of their working
hours on MMMF work (Schneider, 1984). On the basis of estimates
made by Esmen et al. (1982), time-weighted average exposures may
exceed 1 fibres/cm³ only for workers insulating attics with
mineral wool (TWA = 2 fibres/cm³; range, 0.29 - 6.3 fibres/cm³).
Time-weighted average exposures for workers using fibrous glass
in attics or employed in building insulation were estimated to
be 0.7 fibres/cm³ (range, 0.42 - 1.2 fibres/cm³) and 0.11
fibres/cm³ (range, 0.08 - 0.2 fibres/cm³), respectively.

Air at construction sites and in certain other industrial
and domestic environments may contain substantial amounts of
non-fibrous dust. The gravimetric concentration of fibres in
total dust samples has been determined by optical microscopy for
a range of user industries (Schneider, 1979). The ratio weight
of all fibres of all sizes in total dust samples/weight of total
dust had a geometric mean of 0.14, with 90% between 0.06 and
0.33.

Howie et al. (1986) recently investigated fibre release from
filtering facepiece respirators containing "superfine" MMMF.
These respirators are often used for the protection of workers
in dusty occupational environments. Following the use of
several different types of these respirators for either 15 or
40 min, downstream respirable fibre concentrations ranged from
not detectable (<0.1 fibres/cm³) to 200 fibres/cm³, using the
WHO reference PCOM method of monitoring.

5.1.1.2. Ambient air

Few data are available concerning concentrations of MMMF
present in the general environment. The fibrous glass content
of several samples of outdoor air was determined in a study by
Balzer et al. (1971), which was designed principally to
investigate the possible erosion of fibres from air transmission
systems lined by fibrous glass. Mean concentrations on the
rooftops of 3 buildings on the University of California's
Berkeley Campus, determined by PCOM and petrographic microscopy,
were about 2.7 x 10^-4 fibres/cm³ (range, < 5 x 10^-5 - 1.2 x 10^-3
fibres/cm³). Levels at other sites averaged 4.5 x 10^-3
fibres/cm³, the lowest levels being 4 x 10^-4 fibres/cm³. Fibres
other than MMMF may have been included in the results of these
analyses.

Balzer (1976) reported the results of a further study in
which MMMF levels were determined by light and electron
microscopy in 36 samples of ambient air from various locations
in California (Berkeley, San Jose, Sacramento, the Sierra
Mountains, and Los Angeles). Fibre counts were determined by
combining the light microscopic count of fibres greater
than 2.5 µm in diameter and the electron microscopic count of
fibres less than, or equal to, 2.5 µm in diameter. Levels of
glass fibres averaged 2.6 x 10^-3 fibres/cm³ and accounted for
approximately 1/3 of the total fibrous material in the samples.
However, the significance of these results is uncertain, since
the methods of sampling and analysis and the results were not
well described in the published account of this study.

Mean airborne glass fibre concentrations measured by analy-
tical TEM ranged from 4 x 10^-5fibres/cm³ at 1 rural location to
1.7 x 10^-3 fibres/cm³ in 1 out of 3 cities in the Federal
Republic of Germany (1981-82; 9 - 21 samples at each location).
These levels were 3 - 40% of the asbestos concentrations; median
diameters of the glass fibres ranged from 0.25 µm to 0.89 µm
and median lengths from 2.54 to 3.64 µm (Höhr, 1985).

5.1.1.3. Indoor air

On the basis of analysis using PCOM (Balzer et al., 1971;
Esmen et al., 1980) and calculation of the "glass" content of
collected particulate (Cholak & Schafer, 1971), it has generally
been concluded that the contribution of fibrous-glass-lined air
transmission systems to the fibre content of indoor air is
insignificant. Using very conservative assumptions, Esmen et
al. (1980) estimated that the level of fibres in occupied
spaces is of the order of 0.001 fibres/cm³ during the first day
of operation of air transmission systems with medium grade
fibrous glass filters and essentially the same as ambient levels
during the remaining filter life.

Generally, concentrations of MMMF in indoor air are 100 -
1000 times less than those in the occupational environment.
Several studies in which airborne fibre levels in indoor air
were measured by PCOM with polarization equipment have been
carried out in Denmark (Table 12). Although fibres other than
MMMF may have been included in these analyses, birefringent
fibres (mostly organic) were counted separately. Typical
levels, as well as total dust concentrations measured in one of
the studies (Nielsen, 1987), are shown in Table 13.
Table 12. Respirable MMMF fibre concentrations in the indoor environment (static samples)
------------------------------------------------------------------------------------------
Site Number Respirable fibre Comments Reference
of levels (x 10^-6
buildings fibres/cm³)^a
-------------------
Arithmetic mean
and range of
individual samples
------------------------------------------------------------------------------------------
Random sample of 11 60 (0 - 240) Schneider
mechanically venti- (1986)
lated schools

Random sample of 5 110 (60 - 160)^b MMMF ceiling boards with Rindel
kindergardens (sites water-soluble binder et al.
with reported indoor (1987)
air problems were 3 100 (43 - 150)^b Resin binder
excluded)
4 40 (10 - 70)^b No MMMF ceiling boards

140 rooms (day-care 260 (0 - 1330) Water-soluble binder, Nielsen
centres, schools, untreated surface (1987)
offices) selected 75 (0 - 425) Water-soluble binder,
at random, but with untreated surface,
MMMF ceiling boards varnished
70 (0 - 180) Water-soluble binder,
untreated surface
30 (0 - 250) Resin binder
40 (0 - 85) Resin binder
250 (0 - 1070) Resin binder
140 (0 - 820) Resin binder
25 (0 - 80) Resin binder
40 (0 - 480) No MMMF

Sites with reported 6 range, 230 - 2900 One observation Schneider
indoor climate (0.084 fibres/m³) (1986)
problems
------------------------------------------------------------------------------------------
^a Phase contrast optical microscopy with polarization. Length > 5 µm;
diameter < 3 µm; aspect ratio > 3:1.
^b 95% confidence interval.
Table 13. Average concentrations of total dust and
fibres other than MMMF in indoor environments
(static samples)^a
------------------------------------------------------
Site Number of Total dust Organic and other
measure- (mg/m³) bire-fringent
ments fibres
(fibres/cm³)
------------------------------------------------------
Day-care 49 0.26 0.25
centres

Schools 11 0.16 0.064

Offices 39 0.13 0.025
------------------------------------------------------
^a From: Nielsen (1987).

5.1.2. Water supplies

Data on the MMMF content of water supplies are not
available. However, glass fibres have been identified by
optical microscopy in samples of sewage sludge from 5 cities in
the USA (Bishop et al., 1985).

5.2. Historical Exposure Levels

In an analysis of the data from the large European epidemio-
logical study referred to previously, the production history of
each factory was classified into the following 2 distinct
technological phases: (a) an early phase during which a batch
production system was in use and/or no oil added during
production; and (b) a late phase during which modern production
techniques were used and oil was added. A third phase, inter-
mediate between the early and late phases, was also identified
at some plants where a mixture of production types or techniques
operated.

The airborne fibre levels in the early technological phase
in the slag wool/rock wool industry were probably substantially
higher than in the late phase, the corresponding levels in the
intermediate phase being between these two levels (Cherrie &
Dodgson, 1986). However, the pattern in the glass wool plants
was somewhat different.

The basis of these differences rests primarily with changes
over time in the nominal fibre diameters of the MMMF being
produced, and the addition of oil. In the early period in the
slag wool/rock wool industry, the lack of oil and fibres of
relatively fine nominal diameter (3 - 6 µm) contributed to
higher airborne fibre levels. On the other hand, in the glass
wool production industry, it is likely that there was little
change in airborne fibre levels between the early and late
phases. In the early phase, oil was not added during production,
and the nominal diameter of the fibres produced was relatively

large (10 - 25 µm). In the late phase, oil was added during
production, and the nominal diameter of the fibres produced was
smaller (5 - 7 µm). The effects of changes in other factors
including ventilation and production rates were judged to be
less.

Combined experimental and modelling procedures have been
used to estimate past exposure levels in the European MMMF
plants (Dodgson et al., in press). The model is still being
developed and should be considered to be preliminary (Cherrie et
al., in press). It indicates that mean airborne fibre
concentrations for rock wool plants could have been about 1 -
2 fibres/cm³, during the early technological phase, with levels
of about 10 fibres/cm³ for the dustiest work. Current exposure
levels are at least one order of magnitude lower. Corresponding
estimates indicate that the mean airborne fibre levels for the
glass wool plants during the early technological phase were
little different from current concentrations (about 0.1
fibres/cm³ or less).

The validity of the model has been investigated in an
experimental simulation of rock wool production in the early
phase (Cherrie et al., in press). The effects of added oil on
the airborne fibre levels during experimental production were
assessed together with the effects of workers handling batches
of material. Addition of oil resulted in a 3- to 9-fold
reduction in the airborne fibre levels in different situations.
The time-weighted average concentrations were 1.5 fibres/cm³
with oil added and about 5 fibres/cm³ without oil. These values
agreed reasonably well with the predictions from the model.
There was no substantial difference in fibre concentrations
between batch and continuous operation. However, it is possible
that the batch handling was not well simulated.

5.3. Exposure to Other Substances

Polyaromatic hydrocarbons (PAHs) and other combustion
products were present in the working environment, particularly
in the early technological phase of the slag wool/rock wool
industry in Europe, where cupolas were used extensively. In one
plant, the use of an olivin, potentially contaminated with a
natural mineral fibre with a composition similar to tremolite
was reported (Cherry & Dodgson, 1986). The probable average
exposure in the pre-production area was estimated to be 0.1
fibres/cm³. The European slag wool plants used copper slags,
possibly liberating arsenic compounds into the working
environment.

In MMMF plants in the USA, other airborne contaminants have
been measured in areas not necessarily representative of
occupational exposure or in breathing zones (IARC, in press).
The results, obtained periodically over the years 1962-87, are
shown in Table 14. It was emphasized that these measurements
only verify the presence of other contaminants in the plants and
cannot be used to estimate the degree of exposure.

Table 14. Exposure to other airborne contaminants in
MMMF plants in the USA^a
------------------------------------------------------
Contaminant Range of concentrations
------------------------------------------------------
Asbestos 0.02 - 7.5 fibres/cm³
Arsenic 0.02 - 0.48 µg/m³
Chromium (insoluble) 0.0006 - 0.036 mg/m³
Benzene-soluble organics 0.012 - 0.052 mg/m³
Formaldehyde 0.06 - 20.4 mg/m³
Silica (respirable) 0.004 - 0.71 mg/m³
Cristobalite (respirable) 0.1 - 0.25 mg/m³
------------------------------------------------------
^a From: IARC (in press).

6. DEPOSITION, CLEARANCE, RETENTION, DURABILITY^a, AND TRANSLOCATION

6.1. Studies on Experimental Animals

Because of the tendency of fibres to align parallel to the
direction of airflow, the deposition of fibrous particles in the
respiratory tract is largely a function of fibre diameter,
length and aspect ratio being of secondary importance.

Since most of the data on deposition of various MMMF have
been obtained in studies on rodents, it is important to consider
differences between rats and man in this regard. Comparative
differences between rat and man can best be evaluated using the
aerodynamic equivalent of fibres. The ratio of the absolute
diameter to aerodynamic diameter is approximately 1:3. Thus, a
fibre measured microscopically to have a diameter of 1 µm would
have a corresponding aerodynamic diameter of approximately
3 µm. In addition, any curvature of the fibres may have the
effect of increasing the effective aerodynamic diameter.

A comparative review of the regional deposition of particles
in man and rodents (rats and hamsters) has been presented by US
EPA (1980). The relative distribution between the tracheo-
bronchial, and pulmonary regions of the lung in rodents followed
a pattern similar to human regional deposition during nose
breathing for insoluble particles of less than 3 µm mass median
aerodynamic diameter (approximately 1 µm diameter or less).
Fig. 4 and 5 illustrate these comparative differences. As can
be seen, particularly for pulmonary deposition, the percent
deposition of particles is considerably less in the rodent than
in man. These data indicate that, while particles of 5 µm
aerodynamic diameter or greater may have significant deposition
efficiencies in man, the same particles will have extremely
small deposition efficiencies in the rodent. More recent work
by Snipes et al. (1984) indicates that, with particles above
3 µm aerodynamic diameter, the probability of reaching the
pulmonary region falls off rapidly, and that particles of 9 µm
aerodynamic diameter have an extremely small probability of
reaching the pulmonary region in rats and guinea-pigs.

Because of their length, fibres are more likely than spher-
ical particles to be deposited by interception, mainly at bifur-
cations. Available data also indicate that pulmonary penetra-
tion of curly chrysotile fibres is less than that for straight
solid amphibole fibres. However, in studies on rats, in which
the deposition of curly versus straight glass fibres was
examined, the difference was less apparent (Timbrell, 1976).
Clearance from the peripheral respiratory tract is principally a
function of fibre length, with fibres shorter than 15 - 20 µm
in length being cleared more efficiently than longer ones.

-------------------------------------------------------------------------------
^a Durability of MMMF in tissues is a function of their
physical and chemical characteristics.

The results of available studies concerning the deposition,
clearance, retention, durability, and translocation of MMMF in
animal species are presented in Table 15. As for all fibrous
particles, deposition of MMMF in the respiratory tract is
determined principally by fibre diameter. In studies conducted

by Morgan et al. (1980), alveolar deposition of glass fibres in
rats was much less than that for asbestiform minerals, because
of the larger aerodynamic diameter of MMMF. Deposition of
asbestiform and glass fibres, the aerodynamic diameters of which
ranged from 1 to 6 µm), was greatest for fibres with an
aerodynamic diameter of 2 µm (Morgan et al., 1980). However,
there was some deposition of glass fibres with aerodynamic dia-
meters of between 3 and 6 µm. For fibres of constant diameter,
alveolar deposition decreased with increasing fibre length.
Morgan & Holmes (1984b), comparing their results in rats with
those concerning fibre deposition in other species, suggested
that glass fibres with diameters greater than 3.5 µm (aero-
dynamic diameter ~10 µm) are unlikely to be respirable in man
by nose breathing (Timbrell, 1965; Morgan et al., 1980; Hammad
et al., 1982; Hammad, 1984). Fibre deposition in various lobes
of the lungs of rats varied over a narrow range (5.34 - 8.38%)
following inhalation of ceramic fibres. Fibre size distributions
in the various lobes, based on analysis by phase contrast
optical microscopy, were not significantly different (Rowhani &
Hammad, 1984). These results are similar to those observed for
glass wool, rock wool, and glass microfibre by Le Bouffant et
al. (in press).

According to Griffis et al. (1981), there is a fairly rapid
decline in the lung content of glass fibres, immediately
following deposition, presumably because of mucociliary
clearance (t´ in rats _~1 day). This is followed by a much
slower phase assumed to represent alveolar clearance (t´ in
rats _~44.3 days) (Friedberg & Ullmer, 1984). Short fibres are
efficiently cleared by alveolar macrophages (Morgan et al.,
1982a; Morgan & Holmes, 1984b; Bernstein et al., 1984); in rats,
more than 80% of glass fibres of less than 5 µm in length were
cleared by one year (t´ _~60 days). However, macrophage-mediated
clearance appeared to be ineffective for fibres with lengths of
30 and 60 µm (Morgan & Holmes, 1984b).

Table 15. Deposition, durability, clearance, retention, and translocation of MMMF in experimental animals
--------------------------------------------------------------------------------------------------------
Species Study protocol^a Results Reference
--------------------------------------------------------------------------------------------------------

Alderley Park Inhalation for 2 - 3 h of samples Decrease in alveolar deposition Morgan
(strain 1) of glass fibres and asbestiform with increasing fibre length; et al.
SPF rats materials at concentrations of maximum deposition for fibres (1980);
0.40 - 1.63 g/litre; aerodynamic with aerodynamic diameter of Morgan &
diameter of fibres ranged from 2 µm; small but significant Holmes
1 to 6 µm; animals killed deposition of fibres with aero- (1984b)
immediately or 2 days following dynamic diameters of 3 - 6 µm
exposure

Fischer 344 Inhalation of 31 - 52 mg glass 41 - 48% of lung burden cleared Griffis
SPF male fibres/m³ (2/3 respirable; CMD, between daily exposures (i.e., et al.
rats 0.11 µm; CML, 8.3 µm), 6 h/day, half-time for early clearance, (1981)
for 1, 2, 4, or 5 days 1 day)

Beagle dogs Inhalation for 1 h of unspecified 77% of body burden excreted in Griffis
concentration of glass fibres (CMD, 4 days, mainly (> 96%) in faeces et al.
0.15 µm; CML, 5.4 µm); animals (half-time 2 days); 5 - 17% deposi- (1983)
killed 4 days after exposure ted in deep lung; respiratory tract
deposition, 45 - 64%

Male albino Inhalation of _~300 fibres/cc (CMD, Increased alveolar retention of Hammad
rats 1.1 - 1.3 µm; CML, 8 - 20 µm); fibres with decreasing diameter et al.
animals killed 5 days after exposure and decreasing length (maximum (1982)
7.6% for fibres < 0.5 µm in dia-
meter and 21 µm in length)

Table 15. (contd.)
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Species Study protocol^a Results Reference
--------------------------------------------------------------------------------------------------------
Syrian Intratracheal instillation of 0.2 mg Preferential clearance of shorter Holmes
golden sized glass fibres (3 µm in dia- fibres; ferruginous bodies around et al.
hamsters meter; length, 10 - 100 µm); animals fibres > 10 µm in length only; (1983);
killed serially up to 8 months after time of onset of body formation Morgan &
administration decreased with increasing fibre Holmes
length; proportion of coated (1984b)
fibres increased over a period of
about 3 - 4 months and then declined
after 5 months; coating did not
prevent dissolution of fibres;
longer fibres dissolved more
rapidly than shorter ones; fibres
dissolved more rapidly in trachea
than in rat lung

Alderley Park Intratracheal instillation in rats Rock wool fibres dissolved more Morgan &
(strain 1) (0.5 mg) or hamsters (0.4 mg) slowly in the lung than glass Holmes
SPF rats of rock wool (CMD, 1.1 µm; CML, fibres; diameter essentially (1984a,b)
and Syrian 28 µm); animals killed serially unchanged after 18 months; in
golden up to 18 months after administra- hamsters, coating of fibres
hamsters tion < 2 µm in diameter after 2 months

Alderley Park Intratracheal instillation of Fibres with diameter < 3 µm and Morgan
(strain 1) 0.5 ml of 6 samples of glass lengths < 10 µm efficiently cleared et al.
SPF rats fibres (1.5 or 3 µm in diameter; (presumably by macrophage-mediated (1982);
length, 5 - 60 µm); animals processes); fibres 30 and 60 µm in Morgan &
killed serially up to 18 length not cleared to a significant Holmes
months after administration extent over 1 year; longer fibres (1984b)
dissolved more rapidly in a non-
uniform manner leading to fragment-
ation; shorter fibres dissolved
more slowly and uniformly

Guinea-pigs Intrapleural injection of 25 mg Fine structure of coated glass Davis
commercial glass fibre (diameter, fibres in lung identical to that of et al.
0.05 - 0.99 µm); animals killed asbestos bodies (1970)
6 weeks after administration

Fischer 344 Inhalation of 10 mg/m³ rock wool, Glass microfibres more susceptible Johnson
SPF rats glass wool (with and without resin), to etching in lung tissue than et al.
and glass microfibre for 7 h/day, glass or rock wool (1984a)
5 days/week, for 1 year; animals
killed immediately or at unspecified
periods after exposure

Male rats Inhalation of mineral wool (CMD, Ceramic fibres more persistent Hammad
1.2 µm; CML, 13 µm) or ceramic than mineral wool in lung tissue (1984)
fibres (CMD, 0.7 µm; CML, 9 µm)
(_~300 fibres/cc), 6 h/day, for
5 or 6 days; animals killed 5, 30,
90, 180, or 270 days after exposure

Wistar IOPS Inhalation for 1 or 2 years of Fibre concentrations in the air Le Bouffant
AF/Han rats resin-free glass wool or rock and lung much greater for micro- et al.
wool (Saint Gobain), or micro- fibre (JM 100) than for glass and (1984,
fibres (JM 100) (_~5 mg/m³); rock wool; retention and trans- in press)
animals killed immediately or location less for rock and glass
serially for periods up to 16 wool fibres than for microfibres;
months after exposure lengths of glass and rock wool
fibres retained in the lungs
shorter than those of airborne
fibres, whereas glass microfibre
sizes in lung and air similar;
generally, fibres in the lymph
nodes shorter than those in the
lungs

Table 15. (contd.)
--------------------------------------------------------------------------------------------------------
Species Study protocol^a Results Reference
--------------------------------------------------------------------------------------------------------
Male Fischer Intratracheal instillation of 2 Short fibres cleared efficiently Bernstein
344 SPF rats or 20 mg glass fibres (1.5 µm by macrophages with fewer than et al.
in diameter; length, 5 or 60 µm); 10% remaining after 500 days; (1980, 1984)
animals killed serially up to 2 longer fibres dissolved more rap-
years after administration; intra- idly (over 50% in 18 months),
tracheal instillation of 0.5 mg possibly due to partial phago-
glass fibres (1.5 µm in dia- cytosis
meter; length, 5 or 60 µm) or
tracheal inhalation once per week,
for 10 weeks

Pathogen-free Inhalation of ceramic fibre (CMD, Deposition of fibres varied over Rowhani &
adult albino 0.53 µm; CML, 3.7 µm) (_~709 a narrow range (5.43% for the Hammad
male rat fibres/cm³), 6 h/day, for 5 days; right diaphragmatic lobe to (1984)
animals killed 5 days after expo- 8.38% for the right apical lobe);
sure; analysis by PCOM^b fibre burden for all lobes weight
dependent; no significant differ-
ence in fibre size distributions
in various lobes

Female Wistar Intratracheal instillation of 2 mg Half lives for fibres > 5 µm in Bellmann
rats microfibre (JM 104-E glass: 90% of length: JM 104/475, 3500 days et al.
fibre diameters < 0.28 µm, 90% (similar to crocidolite; change (in press)
of fibre lengths < 5.8 µm; JM 104/ in size not detected); JM 104-E glass,
475: 90% of fibre diameters < 0.4 55 days (increase in mean length
µm, 90% of fibre lengths < 8.4 µm; and diameter in first 6 months);
acid-treated microfibre (JM 104-E acid-treated JM 104-1974, 14 days;
glass: 90% of fibre diameters rock wool, 283 days; ceramic wool,
< 0.46 µm, 90% of fibre lengths 780 days
< 6.3 µm); rock wool (90% of
fibre diameters < 5.6 µm, 90% of
fibre lengths < 67 µm); ceramic wool
(90% of fibre diameters < 4.2 µm,
90% of fibre lengths < 177 µm) with
animals killed serially up to 2
years after administration

--------------------------------------------------------------------------------------------------------
^a CMD = Count median diameter.
CML = Count median length.
^b PCOM = Phase contrast optical microscopy.
The degradation of MMMF in lung tissue consists of reduction
of diameter with time, together with pitting and erosion of the
surface visible on TEM (Morgan & Holmes, 1986). Observations
for up to 2 years after intratracheal instillation in rats
showed a wide range in the durability of various MMMF (Bellmann
et al., in press). Morgan & Holmes (1986) noted that relatively
thick MMMF become thinner on dissolution and may assume dimen-
sions that resemble those of the fibrous amphiboles. However,
the in vivo studies in this report, together with the in vitro
observations of Klingholz & Steinkopf (1984), suggest that the
leaching of alkaline ions that accompanies fibre dissolution
results in rapid changes in the nature of the surface of the
fibre, and loss of substance, so that the cell/fibre interface
may be altered. In studies on rats, long glass fibres degraded
more rapidly than short ones (Morgan et al., 1982; Holmes et
al., 1983; Bernstein et al. 1984; Hammad, 1984). It has been
postulated that this may be because the small (short) fibres are
completely engulfed by macrophages and therefore "protected"
from the extracellular environment, which contains more fluids
and enzymes that might facilitate degradation.

