297 917
ASBESTOS
Ambient water Quality Criteria
Criteria and Standards Division
Oltice of Water Planning and Standards
U.S. Environmental Protection Agency
Washington, D.C.
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CRITERION DOCUMENT
ASBESTOS
CRITERIA
Aquatic Life
For freshwater aquatic life, no criterion for asbestos can be
derived using the Guidelines, and there are insufficient data to
estimate a criterion using other procedures.
For saltwater aquatic life, no criterion for asbestos can be
derived using the Guidelines, and there are insufficient data to
estimate a criterion using other procedures.
Human Health
For the maximum protection of human health from the potential
carcinogenic effects of exposure to asbestos through ingestion of
water and contaminated aquatic organisms, the ambient water con-
centration is zero. Concentrations of asbestos estimated to re-
sult in additional lifetime cancer risk of 1 in 100,000 are pre-
sented in the Criterion Formulation section of this document. The
i
Agency is considering setting criteria at an interim target risk
i
level in the range of 10~5, 10~6, or 10~7 with corresponding cri-
teria of 300,000 fibers/1, 30,000 fibers/1, and 3,000 fibers/1,
respectively.
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Introduction
Asbestos is a broad term applied to numerous fibrous
mineral silicates composed of silicon, oxygen, hydrogen,
and metal cations such as sodium, magnesium, calcium, or
iron. There are two major groups of asbestos, serpentine
(chrysotile) and amphibole. Chrysotile is the major type
of asbestos used in the manufacture of asbestos products.
These products include asbestos cement pipe, flooring products,
paper products (e.g. padding), friction materials (e.g.
brake linings and clutch facings), roofing products, and
coating and patching compounds. In 1975, the total consump-
tion of asbestos in the U.S. was 550,900 thousand metric
tons.
Of the 243,527 metric tons of asbestos discharged to
the environment, 98.3 percent was discharged to land, 1.5
percent to air, and 0.2 percent to water. Solid waste dispos-
al by consumers was the single largest contribution to total
discharges. Although no process water is used in dry mining
of asbestos ore, there is the potential for runoff from
asbestos waste tailings, wet mining, and iron ore mining.
Mining operations can also contribute substantially to asbes-
tos concentrations in water via air and solid waste contamina-
tion. In addition to mining and industrial discharges of
asbestos, asbestos fibers, which are believed to be the
result of rock outcroppings, are found in rivers and streams.
The chemical composition of different asbestos fibers
varies widely and typical formulas are presented in Table
1 (U.S. EPA, 1976). It should be noted that the values
obtained from actual chemical analysis of the various fibers
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also may differ slightly from the typical formulas. Although
chrysotile is considered to be a distinct mineral, the five
amphibole minerals are each varieties of other minerals
(Zoltai and Stout, 1976) . These minerals differ from each
other both chemically and physically with the exception
that they all contain silicon and all form fibers when crushed,
Good quality asbestos will form fibers with higher ratios
of length to width than poorer grades.
TABLE 1
Typical Formulas for Asbestos Fibers
1. Serpentines chrysotile Mg3Si2O5 (OH) 4
2. Amphiboles amosite (Mg,Fe) 7SigO22 (OH) 2
crocidolite Na/2 (Mg ,Fe) 5Sig022 (OH)
anthophyllite (Mg,Fe) 7Sig022 (OH) 2
tremolite Ca2Mg5SigO22 (OH) 2
actinolite Ca (Mg,Fe) Si0 (OH)
The basic crystal form of the amphibole minerals is
less complicated than for chrysotile. The basic structure
consists of a double silica chain (Si^O,-,) that is paired
back-to-back with a layer of hydrated cations between the
chains (Speil and Leineweber, 1969).
Some typical physical properties of three different
mineral forms are presented in Table 2 (Gaze, 1965) .
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TABLE 2
Typical physical properties of chrysotile (white
asbestos), crocidolice (blue asbestos), and amosite
Units Chrysotile Crocidolite Amosite
(white asbestos) ... (blue asbestos)
Approximate
diameter of
smallest fibers
Specific
gravity
Average
tensile
strength
micron 0
2
Ib./inch2 3
.01
.55
.5 x 105
0.08
3.37
5 x 105
0.
3 .
. 1.
1
45
75 x
105
Modulus of Ib./inch2 23.5 x 106 27.0 x 106 23.5 x 106
elasticity .
Asbestos minerals, despite a relatively high fusion tempera-
ture, are completely decomposed at temperatures of 1,000°C.
.1 .'" ' v -
Both the dehydroxylation temperature and decomposition tern-
' ' i
perature increase with increased MgO content among the various
amphibole species (Speil and Leineweber, 1969).
The solubility product constants for various chrysotile
11 12
fibers range from 1.0 x 10 to 3 x 10 . Most materials
have a negative surface charge in aqueous systems. However,
since chrysotile has a positive ( + ) charge, it will attract,
or be attracted to, most dispersed materials. The highly
reactive surface of asbestos causes many surface reactions
which are intermediate between simple absorption and a true
chemical reaction. The absorption of various materials
on the surface of chrysotile supports the promise that the
polar surface of chrysotile has a greater affinity for polar
molecules (e.g. H2O,NH3) than for non-polar molecules (Speil
and Leineweber, 1969).
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Of all the asbestos minerals, chrysotile is the most
susceptible to acid attack. It is almost completely destroyed
within one hour in 1 N HCL at 95°C. Amphibole fibers are
much more resistant to mineral acids (Lindell, 1972).
The resistance of the asbestos fibers to attack by
reagents other than acid is excellent up to temperatures
of approximately 100°C with rapid deterioration observed
at higher temperatures. Chrysotile is completely decomposed
in concentrated KOH at 200°C. In general, organic acids
have a tendency to react slowly with chrysotile (Speil and
Leineweber, 1959).
All forms of asbestos available commercially have been
shown to be carcinogenic in mice, rats, rabbits, and hamsters.
Occupational health studies on workers engaged in the mining,
milling amd manufacturing of asbestos have linked exposure
of this mineral to lung carcinomas, mesotheliomas, gastroin-
testinal cancers, and pulmonary asbestosis.
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REFERENCES
Gaze, R. 1965. The physical and molecular structure of asbes-
tos. Ann. N.Y. Acad. Sci. 132: 23.
Lindell, K.V. 1972. Biological effects of asbestos. Int.
Agency Res. Cancer, Lyon, France.
Speil, S., and J.P. Leineweber. 1969. Asbestos minerals
in modern technology. Environ. Res. 2: 166.
U.S. EPA. 1976. Asbestos: A review of selected literature
through 1973 relating to environmental exposure and health
effects. EPA-560/2-76-001. U.S. Environ. Prot. Agency, Wash-
ington, D.C.
Zoltai, T. and J.H. Stout. 1976. Comments on asbestiform
and fibrous mineral fragments relative to Reserve Mining
Co. taconite deposits. Prepared for Minnesota Pollut. Control
Agency.
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CRITERION FORMULATION
No appropriate data on the effects of asbestos on aquatic or-
ganisms are available at this time. Therefore, no freshwater or
saltwater criterion can be derived for asbestos using the Guide-
lines because no Final Chronic Value for either fish or inver-
tebrate species or a good substitute for either value is avail-
able, and there are insufficient data to estimate a criterion
using other procedures.
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ASBESTOS
Mammalian Toxicology and Human Health Effects
Summary
Estimating'a risk factor for ingestion of asbestos
presents significant difficulties. Although gastrointestinal
cancer has been linked to occupational exposures in several
groups of workers, no definitive data exist on the effects ..
of direct ingestion of asbestos, either in animals or humans.
Further, only limited information exists on air exposure
levels for those human studies showing excess risk of gastro-
intestinal cancer and peritoneal mesothelioma. Nevertheless,
the most valuable data on risk are those from human inhalation
exposures, and these will form the primary basis for a pro-
jected criterion.
This document is not an exhaustive review of all asbes-
tos literature nor are all important papers mentioned herein.
\ \ * >\ » '
However, the papers selected are deemed relevant for estimating
dose-response relationships.*
EXPOSURE
Analytical Techniques
The analytical techniques for the measurement of asbes-
tos minerals in air or water samples collected in occupa-
tional or general environmental circumstances are time-con-
suming, and the results are often highly variable. No single
method is suitable for all monitoring circumstances. Techni-
ques appropriate for monitoring workplace exposures are
unreliable when used to evaluate the much lower environmental
concentrations of asbestos, such as those found in water,
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largely because of the presence of quantities of other inorganic
and organic material. Electron microscopic methods used
for environmental monitoring are difficult to perform and
costly. Reproducible results can be obtained in experienced
laboratories if standardized techniques are utilized/ careful
quality control is maintained, and periodic interlaboratory
comparison of results is made. With careful analysis of
water, interlaboratory precision can achieve relative standard
deviations of from 30 to 65 percent (Anderson and Long,
1978; Chopra, 1978) , but without standardization intralaboratory
variability can be as great as a factor of ten, and inter-
laboratory variability can exceed two orders of magnitude
(Brown, et al. 1976)
Environmental - Water: Considerable effort has taken
place in recent years to standardize techniques for the
quantitation of mineral fibers in water. All work to date
has utilized electron microscopy. The presence of numerous
diatom spicules and other non-asbestos fibers in water and
the great difficulty of uniquely identifying mineral species
or classes by optical microscopy would appear to preclude
the use of optical microscopy for even the quantitation
of large asbestos fibers in water. With electron microscopy,
however, relatively few experimental problems remain, and
reproducible results can be obtained by experienced laboratories.
The disadvantage of this method is the cost and time of
analysis and the limited availability of laboratories for
the analysis of samples.
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The U.S. EPA has proposed an interim method for the
analysis of asbestos in water (Anderson and Long, 1978).
From a 1-liter sample, 50 to 500 ml is filtered through
0.1 micron polycarbonate (Nuclepore) filter. A portion
of the filter is placed on an electron microscope grid and ;
dissolved by the Jaffe wick method and scanned by transmission
electron microscopy at 10,000 to 20,000 magnification.
Prior to dissolution, the flat polycarbonate filters are
coated with carbon which serves to enmesh the collected
material and to reduce losses during dissolution of the
filter material by chloroform. Twenty grid squares or 100
fibers are counted. The identification of fiber type is
by morphology for chrysotile and by selected area electron
diffraction for amphiboles. No attempt is made to determine
the amphibole mineral species. If necessary, this can be
done using energy-dispersive X-ray analysis of each fiber.
All individual fibers (length greater than three times width),
irrespective of length are counted in the grid squares scanned,
The fibers in large clumps though are not counted individual-
ly. For surveillance of large numbers of water systems,
the procedures serves to identifiy those with significant
quantities of asbestos present.
A previously used technique of condensation washing
of cellulose acetate Millipore filter pieces on carbon coated
grids using acetone can result in significant losses unless
extreme care is taken. Carbon coating of the Millipore .
filter is ineffective in enmeshing the fibers because many
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of them are trapped deep within the interstices of the membrane
filter. Condensation of acetone on the grid can result
in the formation of pools of solvent on the filter which
wash away fibers. Losses as great as 80 percent have been
reported using this technique (Chatfield, et al. 1978; Beaman
and File, 1976; Chopra, 1978).
Eighteen analytical laboratories participated in an
American Society for Testing and Materials (ASTM) Task Group
study of the measurement of amphibole and chrysotile fibers
in water. Table 1 lists the data on the interlaboratory
precision that has been obtained by this group in the analysis
of both chrysotile and amphibole fibers. The Task Group
concluded:
The transmission electron microscope is the best
basic instrument for the analysis, particularly
when it is equipped with selected area electron
diffraction and energy-dispersive spectroscopy
capabilities. The mean fiber concentrations by
different groups agree within a factor of two.
The interlaboratory reproducibility of 50 percent
can be expected in relatively clean water samples
unless the concentration is low. In samples with
high concentrations of interfering solids, the
precision will not be as good. When applied on
a broad scale there are variable and significant
losses associated with the condensation washing
of samples containing amphibole. The losses are
low and less variable when condensation washing
is used to prepare samples containing chrysotile
(Chopra, 1978) .
Environmental - Air: As with water, the analysis of
ambient air samples by optical techniques introduces signif-
icant difficulties. First, the quantity of asbestos in
ambient air is only a small fraction of the total aerosol.
This aerosol contains large quantities of organic and mineral
material of various origins, including many fibers other
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TABLE 1
Interlaboratory Precision Obtained in the Analysis of Water
Samples for Chrysotile and Amphibole Minerals
n
i
en
Sample
type
Chrysotile
Chrysotile
Chrysotile
Chrysotile
Chrysotile
Chrysotile
Amphibole
Amphibole
Amphibole
Number of
laboratories
reporting
10
9
11
9
9
3
11
4
14
Mean fiber
concentration
(106 fibers of all sizes/1)
877
119
59
31
28
25
139
95
36
Relative
standard
deviation
of analysis (%)
35
43
41
65
32
35
50
52
66
Anderson and Long, 1978. See also Chopra, 1978,
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than asbestos. Therefore, enumeration of fibers collected
in ambient air may have little relevance to the asbestos
material present. In one instance, a comparison of 25 ambient
air samples collected in buildings, some of which were contam-
inated with asbestos, showed no correspondence between concen-
trations of fibers longer than 5 jam, as determined using
optical microscopic techniques, and the total mass of asbestos
present, guantitated by electron microscopic methods (Nicholson,
et al. 1975) . Here, using the National Institute for Occupa-
tional Safety and Health (NIOSH) technique, no fiber concen-
trations measured exceeded 0.03 f/ml, and contributions
to the measured filter concentration from other than asbestos
fibers were felt to be significant. A review (Duggan and
Culley, 1978) of the results of the analysis of six side-
by-side ambient air samples by nine laboratories also high-
lighted the difficulty of using optical microscopy at low
asbestos concentrations. They found that intralaboratory
variability could exceed a factor of 10 and the results
between laboratories could differ by a factor of 100. The
possibility exists that optical techniques using petrographic,
polarized light microscopes or dispersion staining techniques
could produce better results. This has not been investi-
gated, however.
A variety of techniques, each of which utilizes electron
microscopy, have been developed for the analysis of asbestos
in the ambient air. However, at the present time, there
is less agreement on an ideal method than for water analysis.
Two general electron microscopic techniques are utilized
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for the analysis. One involves the collection of asbestos
on cellulose acetate (Millipore) or polycarbonate filters
(Nuclepore) (Samudra, et al. 1978) and its subsequent ..transfer
to electron microscope grids. For samples collected on ;~
cellulose acetate filters, the filter and collected material
are ashed, the ash suspended in water and the suspension
filtered through a polycarbonate filter. Such filters are
then processed using techniques similar to those used for .
water and previously discussed (See "Water" subsection).
Although not well studied, the use of flat surfaced poly-
carbonate filters in field situations may lead to losses
of particles prior to sample preparation for analysis. ::
Direct transfer techniques have other limitations.
Ambient aerosols are made up of agglomerates of particles
with asbestos fibers attached to a variety of other material. "
Chrysotile asbestos, for example, with a negative surface
charge, readily adheres to any of the large number of positively
charged particles, such as clays, in the ambient air. Without
dispersal, these agglomerations can result in the asbestos
being obscured when viewed by an electron microscope. Further,
agglomeration can occur on the filter during the long collec-
tion times required to quantitate low concentrations. In
many cases, these agglomerates, which usually are of respirable
size, contribute the most to the mass of the sample. Also,
they may occur so infrequently that a statistically reliable
measure of their quantity difficult to obtain. To obviate
these difficulties, techniques have been developed in which
collected material and filter are ashed in a low-temperature,
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activated oxygen furnace. The resulting residue is dispersed
by physical means, either through the application of ultrason-
ic energy or grinding, and is enmeshed in a nitrocellulose
or collodian film for mounting on electron microscope grids
or is refiltered through a polycarbonate filter. Such "rub-
out" methods also involve losses and, as with washing tech-
niques, require skilled development of the process. A signif-
icant disadvantage of this procedure is that the initial
physical state of the asbestos is altered prior to enumeration,
Therefore,information on the fiber size distribution is
not available. Only mass concentrations can be determined.
(Nicholson, 1971; Nicholson and Pundsack, 1973).
To date, less uniform agreement has been obtained in
the analysis by different laboratories of air samples than
for water. In one interlaboratory comparison of samples
collected near a road surfaced with serpentinite rock and
analyzed for the mass of chrysotile asbestos, intralaboratory
differences exceeded two orders of magnitude, and interlabora-
tory differences for laboratories using different analysis
techniques exceeded four orders of magnitude. Fiber counts
were similarly variable (U.S. EPA, 1977). On the other
hand, relatively good agreement (average relative standard
deviation of 25, percent) was achieved by three laboratories
in the analysis for amphiboles of 12 samples collected in
Silver Bay, Minnesota (U.S. EPA, ERLD, 1976).
Analysis of amphiboles in air around Lake Superior
by the U.S. EPA and the State of Minnesota has been done
using .a cellulose ester filter for collection. The filter
is shipped to the laboratory where it is ashed in a low
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temperature oxygen-activated furnace. The residue is resus-
pended and filtered through a polycarbonate filter. Good
recovery and low losses are claimed by the investigators
(P.M. Cook, 1978).
Occupational: In occupational circumstances, the current
method of quantitating asbestos air concentrations is to
enumerate all fibers longer than 5 microns (5 jam) collected
on a specified area of filter, utilizing phase contrast,
light microscopy at 400X magnification (NIOSH, 1972). Such.
instrumentation does not allow identification of the fibers
according to mineral type or even sufficient to establish
if they are organic or mineral in origin. In general, when
the principle fiber in an aerosol is known to be asbestos,
this presents no problem. However, in some occupational
circumstances, as with the use of insulation materials,
fibers of various origins are present in the same material,
and this can result in overestimates of the actual asbestos
concentrations.
The adoption of a 5 jam cutoff for the length of fibers
enumerated was imposed by limitations of light microscopy.
It has long been known that fibers longer than 5 pm and
visible by phase contrast microscopy represent only a small
fraction of the total number of asbestos fibers in the air
(Lynch, et al. 1970). This would present no problem were
fiber size distributions similar in different circumstances.