Although ferruginous bodies are not observed in rats exposed
to asbestos or glass fibres, in an early study on guinea-pigs,
it was demonstrated that glass fibres could be coated in the
lung to form bodies with a fine structure identical to that of
asbestos bodies (Davis et al., 1970). In hamsters, various
proportions of the fibres in lung tissue greater than 10 µm in
length became coated to form ferruginous bodies; the time of
onset of formation decreased with increasing fibre length
(Holmes et al., 1983). In studies involving exposure for 90
days (0.4 mg glass fibres/litre), by Lee et al. (1981),
ferruginous bodies were first detected in hamsters by the 6th
month following exposure and in guinea-pigs by the 12th month.
The coating of ferruginous bodies appears to be discontinuous
and does not prevent the leaching and fragmentation of long
glass fibres (Morgan & Holmes, 1984b).

Available data also indicate that rock wool may be more
persistent in lung tissue than fibrous glass (Johnson et al.,
1984a; Morgan & Holmes, 1984a,b). Following intratracheal
instillation in rats, the diameter of rock wool fibres in the
lung was essentially unchanged after 18 months; however, the
ends of the fibres were perceptibly thinner. The results of an
additional study on rats indicated that ceramic fibres were more
persistent in lung tissue than rock wool, even though the mean
diameter of the mineral wool fibres was greater than that of the
ceramic fibres. After 270 days, about 25% of ceramic fibres
were still present in lung tissue compared with 6% of mineral
wool fibres (Hammad, 1984).

Lee et al. (1981) reported that dust particles were present
in the tracheobronchial lymph nodes after 50 days exposure to
0.4 mg glass fibre/litre. Following inhalation of glass wool,
rock wool, or glass microfibre at 5 mg/m³ for 1 year, fibre

concentrations in the tracheobronchial glands of rats were low
(range of means in males and females, 0.1 - 0.8 g/kg dry
tissue), except for microfibres (JM 100), for which mean levels
were 4.8 and 3 g/kg dry tissue, in males and females,
respectively (Le Bouffant et al., 1984) (For comparison, mean
concentrations of glass and rock wool in lung tissue ranged from
0.4 to 2.8 g/kg dry weight; mean levels of microfibre were 5.8 -
12.7 g/kg dry lung tissue). Levels of the various fibre types
in the diaphragm were essentially zero (Le Bouffant et al.,
1984). Generally, levels of fibres in the lymph nodes of
animals exposed for 2 years were higher than those after 1 year
of exposure (Le Bouffant et al., in press). Bernstein et al.
(1984) reported that, following intratracheal instillation of
size-selected glass fibres of diameters of 1.5 µm and lengths
of either 5 µm (short) or 60 µm (long), short fibres were
quickly cleared to the regional lymph nodes, whereas the long
fibres were not. Even 18 months after exposure, there were no
significant quantities of fibres in the lymph nodes of the
groups exposed to long fibres, whereas there were many still
present in the animals exposed to short fibres. Spurny et al.
(1983) reported the presence of glass fibres in the spleen of
rats, 2 years after intratracheal implantation. However, few
experimental details were provided. Recovery of fibres from all
organs examined 90 days after intrapleural injection of fibrous
glass (20 mg JM 104) was reported by Monchaux et al. (1982).

6.2. Solubility^a Studies

The results of studies on the solubility of MMMF in physio-
logical fluids in vitro are presented in Table 16. Since it is
impossible to reproduce in vitro the various conditions of pH
and concentrations of complexing agents in the intra- and
extracellular environment of the lung, the results of disso-
lution studies should be interpreted with caution. However, on
the basis of these investigations, it appears that dissolution
is a function not only of the fibre characteristics, such as
chemical composition and size, but also of the nature of the
leaching solution. In one of these investigations, MMMF were
more soluble than the amphiboles and chrysotile (Spurny, 1983).
However, there is a wide range in the solubility of the various
MMMF, e.g., 30- to 40-fold in the study of Leineweber (1984).
For example, Leineweber (1984) reported that the stability of
various MMMF in physiological saline was as follows: glass fibre
(1 type) > refractory fibre > mineral wool > glass fibre (3
types). However, in distilled water, the order was significantly
different: refractory fibre > glass fibre (2 types) > mineral
wool > glass fibre (2 types).

-----------------------------------------------------------------------
^a Solubility of MMMF is their behaviour in various fluids. In
general, the term is restricted to observations in vitro,
since the persistence of fibres in vivo is a function of
several factors including solubility.

Table 16. The solubility of MMMF
---------------------------------------------------------------------------------------------------
Study protocol Results Reference
---------------------------------------------------------------------------------------------------
Analysis by scanning electron Surface porosity was altered and Spurny (1983);
microscopy, microprobe analysis, alkali elements were increased; in Spurny et al.
X-ray diffraction, X-ray fluores- general, order of stability: (1983)
cence spectroscopy and mass amphiboles > glass fibres > other
spectroscopy of UICC chrysotile MMMF > chrysotile; in some cases,
or crocidolite glass fibres and succession amphiboles > chrysotile
mineral wool in 5 solutions (2N > MMMF; fine diameter fibres degrade
HCl, 2N H₂SO₄, 2N NaOH, water, and more rapidly than coarse fibres
blood-serum)

Analysis by atomic absorption spec- MMMF softened in physiological solu- Forster (1984)
trometry, scanning electron micro- tions and gel forms that is removed
scopy and energy dispersive X-ray in layers; rate of dissolution in
analysis of asbestos, rock wool, Gamble's solution: 10 ng/cm² per h
slag wool, basalt wool, and glass (i.e., fibres with average diameter of
wool (without binders) in deionized 3 µm completely dissolved in < 5 years;
distilled water, KOH (48%), H₂SO₄ those with diameter < 1 µm dissolved
(48%), Ringer's solution, and Gamble's in < 1 year); asbestos stable in
solution physiological solutions

Analysis by atomic absorption spec- Gel formation on the surfaces of all Klingholz &
trometry, electron probe, scanning MMMF within a few weeks, partic- Steinkopf (1984)
electron microscopy, and energy ularly for those with higher alkaline
dispersive X-ray analysis of mineral content; beneath the gel layer,
wool, glass wool, rock wool, and areas of local corrosion ("pitting")
basalt wool (without binders) in lead to loss of structural integrity
Gamble's solution and breakage into shorter lengths

Analysis by BET gas absorption, 40-fold range of durability in Leineweber
scanning electron microscopy, and saline; order of durability: 1 sample (1984)
energy dispersive X-ray of glass fibre > refractory fibre >
spectrometry of 4 samples of mineral wool > 3 samples of glass
fibrous glass, mineral wool, and fibre; order in distilled water
refractory fibre in physiological varied; correlation between the solu-
saline and distilled water bility and total weight percentage
alkalis; surface deposits observed

Table 16. (contd.)
---------------------------------------------------------------------------------------------------
Study protocol Results Reference
---------------------------------------------------------------------------------------------------

Determination of mass and sodium Greater mass dissolved in serum Griffis et al.
content by flame atomic absorption stimulant than in buffered saline; (1981)
spectroscopy of glass fibres in some sodium preferentially dissolved
tris buffered saline or serum in both solvents
stimulant

Analysis (inductive coupled plasma MMMF much more soluble (dissolution Scholze &
method) for silicon, boron, and time for glass or slag wool < 2 years, Conradt
potassium; weight determination and for E glass wool (JM 104) and refrac- (in press)
examination by scanning electron tory fibre, 5 - 6.5 years) than nat-
microscopy ural mineral fibres (dissolution
time > 100 years)
---------------------------------------------------------------------------------------------------
On the basis of available data, it appears that there is a
correlation between solubility in physiological solution and the
alkaline content of MMMF (Klingholz & Steinkopf, 1984;
Leineweber, 1984) and that fibres of fine diameter degrade more
rapidly than coarse ones (Spurny et al., 1983; Forster, 1984).

7. EFFECTS ON EXPERIMENTAL ANIMALS AND IN VITRO TEST SYSTEMS

There are several factors that should be considered when
evaluating experimental data on the biological effects of MMMF.
Most importantly, MMMF should not be considered as a single
entity, except in a very general way. There are substantial
differences in the physical and chemical properties (e.g., fibre
lengths and chemical composition) of the fibres, even within
each of the broad classes of MMMF (continuous filaments,
insulation wools, refractory fibres, and special purpose
fibres), and it is expected that these would be reflected in
their biological responses. Finally, the fibres used for
specific research protocols may be altered to fit the needs of
the study, and the results may not necessarily represent the
true biological potential of the parent material. Therefore,
the potential "toxicity" of each fibrous material must be
evaluated individually.

Notwithstanding the above comments, there are certain
characteristics of MMMF (and other fibres) that are important
determinants of effects on biological systems. The most
important of these appear to be fibre size (length, diameter,
aspect ratio), in vivo persistence^a and durability^a, chemical
composition, surface chemistry, and number or mass of fibres
(dose). In addition, it is imperative to understand that each of
the above characteristics cannot be viewed in isolation from the
others. For example, it is clear that two types of fibres of
identical dimensions could react differently within the host if
they differ in one of the other characteristics. Some of the
apparently inconsistent experimental results of studies reported
in this section may be a function of these factors.

Other considerations relate to the extrapolation of
experimental findings for hazard assessment in man. It appears
that if a given fibre comes into contact with a given tissue in
animals producing a response, a similar biological response
(qualitative) might be expected in human beings under the same
conditions of exposure. There is no evidence that the biological
reaction of animals and human beings differ. However, there may
be quantitative differences between species, some being more
"sensitive" than others.
-----------------------------------------------------------------------------
^a The term persistence refers to the ability of a fibre to
stay in the biological environment, where it was introduced.
The term is of particular use in inhalation and intra-
tracheal instillation studies, because a large percentage of
the fibres that reach the lung are removed by the muco-
ciliary apparatus and relatively few are retained (persist).
The length of time that MMMF persist in the tissue is also a
function of their durability, which is directly related to
their chemical composition and physical characteristics.
The term solubility, as used here, relates to the behaviour
of MMMF in various fluids. In general, the term solubility
is more appropriate for use in in vitro than in in vivo
studies, because, in tissue, the degradation of fibres is a
function of phenomena more than just their solubility.

There has been a great deal of debate concerning the
"relevance" of various routes of exposure in experimental animal
studies to hazard assessment in man. The advantages and
disadvantages of each of these routes are discussed in the
following sections. It was the consensus of the Task Group that
administration by each route has its place in the study of
fibre toxicity, but that it is inappropriate to draw conclusions
on the basis of the results by one route of administration only.
This does not mean that all routes are required for the study of
the toxicity of a given fibre.

Each route cannot be discussed in detail here, but some
general observations can be made. First, positive results of an
inhalation study on animals have important implications for
hazard assessment in man. Strong scientifically based arguments
would need to be made to dissuade one from the relevance of such
a finding to man. Conversely, a negative inhalation study does
not necessarily mean that the material is not hazardous for
human beings, unless it is clear that the number of fibres that
actually reached the target tissue (in this case the lung) was
comparable to the positive control. Rats, being obligate nose
breathers, have a greater filtering capacity than human beings.
However, if it were demonstrated that the "target tissue" was
adequately exposed and that a biologically important response
was not noted, then such a result would be of value for hazard
assessment in human beings.

In contrast to inhalation studies, a negative result in a
properly conducted intratracheal study would suggest that a
given type of fibre may not be hazardous for parenchymal lung
tissue. A positive result, in such a case, would require
further study before assessing the hazard for man, since the
normal filtering capacity of the respiratory tract has been
bypassed, and there is often a non-random distribution in the
lung, i.e., "bolus" effect. In other words, in intratracheal
instillation studies, the lung can be exposed to material with
which it normally would never come into contact. However,
pulmonary clearance mechanisms are still intact, though their
efficiency may be compromised.

The results of studies involving intrapleural instillation
(injection or implantation) and intraperitoneal injection
should be viewed in a similar way to those of investigations
involving intratracheal instillation studies. With these
methods, both filtering and clearances mechanisms are compromised.
However, such studies may be more "sensitive" than inhalation
studies, because a higher number of fibres (> 1.0 µm in dia-
meter) can be introduced than can be in conventional inhalation
studies. Therefore, a negative result in such a case would be
highly relevant in terms of hazard assessment. In contrast, a
positive result should be confirmed by further investigation
involving other routes of exposure before indicting the parti-
cular type of fibre as a human hazard in terms of the tissue
involved (mesothelioma). It should be noted that both of these

routes are primarily relevant to the mesothelium and do not
necessarily predict what happens in the pulmonary parenchyma or
airways.

In vitro short-term studies, e.g., cytotoxicity, cyto-
genicity, and cell transformation studies, have been, and are,
important in understanding the mechanisms of action of fibres.
The results of such studies are of value in the overall assess-
ment of fibre toxicity but should not be used alone for hazard
assessment.

Solubility^a studies play an important part in the under-
standing of the behaviour of fibres behave in various media.
However, several of the mechanisms that determine the persis-
tence of fibres in biological tissues are not taken into
account. Therefore, while an important adjunct in the overall
study of fibres, they are of less importance in hazard
identification.

While it is not the purpose of this publication to outline a
specific set of protocols for the study of the biological
effects of newly developed MMMF, it may provide some guidance
concerning those aspects that should be addressed in experi-
mental studies to investigate the potential toxicity of fibres.

7.1. Experimental Animals

7.1.1. Inhalation

Exposure conditions in inhalation studies approach most
closely the circumstances of human exposure and are most
relevant for the assessment of risks for man. Information on
the design and results of studies in which animals were exposed
to MMMF by inhalation is summarized in Table 17. Such
investigations have been conducted on several species including
the rat, mouse, hamster, guinea-pig, and baboon.

----------------------------------------------------------------
^a The term solubility, as used here, relates to the behaviour
of MMMF in various fluids. In general, the term solubility
is more appropriate for use in in vitro than in in vivo
studies, because, in tissue, the degradation of fibres is a
function of phenomena more than just their solubility.

Table 17. Inhalation studies
--------------------------------------------------------------------------------------------------------
Species Number Protocol Results and comments Reference
--------------------------------------------------------------------------------------------------------
Male A-strain 12 animals each 300 mg crushed "fibreglass Neoplastic, hyperplastic, Morrison
mouse in 3 treatment insulation" (80% of fibres and metaplastic lesions in et al.
groups; 12 were 2.5 µm wide and 6 - 11 the bronchi and near the (1981)
vehicle- and µm long), in bedding, every bronchiole-alveolar junc-
12 unexposed 3 days, for 30 days; 3 days tions in the lung; admini-
control animals later, ip administration of stration of either or both
either retinyl palmitate (50 vitamins resulted in signi-
mg/kg body weight), ascorbic ficantly fewer neoplastic
acid (400 mg/kg body weight), and hyperplastic lesions;
or both; animals sacrificed slightly higher number of
90 days after first expo- metaplastic nodules in group
sure to fibrous glass exposed to retinyl palmitate;
control animals had 5 times
as many particles in the lung
as the vitamin-exposed groups;
limited number of animals; no
control group exposed to air
only; incidence not reported;
administered material not
well characterized

Male albino 20 animals each Exposure to glass fibres at No lung damage in animals Moriset
mouse of in 3 treatment 1070 fibres/cc (87% of fibres exposed to fibrous glass et al.
the Cobs groups; 20 < 8 µm in length and 100% < alone; change in the cell- (1979)
strain control 3 µm in diameter); styrene ularity of the bronchiolar
(Charles animals (300 ppm), fibrous glass lining where apocrine cells
River, (1070 fibres/cc) plus sty- became predominant in animals
CDR-1) rene (300 ppm), or filtered exposed to glass fibres and
air (controls), 5 h/day, 5 styrene; this type of change
days/week, for 6 weeks found in 10% of styrene-
exposed mice while most of
the animals (90%) had thick-
ened bronchiolar walls
because of stratification of
the bronchiolar epithelium;
authors concluded that the
glass fibres were biologi-
--------------------------------------------------------------------------------------------------------

Male Charles rats (46), Exposure to 0.7 x 10⁶ Unlike the other fibrous Lee et
River/Sprague guinea-pigs fibres/litre (> 5 µm) glass dusts administered (asbestos, al. (1981)
Dawley rat, (32), fibres (0.4 mg/litre), 6 h/ Fybex, and PKT), fibrous
albino male hamsters (34) day, 5 days/week, for 90 glass was not fibrogenic;
guinea-pig, days; animals sacrificed at some alveolar proteinosis,
and hamster 20, 50, or 90 days of expo- which had cleared after 2
sure and at 6, 12, 18, or years; authors concluded that
24 months after exposure fibrous glass satisfies
criteria for a "biologically
inert" dust; 18 months and
2 years after exposure, 2/19
exposed rats had bronch-
iolar adenomas compared with
0/19 control animals; how-
ever, numbers were too small
to draw meaningful conclu-
sions concerning carcino-
genicity; study not well
described; limited number of
animals and short exposure
and observation periods

SPF Fischer 2 exposed Exposure to glass fibre All fibres produced variable Johnson &
rat animals; (JM 100), rock wool, resin- degrees of focal fibrosis, Wagner
2 control coated glass wool, uncoated type II alveolar cell pro- (1980)
animals glass wool, or air, at 10 liferation, accumulation of
mg/m³ for 7 h/day, 5 days/ cellular debris and lipid
week, over 50 weeks; animals material and hyperplasia of
sacrificed 4 months after both alveolar cells and cells
inhalation; lung tissue lining the terminal airways;
examined by electron micro- fibrosis less marked than for
scopy UICC chrysotile B; uncoated
glass wool more reactive than
coated variety; very small
number of exposed and control
animals

Rat and 30 in each of Exposure to fibrous glass No discernable differences Gross
hamster the treatment (uncoated, coated with in tissue reactions for et al.
(strains groups; 20 phenol-formaldehyde resin, the 3 different types of fib- (1970)
unspecified) controls for or starch binder) (average rous glass; pulmonary res-
each species diameter, 0.5 µm; average ponse characterized by rel-
length, 10 µm), at _~100 mg/m³ atively small accumulation
6 h/day, 5 days/week, over of macrophages without signi-
24 months; animals sacri- ficant stromal change; authors
ficed at 6, 12, and 24 conclude that fibrous glass
months; intratracheal "biologically inert"
injection of 1 - 10 doses of
3.5 mg of the same dusts in
150 rats and 60 hamsters
--------------------------------------------------------------------------------------------------------

Charles River Not reported Exposure to 0.42 mg/litre At 90 days, macrophage reac- Lee et
CD Sprague (0.73 x 10⁶ fibres/litre > tion with alveolar protein- al. (1979)
Dawley 5 and < 10 µm; average dia- osis, which had disappeared 1
derived male meter, 1.2 µm) glass fibre, year after exposure; ferrug-
rat, albino 6 h/day, 5 days/week, for 90 inous bodies in hamsters and
male days; animals sacrificed at guinea-pigs; study not well
guinea-pig, periods of up to 2 years described; short exposure and
and Syrian after exposure observation periods
male
hamster

Inbred male Unspecified Repeated pulmonary lavage in Profound effects on alveo- Miller
BD-IX rat number in animals exposed to 1340 lar macrophages (similar (1980)
treatment fibres/cm³ JM reference C102 to those observed for croci-
and control glass fibres (diameter, 0.1 - dolite); however, temporal
groups 0.6 µm; length, 5 - 100 µm), variation in the effects ob-
7 h/day, 5 days/week, for served following pulmonary
6 months lavage (Sykes et al., 1983).