However, such is not the case. It has been shown, using
electron microscopy that when chrysotile asbestos concentra-
tions in different exposure circumstances are enumerated,
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the fraction greater than 5 urn may vary by tenfold (from
0.4 percent of the total number of fibers present to approxi-
mately 5.0 percent). When amphibole varieties of asbestos
are also considered, the fraction counted can vary more
than 100-fold (Nicholson, et al. 1972). Thus, we do not
have an accurate yardstick for the quantitation of asbestos
air concentration in the work place. This does not present
serious problems when monitoring for standard compliance
but complicates comparisons of health effects between various
industrial processes such as mining, manufacturing, and
end-product use. It also complicates extrapolations of
dose-response relationships determined in occupational circum-
stances to lower concentrations of asbestos measured in
the general environment by other techniques. Nevertheless,
when assessing exposure in a defined asbestos aerosol, the
precision of optical methods can be good. NIOSH (1976)
has estimated that a coefficient of variation of about 20
percent can be achieved in the assessment of asbestos concen-
trations greater than 0.1 f/ml.
Although fiber counts have been utilized for the assess-
ment of occupational asbestos exposure since 1966, in prior
years other methods, usually involving total particle counts
(fibrous and non-fibrous), were utilized. Some attempts
have been made to relate these earlier counts to present
day fiber concentrations (Lynch and Ayer, 1966). However,
these have been found to depend strongly on the particular
asbestos use process, and no universal conversion factor
is available that would relate total particle concentra-
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tions in a given circumstance with asbestos fiber counts.
It is unfortunate that earlier data have limited relevance,
since the disease experience that we are seeing today is
the result of exposures that took place 20, 30 or more years
previously when work conditions may have been considerably
different from those currently existing. Thus, dose-response
relationships are tenuous and can only be approximate, based
upon current data.
Intercomparison of Techniques: All data, scant as
\i
they are, that relate asbestos disease to exposure are derived
from studies of workers exposed in occupational environments.
In these studies, concentrations of fibers longer than 5
um were determined using optical microscopy or were estimated
from optical microscopic measurements of total particulate
matter. On the other hand, all current low level environmental
assessments utilize electron microscopic techniques which
are not comparable to those used in the workplace since
optical techniques do not provide data on the number of
fibers less than 5 jum in length. To extrapolate dose-response
data obtained in studies of working groups to environmental
exposures, it is necessary to establish the relationship
between optical fiber counts and mass or total fiber number
determined by electron microscopy.
Recent studies have attempted to relate optical fiber
counts (fibers > 5 jum) and TEM counts (all EM-countable
fibers). An interlaboratory comparison of optical versus
EM counts of chrysotile fibers suggested an average relation-
ship between optical counts and TEM counts of 1:1000 (Winer
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and Cossette, 1978). The samples studied included air samples
from six plants (one asbestos-cement, one brake lining,
two treating- mills, and two textile plants). Lower ratios
are expected for amphibole fibers. An analysis by the U.S.
EPA (Personal communication, J. Millette) relating optical
fiber counts of fibers longer than 5 microns to total fiber
counts by transmission electron microscopy gave a ratio
of 400 for six samples of asbestos ceiling insulation material
(which, however, may contain fibers other than asbestos
and were np.t .actual air Samples) . .'Other data by Wallingford
(1978) suggest a ratio as low as 15 for EM count to optical
counts.
Some data exist that relate optical fiber counts (longer
than 5 um) to the total mass of asbestos as determined by
electron microscopic techniques or by other weight deter-
minations of collected airborne asbestos fibers. These
are listed in Table 2 and provide crude estimates of a conver-
sion factor relating, fiber -concentrations (f/ml) to airborne
asbestos mass (jug/m ) .: The proposed standards for asbestos
in Great Britain by the British Occupational Hygiene Society
stated that,a "respirable" mass of 0.12 mg asbestos/m was
equivalent to 2 f/ml (BOHS, 1968). It was not stated how
this relationship was determined. However, if it was from
magnesium determinations in an aerosol, the weight determina-
tion would likely be high because of the presence of other
non-fiberous, magnesium-containing compounds in the aerosol.
Such was the case in the work of Lynch, et al. (1970), and
their values for the conversion factor are undoubtedly over-
estimates. The data of Rohl, et al. (1976) are likely to
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TABLE 2
Measured Relationships
Between Optical Fiber Counts and Mass of Airborne Chrysotile
o
i
H
U>
Sampling situation Fiber* Mass
counts - concentration
(f/ml) . Cug/m3)
Textile factory
BOHS (1968)
(weight versus fiber count) 2 120
Air chamber monitoring
Davis, et al. (1978) 1950 10,000
Monitoring brake repair work
Rohl, et al. (1976)
(E.M. mass versus 0.1 to 4.7 0.1 to 6.6
fiber count) (7 samples)
Textile mill
Friction products mfg.
Pipe mfg.
Lynch, et al. (1970)
Conversion factors
jug/m or jj%
f/ml 10 6f
60
5
*
0.7 to 24a
mean = 6
150b
70b
45b
103f/mg
16
200
170
6.7
13.9
22.5
*A11 fiber counts used phase contrast microscopy and enumerated
fibers longer than 5 jum.
Conversion factor may be low due to losses in E.M. processing.
Conversion factor may be high because of overestimate of asbestos
mass on the basis of total magnesium.
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be underestimates because of possible,losses in the determina-
tion of mass by electron microscopy. No data exist on the
procedures used to determine the mass of chrysotile in the
data presented by Davis, et al. (1978) .
The range of 5 to 150 for the conversion factor relating
mass concentration to optical fiber concentration is great,
and any average value derived from it has a large uncertainty.
However, for the purpose of extrapolating to low mass concen-
trations from fiber count, the geometric mean, 30 ug/m /f/m,
of the above range of conversion factors will be used.
The accuracy of this value is felt to be no more than a
factor of 5 and this uncertainty severely limits any extrapola-
tion in which it is used. In the case of amosite, the data
of Davis, et al. (1978) suggest that a conversion factor
of 18 is appropriate. However, since this data yielded
lower chrysotile values than all other chrysotile estimates,
it may also be low for amosite.
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Ingestion from Water
Asbestos is commonly found in domestic water supplies.
Of 775 recent samples analyzed by electron microscopy under
the auspices of the U.S. EPA, 50 percent had detectable
levels of asbestos, usually of the chrysotile variety (Millette,
1979a). Table 3 lists the distribution of the concentrations
of these samples.
Earlier, asbestos had been reported in a variety of
Canadian water supplies (Cunningham and Pontefract, 1971).
These waters were found to contain from 2.0 to 172.7 xv 10
fibers/1. Two U.S. river systems were also reported to.,
contain chrysotile at average levels of from 0.3 to 1.5
ug/1 (Nicholson and Pundsack, 1973). Other reports include
that of Kay (1973) who found from 0.1 to 4 x 106 f/1 in
various Canadian drinking water sources.
During 1973, large amounts of asbestos-like fibers
of amphibole minerals were found in the waters of Lake Superior,
the source of drinking water for Duluth, Minnesota, and
other cities (Cook, et al. 1974; Nicholson, 1974; Cook,
et al. 1976). Fiber concentrations during normal lake condi-
tions ranged from 20 x 10 to 75 x 10 fibers/1 and from
about 5 to 30 ug/1 in terms of mass (Nicholson, 1974).
During storm conditions amphibole fiber concentrations as
high as 600 x 106 f/1 were observed (Cook, et al. 1976).
Filtration plants now used in Duluth maintain fiber concentra-
tions below 0.1 x 106 f/1 (Millette, 1979a).
Certain U.S. water systems currently have high levels
of asbestos as a result of serpentine or amphibole deposits
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TABLE 3
Distribution of Concentration of Asbestos in 775 Samples of
Drinking Water from 42 States3
Asbestos concentration
(106 fibers of all lengths/1)
Below detectable limits
Less than 1
1-2
2-5
5 - 10 .
Greater than 10
Number of
samples
386
340
13
13
2
21
Percentage
of samples
49.8
43.9
1.7
1.7
0.3
2.7
aMillette (1979a).
For these analyses average detectable limits were 5 x 10
fibers/1. However, significant variations occurred in some
instances due to the presence of non-asbestos fibers.
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in their water sheds. These include Everett, Washington,
with concentrations of chrysotile above 10 f/1; Seattle,
with from 1 to 10 x 10 f/1; and San Francisco, with chryso- .
7
tile concentrations about 10 f/1 in some systems (Millette,
/
1979a; Cooper, et al. 1978).
Under certain conditions, asbestos-cement (A/C) pipe
may also contribute asbestos to municipal water supplies.
Asbestos fiber concentrations in A/C pipe distribution sys-
tems were found to be as high as 38 x 1Q chrysotile and
4 x 10 amphibole fibers/1 in one Florida city; 17 x 10
in another Florida town; and 47 x 10 f/1 in a Kentucky
A/C pipe system. Water at the end of a little used A/C
pipe line in Massachusetts contained as much as 480 x 10
chrysotile f/1 (Millette, 1976). Many of the A/C pipe systems
in Connecticut have been sampled and analyzed (Craun, et
al. 1977). The majority of samples taken after transit
through A/C pipe showed concentrations under 1 x 10 f/1,
and only one sample was over 10 x 10 f/1.