Male baboon 10 animals in Exposure to 7.54 mg/m³ (1122 Fibrosis was slightly more Goldstein
(Papio total; number fibres/cc > 5 µm) of JM C102 marked after 18 and 30 et al.
ursinus) in treated or and C104 fibrous glass 7 h/ months exposure; also pre- (1983,
control groups day, _~5 days/week, for up sent in post-exposure biop- 1984)
unspecified to 35 months; lung biopsy sies; changes similar to those
at intervals (material avail- observed for UICC crocidolite
able for study at 8, 18, (15.83 mg/m³ - 1128 fibres/cc
and 30 months and 6, 8, and > 5 µm) but less severe; no
12 months after exposure) evidence of malignancy;
authors suggested that con-
trary results of others might
be due to the diameter of the
fibre and species of the ex-
erimental animal; small num-
ber of animals and incidence
in control group not reported;
short exposure period in rela-
tion to life span of the
animal

Albino rat 50 animals in Exposure to 2.18 mg/m³ (mean Pulmonary reaction to both Pigott
of the each of the respirable dust) Saffil alu- forms of Saffil was minimal et al.
Alderley treatment mina fibres (aluminum oxide (generally confined to the (1981)
Park (Wistar groups; refractory fibre containing presence of groups of pig-
derived 50 controls about 4% silica), 2.45 mg/m³ mented alveolar macrophages);
strain) thermally aged Saffil or air no pulmonary neoplasms;
(median diameter, _~3 µm; authors concluded that Saffil
median length, 10.5 - 62 µm) may be regarded as a nuisance
for 6 h/day, 5 days/week, type dust, but acknowledged
for 86 weeks; animals sac- that the levels of respirable
rificed at 14, 27, or 53 dust in the atmosphere were
weeks and at 85% mortality low

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

Table 17. (contd.)
--------------------------------------------------------------------------------------------------------
Species Number Protocol Results and comments Reference
--------------------------------------------------------------------------------------------------------
SPF Fischer 56 animals in Exposure to rock wool with- Evidence of reaction to the Wagner
rats each of the out resin (227 fibres/cc; dust in all exposed groups et al.
treatment diameter < 3 µm; length, but less for MMMF than for (1984)
groups; > 5 µm), glass wool with- chrysotile; greater reaction
56 controls out resin (323 fibres/cc; with chrysotile at 12 months
diameter < 3 µm; length > than at 3 months, but little
5 µm), glass wool with resin change for MMMF; in chryso-
(240 fibres/cc; diameter < tile exposed group, 12 lung
3 µm; length > 5 µm), glass neoplasms (11 adenocarcinomas
microfibres (1436 fibres/cc; and 1 adenoma) and broncho-
diameter < 3 µm; length > alveolar hyperplasia (BAH) in
5 µm), UICC Canadian chryso- 5 animals (No. = 48); glass
tile (3832 fibres/cc; dia- microfibre - 1 pulmonary
meter < 3 µm; length > 5 µm) adenocarcinoma, BAH in 3 rats
at _~10 mg/m³, or to air, for (No. = 48); rock wool - 2
7 h/day, 5 days/week for 12 adenomas, BAH in 1 rat (No. =
months; animals sacrificed 48); glass wool with resin -
at 3, 12, or 24 months 1 pulmonary adenocarcinoma,
BAH in 3 rats (No. = 48);
glass wool without resin - 1
adenoma, BAH in 1 rat (No. =
47); controls - 0 neoplasms
and BAH in 1 rat (No. = 48);
incidence not specified

Fischer Group sizes at Exposure to Canadian chryso- At 3 months, minimal to mild McConnell
344 rat final sacrifice: tile or glass microfibres cellular changes in both et al.
47 - 55 in each (JM 100), at _~10 mg/m³ for glass microfibres (gm)- and (1984)
of the treatment 7 h/day, 5 days/week, for chrysotile (chrys)-exposed
groups; 48 - 53 12 months; life-time ob- rats, which progressed
controls servation with interim sac- througout the 12-month expo-
rifices at 3, 12, and 24 sure period - changes less
months; studies conducted in severe for gm- than for chrys;
2 laboratories (NIEHS and progression of changes in
MRC) chrys-exposed rats but not
in gm-exposed animals follow-
ing cessation of exposure;
increased incidence of pul-
monary neoplasia found only
in rats exposed to chrysotile
--------------------------------------------------------------------------------------------------------

Male Syrian Group sizes at exposure to 300 fibres/cc Life span of hamsters ex- Smith
hamster, final sacrifice: (_~0.3 mg/m³), or 3000 posed to glass fibres sig- et al.
female 47 - 60 hamsters fibres/cc (_~3 mg/m³) 0.45- nificantly longer than that (1984,
Osborne- in the treatment µm mean diameter glass of controls (with the excep- in press)
Mendel rat groups and 58 - fibres (no binder), 100 tion of those exposed to 3.1-
112 controls; fibres/cc (_~10 mg/m³) µm mean diameter fibres);
52 - 61 rats -µm mean diameter glass foci of fibre-containing
in each of fibres (silicone lubricant), macrophages for both species
the treatment 10 fibres/cc (_~1.2 mg/m³), exposed to glass fibres, but
groups and or 100 fibres/cc (_~12 "little fibrosis" (peri-
59 - 125 mg/m³) 5.4-µm mean dia- bronchiolar when observed);
controls meter glass fibres (binder- no tumours in MMMF-exposed
coated), 25 fibres/cc (_~9 animals with the exception
mg/m³) 6.1-µm mean dia- of a mesothelioma in 1 ham-
meter glass fibres (binder- ster exposed to 1.8-µm mean
coated), 200 fibres/cc diameter refractory ceramic
(_~12 mg/m³) 1.8-µm mean fibre; asbestosis in crocido-
diameter refractory ceramic lite-exposed hamsters and
fibre (no binder), 200 rats; no pulmonary tumours in
fibres/cc (_~10 mg/m³) crocidolite-exposed hamsters
2.7 µm mean diameter mineral (0/58), but 3/57 (5%) croci-
wool (no binder), 3000 dolite-exposed rats developed
fibres/cc (_~7 mg/m³) UICC lung neoplasms (compared with
crocidolite asbestos or air 0 in controls) (negative res-
(sham and unmanipulated con- ults in positive controls)
trols), nose-only, for 6 h/
day, 5 days/week, for 24
months; life-time observa-
tion
--------------------------------------------------------------------------------------------------------

Table 17. (contd.)
--------------------------------------------------------------------------------------------------------
Species Number Protocol Results and comments Reference
--------------------------------------------------------------------------------------------------------
SPF Wistar 48 exposed Exposure to fibrous ceramic Survival of treated and con- Davis
rats of animals and aluminum silicate glass at trol groups similar; inter- et al.
AF/HAN 40 controls _~10 mg/m³ (95 fibres/cc; stitial fibrosis in animals (1984)
strain diameter < 3 µm; length > exposed to ceramic fibres
5 µm), for 7 h/day, 5 occurred to a lesser, but not
days/week, for 12 months; significantly different, ex-
animals sacrificed at 12, tent than that for chryso-
18, or 32 months tile exposed animals; how-
ever, little peribronchiolar
fibrosis in ceramic fibre-
exposed rats; relatively
large numbers of pulmonary
neoplasms in rats exposed to
ceramic fibre (tumours in 8
animals - 1 benign adenoma, 3
carcinomas, and 4 malignant
histiocytomas) - no tumours
in control animals; pattern
of tumour development differ-
ent from that for asbestos;
large non-fibrous component
of exposure aerosol

SPF Fischer 32 exposed Exposure to glass micro- No significant gross or his- Pickrell
344 rat animals and fibres at 50 000 fibres/cm³, topathological changes et al.
32 controls for 5 - 6 h/day, for 2 or 5 (1983)
days; animals sacrificed at
1, 4, 5, 8, and 12 months
after exposure

Wistar IOPS 24 animals of Exposure to (respirable Simple alveolar macrophagic Le Bouffant
AF/HAN rat each sex in dust fraction) glass wool reaction with slight septal et al.
each treatment (Saint Gobain) at 5 mg/m³ fibrosis (rock and glass (1984, in
group; 24 (73% < 20 µm in length; 69% wool); for glass microfibre, press)
males and 24 < 1 µm in diameter), rock septal fibrosis slightly
females in wool (Saint Gobain) (40% more marked; 1 pulmonary
control group < 10 µm in length, 49% < 2 tumour (undifferentiated
µm in diameter), or glass epidermoid carcinoma) in
microfibre (JM 100) (94% glass wool-exposed male (0
< 5 µm in length, 43% < 0.1 in controls) compared with
µm in diameter), or Canadian 9 in chrysotile-exposed
chrysotile, for 5 h/day, 5 group; digestive tract
days/week, over 12 or 24 tumours (unspecified) in 4
months; animals sacrificed glass wool-exposed animals
at 0, 7, 12, and 16 months (0 in controls); small num-
after 1-year exposure and ber of exposed animals and
0 and 4 months after 2-year incidence not specified
exposure

Female 120 animals Exposure to 3 mg/m³ (252 Life span of rats exposed Mühle et
Wistar in glass fibre fibres/ml > 5 µm) glass to SO₂ alone reduced; no al. (in
rat (with or without fibres (JM 104/Tempstran significant increases in press)
SO₂)-exposed 475), 2.2 mg/m³ (162 fibres/ lung tumour incidence -
groups; 50 ml > 5 µm) crocidolite, 6 1 adenocarcinoma (croci-
animals in mg/m³ (131 fibres/ml > 5 µm) dolite-exposed group), 1
crocidolite-, Calidria chrysotile, glass squamous cell tumour
chrysotile-, fibres, and SO₂ (100 ppm) (glass fibre-exposed
or SO₂-exposed or SO₂ alone, nose-only, group), 1 adenoma (glass
groups; 50 for 5 h/day, 4 days/week, fibre-and SO₂-exposed
sham and 50 for 1 year group); bronchioalveolar
untreated hyperplasia in crocido-
controls lite- and combined glass
(5 - 12 fibre, SO₂-exposed groups
animals per and squamous metaplasia
group examined in 1 animal in each of the
for fibre crocidolite- and glass
retention) fibre-exposed groups;
negative results in posi-
tive control
--------------------------------------------------------------------------------------------------------

Table 17. (contd.)
--------------------------------------------------------------------------------------------------------
Species Number Protocol Results and comments Reference
--------------------------------------------------------------------------------------------------------
F-344 rat; 4 fibre-exposed Exposure for 7 h/day, 5 Pulmonary macrophage aggre- Mitchell
Male groups and 1 days/week; monkeys, 18 gates and granulomas con- et al.
cynomolgus air control months; rats, 21 months; taining glass fibres in (1986)
monkey with 100 rats Group 1: 4 - 6 µm diameter both species; pleural
and 15 monkeys glass fibre > 20 µm long plaques in rats but not
each with red binder (15 mg/m³); in monkeys; no evidence of
Group 2: 0.5 - 3.5 µm diam- pulmonary or mesothelial
eter glass fibre > 10 µm tumours or fibrosis in
long with yellow binder (15 either species
mg/m³); Group 3: < 3.5 µm
diameter glass fibre > 10 µm
long (5 mg/m³); Group 4:
< 3.5 µm diameter glass fibre
< 10 µm long (5 mg/m³)
--------------------------------------------------------------------------------------------------------
ppcf = particles per cubic foot.
MRC = Medical Research Council (United Kingdom).
NIEHS = National Institute for Environmental Health Sciences (USA).
SPF = Specific pathogen free.
7.1.1.1. Fibrosis

No evidence of fibrosis of the lung was observed in most of
the inhalation studies conducted to date on the mouse, rat,
guinea-pig, and hamster, exposed to concentrations of glass
fibres of up to 100 mg/m³ for periods ranging from 2 days to 24
months (Schepers & Delahunt, 1955; Gross et al., 1970; Lee et
al., 1979; Morriset et al., 1979; Lee et al., 1981; Pickrell et
al., 1983; Smith et al., 1984). In general, the tissue response
in these studies was confined to the accumulation of pulmonary
macrophages. However, reversible alveolar proteinosis was
reported in 2 rather limited studies by the same investigators
in which several species were exposed to relatively high concen-
trations of glass fibres (0.4 mg/litre) (Lee et al., 1979,
1981). In the more extensive investigations of McConnell et al.
(1984) and Wagner et al. (1984), in which rats were exposed to
glass microfibres at 10 mg/m³ for 12 months, "minimal inter-
stitial cellular reactions with no evidence of fibrosis" were
reported.

However, in contrast, Johnson & Wagner (1980) reported that
electron microscopic examination of the lung tissue of 2 rats
exposed to glass fibre, rock wool, resin-coated glass wool, or
uncoated glass wool at 10 mg/m³ for 50 weeks, revealed focal
fibrosis. In a limited study, Le Bouffant et al. (in press)
reported slight septal fibrosis that was a little more marked in
rats exposed to glass microfibre than in those exposed to rock
and glass wool. Fibrosis was also observed in baboons exposed
to 7.54 mg/m³ glass fibres for 35 months (Goldstein et al.,
1983). However, the incidence and severity in control animals
were not reported. Moreover, the fibrotic lesions observed in
this study were similar to those caused by lung mites (Pneumo-
nyssus sp.), commonly present in baboons from this geographical
area (McConnell et al., 1974). In a more recent study in which
cynomolgus monkeys were exposed for 18 months to up to 15 mg
glass fibres/m³ with mean diameters of 0.5 - 6 µm, the tissue
response was confined to accumulation of pulmonary macrophages
and granulomas (Mitchell et al., 1986).

In all cases, the tissue reactions in animals exposed to
fibrous glass or glass wool were much less severe than those
produced by exposure to equal masses of chrysotile or
crocidolite (Johnson & Wagner, 1980; Lee et al., 1981; Goldstein
et al., 1983; McConnell et al., 1984; Smith et al., 1984; Wagner
et al., 1984). Moreover, in contrast to fibrotic changes
resulting from exposure to asbestos, tissue responses did not
progress following cessation of exposure to these MMMF
(McConnell et al., 1984; Wagner et al., 1984).

Results concerning the effects of fibre coating on the
potential of fibrous glass or glass wool to cause lung-tissue
damage are limited and contradictory. Whereas Gross et al.
(1970) concluded that there were no discernible differences in
the tissue reactions for uncoated fibrous glass compared with

those for fibrous glass coated with phenol-formaldehyde resin or
starch binder, Johnson & Wagner (1980) concluded that uncoated
glass wool was more reactive than resin-coated varieties.

Pigott et al. (1981) reported minimal pulmonary reaction
(generally confined to the presence of groups of pigmented
alveolar macrophages) in rats exposed for 86 weeks to relatively
low concentrations of normal or thermally aged aluminium oxide
refractory fibres containing about 4% silica (mean respirable
dust concentrations of 2.18 and 2.45 mg/m³, respectively; median
fibre diameter, 3.3 µm). However, it should be noted that the
median fibre diameter of the material is relatively large.
Davis et al. (1984) reported that interstitial fibrosis occurred
to a lesser extent in rats, exposed for 12 months to fibrous
ceramic aluminium silicate glass at 10 mg/m³ (with a rather
large non-fibrous component in the aerosol), than in chrysotile-
exposed animals. In contrast, Smith et al. (1984, in press) did
not find any fibrosis in hamsters and rats exposed to 12 mg/m³
refractory ceramic fibres (with about twice the airborne fibre
concentration) for a period of 2 years.

With respect to the fibrogenic effects of combined exposure
to MMMF and other airborne pollutants, Morriset et al. (1979)
concluded that, though glass fibres appeared to be biologically
inert in their study (possibly because they were in a
nonpathogenic size range), the presence of these fibres enhanced
the toxic effects of styrene in mice (possibly because of the
absorption of styrene on the fibre surface).

The discrepancies in the results of different investigations
concerning the severity of tissue response following inhalation
of glass and ceramic fibres may be the result of variation in
fibre size distribution. For example, Johnson & Wagner (1980)
suggested that the fibrotic changes observed in their study
might have been due to the fact that their samples contained a
greater proportion of fibres longer than 5 µm than those of
other investigators. However, it is difficult to draw general
conclusions in this regard because of inconsistencies in the
characterization of the airborne fibre size distributions and in
doses administered in different studies.

7.1.1.2. Carcinogenicity

In none of the inhalation studies conducted to date has
there been a statistically significant excess of lung tumours in
animals exposed to glass fibres (including glass microfibres) or
rock wool. However, there have only been a few relevant studies
(Gross et al., 1970, 1976; Lee et al., 1981; McConnell et al.,
1984; Wagner et al., 1984; Le Bouffant et al., in press; Mühle
et al., in press; Smith et al., in press), and group sizes at
termination in several of these investigations were small by
current standards. However, in several of the relevant studies,
there were small, but not statistically significant, increases
in tumour incidence in exposed animals. For example, 2/19

(10.5%) Sprague Dawley rats exposed for only 90 days to fibrous
glass at 0.4 mg/litre had bronchiolar adenomas 2 years after
exposure, compared with none in the control group (Lee et al.,
1981). Similarly, there were 1 - 2 neoplasms (2.1 - 4.2%) in
each group of Fischer rats exposed to rock wool (with or without
resin), glass wool, or glass microfibre at 10 mg/m³ for 12
months, compared with none in the controls (Wagner et al.,
1984). No mesotheliomas have been observed in animals exposed
to glass fibres or rock wool by inhalation; moreover, in most of
the carcinogenicity bioassays conducted to date, similar mass
concentrations of chrysotile asbestos have been far more potent
in inducing lung tumours than these MMMF (Lee et al., 1981;
McConnell et al., 1984; Wagner et al., 1984; Smith et al.,
in press). However, data are not sufficient to draw conclusions
concerning the relative potency of various fibre types, because
the concentration of respirable fibres was not reported in many
of these studies.

Morrison et al. (1981) reported "neoplastic, hyperplastic,
and metaplastic lesions in the bronchi and near the bronchio-
alveolar junctions of the lung" in 12 A strain mice sacrificed
90 days after exposure to 300 mg "crushed fiberglass insulation"
(80% of fibres 2.5 µm wide) in bedding, every 3 days for 30
days. However, it is difficult to assess the results of this
study, since there was no control group exposed to air only. In
addition, only the total number of lesions, rather than the
incidence, was specified and the administered material was not
well characterized. Furthermore, these results seem
inconsistent with those of other investigators, particularly in
view of the relatively short exposure period and the small
number of exposed animals.

Pigott et al. (1981) reported the absence of pulmonary
neoplasms in 50 Wistar-derived Alderley Park rats exposed for 86
weeks to relatively low mean respirable dust concentrations of
normal or thermally aged aluminium oxide refractory fibre
containing about 4% silica at 2.18 and 2.45 mg/m³, respectively.
Davis et al. (1984) reported "relatively large numbers of
pulmonary neoplasms" in Wistar rats of the Han strain exposed
for 12 months to fibrous ceramic aluminium silicate glass at
10 mg/m³. Pulmonary neoplasms (3 carcinomas and 1 adenoma)
developed in 8/48 exposed animals (16.6%). However, in 4 of the
animals, the tumours were malignant histiocytomas; these
neoplasms have not generally been associated with asbestos
exposure. There was also one peritoneal mesothelioma in another
animal in the exposed group (the non-fibrous content of the
exposure aerosol in this study was relatively large).

In Syrian golden hamsters exposed to approximately 12 mg
"refractory ceramic fibres"/m³ (200 fibres/cc) for 2 years,
there was a single malignant mesothelioma. However, no other
primary lung tumours were observed in 51 animals surviving the
exposure period, and no primary lung tumours were observed in
similarly exposed Osborne-Mendel rats. It should be noted,

though, that only 3 of the 57 rats and none of the 58 hamsters
that survived the exposure period following inhalation of
3000 fibres/cm³ of crocidolite for 2 years developed lung
tumours in this study (Smith et al., in press).

7.1.2. Intratracheal injection

Administration by the intratracheal route does not simulate
the exposure of man, since an uneven dose of fibres is
artificially deposited in the respiratory tract. For example,
the production of fibrous granulomas in such studies may be a
function of "bolus" events and might not be observed in
inhalation studies where fibre deposition is more diffuse.
Although this limitation must be borne in mind in interpreting
the results of intratracheal studies, such investigations have
confirmed the effects of MMMF observed following inhalation and
have provided additional information on the importance of fibre
size in the pathogenesis of disease. The results of available
studies involving intratracheal administration of MMMF are
presented in Table 18. For example, following intratracheal
administration of uncoated or coated glass fibres (1 - 10 doses
of 3.5 mg) to rats, Gross et al. (1970) observed reversible
polyploid proliferative lesions, but no alveolar fibrosis. For
hamsters, the tissue reaction was similar with the exception
that diffuse, bland, acellular collagenous pleural fibrosis was
also observed. Pickrell et al. (1983) observed proliferation of
bronchioalveolar epithelial cells, chronic inflammation of the
terminal bronchioles and alveolar ducts, and slight pulmonary
fibrosis following intratracheal administration of glass
microfibres to Syrian hamsters (total dose, 2 mg; count median
diameter, 0.2 µm). Fibrosis was not observed in animals
exposed in a similar manner to 2 instillations of 3 types of
glass fibre "household insulation" (total dose, 17 - 21 mg;
count median diameters, 2.3 - 4.1 µm). A dose-related trend
was reported by Renne et al. (1985) in the incidence of alveolar
septal fibrosis in hamsters exposed by the intratracheal route
to 15 weekly doses (0.05 - 10 mg) of fibrous glass with a median
fibre diameter and length of 0.75 and 4.30 µm, respectively.
The authors reported that the pulmonary response to quartz alone
and to quartz in combination with ferric oxide was considerably
more severe than that to fibrous glass. Drew et al. (in press)
reported a granulomatous foreign body response following intra-
tracheal instillation of a single dose of 20 mg of "long"
(nominal diameter and length, 1.5 µm x 60 µm) and "short"
(1.5 µm x 5 µm) glass fibres in rats, which they attributed to
the administration technique. However, following 10 weekly
instillations of 0.5 mg, only a macrophage response was
elicited. In contrast, a much more severe pulmonary response
accompanied by fibrosis resulted from exposure to crocidolite.

Table 18. Intratracheal injection studies
--------------------------------------------------------------------------------------------------------
Species Number in groups Protocol Results and comments Reference
--------------------------------------------------------------------------------------------------------
Rat, 12 - 30 animals Injection (1 - 10 doses) of Rats: reversible polyploid Gross et al.
hamster per test group; 3.5 mg uncoated or coated proliferative lesions but (1970)
20 controls (phenol-formaldehyde resin but no alveolar fibrosis;
of each species or starch binder) "glass hamsters: tissue reaction
fibres" (length < 50 µm) similar to that observed in
rats, except that diffuse,
bland acellular collagenous
pleural fibrosis also seen;
observation period not re-
ported; controls not held
under same conditions as
test group

Male Syrian 20 animals per Instillation of (2 doses) of Glass microfibres produced Pickrell
hamster test group; 2 - 21 mg of one of 2 types proliferation of bronchio- et al.
(Charles 30 controls of "bare glass" or 3 types alveolar epithelial cells, (1983)
River of "household insulation"; chronic inflammation of the
Sch:(SYR)) count median diameters terminal bronchioles and
ranged from 0.1 to 4.1 µm; alveolar ducts, and slight
animals sacrificed at 1, pulmonary fibrosis; no
3.5, and 11 months fibrosis after instillation
of the "household insulation"

Male Syrian 25 animals each Instillation (15 weekly Dose-related trend in the Renne
golden in test, saline, doses of 0.05 - 10 mg incidence of alveolar sep- et al.
hamster and cage control fibrous glass with mean tal fibrosis; the pulmonary (1985)
Lak:LVG groups diameter and length of response to quartz and ferric
0.75 and 4.30 µm, respec- oxide was considerably more
tively; animals maintained severe
until 28% survival in each
group or until 24.5 months
of age

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

Table 18. (contd.)
--------------------------------------------------------------------------------------------------------
Species Number in groups Protocol Results and comments Reference
--------------------------------------------------------------------------------------------------------
SPF Fischer 50 animals per Instillation of 20 mg of A single instillation of Drew
344 male test and short (nominal diameter short or long fibres pro- et al.
rat control groups and length, 1.5 x 5 µm) duced a granulomatous for- (in press)
and long (1.5 x 60 µm) eign body response, whereas
glass fibres or 10 weekly weekly instillations eli-
instillations of 0.5 mg cited only a macrophage res-
glass fibres ponse; severe pulmonary res-
ponse with fibrosis after
exposure to crocidolite

Guinea-pig 5 - 8 animals per Instillation of 0.5 cc of Severity of the tissue Schepers &
test and control 0.5% (1 group) of 5% (2 reaction (no fibrosis) Delahunt
groups mean diameters of 6, 3, inversely proportional (1955)
and 1 µm to the fibre diameter

Guinea-pig 30 animals per Instillation (2 - 8 doses) Tissue reaction varied with Kuschner &
test and control of "short" (< 5 µm) and fibre length, with fibrosis Wright
groups "long" (> 10 µm) glass resulting only following (1976);
fibres; total doses of 12 instillation of "1 mg" Wright &
and 25 mg, respectively Kuschner
(1977)

Male Syrian 136 or 138 8 weekly instillations of Incidence of lung carcinomas Mohr
golden animals per 1 mg JM 104 (wet milled) was slightly less than that et al.
hamster test group glass fibre, 50% with of animals exposed to UICC (1984)
diameters < 3 µm; animals crocidolite; however, the
observed up to week 130 incidence of sarcomas
(thorax) and mesotheliomas
was greater in glass fibre-
exposed animals; not con-
firmed in investigations in
other laboratories
--------------------------------------------------------------------------------------------------------

Table 18. (contd.)
--------------------------------------------------------------------------------------------------------
Species Number in groups Protocol Results and comments Reference
--------------------------------------------------------------------------------------------------------
Female 34 animals per Instillation of 0.05 mg Lung tumours in 5/34 animals Pott
Wistar test and control (20 doses of JM 104/ (1 adenoma), 2 adenocarcin- et al.
rat groups Tempstran 475 glass fibres omas, and 2 squamous cell (1987)
(Wistar- (50% with lengths and carcinomas); 9 lung carcin-
Wll/ diameters < 3.2 µm and omas and 8 mesotheliomas in
KiBlegg) 0.18 µm, respectively) 142 animals with similar
exposure to crocidolite
(length < 2.1 µm; diameter
< 0.2 µm for 50% of fibres)

Syrian 35 animals of Instillation of 1 mg, every "Glass fibre granulomas", Reuzel
golden each sex per 2 weeks, for 52 weeks, of but no tumours and no indi- et al.
hamster test and control 1 glass fibres (88% with cation that the glass (1983);
groups diameters < 1 µm; 58% with fibres enhanced respiratory Feron
lengths < 5 µm); animals tract tumours induced by et al.
observed for up to week 85 benzo( a )pyrene (26 doses (1985)
of 1 mg glass fibres and
1 mg benzo( a )pyrene); no
tumours observed in posi-
tive (crocidolite-exposed)
control group

Osborne- 22 - 25 animals Instillation of 2 mg of For refractory ceramic Smith et al.
Mendel in test groups either glass fibre (mean fibre, significant reduc- (in press)
rat at final diameter, 0.45 µm) or tion in the life span of
and Syrian autopsy; 24 - 1.8-µm mean diameter re- hamsters (479 days compared
golden 25 saline fractory ceramic fibre, with 567 days in vehicle
hamster controls and once a week, for 5 weeks; controls) and a chronic
112 - 125 cage life-time observation inflammatory response in
controls at the lungs of rats (probably
final autopsy due to deposition of large
quantities of foreign mat-
erials); fibrosis in rats
exposed to 0.45-µm mean
diameter glass fibres; no
pulmonary tumours in hamsters
or rats exposed to either
fibre; pulmonary tumours in
8% (rats) and 7.4% (hamsters)
exposed to crocidolite
-----------------------------------------------------------------------------------------------------------------------------
In a study conducted as early as 1955, it was reported that
the severity of the tissue reaction (no fibrosis) following
intratracheal administration of 3 samples of glass fibres (three
0.5-cc doses of 0.5% (1 group) or 5% (2 groups) solutions) was
inversely proportional to fibre diameter (mean values, 6 µm,
3 µm, and 1 µm) (Schepers & Delahunt, 1955). Kuschner &
Wright (1976) observed that the severity of tissue reaction
following intratracheal administration of glass fibres (2 - 8
instillations of 12 - 25 mg) to guinea-pigs varied with fibre
length, with fibrosis resulting only from exposure to samples
containing fibres mainly longer than 10 µm (Wright & Kuschner,
1977).

Mohr et al. (1984) found that the incidence of lung
carcinomas in Syrian golden hamsters following a rather unusual
intratracheal administration technique involving weekly instil-
lations of relatively low doses of fibres (8 weekly doses of
1 mg each of wet-milled JM 104 glass fibres, 50% with diameters
< 0.3 µm) was slightly less than that for animals exposed to
intratracheal administration technique involving weekly instil-
lations of relatively low doses of fibres (8 weekly doses of
1 mg each of wet-milled JM 104 glass fibres, 50% with diameters
< 0.3 µm) was slightly less than that for animals exposed to
UICC crocidolite. Surprisingly, the incidence of sarcomas
(thorax) and mesotheliomas was greater in the glass fibre-
exposed animals. It has been suggested by the authors that these
results might be attributable to the relatively short fibre
lengths of the UICC crocidolite (Pott et al., 1987). In a more
recent but similar study in the same laboratory, lung tumours (1
adenoma, 2 adenocarcinomas, 2 squamous cell carcinomas) were
observed in 5 out of 34 female Wistar rats receiving 20 weekly
applications of 0.05 mg each of JM 104/Tempstran 475 glass
fibres (50% of fibre lengths < 3.2 µm; 50% of fibre diameters
< 0.18 µm) (Pott et al., 1987). In rats exposed to similar
doses of crocidolite on the same schedule (50% of fibre lengths
< 2.1 µm; 50% of fibre diameters < 0.20 µm), lung carcinomas
were observed in 9 and mesotheliomas in 8 out of a total of 142
animals examined.

These results concerning the carcinogenicity of intra-
tracheally administered glass fibres have not been confirmed in
other laboratories. For example, Reuzel et al. (1983) and Feron
et al. (1985) reported "glass fibre granulomas", but no tumours,
in hamsters receiving intratracheal instillations of 1 mg glass
fibres (88% of fibre diameters < 1 µm and 42% > 5 µm length),
once every 2 weeks, for 1 year; moreover, there was no indica-
tion that glass fibres enhanced the development of respiratory
tract tumours induced by benzo( a )pyrene (26 doses of 1 mg glass
fibres and 1 mg benzo( a )pyrene). However, it should be noted
that no tumours were observed in the positive controls (i.e.,
the crocidolite-exposed group). The strain of animals and the
form of glass fibre administered in this study were similar to
those used by Mohr et al. (1984). Feron et al. (1985) suggested
that the discrepancies between the results of the 2 investiga-
tions might be attributable to the differences in the length of
the observation periods (85 weeks compared with 113 weeks in the

Mohr et al. (1984) study) or to the effects of prolonged
repeated dosing (i.e., disturbance of fibres by acute pulmonary
reaction after each of the 26 doses). Kuschner (in press)
suggested that the difference might be due to different
instillation techniques.

In an additional study by Smith et al. (in press), the mean
life span of 25 hamsters receiving 2 mg of 1.8-µm mean diameter
refractory ceramic fibre, intratracheally, once a week, for 5
weeks, was significantly reduced (479 days compared with 567
days in vehicle controls). However, no pulmonary tumours were
observed in the hamsters or in rats receiving either 0.45-µm
mean diameter glass fibres or 1.8-µm mean diameter refractory
ceramic fibre, on a similar schedule. Two out of 25 rats (8%)
and 20 out of 27 hamsters (74%) similarly exposed to crocidolite
developed pulmonary tumours. Pulmonary response to the various
types of MMMF in this investigation was restricted to a chronic
inflammatory reaction in rats exposed to the ceramic fibre
(believed to be due to deposition of large quantities of foreign
materials in the lung) and fibrosis in the same species exposed
to glass fibres with a mean diameter of 0.45 µm.

7.1.3. Intrapleural, intrathoracic, and intraperitoneal
administration

Although introduction of mineral fibres into the pleura and
peritoneum of animal species does not simulate the route of
exposure of man, such studies have made it possible to clarify a
number of questions that could not feasibly have been investi-
gated using the inhalation model. Studies involving intrapleural
or intraperitoneal injection also serve as useful screening
tests to develop priorities for further investigation. Both
have been used to assess the potential for fibres to induce
mesothelioma, when placed in contact with a target tissue. In
addition, the fibrogenic potential of both particles and fibres
has been examined in studies involving intraperitoneal injection
and short observation periods. However, factors that affect
fibre deposition and translocation, and defence mechanisms that
determine retention of fibres within the lung are not taken into
consideration in this experimental model and these disadvantages
must always be borne in mind in interpreting the results of
such studies.

Both fibrosis and malignant tumours have resulted following
the implantation of various types of MMMF into the pleural,
thoracic, or peritoneal cavities of various species; the results
of the relevant studies are summarized in Table 19. These
investigations have been most important in focusing attention on
the role of fibre size and shape in the induction of disease.
For example, in studies by Davis (1972, 1976), intrapleural
injection of long-fibred samples of fibrous glass produced
massive fibrosis, while short-fibred samples produced only
discrete granulomas with minimal fibrosis. In 1972, on the
basis of their study involving intrapleural implantation of 17
fibrous materials (including 6 types of fibrous glass) in rats,

Stanton & Wrench (1972) 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". In subsequent studies by the same authors, involving
intrapleural implantation of numerous dusts including fibrous
glass, it was found that the probability of development of
pleural sarcomas was best correlated with the number of fibres
with diameters of less than 0.25 µm and lengths greater than
8 µm (Stanton et al., 1977, 1981; Stanton & Layard, 1978).
However, probabilities were also "relatively" high for fibres
with diameters < 1.5 µm and lengths > 4 µm. On the basis of
an extensive series of studies involving intraperitoneal
administration to rats of asbestos, fine glass fibres, and
nemalite, Pott (1978) hypothesized a model in which the carcino-
genic potency of fibres is a continuous function of length and
diameter. Based on the results of further studies, which
indicated that tumour incidence for long, thin, nondurable
fibres was less than that for durable fibres in the same size
range, Pott et al. (1984) concluded that carcinogenicity is
also a function of the durability of fibres in the body.

In general, chrysotile has been more potent than equal
masses of glass fibres in inducing tumours following intra-
pleural injection (Monchaux et al., 1981; Wagner et al., 1984).
However, the potency of glass fibres varies markedly as a
function of fibre size distribution; intraperitoneal administra-
tion of continuous glass filament with mean diameters of 3, 5,
and 7 µm did not increase tumour incidence (Pott et al., 1987).
On the basis of studies involving intrapleural injection of
rock-, slag-, or glass wool or glass microfibres, it also
appears that tumour incidence is roughly proportional to the
number of fibres injected (Wagner et al., 1984). In a recent
study, in which actinolite and a basalt wool that contained
equal numbers of fibres (length > 5 µm) were administered to
rats, tumour incidence was similar, though the diameters
differed by an order of magnitude (0.1 µm versus 1.1 µm) (Pott
et al., in press). However, it should be noted that the fibre
length distributions were substantially different as was the
mass injected.

Table 19. Intrapleural, intrathoracic, and intraperitoneal administration
--------------------------------------------------------------------------------------------------------
Species Number in groups Protocol Results and comments Reference
--------------------------------------------------------------------------------------------------------
SPF Sprague 8 groups of 48 Intrapleural injection of Mesotheliomas in 6 (12.5%) Wagner
Dawley rat animals each; 20 mg respirable samples of chrysotile-exposed rats, et al.
24 controls of uncoated and resin- 4 (8.3%) exposed to glass (1984)
coated Swedish rock wool, fibres, 3 (6.25%) exposed to
German slag wool, and Eng- rock wool with resin, 2 (4.2%)
lish glass wool, American exposed to rock wool without
glass microfibres (JM 100), resin, 1 (2.1%) exposed to
and chrysotile; number of glass wool, and none exposed
fibres > 5 µm ranged from to slag wool; tumour incidence
1.2 x 10⁸ to 4.2 x 10⁸; roughly proportional to number
value for chrysotile, of fibres injected
196 x 10⁸

Wistar and ~50 animals; Intraperitoneal administra- Tumour incidence varied Pott
Sprague 50 controls tion of 2 - 10 mg different from none (rock wool) to et al.
Dawley rat preparations of glass micro- 73% (JM 104, 1-h ball (1984)
fibres (JM 100, 104), bas- milling); carcinogenicity
alt wool, rock wool, and reduced by HCl and NaOH
slag wool, and chemically
treated (HCl or NaOH) glass
microfibres (JM 104)

SPF Wistar 32 animals in Intraperitoneal injection of Tumours in 3 (9.3%) animals Davis
rat of the exposed group 25 mg fibrous ceramic alum- (compared with 90% in chrys- et al.
AF/HAN inium silicate glass otile-exposed animals); (1984)
strain first tumour occurred _~850 days
after injection compared with
200 days for chrysotile (con-
trasts with the results of
inhalation study); no concur-
rent control group

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

Sprague 10 groups of 10 Exposure to 3000 WL radon/ Proportion of lung cancer Bignon
Dawley rat animals inhaling day, for 10 h/day, 4 days/ in radon only exposed rats et al.
radon and week, over 10 weeks; 2 weeks was 28% compared with 68% in (1983)
receiving later, intrapleural injec- group with combined exposure
intrapleural tion of 2 mg of one of 10 to radon and intrapleural
injection of mineral dusts (including injection of mineral dust
various mineral JM 104 glass fibres); life- (tumour type also varied); in
dusts; 60 span observation glass fibre-exposed group, no
controls exposed mesotheliomas but tumours in
to radon only 6 (60%) animals; number in
each group too small to allow
comparison of effect by fibre
type

Balb/C 18 - 25 animals Intrapleural injection of Long-fibred samples Davis
mouse and in exposed group 10 mg of 4 samples of boron produced massive fibrosis, (1976)
rat (strain silicate glass fibre (long- while short fibred samples
unspecified) or short-fibred samples produced only discrete
with mean diameters of 0.05 granulomas with minimal
or 3.5 µm); animals killed fibrosis; in first study,
2 weeks - 18 months after no tumours in 37 mice sacri-
injection; intraperitoneal ficed at 18 months; in second
injection of 10 mg long- study, 3 tumours in 18 rats and
fibred, 0.05-µm diameter and 3 tumours in 25 mice; no
sample in both mice and rats; control group and observation
life-span observation period in first study short

SPF Male 45 exposed; Intrapleural injection of Survival times for animals Lafuma
Sprague 32 controls 20 mg glass fibre (JM 104; injected with glass fibres et al.
Dawley rat mean length, 5.89 µm; mean longer than for controls; (1980);
diameter, 0.229 µm); life- tumours in 13% of animals Monchaux
span observation (similar to that for leached et al.
(44 - 64% Mg removed) (1981)
chrysotile

Wistar rat 40 rats in test Intraperitoneal administra- Tumours in 57.5% of animals; Pott
groups; 80 tion of 4 doses of 25 mg time to first tumour, 197 et al.
controls weekly of uncoated glass days; authors mention that, (1974)
fibres (72.6% < 5 µm long; in current studies, lowest
mean diameter, 0.5 µm); effective dose of glass
life-time observation fibres was 2 mg

SPF Wistar 24 (12 males, 12 Intraperitoneal injection of Mild chronic inflammatory Pigott &
rat females) in test 20 mg of 2 commercial grades response with a mild amount Ishmael
(Alderley and control of the refractory alumina of collagen compared with (1981)
Park groups fibre SAFFIL; animals sac- peritoneal asbestosis in rats
strain) rificed up to 1 year after receiving UICC Rhodesian
injection chrysotile

Wistar (2 50 females of Intraperitoneal injection of Tumours in _~51% (Wistar- Pott
sources), each strain in 10 mg glass fibres (JM 104) Ivanovas) - 79.6% (Wistar- et al.
SIV and test groups Hagemann) of animals (1980)
Sprague
Dawley rat

European 20 hamsters in Intraperitoneal injection of Tumours in 3 animals (15%) - Pott
hamster each test group 50 mg glass fibres (JM 106) based on results for UICC et al.
crocidolite and glass (1980)
fibres; authors concluded
"rats more sensitive for
testing carcinogenicity of
fibres than European
hamsters"
--------------------------------------------------------------------------------------------------------

Table 19. (contd.)
--------------------------------------------------------------------------------------------------------
Species Number in groups Protocol Results and comments Reference
--------------------------------------------------------------------------------------------------------
Syrian 60 males in each Intrapleural injection of Tumours in 15% for sample Smith
golden exposed group; 25 mg of 6 samples of glass with mean diameter 0.1 µm et al.
hamster 60 controls fibres and 82% longer than 20 µm; (1980)
3.3% incidence for sample
with 0.33 µm mean diameter
and 46% longer than 20 µm;
similar incidence for sample
with 1.23 µm mean diameter
and 34% longer than 20 µm; no
tumours in hamsters treated
with fibres with mean dia-
meters of 0.09, 0.41, or
0.49 µm, but with only 0 -
2% of fibres longer than
10 µm

Balb/C 25 in each Intrapleural injection of Long-fibred dust specimens Davis
mouse exposed group 10 mg of several fibrous produced widespread cellular (1972)
dusts including 2 samples granulomata, which formed
of boron silicate glass firm adhesions, gradually re-
fibre (mean diameters, placed by fibrous tissue;
0.05 - 1 µm and 2.5 - 4 µm; short-fibred dust specimens
length < 10 µm) and three produced smaller granulomata
"man-made insulation fibres" without adhesions; non-
(alumino-silicate: mean dia- fibrous mineral rocks, when
meter, 4 µm; calcium-sili- finely ground, also produced
cate: mean diameter, 10 µm; small non-adherent granulo-
calcium-alumino-silicate: mata; final degree of fibro-
mean diameter, 4 µm); ani- sis correlated with initial
mals killed 2 weeks - 18 cellularity of lesions; no
months after exposure mention of control group