' '
While there are an estimated 200,000 miles of A/C pipe
now in use in the United States, it is apparent that not
all A/C pipe sheds fibers. If the water is non-aggressive
the pipe does not erode and contribute fibers to the water.
Studies of five A/C pipe systems over a one year period
showed that fibers were present in the water from the two
systems with aggressive waters, and few, if any, fibers
could be found in water samples from three systems with
non-aggressive waters (McFarren, et al. 1977).
C-17
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Sampling of representative water utilities throughout
the United States has indicated that over half of the samples
had water which was moderately aggressive and 16.5 percent
had very:aggressive water (Table 4) (Millette, et al. 1979b).
Water supplies in both the very aggressive and moderately
aggressive categories are potentially capable of eroding
asbestos-cement pipe (i.e., 68.5 percent of U.S. water
systems) although the very aggressive waters could be expected
to result in the contribution of much higher fiber concentra-
tions.
Most data on asbestos in water are expressed in terms
of fiber concentrations/ enumerating fibers of all sizes
using appropriate electron microscope techniques. Some
estimates exist (Millette, 1979a) relating chrysotile fiber
concentrations to mass concentrations. Because the number-
to-mass relationship is highly dependent on average fiber
length and diameter, knowledge of the source of the fibers
in the water is important in determining a conversion factor.
Some average conversion factors are listed in Table 5.
Similar information on the relationship of fiber count
and mass have been published by Kay (1973), whose data sug-
gest that 10 fibers corresponds to from 2 x 10~ to 2 x
10~ ug in water systems. Data on asbestos concentrations
from erosion of fibers from A/C cooling tower panels indi-
cate that the mass of 10 fibers is from 0.01 to 0.2 ug
(Lewis, 1977).
Based on the aforementioned data, it is concluded that
the majority (approximately 95 percent) of water consumers
C-18
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TABLE 4
Representative Average Water Utility Aggressiveness Indices3
Highly aggressive 16.5 percent
Moderately aggressive0 52 percent
Nonaggressive 31.5 percent
aMillettef et al. (1979b).
bHighly aggressive: pH + log1Q(AH)<10.0
°Moderately aggressive: pH + log (AH) =10.0 - 12.0
Nonaggressive: pH + log (AH) >12.0
where A = total alkalinity in ing/1, CaCO3
H = calcium hardness as mg/1, CaGO^
C-19
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TABLE 5
Relationship of Total Fiber Counts
by Electron Microscopy and Mass of
Chrysotile Asbestos in Water
Average mass in ug
Fiber Source of 10 fibers of all lengths
Natural erosion of serpentine rock
(shorter fibrils) 0.002
A/C pipe (longer fibers) 0.01
Contributions from commercial dump
site runoff and untreated discharge
(mere fiber bundles) 0.05
aFrom; Millette, 1979a.
C-20
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in the United States are exposed to asbestos fiber concentra-
tions of less than 10 f/1. in a few areas people are exposed
to concentrations between 1 and 10 million f/1 with intermit-
tent exposures over 100 million f/1. There is at least
one area where exposure is over 100 million f/1. Persons
using asbestos-cement pipe in areas where the water is non-
aggressive or is treated to prevent corrosion are generally
not additionally exposed. In areas of aggressive water,
however, the consumer may be exposed to added asbestos fiber
concentrations of from fewer than 1 million to over 100
million fibers per liter, depending on factors such as length
of pipe, flow rate and mineral content of the water.
The mass concentrations of chrysotile asbestos in the
water of cities with less than 10 f/1 are likely to be
less than 0.01 jug/1, corresponding to a daily intake of
less than 0.02 ;jg. However, in areas with significant contam-
ination, whether from natural sources, man's activities,
or erosion from A/C pipes, the intake of asbestos from water
sources can exceed 2 jag/day.
Ingestion from Foods
There are scant data on the contribution of food pro-
ducts to population asbestos exposure. Cunningham and Ponte-
fract (1971) showed that various beers and wines could con-
tain quantities of asbestos fibers similar to those found
in water systems (10 to 10 f/1). The source of this contam-
ination could be from natural water sources or from the
erosion of asbestos fibers from filters used to purify the
product. Asbestos filters are currently used for the purifi-
C-21
-------
cation of beverages and a variety of other food products,
but little data exist on possible fiber contamination from
such sources. Contamination of drinking water by fibrous
glass and other synthetic fibers used in cartridge filters
q
has been measured at concentrations in excess of 10 f/1
(Cook, et al. 1978).
Exposure from Drugs
Erosion of chrysotile from asbestos filters, used to
purify parenteral drugs, has been documented (Nicholson,
et al. 1972). Contamination levels up to 1 ug/dose were
noted in approximately one-third of drugs tested, indicating
that filter erosion can be significant. Because of these
findings, the use of asbestos filters for drug purification,
without subsequent clean-up, has been prohibited by the
F, p. A. (1976) .
Inhalation
General Population Exposures: Asbestos of the chrysotile
variety has been found to be a ubiquitous contaminant of
ambient urban air. A study of 187 quarterly composite samples
collected in 48 U.S. cities from 1969 to 1970 showed chrysotile
asbestos to be present in virtually all metropolitan areas
(Nicholson, 1971; Nicholson and Pundsack, 1973). Table
6 lists the distribution of values obtained in that study.
Each represents an average of from five to seven 24-hour
samples and thus averages over possible peak concentrations
which could occur periodically or randomly. A second set
of ambient air analyses is also shown for comparison (U.S.
EPA, 1974). These studies utilized different analytical
C-22
-------
n
i
K>
U>
TABLE 6
Distribution of 24-Hour Chrysotile Asbestos
Concentrations in, the Ambient Air of U.S. Cities'
Electron Microscopic
Mount Sinai
School of Medicine
Asbestos
Concentration
(ng/m3)
less than
1.0
2.0
5.0
10.0
20.0
50.0
100.0
Number
of
samples
61
119
164
176
184
185
187
Percentage
of
samples
32.6
63.6
87.7
94.2
98.5
99.0
100.0
Analysis
Memor
Number
of
samples
27
60
102
124
125
127
127
Battelle
ial Institute
Percentage
of
samples
21.3
47.2
80.1
97.6
98.5
100.0
100 . 0
aNicholson (1974) and U.S. EPA (1974)-,
-------
techniques but the results agree well. In both studies,
98.5 percent of the 24-hour samples had chrysotile asbestos
concentrations of less than 20 ng/m . Of the three samples
greater than 20 ng/m analyzed by the Mount Sinai School
of Medicine, one was in a city having a major shipyard and
another in a city that had four brake manufacturing facilities.
Thus/ these samples may include a contribution from a specific
source in addition to that of the general ambient air.
Similar data with the same range of mass concentrations,
have recently been reported from France, providing evidence
of the presence of chrysotile in the ambient air of Paris
(Sebastien, et al. 1976).
In a study of the ambient air of New York City, in
which samples were taken during daytime working hours, values
higher than those mentioned above were obtained (Nicholson,
et al. 1971). These were six-to-eight hour samples col-
lected between 8:00 A.M. and 5:00 P.M., and they reflect
what could be intermittently higher concentrations from
construction activities or automobile usage during those
hours compared to night-time periods for example. Table
7 records the chrysotile content of 22 samples collected
in the five boroughs of New York. It should be noted that
the samples analyzed in all of the studies discussed above
were, taken during a period when fireproofing highrise buildings
by spraying asbestos-containing materials was permitted.
The practice was especially common in New York City. While
9
no sampling station was known to be located adjacent to
an active construction site, unusually high levels, could
C-24
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TABLE 7
Chrysotile Content of Ambient Air in
New York City by Borough
(6 to 8-Hour Daytime Samples)3
Asbestos air level in
10~9 g/m3 (ng/m3)
o
i
to
Sampling
locations
Manhattan
Brooklyn
Bronx
Queens
Staten Island
Number of
samples
7
3
4
4
4
Range
8-65
6-39
2-25
3-18
5-14
Average
30
19
12
9
8
aNicholson, et al, 1971.
-------
nevertheless have resulted from the procedure.
To determine if construction activities could indeed
be a significant source of chrysotile fiber in the ambient
air, six-to-eight hour daytime sampling was conducted in
lower Manhattan in 1969 near sites where extensive spraying
of asbestos-containing fireproofing material was taking
place. Table 8 shows the results of this sampling and demon-
strates that spray fireproofing did contribute significantly
to asbestos air pollution. In some instances, chrysotile
asbestos levels approximately 100 times the concentrations
typically found in ambient air were observed.
Asbestos contamination has also been documented by
analysis of samples collected within buildings. In a study
of 116 samples collected in or near 19 buildings (primarily
office) in 5 U.S. cities, average chrysotile air concentra-
tions ranged from 2.5 ng/m to 200 ng/m , with individual
measurements from 0 to 800 ng/m (Nicholson, et al. 1975).
Ppr the outside air, the variation for the average concentra-
tion at 3 given site extended from 0 to 48 ng/m . Buildings
in which a loose asbestos fireproofing material was applied
to the structural steel surfaces had evidence of significant
asbestos contamination. Also, schools in which similar
material had been applied have been found to be seriously
contaminated. Optical fiber counts exceeding 2 f/ml in
a library and other areas of student use were observed during
activities which disturbed loose asbestos (Sawyer, 1977;
Nicholson, et al. 1978). Ambient air chrysotile concentrations
in schools, in absence of any disturbance of the asbestos
C-26
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TABLE 8
Chrysotile Air Levels Near Spray Fireproofing Sites in "New York City
(6 to 8 Hour Daytime Samples)3
o
i
to
Sampling
locations (distance from site)
1/8 - 1/4 mile
1/4 - 1/2 mile
1/2 - 1 mile
Number of
samples
11
6
5
Asbestos air level
10~9 g/m3 (ng/m3)
Range Average
9-375 60
8-54 25
3.5 - 36 18
(The above concentratibns reflect both downwind and upwind sampling loca.-
tions»)
aNicholson,4t al. (1971)
-------
ranged up to 2,000 ng/m3 (Nicholson, et al. 1978; Sebastien,
et al. 1976). Finally, analysis of the air of asbestos
workers' homes indicate that chrysotile concentrations as
high as 5,000 ng/m can be encountered (Nicholson, et al.
1978).
Figure 1 summarizes the ranges of chrysotile concentra-
tions in the variety of environmental and occupational circum-
stances discussed above. The concentration ranges are only
approximate and in most cases are limited because of the
limited number of samples taken in given circumstances.
Extension to higher and lower concentrations would be expec-
ted with the availability of more data.
Although the fate of the asbestos in inspired air is
only approximately known, it appears that eventually more
than half the asbestos inhaled will be swallowed (See "Effects"
section )* Assuming that an individual breathes 10 m in
24 hours, most ambient air levels of chrysotile (1 to 10
ng/m ) result in exposures to the gastrointestinal tract
less than 0.05 jug/day of asbestos, although, in some circum-
stances, inhalation could produce gastrointestinal exposures
exceeding 0.1 pg/day. These exposures are to be compared
with those from water ingestion which lead to daily intakes
of less than 0.02 ;ug (See "Ingestion from Water" subsection).
Though the data of Tables 3 and 6 are not related to the
same population bases, it would appear that inhalation can
give rise to exposures at least equal to that of direct
ingestion for most of the population of the United States.
C-28
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Chrysotile Air Concentration
(ng/m3)
Sampling Circumstance 10"1 10^ 101 102 10^ 104 105
24-hour urban ambient air
6 to 8 hour daytime urban _ _ _ _
ambient air
Vicinity of spraying of _ _
asbestos material prior
to 1972
n Air of buildings with
i asbestos-sprayed plenums
vo
Homes of asbestos workers
Interiors of school buildings
Occupational
Figure 1: Environmental Air Concentrations of Chrysotile Asbestos
-------
Only after 1966 has occupational monitoring attempted
to quantify asbestos exposures by fiber counting techniques.
Since then, considerable data have accumulated on occupational
exposure of workers to asbestos. A large compilation of
such data is included in the 1972 Asbestos Criteria Document
(NIOSH, 1972). Levels during the period from 1966 through
1971 were generally under 10 f >Sum/ml, although concentrations
exceeding 100 f/ml were observed, particularly in two plants
producing amosite insulation materials and in uncontrolled
textile mills. Data on earlier exposures are lacking although
some estimates have been made of insulation workers exposure
(Nicholson, 1976) and factory environments (BOHS, 1968;
Newhouse and Berry, 1979). Although average exposures of
10 to 40 f/1 are likely to have prevailed, peak or localized
exposures in excess of 100 f/1 would have been encountered
often by some individuals.
For purposes of estimating dose-response relationships,
those data that are available for given work environments
will be discussed in conjunction with the measured health
effects.
PHARMACOKINETICS
Absorption and Distribution
Ingestion: A key question in the evaluation of cancer
risk associated with the ingestion of asbestos in water
is whether microscopic fibers under normal alimentary canal
conditions can migrate through the gastrointestinal mucosa.
Such movement of fibers could enable their residence in
bowel wall or, following hematogenous or lymphatic transport,
C-30
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the peritoneum and other organ tissues.
Some studies of tissues of animals that had ingested
fibers report no evidence of fiber transport through the
gastrointestinal lining (Gross, et al. 1974). These results,
however, have been called into question on the basis of
the insensitivity of the assay technique used (Cooper and
Cooper, 1978). Evidence for such movement is reported in
other studies (Cunningham and Pontefract, 1973). Cunningham,
et al« (1977) observed chrysotile fibers in the blood and
tissues of rats which previously were fed a diet of one
percent chrysotile asbestos for six weeks. Westlake, et
al. (1965) identified chrysotile fibers in the colon mucosai
of rats fed chrysotile asbestos Scanning electron micrographs
have revealed large amosite asbestos fibers penetrating
epithelial cells of rat jejunal mucosa tissue (Storeygard
and Brown, 1977). Kidney cortex tissue of a neonate baboon
fed chrysotile for nine days was found to contain a statis-
tically significant (P = 0.005) excess of chrysotile fibers
compared to kidney cortex tissue from an unexposed neonate
baboon (Patel-Mandlik and Hallenbeck, 1978). Cunningham
and Pontefract (1974) observed passage of chrysotile fibers
from the blood across the placenta to the fetus.
Ingestion of small particles other than asbestos has
also resulted in the subsequent observation of particle
accumulation in tissues of animals. Mice that drank water
suspensions of 2 urn diameter latex spheres for two months
were found to have the latex particles accumulated in macro-
phages in intestinal Peyer's patches (LeFevre, et al. 1978).
C-31
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Latex particles of 0.22 jam were reported to migrate from
rat stomachs to lymphatics of the mucosa and also to liver
and kidney tissues (Sanders and Ashworth, 1960). Much larger
particles of silica, opal phytoliths from plants, are obser-
ved in digested mesenteric lymph node and kidney tissue
from sheep which eat cereal chaff and grains (Nottle, 1977).
Evidence for the human intestinal uptake ("persorption")
of particles as large as 75 jam is provided by the observa-
tion of starch granules in blood only minutes after ingestion
(Volkheimer, 1974). Sleep, smoking, and caffeine are reported
to increase the number of starch particles in the blood.
Dyed cellulose particles are also identified in human blood
and urine following ingestion of specially stained plant
food (Schreiber, 1974). The cellulose fibers are found
in urine several weeks after ingestion. Langer (1974) found
asbestos fibers in extrapulmonary organ tissues of asbestos
workers, although fewer than in lung and pleura tissue.
More fibers in kidney than in liver, pancreas, adrenal,
or spleen tissue. Fiber concentrations in human extrapulmonary
organ tissues from individuals with a history of ingestion
of fibers (no inhalation exposure) with drinking water have
not been reported due to lack of required analytical sensitivity
(Cook, 1978).
Human urine sediment examined by transmission electron
microscopy may contain amphibole fibers which originate
from ingestion of drinking water contaminated with these
mineral fibers (Cook and Olson, 1979). Ingestion of filtered
water results in eventual disappearance of amphibole fibers
C-32
-------
from urine. These observations provide direct evidence
for the passage of mineral fibers through the human gastro-
intestinal mucosa under normal alimentary canal conditions.
Measured concentrations of amphibole fibers eliminated in
urine represent approximately 1 x 10~ of the number of
fibers ingested with drinking water. To the extent that
some fibers are permanently retained by the body or elimi-
nated by other routes after passage across the gastrointes-.
tinal wall, the urine concentrations are an underestimate
of ingested fiber absorption.
Inhalation: Inhalation of asbestos dust is accompanied
by ingestion of many fibers cleared from the respiratory
tract by mucociliary action. The occurrence of peritoneal
mesothelioma, excess gastrointestinal tract cancers, and
possibly cancers at other non-respiratory tract sites .could
result from migration of fibers through the gastrointestinal
mucosa. The amount of inhaled asbestos which is .eventually
ingested is important for an assessment of cancer risk based
on the excess gastrointestinal cancer observed for occupational
exposures (See "Effects" section).
Whether inspired asbestos fibers will be deposited
in the lung depends strongly upon their diameter. Timbrell
(1965) has shown that a fiber, independent of its length,
behaves aerodynamically like a particle having a diameter
three times as great. Brain and Volberg (1974) have developed
a model for aerosol deposition in the respiratory tract
according to aerodynamic parameters. They indicate that
about 50 percent of particles with a mass median diameter
C-33
-------
of less than O.lpm will be deposited on nonciliated pul-
monary surfaces. This fraction falls slowly to 25 percent
at 1 pm and to zero at above 10 pm. Deposition on nasal
and pharyngeal surfaces becomes important at 1 pm and rises
rapidly to be the dominant deposition site for particles
10 /am in diameter or greater. Thus, few fibers with a diameter
as large as 2 jum are likely to penetrate into the alveolear
spaces, although finer fibers, even as long as 200 jam, may
do so.