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

Female Wistar 10 in each group Intraperitoneal injection of Initial foreign body reac- Engle-
albino rat 50 mg of several fibrous tion followed by fibroblast brecht &
dusts including "long" (mean infiltration, fibrosis, and Burger
length, 12.9 µm) and "short" a few areas of reactive (1975)
(mean length, 2.4 µm) fibrous mesothelium, but no malignant
glass; animals killed at transformation; tissue res-
periods of up to 330 days ponse of long and short
after exposure fibres similar; authors con-
cluded that "mechanical irri-
tation does not contribute to
the induction of mesotheliomas"

SPF Wistar up to 36 in each Intrapleural injections of Occasional mesotheliomas for Wagner
rat of exposed groups 20 mg ceramic fibres, fibre- ceramic fibre (3) and glass et al.
glass, glass powder, alum- powder (1); none for glass (1973)
inium oxide, and 2 samples fibres compared with (23) and
of SFA chrysotile; life- (21) for the SFA chrysotile;
time observation estimated carcinogenicity
factors (x 10⁹) were: for
ceramic fibres, 0.16; for
glass powder, 0.04; for SFA
chrysotile, 2.28 - 2.85;
authors concluded that results
were consistent with the hypo-
thesis that finer fibres are
more carcinogenic

Female SPF 30 - 50 rats in Intrathoracic implantation Probability of pleural sarc- Stanton &
Osborne- test and control on a fibrous glass vehicle oma best correlated with the Wrench
Mendel rat groups of 40 mg of 72 samples of 12 number of fibres with a dia- (1972);
different fibrous materials meter < 0.25 µm and length Stanton
(including 22 samples of >8 µm, but relatively high et al.
fibrous glass); 2-year correlations also noted for (1977,
observation period fibres with a diameter up to 1981);
1.5 µm and length > 4 µm; Stanton &
morphological observations Layard
indicated that short fibres (1978)

and large diameter fibres
were inactivated by phago-
cytosis and that negligible
phagocytosis of long, thin
fibres occurred; authors con-
cluded that "the simplest
incriminating feature for
both carcinogenicity and
fibrogenicity seems to be
a durable fibrous shape, per-
haps in a narrow range of size"

SPF albino 40 animals in Intraperitoneal injection of Nodular deposits of connec- Styles &
Wistar rat exposed and 0.2 ml of a 10% suspension tive tissue; no fibrosis Wilson
(Alderley control groups of Saffil alumina (median (1976)
Park strain) diameter, 3.6 µm; median
length, 17 µm) or Saffil
zirconia (median diameter,
2.5 µm; median length, 11
µm); animals killed 6 months
after dosing

Female Wistar 30 - 32 animals Intraperitoneal injection of Significant increases in Mühle
rat in exposed and 0.5 mg glass fibre (JM 104; tumour incidence for glass et al.
control groups 90% of fibre lengths < 8.2 fibre (17%), crocidolite (in press)
µm, 90% of fibre diameters (55%), and Canadian chryso-
< 0.42 µm), 0.5 mg crocido- tile (84%); incidence in
lite (90% of fibre lengths Calidria chrysotile-
< 7.7 µm, 90% of fibre dia- exposed group similar to
meters < 0.36 µm), 0.5 mg controls (6%)
Calidria chrysotile, 1 mg
UICC Canadian chrysotile B
(90% of fibre lengths < 3.6
µm, 90% of fibre diameters
< 0.18 µm)

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

Table 19. (contd.)
--------------------------------------------------------------------------------------------------------
Species Number in groups Protocol Results and comments Reference
--------------------------------------------------------------------------------------------------------
Male Syrian _~25 animals per Intraperitoneal injection of Abdominal mesotheliomas in Smith
hamster and test and control 25 mg of 0.45-µm mean dia- 32% of rats exposed to glass et al.
female groups at meter fibrous glass, 1.8- fibre, 83% in rats exposed (in press)
Osborne- necropsy µm mean diameter refractory to refractory ceramic fibre,
Mendel rat ceramic fibre or crocidolite 80% in rats exposed to croc-
(fibre size distributions dolite (0 in controls); ab-
similar to those presented dominal mesotheliomas in 13
in Table 17); life-span and 24% of hamsters exposed
observation to refractory ceramic fibre,
40% in hamsters exposed to
crocidolite (0 in controls)

Female number examined Intraperitoneal administra- Potency to induce tumours Pott
Sprague in each group tion (single or up to 5 related principally to size et al.
Dawley and ranged from repeated doses); total ad- distribution of the fibres (1987)
Wistar rat 30 to 99 ministered material of and to durability; tumour
treated or untreated samples incidence for MMMF varied
of JM 100 (2 - 10 mg) or from 2.1 to 87% (the latter
JM 104 (5 - 10 mg) glass incidence occurred in the
microfibres, JM 106 (10 mg), study using 5 mg NaOH-
slag wool (Rheinstahl; treated JM 104 glass micro-
Zimmerman) (40 mg), Swedish fibres); no increase in
rock wool (75 mg), ES5 (10 - tumour incidence with glass
40 mg) and ES7 (40 mg) glass filaments with diameters of
filaments, and basalt wool 3, 5, and 7 µm
(Grünzweig & Hartman) (75 mg);
intraperitoneal administra-
tion of ES3 (50 - 250 mg) or
ES5 (250 mg) glass filaments
by laparotomy
--------------------------------------------------------------------------------------------------------

Table 19. (contd.)
--------------------------------------------------------------------------------------------------------
Species Number in groups Protocol Results and comments Reference
--------------------------------------------------------------------------------------------------------
Female Wistar 35 - 50 per group; Intraperitoneal administra- Fibre number (length > 5 Pott
rat 100 controls tion (single or 5 repeated µm; diameter < 3 µm) in- et al.
doses) of 0.01 - 0.25 mg jected versus tumour rate (in press)
actinolite, 0.05 - 1 mg reported: actinolite, 100x10⁶
chrysotile, 5 mg glass fibre fibres (56% tumours); chry-
JM 104/475, 75 mg basalt sotile, 200x10⁶ fibres
wool, 45 mg ceramic wool (68% tumours); JM 104/475,
(Fibrefrax), 75 mg ceramic 680x10⁶ fibres (64% tumours);
wool (Manville) basalt wool, 60x10⁶ fibres
(57% tumours); ceramic wool
(Fiberfrax), 150x10⁶ fibres
(70% tumours); ceramic wool
(Manville), 21x10⁶ fibres
(22% tumours)

Rat 125 (63 males, 62 Intrapleural 3-fold injec- Mesotheliomas in 54.5% Pylev
females) tion of 20 mg artificial et al.
Na, Mg-hydroxyamphibole (1975)
(90% < 5 µm in length)
--------------------------------------------------------------------------------------------------------
WL = Working levels.
UICC = Union Internationale Contre le Cancer.
SPF = Specific pathogen free.
JM = Johns Manville.
The carcinogenic potency of glass fibres (JM 104) following
intraperitoneal administration was reduced when the fibres were
pre-treated with hydrochloric acid (Pott et al., 1984); the
authors suggested that this was a function of the lower dura-
bility of the acid-treated fibres (Bellmann et al., in press).
In a study by Bignon et al. (1983), the proportion of lung can-
cer was greater in rats exposed by inhalation to radon and then
administered intrapleural injections of one of 10 mineral dusts
(including glass fibre) than in rats exposed only to radon.

Pigott & Ishmael (1981) observed only a "mild chronic
inflammatory response" 12 months following intraperitoneal
injections of 20 mg of two commercial grades of refractory
alumina fibre. Styles & Wilson (1976) observed nodular deposits
of connective tissue, but no fibrosis, following intraperitoneal
injection of alumina and zirconia fibre (0.2 ml 10% suspension).
On the basis of the results of a study in which 20 mg of various
fibrous dusts were injected intrapleurally in rats, Wagner et
al. (1973) estimated the carcinogenicity factor (x 10⁹) for
"ceramic fibre" to be 0.16 compared with 2.28 - 2.85 for SFA
chrysotile. Following intraperitoneal administration of 25 mg
of fibrous ceramic aluminium silicate glass to rats, Davis et
al. (1984) observed tumours in 9.3% of the exposed animals
compared with 90% in similar studies with chrysotile. Moreover,
time to first tumour was 850 days for ceramic fibres compared
with 200 days for chrysotile. However, in a recent study,
abdominal mesotheliomas were observed in 83% (19 out of 23) of
Osborne-Mendel rats receiving a single intraperitoneal injection
of 25 mg of 1.8-µm (mean diameter) refractory ceramic fibres
(Smith et al., in press).

The need for caution in the extrapolation of the results of
studies involving injection or implantation in body cavities to
predict the potency of various fibre samples, even with respect
to the induction of mesotheliomas cannot be overemphasized. The
relevance of these types of studies to other types of cancer,
such as lung cancer, has not been established.

7.2. In Vitro Studies

Several important factors that influence the pathogenicity
of fibrous dusts in vivo (e.g., deposition, clearance, and
immunological function) are absent in in vitro systems.
Moreover, the results of such assays vary considerably,
depending on the test system used. However, on the basis of
available results for all fibres, it appears that a combination
of in vitro tests may be useful in predicting the fibrogenicity
of fibres in vivo. The predictive value of in vitro tests for
the carcinogenicity of fibrous dusts is, at present, less well
established, but there has been some consistency between the
results of specific in vitro assays and the induction of meso-
theliomas in in vivo studies involving intrapleural administra-
tion. In general, therefore, in vitro assays are considered to

be useful for the investigation of mechanisms of disease induced
by fibre dusts and possibly as preliminary screening tests for
pathogenic fibres.

The results of in vitro studies on various types of MMMF are
presented in Table 20. To date, the effects of glass fibres of
various size distributions have been examined in a wide range of
systems including bacteria, cultured erythrocytes, fibroblasts
and macrophages from several animal species, macrophage-like
cell lines and cultured human fibroblasts, erythrocytes, lympho-
cytes, and bronchial epithelial cells. In most of the assays,
cytotoxicity or cytogenetic effects have been a function of
fibre size distribution, with longer (generally > 10 µm), thin-
ner (generally < 1 µm) fibres being the most toxic (Brown et
al., 1979b; Lipkin, 1980; Tilkes & Beck, 1980, 1983a,b; Hester-
berg & Barrett, 1984; Forget et al., 1986; Hesterberg et al.,
1986). In general, "coarse" fibrous glass (with relatively
large fibre diameters, e.g., JM 110) has been less cytotoxic in
most assays than chrysotile or crocidolite (Richards & Jacoby,
1976; Haugen et al., 1982; Nadeau et al., 1983; Pickrell et al.,
1983). However, the cytotoxicity or transforming potential of
"fine" glass (e.g., JM 100) has approached that of the asbestos
varieties (Pickrell et al., 1983; Hesterberg & Barrett, 1984).

Results concerning the effects of fibre coating on toxicity
in in vitro assays have been contradictory. Brown et al. (1979a)
reported that "clean" samples of rock, glass, and slag wool
(i.e., resin removed by pyrolysis) were slightly more cytotoxic
for V79-4 and A549 cells than were resin-coated samples of the
same materials. In contrast, Davies (1980) found that removal
of the binder from rock and slag wools and resin from glass wool
had no effect on their cytotoxicity for mouse peritoneal
macrophages.

With respect to genotoxicity, glass fibres (JM 100 and 110)
did not induce point mutations in E. coli or S. typhimurium
(Chamberlain & Tarmy, 1977). Casey (1983) did not observe any
effects of fine (JM 100) or coarse (JM 110) fibrous glass on
sister chromatid exchange in CHO-K₁ cells, human fibroblasts, or
lymphoblastoid cells. However, a variety of fibrous materials
delayed mitosis in human fibroblasts and CHO-K₁ cells. The order
of potency in CHO-K₁ cells was chrysotile > fine glass (JM 100)
> crocidolite > coarse glass (JM 110). JM 100 glass fibres
induced chromosomal breaks, rearrangements, and polyploidy in
CHO-K₁ cells, while JM 110 glass fibres did not have any effect
(Sincock et al., 1982). Oshimura et al. (1984) reported that
glass microfibres (JM 100) induced cell transformation and
cytogenetic abnormalities in Syrian hamster embryo (SHE) cells.
The cytotoxicity, transforming frequency, and micronucleus
induction frequency of glass microfibres (JM 100) in SHE cells
was reduced by milling (i.e., decreasing the length) (Hesterberg
et al., 1986).

Table 20. In vitro studies
--------------------------------------------------------------------------------------------------------
Fibre type Fibre size distribution Results Reference
--------------------------------------------------------------------------------------------------------
Fibrogenic effects

Glass fibres JM 100: mean length, Increase in total protein at 48 h and in Aalto & Hepple-
2.7 µm; mean total protein and collagen synthesis at ston (1984)
diameter, 0.12 µm; 96 h in rat fibroblasts; short fibres
JM 110: mean length, more fibrogenic than long ones at 96 h
26 µm; mean diameter,
1.9 µm

Glass fibre Not reported Initial slight fibrogenic response with Richards & Morris
dust; glass fibre compared with pronounced (1973)
chrysotile effect of chrysotile asbestos on
asbestos rabbit lung fibroblasts

Alumina and Saffil alumina: median Low cytotoxicity for rat peritoneal macro- Styles & Wilson
zirconia length, 17 µm; median phages; non-fibrogenic in intraperitoneal (1976)
fibres diameter, 3.6 µm; injection studies
Saffil zirconia: median
length, 11 µm; median
diameter, 2.5 µm

Cytotoxicity

Glass fibres % of fibres < 0.6 µm Fibres < 10 µm in length not cytotoxic for Brown et al.
in diameter and > 5 µm V79-4 cells, A549 cells, or mouse peri- (1979b)
in length: JM 100T, toneal macrophages
36%; JM 110T, 27.4%;
JM 100R, 36.7%; JM 110R,
34.6%

Glass fibres Homogenized GF/D Mildly cytotoxic for cultured human Haugen et al.
Whatman filters bronchial epithelial cells; chrysotile (1982)
washed in HCl; 1000 times more cytotoxic than glass fibre
fibre size distribution
not reported

Glass fibres Not reported Not toxic for human peripheral blood Nakatani (1983)
lymphocytes; "large" glass fibre as
cytotoxic for mouse peritoneal macro-
phages as chrysotile; "small" glass
fibre not cytotoxic in this assay

Glass fibres "Respirable"; Morphological changes and alterations Richards & Jacoby
not reported in reticular deposition in rabbit (1976)
lung fibroblasts less severe for
chrysotile

Glass fibres JM 100: mean diameter, Toxicity in phagocytic ascites tumour Tilkes & Beck
0.23 µm (99.8% < 10 cells from Wistar rats correlated with (1980)
µm long); JM 104: mean fibre lengths and diameter
diameter, 0.32 µm
(99.1% < 10 µm long);
GFF: mean diameter,
0.43 µm (99.1% < 20
µm long); GFF: mean
diameter, 0.19 µm
(99% < 3 µm long)

Table 20. (contd.)
--------------------------------------------------------------------------------------------------------
Fibre type Fibre size distribution Results Reference
--------------------------------------------------------------------------------------------------------
Glass fibres 1. 83.8% < 1 µm long; Long narrow glass fibres as toxic for phago- Tilkes & Beck
100% < 0.3 µm wide cytic ascites tumour cells from Wistar (1983a)
2. 75% > 5 µm long; rats as chrysotile; fibres with diameters
99.7% < 0.3 µm wide 3 µm, non-toxic; toxicity increased with
3. 15.5% > 5 µm long; increasing fibre length
22.3% < 0.3 µm wide
4. 99.3% > 5 µm long;
82.9% < 0.3 µm wide
5. 44.1% > 5 µm long;
3.4% < 0.6 µm wide
6. 90.1% > 5 µm long;
4.1% < 0.6 µm wide

Glass fibres Owens Corning beta- Significant increase in squamous cell Woodworth et al.
fibre: 99% > 10 µm metaplasia and labelling index in organ (1983)
long; 3% < 3 µm wide; cultures of hamster trachea (similar to
JM 100: 46% > 10 µm crocidolite)
long; 50% < 0.2 µm
wide

Glass fibres, Not reported; glass Some binding of carcinogens (benzo( a )- Harvey et al.
glass wool fibres from "GF/C pyrene, nitrosonornicotine, N -acetyl-2- (1984)
microfilter" aminofluorene) by fibrous glass and
glass wool, but less than that for most
other mineral fibres examined, such as
chrysotile and attapulgite; negligible
haemolysis in sheep erythrocytes or
cytotoxicity in P388 D₁ cells
Table 20. (contd.)
--------------------------------------------------------------------------------------------------------
Fibre type Fibre size distribution Results Reference
--------------------------------------------------------------------------------------------------------
Three types Microfibre insulation: Cytotoxicity of microfibre insulation in Pickrell et al.
of glass CMD, 0.1 - 0.2 µm; pulmonary alveolar macrophages from (1983)
fibre- household insulation, beagle dogs similar to that of crocido-
containing CMD, 2 - 4 µm lite; household insulation fibres non-toxic
household
insulation;
microfibre
insulation
material

Glass fibres; JM 100, JM 110, and "Fine" glass fibres (JM 100) more cytotoxic Davies (1980)
rock, slag, JM 100 (respirable); for mouse peritoneal macrophages than UICC
and glass size distribution crocidolite, but "coarse" glass fibre had
wool not reported little activity; removal of binder from
rock and slag wools and resin from glass
wool had no effect

Glass fibres JM 104; 90% < 15 Induced a small release of beta-galacto- Jaurand et al.
µm in length and sidase, but was not cytotoxic for rabbit (1980)
0.5 µm in diameter alveolar macrophages

Glass fibres Not reported "Long" fibres produced a protracted patho- Bruch (1974)
genic but not cytotoxic effect in guinea-
pig alveolar macrophages; for short fibres,
morphological pattern similar to that for
inert dusts

Glass fibres JM 100-milled to alter Glass fibres induced dose-dependent release Forget et al.
fibre lengths of prostaglandins and beta-d-glucuronidase (1986)
(size distribution from perfused rat alveolar macrophages,
not reported) cell aggregation and mortality; long fibres
more active than short ones

Glass fibres Fibre size Cytotoxicity in guinea-pig- and rat-lung Tilkes & Beck
distribution as for macrophages related mainly to fibre size (1983b)
Tilkes & Beck distribution; depression of phagocytosis
(1983a)

Glass fibres, Not reported Glass fibre (GF/C filters) less cytotoxic Dumas & Page
glass wool for 3T3 fibroblasts than several forms of (1986)
chrysotile and attapulgite but more cyto-
toxic than UICC crocidolite; minimal cyto-
toxicity of Pyrex (glass wool)

Glass fibres JM 100 - mean length, Cytotoxic in primary cultures and perm- Ririe et al.
15 µm; mean diameter, anent cell line of rat tracheal epithelial (1985)
0.2 µm; JM 100 cells; toxicity reduced with milling of
(milled) - mean the fibres
length, 2 µm; mean
diameter, 0.2 µm

Glass fibres, Glass fibres: lengths Glass fibres increased cell permeability Beck et al.
glass powder ranged from 1 to 20 µm of guinea-pig alveolar and peritoneal (1972); Beck
and diameters from macrophages; glass powder had little & Bruch (1974);
0.25 to 1 µm; glass effect Beck (1976a,b)
powder particle size
< 3 µm

Glass fibres, JM 100 glass fibres Glass fibres induced ornithine decarboxy- Marsh et al.
glass and particles; size lase activity (ODC) in hamster tracheal (1985)
particles distribution not epithelial cell cultures, while glass
reported particles did not

Borosilicate Fibre size Cytotoxicity in P388 D¹ macrophage-like Lipkin (1980)
glass fibres distribution as for cells correlated well with potency in
sample used by tumour induction reported by Stanton &
Stanton & Layard Layard (1978) in intrapleural implanta-
(1978) tion studies

Rock wool, Not reported Cytotoxic for V79-4 and A549 cells; "clean" Brown et al.
slag wool, (resin removed by pyrolysis) samples (1979a)
and glass slightly more active than resin-
wool coated variety

"Ceramic Elutriated sample; 89% Ceramic fibre less cytotoxic for P388 D1 Wright et al.
fibre" of fibre lengths < 5 cells than chrysotile samples and most (1986)
µm; fibre diameters of the amphibole samples
< 3 µm; 7.4 fibres/
10^-10 g (small number
compared with
different types of
chrysotile)

Ceramic Not reported Ceramic fibres were inert in the V79/4 Brown et al.
cell colony inhibition assay, but in- (1986)
creased the diameter of the A549 cells

Xonotlite Diameter, < 0.1 µm; Fibres phagocytosed by primary rat Denizeau et al.
(synthetic) length, < 2 µm hepatocytes in culture, based on ultra- (1985)
(100%) structural analysis

Mineral wool, Mineral wool: Mineral wool not cytotoxic for rat alveo- Nadeau et al.
glass fibre D_f = 3.3 µm, L_f = lar macrophages, nor haemolytic for rat (1983)
221.4 µm; glass erythrocytes, but increased oxidant pro-
fibre: D_f = 0.2 µm, duction in rat macrophages; glass micro-
L_f = 11.4 µm fibres induced haemolysis, but to a lesser
extent than chrysotile

Genetic and related effects

Glass fibres JM 100 (fine) and No effects on sister chromatid exchange in Casey (1983)
JM 110 (coarse); CHO-K₁ cells, human fibroblasts, or lympho-
size distribution blastoid cells; mitotic delay in CHO-K₁
not reported cells and human fibroblasts; order of
induced delay in CHO-K₁ cells: chrysotile >
fine glass > crocidolite > coarse glass