Once inhaled, a large fraction of the inhaled dust
is rapidly cleared from the respiratory tract by mucociliary
action although some fibers will remain in the lung and
be found there decades after exposure (Pooley, 1973; Langer,
1974) . Because of the ubiquitous exposure of individuals
to asbestos, chrysotile fibers can be found in the lungs
of most urban dwellers (Langer, et al. 1971; Gross, et al.
1973) . Additionally, larger fibers trapped in the lungs
may become coated and form asbestos bodies. These can be
readily observed by optical microscopy in tissue sections
and in lung smear (Thomson, 1963; Langer, et al. 1973).
The number of fibers or asbestos bodies found in given circum-
stances depends strongly upon the nature of the previous
exposure of the individual.
The clearance of asbestos from the respiratory tract
of rats has been studied directly in a series of experiments
(Morgan, et al. 1975; Evans, et al. 1973). Samples were
made radioactive by neutron irradiation, which enabled the
mass of asbestos in various tissues to be determined. In
C-34
-------
a series of 30-minute exposures with different varieties
of chrysotile, the deposition and clearance in the respiratory
tract were followed. At the conclusion of the inhalation,
the distribution in various organ systems was determined.
The results are shown in Table 9. As can be seen, rapid
clearance from the upper respiratory tract occurs with up
to two-thirds of the fibers being swallowed and found in
the gastro-intestinal tract. Long term respiratory tract
clearance or drainage via the lymphatics leads to additional
dissemination.
Other data on the deposition and retention of inhaled
asbestos have been reported by Wagner, et al. (1974). Figure
2 shows the dust content of rat lungs following exposures
to different asbestos varieties. As can be seen, the chrysotile
content of the lung does not build up as significantly as
that of the amphiboles for similar exposure circumstances.
This is likely the result of some dissolution pf chrysotile
by body fluids.
Excretion
Most inhaled or directly ingested asbestos particles
which pass through the gastrointestinal tract are excreted
in feces (Cunningham, et al. 1976). As mentioned previous-
ly, some fibers are absorbed by the gastrointestinal tract
and are eventually eliminated through the urinary tract
(Cook and Olson, 1979).
C-35
-------
TABLE 9
Distribution of Fiber at the Termination of Exposure
(% of Total Deposited)3'6
Fiber
Nasal .
passages
Esophagus
GI tract
Lower
respiratory
tract
Chrysotile A
Chrysotile B
Ampsite
Croc idol ite
Ahthophyllite
Fluor amphibole
''.***'':'.
,8 ± 2 ''.'''
-6 +!: '>,
8 + 3
7 + 2
"*:??':'::<
2 + 1
'r±.;;i. v\-
2 + 1
2 + 1
2 + 1
;;;a + i
51 + 9
54 + 5
57 + 4
51 + 9
61 + 8
67 + 5
38 + 8
36 + 4
35 + 5
39 + 5
30 + 8
29 + 4
Morgan, et al. (;1975) .
. ;. i- , .
3Me:an and SD.
C-36
-------
Weight of *J»«
in'luaga (.-n|)
15 -
S
After removal
(rota «xpo»ur»
Aophibola*
24 Tim* (month*)
r r s ' i
I0000 20000 10000
Cumulative de«* (ir.jr/m1 hours)
Mean weight of dust in longs of rau in relatioa to do.«e and time.
Figure 2. Mean weight of dust in lungs of
rats in relation to dose and time
(Wagner, et al. 1974).
C-37
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EFFECTS
Acute, Subacute, and Chronic Toxicity
Acute effects are of little consequence in the inhala-
tion exposure of individuals to high concentrations of asbes-
*-
tos dust. Some temporary breathing difficulty has been
reported by workers in various circumstances, but such discom-
fort has not limited employment in the industry.
:.;_Shor,t-term effects have been described in a recent
study by Harliss, et al. (1978) who found airflow abnorma-
lities in 17 of 23 individuals examined 1.5 and 8.0 months
fpllowing a relatively intense five-month exposure to asbes-
tos. Of the 17, 12 were non-smokers or current light or
ex-light smokers (less than ten pack years). The obstructive
abnormalities were usually present in measurements both
of one minute forced expiratory volume and of closing volume
determinations.
Although human data on initial changes are unavailable,
Holt, et al. (1964) described early (14-day) local inflam-
matory lesions found in the terminal bronchioles of rats
following inhalation of asbestos fibers. These consisted
of multinucleated giant cells, lymphocytes and fibroblasts.
Progressive fibrosis followed within a few weeks of the
!
first exposure to dust. (These early alterations in animals
may be related to the early human findings above). Davis,
et al. (1978) described similar early lesions in rats consist-
ing ol: a proliferation of macrophages and cell debris in
the terminal bronchioles and alveolae.
C-38
-------
Jacobs, et al. (1978) fed rats 0.5 rag or 50 mg of chrysotile
daily for one week or 14 months and subsequently examined
gastrointestinal tract tissue by light and electron michroscopy.
No effects were noted in esophagus, stomach or cecum tissue
but structrual changes in the ileum were seen, particularly
of the villi. Considerable cellular debris was present
by light microscopy in the ileum, colon and rectum tissue.
The electron microscopic data confirmed that of light micro-
scopy and indicated the observed changes were consistent
with a mineral-induced cytotoxicity.
A single oral administration of from 5 to 100 mg/kg
of chrysotile to rats has produced a subsequent increase
in thymidine in the stomach, duodenum, and jejunum (Amacher,
et al. 1975). This suggests that an immediate response ..
of cellular proliferation and DNA synthesis may be stimulated
by chrysotile ingestion.
The long-term disease entity, asbestosis, resulting
from the inhalation of asbestos fibers is a chronic, progres-
sive pneumoconiosis. It is characterized by fibrosis of .
the lung paremchyma, usually radiologically evident after
ten years from first exposure, although changes can occur
earlier following more severe exposures. Shortness of breath
is the primary symptom; cough is less common; and signs
such as rales, finger clubbing, and, in later stages of
the disease, weight loss appear in a proportion of cases.
The disease was first reported seven decades ago (Murray,
1907) and has occurred frequently among workers occupationally
exposed to. the fiber in ensuing years. Characteristic x-
C-39
-------
ray changes are small irregular opacities, usually in the .
lower and middle lung fields, often accompanied by evidence
of pleural fibrosis or thickening, and/or pleural calcification,
Both the visceral and/ more commonly, parietal pleura may
be involved. The mechanism of action and translocation
of asbestos fibers to the parietal pleura is uncertain;
both direct migration (Kiviluoto, 1960) or transport via
lymphatics (Taskinen, et al. 1973) have been suggested.
Currently, 50 to 80 percent of individuals in occupa-
tional groups with exposures beginning more than 20 years
earlier - have been found to have abnormal x-rays. These
include asbestos insulation workers (Selikoff, et al. 1965),
miners and millers (Mount Sinai, 1976) and asbestos factory
employees (Lewinsohn, 1972). In many circumstances the
disease progresses following cessation of exposure; in a
group employed in an asbestos factory for various periods
of time between 1941 and 1954, x-ray changes were observed
years following exposure in individuals having exposures
as short as one week (personal communication, I.J. Selikoff).
Restrictive pulmonary dysfunction is also seen with
asbestos exposures and may be accompanied by diffusional
defects or airway obstruction (Bader, et al. 1961). In
the early stages of asbestosis, there' is limited correlation
between physiologic parameters, such as lung function tests.
Later, x-ray changes and the lung function deficits are
more highly correlated, but still incompletely so.
The above chronic effects are common among occupational
groups directly exposed to asbestos fibers. They also,
C-40
-------
however, extend to those employed in other trades working
near the application or removal of asbestos. Among workers
other than insulators employed at a shipyard for longer '
than 15 years, 48 percent were found to have abnormal,x- ,.
rays (Selikoff, et al. 1979a)» Similar data were obtained,
in a.study of maintenance personnel in a chemical plant
(Lilis and Selikoff, 1979). Even family contacts (wives,.
children, etc.) of workers can be affected. Anderson,.et
al. (1976) have shown that 36 percent of 626 family contacts
of workers employed some time between 1941 and 1954 at an .
asbestos insulation manufacturing facility had x-ray abnorm- .
alities years later characteristic of asbestos exposure., .-.-.
In addition to disease and disablement during-life, . .
asbestosis has accounted for a large proportion of deaths
among workers. The first reports of the disease (Auribault,,
1906; Murray, 1907) described complete eradication of working
groups. Much improvement in dust control has.taken place
in the.industry since the turn of the century, but even v
recently those exposed in extremely dusty environments,
such as textile mills, may have as much as 40 percent of
their deaths attributable to this cause (Nicholson, 197.6) .
Groups with lesser exposures for 20 or more years, such
as in mining and milling (Mount Sinai, 1976) or insulation ;..
work (Selikoff, et al. 1979) may have from 5 percent to,
20 percent of their deaths from pneumoconiosis. All varieties
of asbestos appear equally capable of producing asbestosis,
in both man (Irwig, et al. 1979) and animals (Wagner, et
al. 1974). in groups exposed at lower concentrations such
C-41
-------
as the families of. workers, there is less incapacitation,.
and death from asbestosis has not been reported.