Glass fibres JM 100: mean length, JM 100 glass fibres as active as chryso- Hesterberg &
9.5 µm; mean diameter, tile in transforming Syrian hamster Barrett (1984)
0.13 µm; shorter fibre embryo cells; thick glass fibres (JM 110)
samples of similar 20 times less potent than thin (JM 110)
diameter produced by ones; 10-fold decrease in transformation
milling; JM 100: mean with reduction of fibre length from 9.5
diameter, 0.8 µm to 1.7 µm (JM 100); no transformation
for fibre length of 0.95 µm

Glass fibres "AAA" glass fibre Sizes of glass fibres that promote growth Maroudas et al.
of different in BHK 21 or 3T3 fibroblasts (> 20 µm (1973)
size distributions in length) similar to sizes that induce
mesotheliomas following intrapleural
implantation

Table 20. (contd.)
--------------------------------------------------------------------------------------------------------
Fibre type Fibre size distribution Results Reference
--------------------------------------------------------------------------------------------------------
Glass fibres JM 100-milled (average Glass fibres phagocytosed by Syrian ham- Hesterberg et al.
length, 2.2 µm) and ster embryo cells and accumulated in peri- (1986)
unmilled (average nuclear region of the cytoplasm; milling
length, 15.5 µm) (95 - of glass fibres (resulting in a 7-fold
98% of fibre diameters decrease in length) reduced percentage of
< 0.5 µm) phagocytosis, cytotoxicity, transformation
frequency, and micronucleus induction
frequency

Glass fibres JM 100 (mean length, No mutagenic activity in bacterial Chamberlain &
2.7 µm, mean diameter, strains of Escherichia coli or Salmo- Tarmy (1977)
0.12 µm); JM 110 (mean nella typhimurium at levels of up to
length, 26 µm; mean 1000 µg/plate
diameter, 1.9 µm)

Glass fibres JM 100 (mean diameter, JM 100 fibres induced cell transformation Oshimura et al.
0.1 - 0.2 µm; mean and cytogenetic abnormalities in Syrian (1984)
length varied by hamster embryo cells; JM 110 fibres and
milling); JM 110 milled JM 100 fibres much less potent for
(mean diameter, 0.8 both end-points
µm)

Glass fibres, 1.5 - 2.5 µm diameter; Exposure of CHO-K₁ cells to one concen- Sincock & Sea-
glass powder fibre size tration of glass fibre did not increase bright (1975)
distribution described the frequency of chromosomal aberrations
by Wagner et al. or polyploid cells
(1973)

JM 100 glass Mean particle lengths JM 100 fibres caused chromosomal breaks, Sincock et al.
fibres, between 2.7 and 26 µm; rearrangements, and polyploidy in CHO-K₁ (1982)
JM 110 glass mean particle cells; no effects with JM 110 fibres
fibres diameters between 0.12
and 1.9 µm

JM glass Not reported Dose-dependent interference with develop- Krowke et al.
fibres ment of limb buds in 11-day-old mouse (1985)
embryos in culture
--------------------------------------------------------------------------------------------------------
JM = Johns Manville.
CMD = Count median diameter.
CHO = Chinese hamster ovary.
Few data are available on the toxicity of MMMF other than
glass fibres in in vitro assays. However, Styles & Wilson
(1976) reported that the cytotoxicity of Saffil alumina and
Saffil zirconia fibres (size range unspecified) in rat peri-
toneal macrophages was low; this agreed well with the lack of
fibrogenicity observed in intraperitoneal injection studies with
the same materials. Wright et al. (1986) reported that "ceramic
fibre" (type and source unspecified) was less cytotoxic for
P₃88 D₁ cells than chrysotile and the amphiboles.

7.3. Mechanisms of Toxicity - Mode of Action

The results of toxicological studies have demonstrated the
importance of fibre dimension, persistence, and durability in
the pathogenesis of fibrous dust-related diseases. Surface
charge and chemical composition may also play an important role.
However, the mechanisms by which respirable fibrous materials
cause fibrosis and cancer are not well understood. The sequence
of cellular events leading to fibrosis has been hypothesized on
the basis of observations in animals after inhalation or intra-
tracheal instillation of asbestos (Davis, 1981). It is likely
that the sequence of events in the induction of fibrosis by
other fibres of similar dimensions and durability is similar.
Short fibres deposited on the alveolar surface are phagocytosed
by macrophages and removed by the mucociliary escalator. Fibres
longer than 10 µm are often surrounded by groups of macro-
phages, which may fuse to form multinucleated giant cells. Some
of the dust-containing macrophages become incorporated into the
lung parenchyma and die, and the fibres are rephagocytosed by
new populations of macrophages. The presence of these fibres in
distal airways stimulates excess deposition of collagen and
reticulin fibres.

The deposition of fibres in the pulmonary region of the
respiratory tract is thought to be important only if the fibres
can penetrate into the interstitium where interstitial macro-
phages can phagocytose them. In the process, the macrophage is
impaired; this may "trigger" adjacent fibroblasts in the inter-
stitium to start producing more collagen, leading eventually to
fibrosis.

Several mechanisms by which asbestos and possibly other
fibrous materials cause cancer have been suggested. Because of
the lack of activity of most of these materials in gene mutation
assays, it has been suggested that they may act by epigenetic
mechanisms (NRC, 1984). For example, it has been proposed that
asbestos acts primarily as a promoter or cocarcinogen or that
cancer occurs secondarily to the induction of inflammation or
fibrosis. However, results of in vitro studies in which chromo-
somal aberrations have been induced by glass fibres (Oshimura et
al., 1984), suggest that the fibres can directly affect the
genetic material.

Generation of reactive oxygen metabolites by fibrous
materials in in vitro assays has also been observed and has been
postulated to play a role in cytotoxicity (Goodglick & Kane,
1986). It may also be that fibrogenesis and carcinogenesis may
be a result of several of these mechanisms.

8. EFFECTS ON MAN

8.1. Occupationally Exposed Populations

8.1.1. Non-malignant dermal and ocular effects

The effects of MMMF on the skin were recognized as early as
the turn of the century (HMSO, 1899, 1911). Fibrous glass and
rock wool fibres (mainly those greater than 4.5 - 5 µm in dia-
meter) cause mechanical irritation of the skin characterized by
a fine, punctate, itching erythema, which often disappears with
continued exposure (Hill, 1978; Björnberg, 1985). Possick et
al. (1970) described the effects of short glass fibres tempor-
arily piercing the epidermis producing sensations varying from
itching and burning to pain. They suggested that skin penetra-
tion was directly proportional to fibre diameter and inversely
proportional to fibre length. The primary lesion is a papule or
papulo-vesicle, and the authors quote histological reports of
oedema of the upper dermis with round cell infiltrates.
Secondary lesions include bacterial infections, which develop as
a result of scratching, and lichenification. Urticaria occurs
in dermatographic subjects.

Data concerning the incidence or prevalence of dermatitis in
workers exposed to MMMF are sparse. Sixty-one percent of 62
glass wool workers in a Swedish plant had cutaneous signs or
symptoms at the end of a working day; 45% had visible dermal
lesions (Björnberg, 1985). Twenty-five percent of 315 subjects
exhibited skin reactions at 72 h when patch tested for 48 h with
rock wool (Björnberg & Löwhagen, 1977) and, in a study on 135
Italian fibrous glass production workers, the prevalence of
dermatitis was reported to be 19% (Arbosti et al., 1980).
However, according to Gross & Braun (1984), much lower
prevalences were reported in investigations previously conducted
in the USA. In a study on 467 glass wool workers, Maggioni et
al. (1980) reported that 14% had skin disease, mainly primary
irritative dermatitis.

There are also few reliable data concerning the tolerance of
workers to MMMF-induced dermatitis. Björnberg et al. (1979)
described a group of 60 workers at a glass wool factory; after
counselling, 38 were able to continue work but 22 had to be
transferred to work with less potential for fibre exposure; 6 of
these workers eventually had to leave their jobs because of this
irritation.

The irritant dermatitis induced by MMMF may be complicated
by an urticarial and eczematous reaction that sometimes mimics
an allergic response, both clinically and histologically. In
addition, allergic reactions to resins used in MMMF production
occasionally occur (Fisher, 1982). For example, allergic
dermatitis in 54% of 160 workers engaged in glass fibre
manufacture was attributed to exposure to epoxy resin (Cuypers
et al., 1975); however, coating with phenol-formaldehyde did not
have any effects on skin reactions induced by rock wool
(Björnberg & Löwhagen, 1977). Conde-Salazar et al. (1985),

in their case report of severe dermatitis in a glass fibre
spinner sensitized to epoxy oligomer, commented that glass
fibres per se produced only an irritant dermatitis.

Until recently, reports of eye irritation in populations
exposed occupationally to MMMF were restricted to a few isolated
cases in the early literature (Gross & Braun, 1984). However,
in a recent Danish study, the frequency of eye symptoms
significantly increased and the number of microepithelial
defects on the medial bulbar conjunctiva and, in some cases, the
neutrophil count of the conjunctival fluid were increased after
4 days of exposure in 15 rock wool workers (employed for > 6
months) compared with controls matched for age, sex, and smoking
habits. While there were no ophthalmological differences
between exposed workers and controls on Monday morning, an
excess of mucous was found in exposed workers, suggesting that
the effect was not completely reversible over the weekend
(Stokholm et al., 1982).

8.1.2. Non-malignant respiratory disease

In reports that appeared in the early literature, several
cases of acute irritation of the upper respiratory tract and
more serious pulmonary diseases, such as bronchiecstasis,
pneumonia, chronic bronchitis, and asthma were attributed to
occupational exposure to various MMMF. On the basis of recent
reviews of these isolated reports, several authors (Hill, 1978;
Upton & Fink, 1979; Saracci, 1980; Gross & Braun, 1984; Wright,
1984) have concluded that exposure to MMMF was probably
incidental rather than causal in most of these cases, since the
reported conditions have not been observed in most of the more
recently conducted epidemiological studies. These case reports
are not considered further here.

The epidemiological studies of non-malignant respiratory
disease in populations exposed occupationally to MMMF are mainly
of two types: cross-sectional investigations of the prevalence
of signs and symptoms of respiratory disease and historical
prospective (cohort) studies of mortality due to non-malignant
respiratory disease.

8.1.2.1. Cross-sectional studies

The design and results of the available cross-sectional
studies of respiratory effects in MMMF production workers are
summarized in Table 21. Most of these studies have involved one
or a combination of the following elements: determination of
respiratory symptoms through administration of questionnaires,
pulmonary function testing, and radiological examination of the
lung. Limitations that should be borne in mind in reviewing the
results of cross-sectional studies include the following:
persons who have left employment because of ill health are
selectively excluded and health effects are monitored at only
one particular time (i.e., prevalence rather than incidence is
determined). Nevertheless, such investigations do provide
useful preliminary data.

Table 21. Cross-sectional studies of respiratory effects in MMMF-exposed workers^a
--------------------------------------------------------------------------------------------------------
Study protocol Results Comments Reference
--------------------------------------------------------------------------------------------------------
Examination of chest No unusual pattern of radio- Ad hoc radiological assessments Wright
radiographs of 1389 logical densities; frequency by one reader difficult to inter- (1968)
employees in a glass no higher in those with pret epidemiologically
wool manufacturing greatest exposure than in
plant (> 10 years those with the least
exposure to dust
concentrations from
0.93 to 13.3 mg/m³)

Examination of chest Radiographic abnormalities Not possible to interpret Nasr
radiographs of 2028 in 16% of workers; strength relationship between response et al.
male workers in the of correlation between pre- and duration of employment, be- (1971)
fibrous glass plant valence and mean duration of cause of confounding with age in
studied by Wright employment and between pre- grouped data; within-group anal-
(1968) (two-thirds valence and mean age similar; yses or logistic regression anal-
employed for > 10 no difference in prevalence yses of data could be useful
years) between office and production
workers

Examination of No significant difference Numerical data to support con- Utidjian &
respiratory symptoms in the prevalence of chronic clusions not provided Cooper
(determined by respiratory illness between (1976)
questionnaire), highest and lowest exposure
radio-graphic category
changes, and
pulmonary function
(VC, FEV₁, and
VC/FEV₁) in 232
employees in the
fibrous glass plant
studied by Wright
(1968) and Nasr et
al. (1971); for sub-
sample of 30,

Table 21. (contd.)
--------------------------------------------------------------------------------------------------------
Study protocol Results Comments Reference
--------------------------------------------------------------------------------------------------------
comprehensive
physical
examination, chest
fluoroscopy,
electrocardiogram,
VC, FVC₁, FVC₂,
FVC₃, mid-expiratory
flow rate, maximal
voluntary
ventilation,
residual volume, and
pulmonary diffusing
capacity

Comparison of No evidence of pulmonary Well-controlled study of a Hill
respiratory symptoms effects due to exposure "survivor population" of et al.
(determined by MRC to fibrous glass, but current employees (1973)
questionnaire), 45% of exposed population
radiographic had suffered for a short
changes, and period from "new starter's
pulmonary function glass-fibre rash"
(peak expiratory
flow, FEV₁, and FVC)
in 70 fibrous glass
wool workers
(exposed for a mean
period of 19.85
years; mean level,
0.9 respirable
fibres/cm³) and
controls matched
for age, sex,
height, and weight,
and living in the
same geographical
area

Examination of Some indication of chronic Only study that includes Hill
respiratory symptoms non-specific lung disease ex-employees; absence of re- et al.
(determined by MRC related to level but not lationship with indices of dura- (1984)
questionnaire), to length of exposure to tion of exposure suggests pos-
radiographic fibres; prevalence of sible confounding with exposure
changes, and small opacities related to to other dusts
pulmonary function environmental pollution
(VC, FEV) in 340 (never having lived in a
workers (> 10 smoke-free zone), and to
years exposure) from previous employment in
a glass wool dusty occupations, but no
manufacturing plant significant relationship
with either length or
level of exposure to MMMF

Examination of No relationship between res- Results suggest that fibres with Weill
respiratory symptoms piratory symptoms or adverse small diameters have an effect et al.
(determined by ATS effects on pulmonary func- on the lung parenchyma; sound, (1983,
questionnaire), tion and exposure; greater well-documented study; replica- 1984)
radiographic prevalence of small opacities tion and confirmation desirable
changes, and among current smokers in 2
pulmonary function plants producing ordinary and
(FVC, FEV₁, fine fibres; for non-smokers,
FEV₁/FVC, FEF 25-75, greater prevalence observed
RV, VC, TLC, DL, in only 1 of these plants;
DL/ALVOL) in 1028 among smokers, prevalence of
workers in 7 glass small opacities increased
wool and mineral with increasing length of
wool plants exposed employment, and authors con-
for a median period cluded that exposure to MMMF
of 18 years to with small diameters may lead
median levels from to low-level profusion of
< 0.032 to 0.928 opacities
fibres/cm³

Survey of workers Prevalence of breathlessness No convincing evidence that Moulin
with > 1 year and nasal cavity symptoms exposure to fibres affects et al.
employment at 2 significantly higher in ex- respiratory system (1987)
glass wool factories posed workers at factory A
(A and B); age- and only; no other significant
smoking habit- differences; bronchitic symp-
stratified sample toms a little more frequent
from factory A (n = in both exposed groups ( P >
367); all eligible 0.05); in nested case-control
from factory B (n = study, a significantly
157); respiratory shorter mean period of employ-
symptoms ment for cases in factory A
(questionnaire),
clinical
examinations, chest
radiography,
spirometry, CO-
transfer factor for
those working with
fibres compared with
those not exposed at
same factory
(factory A: 114,
factory B: 34)

Examination of Positive association bet- Evidence of errors in question- Engholm &
exposure and ween handling of MMMF and naire-determined exposure to Von
respiratory symptoms bronchitis asbestos undermines interpreta- Schmalensee
(determined by self- tion of the association as causal (1982)
administered
questionnaire) in
135 000 male Swedish
construction
workers; separate
analysis for
"former", "never",
and present smokers;
control for age and
asbestos exposure

Examination of chest No radiographic evidence Radiological procedures not docu- Carpenter &
radiograms of 84 attributable to mineral mented adequately Spolyar
workers in a rock wool exposure (1945)
and slag wool plant
(exposure periods, 7
- 26 years)

Examination of Wheezing and breathlessness Effects of work-place exposure Ernst
respiratory symptoms related primarily to current may have been underestimated et al.
(determined by self- smoking and asthmatic pre- due to selective withdrawal (1987)
administered disposition antedating work; from the active work-force and
questionnaire) in these symptoms also related to inaccuracies in exposure
537 insulators to occupational exposure in (based on duration of employ-
working in Quebec in subjects with prior airways ment only); not possible to
1982 without hyperreactivity separate exposure to asbestos,
asbestosis; logistic MMMF, and dust
regression analysis
with smoking,
reactivity before
employment and
occupational
exposure to dust and
mineral fibre as
risk factors
(workers without
asbestosis in 558
respondents out of
644 identified
subjects)

Examination of 7 cases of "work-related No control data; cause of the Finnegan
respiratory symptoms asthma" identified asthma not identified et al.
(determined by (1985)
questionnaire) and
spirometry in 235
workers in a
continuous filament
glass fibre plant
(83% of the shop
floor workers and 21
others who were
infrequently or
never on the shop
floor); prick testing
and bronchial
challenge in some
workers identified
as having work-
related asthma

Examination of No relationship between Preliminary results of a longi- Lockey
respiratory symptoms chronic cough, phlegm, tudinal investigation (in press)
(determined by ATS dyspnoea, or effects on
questionnaire) and pulmonary function and
pulmonary function length of employment; res-
(FVC, FEV₁) in piratory symptoms related
> 4000 workers in to smoking and pulmonary
14 US and Canadian function related to smoking
fibrous glass (type and age
unspecified) plants
exposed for a median
period of 7.7 years
(males) to < 0.5
fibres/cm³

Comparison of Higher incidence of chronic Maggioni
respiratory symptoms and dysplastic pharyngo- et al.
(determined by laryngitis in workers (> 5 (1980);
questionnaire), years) exposed to highest Saracci &
radiographic concentrations; skin disease Simonato
changes, and (mainly primary irritative (1982)
pulmonary function dermatitis) in 14% of the
in 467 glass wool working population
workers (exposed for
a mean period of 13
years) and in
controls

Comparison of No significant differences Not possible to generalize from Malmberg
respiratory symptoms in pulmonary function bet- careful, detailed physiology in et al.
(determined by ween exposed and control only 21 subjects (1984)
questionnaire) and groups; some symptoms of
pulmonary function chronic bronchitis in ex-
(lung volume, posed group
airway resistance,
forced expiratory
flow, closing
volume, transfer
factor) in 21
employees (> 45
years old) of a rock
wool manufacturing
plant (mean exposure
for 17.6 years to
0.19 respirable
fibres/cm³) and in
43 controls (50 -70
years of age)
(values corrected
for differences in
age, body weight,
and smoking habits)

Spirometry and Slightly increased elastic Length or extent of exposure un- Sixt
determination of recoil in exposed subjects; known; bias may have been intro- et al.
lung volumes, authors could not exclude duced by low (47%) response rate, (1983)
closing volumes, the possibility that fibrous and hyper-critical inclusion
slope of the glass could cause a faint criteria
alveolar plateau, and probably harmless
maximum expiratory fibrous reaction in the lung
flow in air and parenchymma
after helium-oxygen
breathing and
elastic recoil
pressures in 8 sheet
metal workers
exposed to fibrous
glass compared
with 7 sheet metal
workers "never
exposed" to fibrous
glass (workers with
no history of
smoking, pleural
plaques, or asbestos
exposure chosen from
251 respondents out
of 532 workers
surveyed)

Examination of In original study group, Longer follow-up required to Stahuljak-
pulmonary function mean pre-shift values of FVC, detect possible exposure- Beritic
(FVC, FEV₁, and MEF FEV₁, and MEF 50% signifi- related lung function decre- et al.
50%) in 162 rock cantly lower than reference ments (1982)
wool workers values, but no relation-
(exposed to 0.003 - ship with cumulative exposure;
0.463 respirable in second study, no change in
fibres/cm³); 5 years pulmonary function associated
later, examination with MMMF exposure
of pulmonary
function in 102
people from
original population
exposed only to MMMF
in the interval
--------------------------------------------------------------------------------------------------------
^a Abbreviations
MRC = Medical Research Council (United Kingdom).
ATS = American Thoracic Society.
FEV₁ = Forced expiratory volume in 1 second.
FVC = Forced vital capacity.
FEF 25-75 = Forced expiratory volume during the mid-half of the forced vital capacity.
RV = Residual volume.
VC = Vital capacity.
TLC = Total lung capacity.
DL = Diffusing capacity.
DL/ALVOL = Ratio of diffusing capacity to alveolar volume.
MEF 50% = Maximal expiratory flow rate at 50% of forced vital capacity.
Hill et al. (1973) compared radiographic appearances,
reports of respiratory symptoms, and lung function measurements
in 70 workers who had been exposed at a glass wool factory in
England for an average of nearly nearly 20 years, with those of
other workers, matched for sex, age, height, and weight, who
were from the same geographical area but had not been exposed to
fibrous dust. The frequency of any abnormalities among those
exposed was no higher than in the controls. Hill et al. (1984)
later examined 74% of 340 workers and ex-employees, in the 55 -
74 year age group, who had been employed for more than 10 years
at the same factory, and also samples of other groups of
employees and ex-employees for whom participation rates were low
(121/250 overall). The results of the second study indicated
some occupationally related chronic non-specific lung disease in
the 340 fibrous glass workers examined. The statistically
significant impairment of lung function was reported to be more
severe among workers in occupational groups designated as likely
to have had high exposure to fibres, but there was no relation-
ship with length of time employed in these groups. Eleven
percent of all 340 workers studied had small opacities on their
chest radiographs of profusion category higher than 0/1 in the
ILO (1980) international classification. A subgroup of 161
men, who had no history of occupational exposure to any dusts
other than glass fibres, included 15 (9%) with category 1/0 or
higher, but there was no statistically significant relationship
between the occurrence of these signs and either intensity or
duration of exposure to glass fibres. The factory concerned is
included in the European study of mortality discussed in
sections 8.1.2.2 and 8.3.