Extra-pulmonary chronic effects reported include "asbes-
tos corns" from the penetration of asbestos fibers into
the skin and their incorporation in dermal layers, and instances
of Caplan's syndrome (rheumatoid pneumoconiosis). No chronic,
non-malignant gastrointestinal effects are reported.
Tetratogenicity
No data exist on the presence or absence of tetrato-
genic effects from the inhalation or ingestion of asbestos,
although transplacental transfer of asbestos has been reported
(Pontrefract and Cunningham, 1973; Cunningham and Pontre-
fract, 1974).
Mutagenicity
In a preliminary study chromosomal aberrations were
seen in Chinese hamster cells cultured in a medium containing
0.01 mg/ml of either chrysotile or crocidolite (Sincock
and Seabright, 1975). No aberrations were seen in culture
with coarse glass fibers or with control media. A more
extensive series of experiments by Sincock (1977), using
several chrysotile and crocidolite samples, showed that
both positive transformation of morphology and positive
genetic responses result from the passive inclusion of asbes-
tos in culture media of CHO-Kl Chinese hamster cells. Very
fine fibrous glass produced the same abnormalities, but
chemically leached asbestos fibers produced fewer abnormalities
than those untreated. The principal results are shown in
Table 10.
C-42
-------
TABLE 10
Effects of Different Treatments on Chromosomes of CHO-KI - Chinese Hamster Cells
a
o
i
f.
u>
Polyploids
Cells with fragments
Other abnormalities
SPA.
chryso-
tile
28
13
33
Percent abnormal karyotypes
Polyploids
Cells with fragments
Other abnormalities
Percent abnormal cells
Rhodesian
chryso-
tile a
23
13
10
34
Rhodesian
chryso-
tile a
23
14
9
62
Rhodesian
chryso-
tile a
leached
6
0
0
6
Canadian
chryso-
tile b
27
11
15
34
Canadian
chryso-
tile b
26
9
16
42
UICC
crocido-
lite
26
10
29
39
Canadian
chryso-
tile b
leached
10
0
4
14
UICC
antho-
phyllite
2
10
9
56
UICC
crocido-
lite
26
14
28
57
UICC
amosite
14
16
13
26
UICC
crocido-
lite
milled
6
9
3
16
Glass
110
3
0
0
41
Glass
110
6
0
0
6
Control
4
0
0
3
Control
4
0
0
4
aThis table summarizes the principal results reported in Sincock (1977).
Results were obtained using 48-hr exposure; 100 cells were scored from
each culture. Categories of genetic damage were not mutually exclusive.
-------
Chamberlain and Tarmy (1977) tested UICC asbestos samples
of chrysotile, amosite, anthophyllite, and samples of super-
fine chrysotile on several strains of E. coli and S_. typhimu-
rium bacterial systems in which mutagenicity to exogenous
materials appears to correlate well with animal carcinogenic
test data. Several positive and negative controls were
used in all experiments. No mutagenicity was observed in
any of the bacterial strains. The authors point out that
prokaryotic cells (bacteria) do not phagocytize the fibers
as do eukaryotic cells, such as macrophages.
Carcinogenicity - Animal Data
Ingestion: Limited data exist on the carcinogenicity
of asbestos administered by ingestion. With the exception
of an abstract which reported negative data from 12 animals,
published in 1967 (Bonser and Clayson, 1967), no reports
were extant on the effects of ingested asbestos until the
finding of large amounts of cummingtonite-grunerite fibers
in Lake Superior and the drinking water of Duluth, Minnesota
focused attention on the problem. As an outgrowth of the
Reserve Mining Company trial in which the federal government
sought abatement of the Lake Superior pollution, two compila-
tions from four laboratories were made of studies which
showed negative results on the ingestion of asbestos.
Smith (1973) reported results of feeding 45 hamsters
one percent chrysotile or amosite in their diet. A neoplasm
of the mesentry of the colon was found, which was discounted
because no fibers were identified in the tumor; no details
were given concerning how the fibers were sought. The actual
C-44
-------
dosage of asbestos was not given, nor were other relevant
experimental details provided. However, the finding of
fibers in tumor tissue would be unlikely and, as these tumors
are rare in hamsters, this result cannot be dismissed out
of hand.
Gross, et al. (1974) reported the results of a series
of feeding experiments with chrysotile and crocidolite.
The data were the unpublished results of various experiments
conducted over the previous ten years by three laboratories.
All available data on these experiments are listed in Table
11. The data are flawed for several reasons. The numbers
in each experimental group were small, the doses administered
limited, and significant information on experimental proce-
dures lacking. Also, systematic histological examination,
which was of most significance, was done on only 53 of over
200 animals.
Wagner, et al. (1977a) fed groups of 32 rats 100 milli-
grams per day of chrysotile or talc in malted milk for 100
days over a 6-month period of time. A small decrease in
survival time was observed in the two study groups: 614
and 618 days versus 641 for the controls. Two gastric leio-
myosarcomas were observed, one in each exposure group.
Interpretation of the results of this experiment, too, is
difficult because of the small number of animals in exper-
imental groups.
As an outgrowth of concern for the use of asbestos
filters in the purification of wine products and the pos-
sible effects of erosion of asbestos fibers from those fil-
C-45
-------
TMU 11
Summary of Experiments on the Effects of Oral Ingestion of Asbestos
Animal species
Material
administered
Dosage
Animals examined
for tumors
Findings Average sur-
(malignant tumors) vival time
o
i
Gibel. et al. (1976)
25 male and 25
female Wistar
rats
25 male and 25
female Wistar
rats
25 male and 25
female Wistar
rats
32 Wistar SPF
rats
32 Wistar SPF
rats
16 Wistar SPF
rats
10 male rats
asbestos filter 50 mg/kg bw/day
material contain- in the diet for
ing 52.6% life
chrysotile
talc
50 mg/kg bw/day
in the diet for
life
42
45
control
UICC Canadian 100 mg/day 5
chrysotile in days/week for
malted milk powder 100 days
control 49
Wagner, et al. (1977)
32
Italian talc
control
100 mg/day 5
days/week for
100 days
32
control 16
Gross, et al. (1974)
ball-milled 5% by weight 10
chrysotile mixed : of feed mix
with laboratory foe 21 months
chow
4 kidney carcinomas 441 days
3 reticulosarcomas
4 liver-cell carcinomas
1 lung carcinoma
3 liver-cell carcinomas 649 days
2 liver-cell carcinomas 702 days
1 gastric leiomyosarcoma 618 days
1 gastric leiomyosarcoma 614 days
none
none
641 days
sacrificed
-------
TABLE 11 (cont.) '
Summary of Experiments on the Effects of Oral Ingestion of Asbestos
o
*.
-4
Animal species
-
5 "laboratory"
rats
31 Wistar
SPF rats
33 Wistar
SPF rats
34 Wistar
SPF rats
24 Wistar
SPE rats
35 Wistar
SPF rats
28 Wistar
SPF rats
24 wist-.ar
SPF rats
Material
administered
control
Rhodes! an
chrysotile
0.2%-0.4%
crocidolite in
butter 0.2% -
0.4% mixture
crocidolite in
butter 0.2% -
0.4% mixture
control (butter)
N W Cape
crocidolite
in butter
(0.2%-0.4%)
Transvaal
crocidolite in
butter (0.2% to
0.4%)
control
(butter)
Dosage Animals examined
for tumors
Gross, et al. (1974)
control 5
10 mg weekly 31 less "a few"
for 16 weeks
5 mg weekly 33 less "a few"
for 16 weeks
10 mg weekly 34 less "a few"
for 16 weeks
control ; (24?)
,-. - - i,
10 mg weekly 35 less "a few"
for 18 weeks
10 mg weekly 28 less "a few"
for 18 weeks
control (24?)
Findings
(malignant tumors)
,
none
2 breast carcinoma
none
. . .
1 lymphoma
3 breast carcinoma
1 thigh sarcoma
none
none
none
Average sur-
vival time
sacrificed
not stated
not stated
not stated
not stated
not stated
not stated
not stated
-------
TABLE 11 (cont.)
Summary of Experiments on the Effects of Oral Ingestion of Asbestos
Animal species Material Dosage
administered
Animals examined
for tumors
Findings
(malignant tumors)
Average sur-
vival time
10 male Wistar 1% chrysotile+
rats
Cunningham, et al. (1977)
7
o
^
GO
10 male Wistar control
rats
40 male Wistar 1% chrysotile
rats
not given
36
40 male Wistar control
rats
38
2 kidney not given
1 peritoneal
1 lymphoraa
1 fibrosarcoma
1 brain
1 pituitary
1 peritoneal not given
fibrosarcoma
3 thyroid not given
1 bone
1 liver
1 jugular body
2 leukemia/lymphoma
1 adrenal
1 large intestine
anaplastic carcinoma
1 small intestine
fibrosarcoma
1 thyroid not given
1 liver
2 adrenals
1 kidney
nephroblastoma
1 leukemia/lymphoma
5 subcutaneous tissue
-------
ters into the final product, a study was undertaken-in which
,i , . . .
asbestos filter material was fed to rats (Gibei;et al.