Moulin et al. (1987) conducted a cross-sectional survey of
workers in two glass wool manufacturing plants in France. A
total of 524 subjects (367 in factory A and 157 in factory B)
were examined for respiratory symptoms, radiological pulmonary
changes, and functional respiratory alterations. In each
factory, the prevalences of abnormalities among those exposed to
fibres were compared with findings in unexposed workers
(administrative, oven, and polystyrene workers). The only
statistically significant differences between the two groups
were higher prevalence rates of breathlessness and nasal cavity
symptoms in the exposed workers at factory A. The prevalence of
chronic bronchitis was increased slightly among exposed workers
at both factories. No other exposure-related effects on the
respiratory system were observed. The authors also used a case-
control approach in which cases were the subjects in the
quartile showing the worst results from the various examinations
and the age-matched controls were chosen from among the others.
There was no difference as to duration of exposure in factory B,
while cases had a shorter period of employment in factory A.
The results of this study do not indicate any consistent effects
of exposure to glass wool fibres on the respiratory system.

Weill et al. (1983, 1984) reported results based on a very
detailed statistical analysis of observations on 1028 men
working at 7 North American glass wool or mineral wool

factories. All 7 factories were included in the comprehensive
US mortality study discussed in sections 8.1.2.2 and 8.1.3. A
statistically significant increase in the chance of finding
small opacities (category 0/1 or higher) with increasing length
of employment at the factories was found among some 450 current
cigarette smokers. The highest profusion category on the ILO
(1980) scale, as determined from the median of independent
assessments by 3 readers on 6 films, was category 1/1. There
was no evidence in this study that exposure to fibres increased
the prevalence of respiratory symptoms or impairment of lung
function.

Three reports refer to separate cross-sectional surveys,
carried out at different times, of workers at one large factory
producing continuous filament glass fibres (Wright, 1968; Nasr
et al., 1971; Utidjian & Cooper, 1976). The last survey was of
a stratified approximately 10% random sample of the workers and
included the use of a respiratory symptom questionnaire and
measurement of lung function. The earliest of these studies
(Wright, 1968) did not include those who had been employed by
the company for less than 10 years, but Nasr et al. (1971)
studied nearly all male employees (N = 2028), including 196
office workers. Radiographic appearances were characterized
using different conventions.

Wright (1968) did not find any unusual radiological
patterns, and the frequency of various radiological appearances
among those characterized subjectively as "likely to have had
highest exposure" was no greater than in those considered to
have least exposure. Nasr et al. (1971) reported very similar
prevalences of radiographic abnormalities among the office and
production workers (17% and 16%, respectively). Mean ages and
mean durations of employment in 6 age groups were correlated
almost perfectly, and these mean values were each correlated
positively with the prevalence rates in the age groups. Thus,
there was almost total confounding between the average age and
duration of employment in the grouped data.

Utidjian & Cooper (1976) failed to demonstrate any
significant differences in the prevalence of chronic respiratory
illness or impairment of lung function between categories of
workers designated as likely to have had the highest and lowest
exposures to airborne fibres in the same plant. However,
neither tabular nor graphical presentations of results were
included in their brief report.

Engholm & Von Schmalensee (1982) collected data, through
self-administered questionnaires, on occupational histories,
smoking habits, and respiratory symptoms in 135 000 men working
in the Swedish construction industry. Reports of respiratory
symptoms indicative of chronic bronchitis were grouped according
to age, duration of exposure to MMMF, smoking habits, and
whether or not there had been any occupational exposure to
asbestos. Standardized prevalence rates of bronchitic symptoms,
adjusted for age and for histories of exposure to asbestos,

increased consistently with increasing years of exposure to MMMF
in each smoking category. The authors discuss likely sources of
bias in their results, including the possibility that factors
not considered in their analysis may have been correlated with
duration of exposure to MMMF and with the occurrence of
bronchitic symptoms (confounding). They argue that their
results are unlikely to be explained in this way. This argument
is weakened by their observation of a possible association
between bronchitis and exposure to asbestos in their data and
subsequent demonstration of substantial errors in the self-
administered-questionnaire-determined exposures for asbestos
(Engholm et al., in press).

Other studies listed in Table 20, with apparently negative
or equivocal results, are even more difficult to interpret
epidemiologically, because of: the small numbers of persons
studied, the selection criteria adopted to justify inclusion in
analyses, the absence of information on likely intensity or
duration of exposure to fibres, or incomplete documentation of
study procedures and findings.

In summary, results from available cross-sectional studies
indicate that occupational exposure to various types of MMMF may
be associated with adverse effects on the respiratory tract, but
no consistent pattern has emerged. Findings suggesting this
association require confirmation, preferably in longitudinal
investigations of exposed cohorts, including ex-employees. In
particular, follow-up of the observed increased prevalence of
small opacities in smokers exposed to MMMF would be valuable.

8.1.2.2. Historical prospective studies

The design and results of relevant historical prospective
analytical epidemiological studies are presented in Table 22.
The most extensive historical prospective studies of disease
incidence and mortality in populations occupationally exposed in
the production of MMMF have been those conducted in the USA by
Enterline et al. (in press) and in 7 European countries by
Simonato et al. (1986a,b, in press). The results of studies on
widely overlapping- or sub-cohorts of these 2 large investiga-
tions have also been reported (Enterline & Henderson, 1975;
Bayliss et al., 1976; Robinson et al., 1982; Morgan et al.,
1984; Andersen & Langmark, 1986; Bertazzi et al., 1986; Claude &
Frentzel-Beyme, 1986; Gardner et al., 1986; Olsen et al., 1986;
Teppo & Kojonen, 1986; Westerholm & Bolander, 1986). Discussion
will be restricted mainly to results of: the complete cohorts in
the 2 large investigations (Simonato et al., 1986a,b, in press;
Enterline et al., in press), studies of two smaller, but
distinct, cohorts of production workers (Moulin et al., 1986;
Shannon et al., in press), and a cohort and case-control study
of construction workers (Engholm et al., in press).

Table 22. Historical prospective (cohort) and case-control studies of MMMF-exposed workers
--------------------------------------------------------------------------------------------------------
Study protocol Results^a Comments Reference
--------------------------------------------------------------------------------------------------------
16 661 male workers Compared with local rates, Asbestos may have been used in Enterline
in 11 fibrous glass no excess of mortality from some of the mineral wool plants; et al.
(6 glass wool, 3 NMRD for glass wool or con- race unknown for about 30% of (1983,
glass filament, and tinuous filament workers, the cohort, so white male death in press);
2 mixed) and 6 statistically nonsignifi- rates used for expected values; Enterline &
mineral wool plants cant excess in mineral average exposure for glass fila- Marsh
in the USA employed wool workers; significant ment, 0.011 fibres/cm³; for glass (1984)
for 1 year (6 months excess in all malignant wool, 0.033 fibres/cm³; for mixed
at 2 plants) between neoplasms and lung cancer fibrous glass, 0.059 fibres/cm³;
1945 and 1963 (1940- 20 years or more after and for mineral wool, 0.352
63 for 1 plant) first employment (mal- fibres/cm³; 147 of the 301 res-
followed up to 1982 ignant neoplasms, O:E = piratory cancer deaths 20 years
(98% traced; 4986 735:678; lung cancer, O:E = from first exposure occurred at
deaths; caused 288:255.5) compared with one plant (validity of use of
determined for 97% local rates; excess of res- local rates for this plant ex-
of deaths); piratory cancer greatest in amined); smoking survey showed
comparison with age- mineral wool workers (O:E = smoking habits of MMMF workers
and calendar- 45:34.4 for those with > 20 similar to those of US white
adjusted mortality years from first exposure); males
rates for males in in workers with 30 years
the USA or county from first exposure, ex-
(malignant neoplasms cess of respiratory cancer
only); exposure in all but continuous fila-
estimate based on ment production (significant
environmental survey only in mineral wool wor-
and information kers); excess (nonsignificant)
concerning changes of respiratory cancer among
in control over the 1015 workers "ever exposed"
study period in the production of small
diameter fibres compared with
those "never exposed" in this
sector (O:E = 22:17.8; for
those with > 30 years after
first exposure, O:E =
6:3.03); little relationship
between respiratory cancer and

Case-control study Statistically significant Enterline
of all MMMF workers relationship between esti- et al.
from above cohort mated cumulative exposure (in press)
who died of NMRD or and respiratory cancer in
respiratory cancer mineral wool, but not in
between January 1950 fibrous glass workers after
and December 1982 control for smoking (deter-
(cases) and a 4% mined by telephone interviews
random sample of of workers or their families)
workers stratified
by plant and year of
birth (controls)

21 967 workers in 13 No excess in NMRD compared Largest cohort studied to date; Saracci
MMMF plants (7 rock with national rates (O:E = advantage that some cancer inci- et al.
wool, 4 glass wool, 165:164.9) in total cohort dence data available; however, (1984a,b);
and 2 continuous or any sector; significant workers with < 1 year of employ- Simonato
filament) in 7 excess of mortality from ment comprised about 1/3 of the et al.
European countries all neoplasms (O:E = cohort; past manufacture of glass (1986a,b,
followed from first 661:597.7), due mainly to wool in one of the continuous in press)
employment (1900-55) significant excess of filament plants; in "early tech-
to 1982 (95% traced; lung cancer (O:E = 189:151.2) nological phase" of rock wool/
2719 deaths; causes and non-significant excess slag wool production, airborne
determined for 98.3% in cancers of the buccal fibre concentrations higher due
of deaths) (> 1 year cavity and pharynx (O:E = to absence of dust suppressing
employment in 13:10.6), rectum (O:E = agents; for glass wool, however,
English and Swedish 33:27), larynx (O:E = changes in airborne fibre con-
plants); comparison 9:6.3), and bladder (O:E = centrations between early and
with national 24:17.9); no relationship "intermediate technological

Table 22. (contd.)
--------------------------------------------------------------------------------------------------------
Study protocol Results^a Comments Reference
--------------------------------------------------------------------------------------------------------
mortality and, where with time since first expo- phase" less marked due to
available, incidence sure for any of the tumour opposing effects on airborne
specific for types except lung cancer fibre levels of use of dust sup-
calendar period, (O:E = 29:16.8 for > 30 pressants and reduction of fibre
sex, and age, and years from first exposure) diameters; in the "early techno-
adjusted, in some and bladder cancer; in- logical phase" of rock wool/
cases, for local crease in mortality from slag wool production, use of
variations; lung cancer for all sectors arsenic-containing slags, and
historical (continuous filament, glass poor ventilation (resulting in
environmental wool, and rock wool/slag potential exposure to PAHs);
investigation wool) compared with national data on smoking habits not
rates with relation with available; some use of asbestos
time from first exposure for in some plants
rock wool/slag wool and glass
wool subcohorts; when ad-
justed for local rates, in-
crease in mortality from
lung cancer for rock wool/
slag wool workers, only,
related to time from first
exposure; no relationship
of lung cancer with duration
of employment; excess of lung
cancer greatest in rock wool/
slag wool workers employed
in the "early technological
phase" (SMRs = 257 and 214
for comparison with local and
national rates, respectively);
for bladder cancer, excess in
glass wool and rock wool/slag
wool workers related to time
from first exposure in rock
wool/slag wool production;
lung cancer incidence increased
in rock wool/slag wool sub-
cohort related to time from
--------------------------------------------------------------------------------------------------------

2557 men with > 90 Deaths from NMRD fewer Data on smoking not available, Shannon
days employment in a than expected; significant but increase probably too large et al.
glass wool plant excess of lung cancer (O:E = to be attributable solely to (1984a,b,
between 1955 and 19:9.5) among "plant only" this cause; local mortality in press)
1977 followed to employees not related to rates for lung cancer similar
1984 (97% traced; duration of, or time since to those of Ontario and Canada;
155 deaths); first, exposure no historical exposure data
comparison with age-
and calendar-
specific death rates
of Ontario males

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

Case-control study Smoking and population May be selection bias since pos- Engholm
of 518 construction adjusted relative risk sibly a "survivor population"; et al.
workers with for MMMF exposure (adjusted construction workers frequently (1984,
respiratory cancer for asbestos exposure) - exposed to many dusts and trem- in press)
from above cohort 1.21 and for asbestos expo- endous difficulty in character-
compared with sure (adjusted for MMMF izing exposure that was inter-
maximum of 5 exposure) - 2.53 mittent, varied in intensity,
controls each and based largely on worker re-
matched for age, call
time of first check-
up, and survival;
smoking habits and
residence (urban/
rural) taken into
account in the
analyses

Table 22. (contd.)
---------------------------------------------------------------------------------------------------------
Study protocol Results^a Comments Reference
---------------------------------------------------------------------------------------------------------
1374 men with > 1 Significantly higher inci- Large loss to follow-up; those Moulin
year employment in a dence of cancers of the lost were considered to be et al.
glass wool factory larynx (SIR = 2.3), alive; authors reported that (1986)
between 1975 and pharynx (SIR = 1.4), and mortality in region where plant
1984 followed up to buccal cavity (SIR = 3) in located did not differ signifi-
1984 (92.7% traced); production but not in ficantly from comparison regions,
comparison with age- administration and main- but did not indicate basis for
and calendar- tenance workers; some rel- the conclusion; it was also
specific incidence ationship between SIRs and reported that tobacco smoking
for 3 regional duration of exposure (not no more frequent in cohort than
French cancer statistically significant) in general population (based on
directories (not estimates in workers in 1983);
including population mean time since first exposure,
in the region where 17.6 years; number of expected
the plant was lung cancers in workers with
located) more than 20 years exposure
small; study conducted due to
observation by an industrial
physician of an excess of can-
cers of the upper respiratory
and alimentary tracts - essen-
tially confirmation of a case
report

--------------------------------------------------------------------------------------------------------
^a Excesses that were statistically signficant at P < 0.05 are described as "significant"; all other
excesses were not statistically signficant.
NMRD = Non-malignant respiratory disease.
MRD = Malignant respiratory disease.
SMR = Standardized mortality ratio.
SIR = Standardized incidence ratio.
Standardized Mortality Ratios (SMRs) for non-malignant
respiratory disease and their statistical significance at the
conventional level of P = 0.05 for the main results in the
European and US studies are presented in Table 23. In both
studies, the authors preferred the use of local rates to
national rates for the purposes of comparison and presented
evidence of the reasons for this in fibrous glass workers
(Gardner et al., 1986; Enterline et al., in press).

There has been little evidence of an excess of mortality
from non-malignant respiratory disease (NMRD) in the cohort and
case-control studies conducted to date. In the extensive
European study of 21 967 production workers, there was no excess
mortality from NMRD in the total cohort, in any production
sector (i.e., continuous filament, glass wool, or rock wool/slag
wool), or on analysis according to time from first exposure or
duration of employment (Simonato et al., 1986a,b, in press). In
the large cohort of 16 661 production workers in the USA, there
was no excess mortality from NMRD in glass wool workers compared
with local rates^a (O = 144, SMR = 103), though there was a
statistically significant excess compared with national rates
(O = 158, SMR = 134). In mineral wool workers, there was a
statistically nonsignificant excess of NMRD compared with both
local (O = 31, SMR = 140) (Enterline et al., in press) and
national rates (O = 31, SMR = 145) (Enterline & Marsh, in
press). In continuous filament workers, there was no excess
compared with either local (O = 35, SMR = 98) or national rates
(O = 41, SMR = 90).
---------------------------------------------------------------------
^a In the US study, SMRs based on local rates are for the
period 1960-82; SMRs based on national rates are for the
period 1946-82.

Table 23. Non-malignant respiratory disease mortality - epidemiological
studies of MMMF production workers^a
-------------------------------------------------------------------------
Feature Study Fibre type
Glass Glass Rock wool/
filament wool^b,c slag wool
---------------------------------------------------------------------------
Number of USA 35 144 31
deaths from Europe 13 93 59
non-malignant ----------------------------------------------------------
respiratory Standardized mortality ratios compared with local rates^d,e
disease

Non-malignant USA 98 102 140
respiratory Europe 96 105 94
disease (national)
mortality

Time since USA 0/124/110/69 52/92/118/93 0/230/134/123
first expo- Europe 0/145/159/0 63/118/115/113 101/90/72/142
sure (< 10/ (national)
10-19/20-29/
30+ years)

Duration of USA 116/78 136/118
employment Europe 240/0 121/71 90/114
(< 20/20+ (national)
years) (> 20
years since
first exposure)

Estimated USA 97/130/107/0 126/79/74/95 158/141/160/117
cumulative
exposure (in-
creasing in-
tervals of
fibre/cm³
x months)

Small dia- USA
meter fibres
- ever/never - 110/97 -
exposed

- by time - 0/44/164/113 -
since first
exposure
(ever ex-
posed)
-------------------------------------------------------------------------
^a IARC (1985) and Enterline & Marsh (in press).
^b Data for "fibrous glass-both" and "fibrous glass-wool" plants in the
USA study combined.
^c In the only additional relevant study of a much smaller cohort of
glass wool production workers, there was no excess of mortality
from non-malignant respiratory disease (O = 4, SMR = 55) compared
with provincial rates (Shannon et al., in press).
^d Local rates, unless otherwise specified.
^e No SMRs nor trends shown in this table are statistically significant
at the conventional P = 0.05 level.

The results of analyses of NMRD mortality with time from
first exposure, or duration of exposure, or cumulative fibre
exposure did not showed any trends for either the glass wool or
rock wool workers. Among glass wool workers "ever exposed" to
small diameter fibres, there was no excess of NMRD mortality but
a slight statistically insignificant increase with time since
first exposure.

Shannon et al. (in press) studied 2557 glass wool workers
with more than 90 days employment and found 4 deaths from NMRD,
whereas 7.3 would have been expected (SMR = 55). Engholm et al.
(in press), in their study of 135 026 Swedish construction
workers potentially exposed to MMMF and asbestos, found 193
deaths from NMRD compared with 418 expected; this gave an
unusually low SMR of 46.

8.1.3. Carcinogenicity

Standardized mortality ratios (SMRs) and their statistical
significance at the conventional level of P = 0.05 for the main
results in the European and US studies are presented in Table
24. In both studies, the authors preferred the use of local
rates to national rates for the purposes of comparison and
presented evidence of the reasons for this in fibrous glass
workers (Gardner et al., 1986; Enterline et al., in press).

8.1.3.1. Glass wool

In the European study (Simonato et al., 1986a,b, in press),
there was no significant excess of mortality from lung cancer
(O = 93, SMR = 103) among glass wool production workers, when
compared with local mortality rates. However, there was a
statistically non-significant relationship between lung cancer
mortality and time from first exposure. When compared with
national mortality rates, there was a statistically significant
excess of lung cancer that was related (O = 93, SMR = 127) (not
statistically significantly) to time from first exposure. There
was no relationship between lung cancer mortality and duration
of employment. No excess was discernible among workers employed
in the "early technological phase", whichever reference rate was
used.

In the USA glass wool subcohort (Enterline et al., in
press), the SMR for lung cancer was 109 (O = 267, statistically
nonsignificant), based on local rates, and 116 (O = 267,
statistically significant), based on national reference rates.
After 20 years from the onset of exposure, the SMR was not
statistically significant compared with local rates (111) but
was statistically significant compared with US rates (124),
based on 207 observed cases. There was a statistically
nonsignificant increase with time since first exposure, but the
rend was less evident when local rates were used. There was no
relationship between respiratory cancer mortality and duration
of exposure, or cumulative fibre exposure. There was also an
excess (not statistically significant) of mortality due to lung
cancer among 1015 workers "ever exposed" in the production of

fibres of nominal diameter < 3 µm (O = 22, SMR = 124), where
measured fibre levels were higher than in other production
sectors, compared with those "never exposed" in this sector.
The excess showed an increasing but non-significant relationship
with time from first exposure.

Table 24. Lung cancer mortality - epidemiological studies of MMMF
production workers^a
-------------------------------------------------------------------------
Feature Study Fibre type
Glass Glass Rock/slag
filament wool^b,c wool
---------------------------------------------------------------------------
Number of USA 64 267 60
deaths from Europe 15 93 81
lung cancer ---------------------------------------------------------
Standardized mortality ratios compared with local rates

Lung cancer USA 92 109 134 ( P < 0.05)
mortality Europe 97 103 124

Time since USA 104/53/119/80 92/108/108/114 90/157/127/135
first expo- Europe 176/76/0/0 68/113/100/138 104/122/124/185
sure (< 10/
10-19/20-29/
30+ years)

Duration of USA 110/106^d 145/111
employment Europe 0/0 118/60 143/141
(< 20/20+
years) (> 20
years since
first exposure)

Estimated USA 96/51/109/63 120/109/81/108 185/164/119/104
cumulative
exposure (in-
creasing
intervals of
fibre/cm³
x months)

Technological Europe
phase
- early/inter- - 92/111/77 257/141/111
mediate/late ( P < 0.05)^e

- by time since - 108/70/80/121 0/0/317/295
first exposure
(early phase)

Small dia- USA
meter fibres
- ever/never - 124/105 -
exposed
-------------------------------------------------------------------------

Table 24. (contd.)
--------------------------------------------------------------------------
Feature Study Fibre type
Glass Glass Rock/slag
filament wool^b,c wool
---------------------------------------------------------------------------
Standardized mortality ratios compared with local rates

- by time - 61/128/105/198 -
since first
exposure
(ever ex-
posed)

Estimated con- USA lower intermediate higher
centrations of (highest in
respirable small diameter
fibres fibre produc-
tion facilities)
-------------------------------------------------------------------------
^a Modified from: IARC (in press).
^b Data for "fibrous glass-both" and "fibrous glass-wool" plants in the
USA study combined.
^c In the only additional relevant study of a much smaller cohort of
glass wool production workers, there was a statistically significant
excess of lung cancer mortality compared with provincial rates (O
= 19, SMR = 199), which was not related to time from first
exposure (< 10 years, SMR = 241; 10+ years, SMR = 195) or duration of
employment (< 5 years, SMR = 291; > 5 years, SMR = 174) (Shannon et
al., in press).
^d Data reported for "fibrous glass" (type unspecified) subcohort.
^e Statistical test for linear trend.

A case-control study nested in the US cohort was conducted
by Enterline et al. (in press) with an initial number of 211
respiratory cancer cases among "fibrous glass" (type
unspecified) workers and 374 controls. The logistic analysis
performed indicated a statistically significant association
between lung cancer and the smoking habits of workers but not
between lung cancer and cumulative fibre dose.

In a glass wool plant in Ontario, there was a statistically
significant (2-fold) excess of mortality from lung cancer,
compared with provincial rates, among 2557 "plant only"
employees with more than 90 days employment (O = 19, SMR = 199)
(Shannon et al., in press). The lung cancer rates did not
appear to be related to time from first exposure or duration of
employment.

The rate of mesothelioma in glass wool production workers in
the large US study was not excessive. Two cases were reported.
No cases in glass wool workers were reported in the European
study.

Moulin et al. (1986) reported a statistically significant
higher incidence of cancers of the buccal cavity (O = 9,
Standardized Incidence Ratio (SIR) = 301) in production workers
with more than 1 year of employment in a glass wool factory in
France; the excess was related to duration of exposure but not
significantly so. This study was conducted following an
observation by an industrial physician of an excess of cancers
of the upper respiratory and alimentary tracts and must,
therefore, be considered to be essentially a confirmation of a
case report. On their own, therefore, these findings do not
constitute convincing evidence of a real association. Moreover,
the reported SIRs were based on comparison with rates of regions
other than the one in which the plant was located.

A statistically nonsignificant excess of mortality due to
laryngeal cancer was observed in a subcohort of the European
study among 1098 Italian workers employed for at least 1 year in
a plant manufacturing glass wool (Bertazzi et al., 1986). There
was some relationship with time from first exposure, but the
number of cases was small (O = 4, SMR = 190). These findings
were limited to the Italian plant and were not consistent with
either the results of the complete European or US studies.
Moulin et al. (1986) also reported a statistically non-
significant excess in the incidence of cancer of the larynx (O =
5, SIR = 230) in their cohort of 1374 glass wool production
workers with more than 1 year of employment. However, this
observation should be interpreted with caution, owing to the
limitations of this study mentioned earlier.

8.1.3.2. Rock wool and slag wool

In the European subcohort of rock wool/slag wool production
workers, there was a statistically nonsignificant excess of
mortality from lung cancer, which was the same compared with
either local or national mortality rates (O = 81, SMR = 124).
There was a statistically nonsignificant relationship with time
from first exposure (Simonato et al., 1986a,b, in press) but not
with duration of employment. The excess was concentrated among
workers employed in the "early technological phase" (with large
SMRs of 257 and 214 for local and national comparisons,
respectively, both statistically significant and based on 10
observed cases), in which airborne fibre levels were estimated
to have been much higher. The use of copper slag containing
arsenic was also reported in one factory during this period and
ventilation was generally poor, possibly resulting in some
exposure to polycyclic aromatic hydrocarbons (PAHs) from the
furnaces. Other environmental contaminants that might have had
an influence on the lung cancer mortality excess have also been
analysed. A statistically significant increase in lung cancer
mortality after 20 years since first exposure was associated
with the use of slag (O = 23, SMR = 189). However, these
findings are difficult to interpret due to the wide overlapping
between the period of use of slag and the early technological
phase. Neither the use of bitumen and pitch nor the presence of
asbestos in some products explained the excess of lung cancer

(Simonato et al., in press). The results of analysis of data on
lung cancer incidence in the European cohort were similar to
those reported for mortality.

Enterline et al. (in press) studied a cohort of 1846 white
male workers from 6 US plants that produced slag wool or rock
wool/slag wool. The SMRs for respiratory cancer were 134 (local
rates) and 148 (national rates), both statistically significant,
based on 60 observed cases. After 20 years since first exposure,
the SMRs were 131 (local rates) and 146 (national rates), the
latter being statistically significant, based on 45 observed
cases. No clear trend with time since first exposure was found,
and there was no relationship with duration of employment, or
with estimated cumulative exposure in this subcohort of the US
study. It was reported that one of the plants studied used a
copper slag containing arsenic.

A case-control study nested in the US rock wool/slag wool
production subcohort was also carried out using the same
methodology as that for the glass wool production workers. The
study comprised 45 respiratory cancer cases and 49 controls.
Only the relationship between lung cancer and smoking was
statistically significant ( P < 0.001). In a further analysis,
using 38 cases and 43 controls, there was a statistically
significant relationship between lung cancer and estimated
cumulative fibre dose ( P < 0.01), after controlling for years
of smoking, time since starting to smoke, and interaction terms
between smoking and exposure. Reservations about the model used
for this analysis complicate the interpretation of these
results.

Only one case of pleural mesothelioma was reported in the
rock wool/slag wool production workers in the US cohort.
Similarly, in the large European cohort (Simonato et al.,
1986a,b, in press), only one pleural mesothelioma occurred in a
rock wool/slag wool production plant with a brief latency period
following a relatively short exposure time. This single case
does not represent an excess.

In the European study, there was a statistically significant
excess in the incidence of cancer of the buccal cavity and
pharynx (O = 22, SIR = 180), which showed a statistically
nonsignificant relationship with time from first exposure. Also
observed in the European study was a statistically non-
significant excess in bladder cancer mortality (O = 13, SMR =
137) in the rock wool/slag wool production sectors, which was
related at a statistically significant level to time from first
exposure (IARC, 1985). In neither of these cases was there an
association with the early technological phase when fibre levels
were estimated to be higher.

8.1.3.3. Glass filament

In the glass filament subcohort of the European study, there
was no excess of mortality from lung cancer compared with local

mortality rates (O = 15, SMR = 97), but a small excess (not
statistically significant) compared with national rates (O = 15,
SMR = 120), which was not related to time from first exposure
(Simonato et al., 1986a,b, in press). However, it should be
noted that the length of follow-up of the continuous filament
workers in this study was short.

No excess for lung cancer was reported by Enterline et al.
(in press) from the follow-up of 3435 white male workers
employed in glass filament production in the large US study.
The SMRs for respiratory cancer were 92 (local rates) and 95
(national rates), based on 64 observed cases. There was no
relationship with time since first exposure, or with estimated
cumulative fibre dose.

8.1.3.4. Mixed exposures

Engholm et al. (in press) reported the results of the
follow-up of a large cohort of construction workers in Sweden.
The SIR for lung cancer was 91 based on 440 observed cases. The
authors also investigated the possible influence of exposure to
asbestos and to MMMF using a nested case-referent approach.
After adjusting for asbestos exposure, the relative risk for
exposure to MMMF was 1.21 (95% CI: 0.60 - 2.47), while it was
2.53 (95% CI: 0.77 - 8.32) for asbestos after controlling for
potential MMMF exposure. A wide overlapping of asbestos and
MMMF exposures makes the analysis and interpretation of the
results of this study difficult.

8.1.3.5. Refractory fibres

No published epidemiological studies are available.

8.2. General Population

With the exclusion of isolated case reports of respiratory
symptoms and dermatitis associated with exposure to MMMF in the
home and office environments, and 2 limited cross-sectional
studies of ocular and respiratory effects in offices and
schools, adverse effects on the general population have not been
reported. For example, Newball & Brahim (1976) attributed
respiratory symptoms in members of a family to fibrous glass
exposure from a residential air conditioning system. Dermatitis
has been observed in individuals exposed to disturbed MMMF
insulation in office buildings (Verbeck et al., 1981; Farkas,
1983) and to clothing contaminated during laundering with MMMF-
containing materials (Lucas, 1976).

A significant increase in the incidence of "smarting" and
watering eyes, swollen eyelids, disturbance of sight, conjunc-
tival hyperaemia, and "smarting" of the nose was observed in 39
persons working in buildings with ceilings made of compressed
mineral wool compared with a control group of 23 persons,
matched for age, sex, and smoking habits, who were working in

buildings with plaster ceilings. In 5 of the exposed indivi-
duals, mineral fibres were present in the conjunctival mucous
threads compared with 0 in the control group. It was also
reported that the occurrence of symptoms and conjunctival
hyperaemia were significantly reduced by surface treatment of
the mineral wool ceiling (Alsbirk et al., 1983).

The association between various signs and symptoms of
disease and exposure to MMMF in adults and children in 24
kindergartens was investigated in one Danish county in Autumn
1984 (Rindel et al., 1987). In 10 kindergartens, the ceilings
were covered with MMMF products with water-soluble binder (Group
A), 6 had resin-bound ceiling covering material (Group B), and 8
had ceilings on which MMMF was not apparent (Group C). The
investigation included questionnaires for the adults (n = 200,
92% response) concerning health and socio-economic status,
smoking habits, and contact lens use (mode of administration not
stated); questionnaires for children (n = 900, 90% response)
were completed by their parents. In addition, for 3 months,
daily records were kept by the adults of their own signs and
symptoms of disease and those of the children. All subjects
were also clinically examined by a doctor. Concentrations of
fibres and dust, carbon dioxide levels, temperature, humidity,
and air speed were also determined. Mean total airborne MMMF
levels were similar in Groups A and B (23 fibres/m³ and 40
fibres/m³, respectively), but ranged from 0 to 77 fibres/m³ in
Group C. Among children, there was no correlation between
disease symptoms and MMMF concentrations. For adults, eye
irritation was significantly related to respirable ( P = 0.03)
and non-respirable ( P = 0.004) MMMF. The presence of settled
MMMF on surfaces was correlated with adult skin irritation ( P =
0.005). However, the authors concluded that the total MMMF in
air derived from ceiling coverings did not explain the reported
symptoms and diseases. Unless the adults were not informed of
the hypothesis to be tested, and the physician involved
"blinded", it is difficult to see how bias could have been
avoided.

There have not been any mortality or cancer morbidity
studies concerning exposure to MMMF in the general population.

9. EVALUATION OF HUMAN HEALTH RISKS

Whenever possible, emphasis is placed on data obtained in
epidemiological studies of human populations exposed to MMMF,
though few data on quantitative exposure-response relationships
are available. Information from animal and in vitro studies is
used mainly in the comparative assessment of the potency of
various fibre types and sizes, particularly when human
epidemiological studies are lacking or the results are not clear
cut, as is the case for some MMMF.

9.1. Occupationally Exposed Populations

There have been isolated reports of dermatitis and eye
irritation in workers exposed to MMMF (section 8.1.1). However,
no human data are available concerning the exposure-response
relationship for these effects, and animal studies have not been
conducted to evaluate either of them specifically.

In addition, there has been some suggestion of non-malignant
respiratory effects (e.g., decrements in lung function) in MMMF-
exposed workers (section 8.1.2), but some of these studies have
been methodologically weak. In the study regarded as the best
to date, a slight excess of small radiological opacities was
observed, but this was not accompanied by ventilatory decrement
or increase in respiratory symptoms. The results of experimental
animal studies have indicated that MMMF might be potentially
fibrogenic, especially when introduced into body cavities
(pleural and peritoneal) (section 7.1.1.1). However, a
significant fibrogenic response has not been seen in inhalation
studies, to date, though it should be noted that the information
in this regard is more complete for glass fibres than for other
MMMF. Thus, it is not possible, on the basis of available data
from human epidemiological and experimental animal studies, to
draw definite conclusions concerning the nature and extent of
the possible non-malignant hazards for the respiratory system
resulting from exposure to MMMF.

An important concern is the potential risk of cancer in
workers exposed to MMMF. Although there is no evidence that
pleural or peritoneal mesotheliomas have been associated with
occupational exposure in the production of various MMMF, there
have been indications of increases in lung cancer mortality from
the main epidemiological studies of workers in some sectors of
MMMF production, including the two most extensive investigations
of workers in Europe and the USA (section 8.1.3).

In the rock wool/slag wool production industry, the
standardized mortality ratios for lung cancer in the large
European and US cohorts were 124 and 134, respectively (Simonato
et al., 1986a,b, in press; Enterline et al., in press). In the
glass wool production industry, the corresponding SMRs were 103
and 109, respectively. There has been no increase in lung
cancer mortality in continuous filament production workers; SMRs
in the European and US studies were 97 and 92, respectively.

However, available data are too few to establish a quantitative
exposure-response relationship for lung cancer mortality in
relation to airborne fibre concentrations.

There has been some suggestion in these cohort studies of
increases in cancer at sites other than the lung, but, it is not
possible, on the basis of the available data, to draw any
conclusions concerning the possible role of occupational
exposure during MMMF production in the etiology of these other
malignant diseases.

It has been suggested that other factors present in the
work-place may have contributed to the increased lung cancer
mortality observed, such as the presence of contaminants in the
slag used, particularly in the early phase of mineral wool
production in the European study. However, where it has been
possible to study such contaminants, including asbestos and
arsenic in copper slag, the lung cancer excess was not explained
by their presence. Furthermore, it is not likely that any known
potential confounding factors for lung cancer mortality,
including cigarette smoking, could explain the high rates
observed in the early technological phase of the rock wool/slag
wool industry in Europe. The hypothesis that the airborne fibre
concentrations are the most important determinants of lung
cancer risk is supported by the observation of a qualitative
relationship between the standardized mortality ratios and past
estimated airborne fibre levels in the various sectors (rock
wool/slag wool, glass wool, and continuous filament) of the
production industry. Moreover, while not statistically
significant, there was a rise in lung cancer risk that increased
with length of time since first exposure in workers involved in
the production of smaller diameter (< 3 µm) glass wool fibres
in the USA. Airborne fibre levels measured in this sector are
higher than those in the rest of the glass wool production
sector. However, it should be emphasized that, at the lower
fibre concentrations associated with the improved production
conditions of the late technological phase, no excess of lung
cancer mortality has been observed in the European rock
wool/slag wool workers.

Airborne MMMF concentrations present in work-places with
good work practices are generally of the order of, or less than,
1 fibre/cm³ (section 5). However, data reviewed in section 5
indicate that mean airborne fibre levels for some workers in the
ceramic fibre and small diameter (< 1 µm) glass wool fibre
manufacturing sectors may be similar to those to which workers
were exposed in the early production phase. Therefore, although
only a small proportion of workers are employed in these
segments of the industry, their lung cancer risk could
potentially be elevated. However, epidemiological data are not
yet available on workers in the ceramic fibre industry.
Elevated average concentrations of fibres during the blowing or
spraying of insulation wool in confined spaces have also been
recorded and, though the time-weighted average exposure for

individual workers may not be as high (section 5), their lung
cancer risk could similarly be increased, if protective
equipment is not used.

The results of animal studies, in toto, indicate that the
excess of lung cancer observed in the epidemiological studies in
some sectors of the MMMF production industry is biologically
plausible (section 7.1). Although in inhalation studies
(probably the most relevant studies for risk assessment in man)
conducted to date, MMMF have not induced a significant
carcinogenic response, the carcinogenic potential of many MMMF
has been demonstrated when they have been introduced directly
into the pleural and peritoneal cavities. The results of these
studies clearly show that the carcinogenic potential in animals
is directly related to fibre size and durability. In addition,
glass fibres have been shown to cause chromosomal alterations
and cell transformation in vitro, but little information in
this regard is available for the other MMMF (section 7.2).

9.2. General Population

There have been isolated case reports of respiratory
symptoms and dermatitis associated with exposure to MMMF in the
home and office environments (section 8.2). However, available
epidemiological data are not sufficient to draw any conclusions
in this respect. As with occupationally-exposed populations, it
is the potential risk of lung cancer at low levels of exposure
that is of most concern, but no direct evidence is available
from which to draw conclusions.

Available data on occupationally-exposed populations are not
yet sufficient to estimate quantitatively, by extrapolation to
low levels, the risk of lung cancer in the general population
associated with exposure to MMMF in the environment. Moreover,
the available information is inadequate to characterize exposure
to MMMF in the general environment. However, levels of MMMF in
the typical indoor and general environments, measured to date,
are very low compared with present levels in most sectors of the
production and user industry and certainly much lower (by
several orders of magnitude) (sections 5.1.1.2 and 5.1.1.3) than
some past occupational exposure levels associated with raised
lung cancer risks. It should also be noted that such increases
in lung cancer risk have not been observed among workers
employed under the improved conditions of the late technological
phase and followed up for a sufficient length of time.

The overall picture indicates that the possible risk of lung
cancer among the general public is very low, if there is any at
all, and should not be a cause for concern if the current low
levels of exposure continue.

10. RECOMMENDATIONS

10.1. Further Research Needs

10.1.1. Analytical methods

The current reference scheme for the measurement of MMMF
concentrations in the occupational environment by the membrane
filter optical and scanning electron microscopic methods should
continue.

There is also a need to standardize methods of measurement
of MMMF in ambient and indoor air; ideally, such methods should
determine both the total mass of dust and the number of fibres
likely to be deposited in the respiratory system. Where
scanning electron or transmission electron microscopy are used,
fibre size distribution should be fully characterized. Greater
standardization of sample preparation and measurement methods
for the determination of MMMF in other media, including
biological tissues, is also desirable.

Further research on the development of automated fibre
counting methods, which may improve the consistency of results
obtained in different laboratories, should be conducted. The
development of cheaper and more practical methods of determining
fibrous particulates is also desirable.

For fibrous dusts with the potential for causing non-
malignant and malignant diseases of the airways and lung
parenchyma, attention should, in future, be paid to the
measurement and study of the effects of the fraction of fibres
(inhalable) that is mainly deposited on the surface of the
airways as well as the fraction ("respirable") with a high
efficiency for airway penetration and deposition in the
alveoli.

10.1.2. Environmental exposure levels

There is a need to determine levels of MMMF in the
environment that are representative of general population
exposure, and it is recommended that respirable levels of MMMF
in ambient and indoor air should be measured by appropriate and
preferably standardized methods of sampling and analysis.
Analysis of the MMMF contents of tissues in both occupationally
exposed groups and the general population is also recommended.

10.1.3. Studies on animals

Standardized reference samples of MMMF products as well as
size-selected fibre samples should be developed for use in
experimental animal studies. Complete characterization and
reporting of the fibre size distributions of MMMF used in such
investigations is also essential.

Research to investigate the relative potencies of the
various MMMF types (preferably by routes of exposure that
simulate those of man, e.g., inhalation) should continue. The
effects of fibre coating on the potential of MMMF to cause
disease should be further examined and investigations of the
effects of concomitant exposure to MMMF and other airborne
pollutants (such as tobacco smoke) should be conducted.

Studies should be undertaken to examine further the
mechanisms by which fibrous materials cause disease.
Particularly relevant for the assessment of risks associated
with exposure to the MMMF is the examination of the biological
significance of the durability of fibres in tissue. Development
of short-term models of durability are needed, as well as a
comparison of durability in different locations in the body.

Studies on the relationship of fibrogenicity and carcino-
genicity are of special importance as is a better understanding
of the mechanisms of fibre toxicity, especially at the cellular
level (interaction of macrophages, etc.). Cytotoxicity and
genotoxicity studies should be extended to all MMMF (currently
available only on glass fibres).

As new fibres are developed, they should be subjected to
systematic investigation for the assessment of health hazard.
It would be desirable to develop a standard set of study
protocols for use in this regard.

10.1.4. Studies on man

Further study of the prevalence of dermatitis and eye
irritation in populations exposed occupationally to MMMF is
warranted. The respiratory effects observed in cross-sectional
studies of MMMF workers should be further investigated using
standardized methods to measure effects, including the
International Classification of Radiographs of Pneumoconiosis,
in appropriately designed epidemiological studies (WHO, 1983b).

Follow-up of MMMF-exposed workers examined in the historical
prospective studies reported to date should continue. The
possibilities of extending these investigations to meaningful
studies (in terms, for example, of size and time since first
exposure) on workers who have entered the glass wool and rock
wool industries more recently, those working with refractory
(including ceramic) fibres, special purpose fibres, or other
new fibres, and workers in the user industries should be
explored. These studies should be accompanied by the collection
of agreed comprehensive industrial hygiene data in advance of
the epidemiological analyses. Where possible, continued
attempts should be made to control for confounding factors, such
as cigarette smoking (perhaps by nested case-referent studies)
and past exposure to asbestos (perhaps by lung fibre burden
studies).

10.2. Other Recommendations

10.2.1. Classification of MMMF products

There is a need for setting up a systematic scheme for the
classification of the various MMMF products manufactured.

There is also a need to give guidance concerning the
potential for fibre release from MMMF products. As a first
step, information on fibre diameters in the bulk material is
essential.

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    See Also:
       Toxicological Abbreviations
       Man-made Mineral Fibres (IARC Summary & Evaluation, Volume 43, 1988)