1976). Twelve malignant tumors developed in: experimental
animals, including four kidney tumors. No tumors of this
site were found in control groups. This observation of
renal cancer takes on significance in the light of the finding
of an elevated risk of kidney cancer among asbestos insula-
tion workers (Selikoff, et al. 1979) and a high excretion
of asbestos fiber in the urine of humans drinking fiber-
contaminated water (Cook and Olson, 1979). However, this
report provides only limited experimental detail, and the
filter material was composed of sulfated cellulose and a
condensation resin in addition to 52.6 percent chrysotile
asbestos. The presence of other substances confounds the
study in relation to asbestos carcinogenicity.
Cunningham, et al. (1977) conducted two limited feeding
studies of male Wistar rats. One percent chrysotile asbes-
tos with five percent corn oil was added to rat chow diet
and fed to groups of 10 and 40 rats in two separate exper-
iments. In the first study, six of seven surviving animals
were found with tumors whereas only one malignancy was observed
in eight controls (See Table 11). No gastrointestinal tumors
were seen, but two of the treated group tumors were kidney
nephroblastomas. In the second, larger study, 11 tumors
each were observed in treated and control groups of 40 animals.
Two of the malignancies in the asbestos-fed group were of
the gastrointestinal tract and one of the control group
was a nephroblastoma, lessening the significance of the
finding of this tumor in the other treated group. With
C-49
-------
the limited number of animals in this study, the evidence
for carcinogenicity of asbestos (by feeding) is inconclusive.
Currently, a very large and carefully designed feeding
experiment is being conducted under the auspices of the
National Institute of Environmental Health Sciences. Results,
however, are not anticipated until late 1980. Meanwhile,
all previously reported experiments on ingested asbestos,
whether positive or negative, have significant limitations.
To extrapolate such data to man for use as a criteria for
a standard would not be appropriate.
Inhalation: Although lung cancer was suggested as
being causally related to human asbestos exposure in case
reports in 1935 (Lynch and Smith, 1935; Gloyne, 1935), strongly
indicated to be so in 1947 (Merewether, 1947), and unequivocally
associated in a cohort study by Doll (1955), no positive
animal data of consequence were forthcoming until 1967 when
Gross, et al. (1967) showed that lung cancer could be produced
by asbestos inhalation exposure. An early experiment of
Nordmann and Sorge (1941) described two lung tumors in 10
of 100 mice surviving 240 days following exposure to high
concentrations of chrysotile. This work, however, was called
into question by Smith, et al. (1965) on the basis of the
histology of the malignancies. Lynch, et al. (1957) exposed
AC/F, hybrid mice to commercial chrysotile and observed
a higher incidence of pulmonary adenomas in exposed animals,
45.7 percent (58/127), compared to controls, 36.0 percent
(80/222). No malignant tumors were reported, and the increase
of adenomas was not significant at the 0.05 level.
C-50
-------
The first unequivocal data showing a relationship between
asbestos inhalation and malignancy was that of Gross, et
al. (1967) who observed carcinomas in rats exposed to a
mean concentration of 86 mg/m chrysotile for 30 hours/week
from the age of six weeks. Of 72 rats surviving for 16
months or longer, 19 developed adenocarcinomas, 4 developed
squamous cell carcinomas, and 1, a mesothelioma. No malig-
nant tumors were found in 39 control animals. A search
was made for primaries at other sites which could, have metas-
tasized. None were found. These and other data are sum-
marized in Table 12. '
Reeves, et al. (1971) found two squamous cell carcinomas
in 31 rats sacrificed after two years followingexposure
3
tp about 48 mg/m of crocidolite. No malignant tumors were
reported in rabbits, guinea pigs, hamsters, or in^,ariimals
exposed to similar concentrations of chrysotile or amosite.
No details of the pathological examinations were given.
In a later study (Reeves, et al. 1974), malignant tumors
developed in 5 to 14 percent of the rats surviving 18 months.
Lung cancer and mesothelioma were produced by exposures
to amosite and chrysotile and lung cancer by crocidolite
inhalation. Again, significant experimental details were
lacking; information on survival times and times of sacrifice
would have been useful. Available details of the exposures
and results are given in.. Table 13. While the relative carcino-
genicity of the fiber types was similar, it was noted that
the fibrogenic potential of chrysotile, which had been sub-
stantially reduced in length and possibly altered (Langer,
C-51
-------
o
I
tn
K)
TABLE'12
Summary of Experiments on the Effects of Inhalation of Asbestos
Animal species
132 male white
rats
55 male white
cats
206 rats
106 rabbits
139 guinea pigs
214 hamsters
219 rats
216 gerbils
Material
administered
ball-and-
hammer-milled
Canadian
chrysotile with/
without 0.05 ml
intratracheal 5%
NaOH
controls
with/without
5% NaOH
ball-milled
chrysotile,
amosite, and
crocidolite
ball-and-
hammer-milled
Dosage
Gross,
42-146 mg/m3
(mean cone. ,
86 mg/m ) for
30 hrs/week
control
Reeves,
48+2 mg/m for
16 hrs/week up
to 2 yrs
Reeves,
48+2 mg/m for
16 hrs/week up
Animals examined
for tumors
et al. (1967)
72
39
et al. (1971)
not available
et al. (1974)
120 rats
116 gerbils
Findings
(malignant tumors)
17 adenocarcinomas
4 squaraous-cell sarcomas
7 f ibrosarcomas
1 mesothelioma
none
.
2 squamous-cell
carcinomas in 31
animals from croci-
dolite exposure
10 malignant tumors
in rats
2 in mice (See Table 13)
Average sur-
vival time
not available
not available
no information
periodic sacri-
fices were made
no information
periodic
100 mice chrysotile,
72 rabbits amosite, and
108 guinea pigs crocidolite
to 2 yrs
10 mice
30 rabbits
43 guinea pigs
sacrifices
were made
-------
n
i
en
CJ
Animal species
13 groups of
approx. 50 & 15
of about 25
Wistac SPF
rats
CO Wistar
male & female
cats
Summary of
Material
administered
amosite
anthophyllite
crocidolite
Canadian
chrysotile
Rhodes i an
chrysotile
(UICC samples)
superfine
chrysotile
TABLE 12
(continued)
Experiments on the Effects of Inhalation of Asbestos
Dosage . Animals examined
for tumors
Wagner, et al. (1974)
10.1-to 14.7 849
mg/ra for 1
day to 24 months,
35 hrs/week
Wagner, et al. (1977)
10.8 mg/m
37.5 hrs/wk
for 3, 6, or
12 months
Findings
(malignant tumors)
Average sur-
vival time
(See Tables 669 to 857 days
14 and 15) versus 754 to 803
All asbestos vari- for controls.
ties produced Survival times
mesothelioma and not significantly
lung cancer, some affected by
from exposure as exposure.
short as 1 day
1 adenocarcinomas of the
lung in 24 animals exposed
for 12 months
CO Wistar
male & female
rats
non-fibrous
cosmetic talc
Davis, et al. (1978)
46 groups of UICC samples of
approx. Han SPF amosite '
.rats and 20 Han chrysotile
SPF r.ats crocidolite
2 mg/m and
10 mg/mj 35
hours/wk for
224 days
208
none
7 adenocarcinomas
3 squamous-cell
sarcomas 1 pleural
mesothelioma 1
peritoneal
mesothelioma
(See Table 16)
not available
sacrificed at
29 months
20 Han SPF .rats control
control
20
none
-------
o
I
TABLE 13
Experimental Inhalation Carcinogenesis
: . ...
Fiber .Exposure . Animals
mass? fiber examined
(rag/raj) (f/ml)
Chrysotile 47.9 54 43
Amosite 48.6 864 46
Crocidolite 50.2 1105 46
Controls 5
Rats
.Malignant tumors Animals
examined
1 lung papillary 19
carcinoma
1 lung squamous-cell
carcinoma
1 pleural mesothelioma
2 pleural mesotheliomas 17
3 squamous-cell 18
carcinomas
1 adenocarcinoma
1 papillary carcinoma -
all of the lung
none 6
Mice
Malignant tumors
none
none
2 papillary
carcinomas
of bronchus
1 papillary
carcinoma of
bronchus
*Reeves, et al. (1974)
The asbestos was comminuted by vigorous milling, after which
6.08% to 1.82% of the airborne mass was of fibrous morphology
(3:1 aspect ratio) by light microscopy.
-------
et al. 1977) by milling, was much less than that of the
amphiboles. These results were also discussed in a later
paper by Reeves (1976).
In an extensive series of experiments, Wagner, et al..
(1974) exposed groups of Wistar SPF rats to the five UICC
asbestos samples at concentrations from 10 to 15 mg/m for
times ranging from 1 day to 24 months. For all exposure
times there were 50 adenocarcinomas, 40 squamous-cell carcin-
omas and 11 mesotheliomas produced. None appeared prior
to 300 days from first exposure. Considerable experimental
detail is provided in the paper. The significant data are
presented in Tables 14 and 15, and Figure 3 shows the dose-
response data for.lung carcinomas. These tumors follow-
a reasonably good linear relationship for exposure times
of three months or greater. The incidence in the one-day
exposure group, however, is considerably greater than expected
''.', . \ '.-_-,
It was noted that exposure had a limited effect on length
of life. Average survival times varied from 669. to 857,
for exposed animals versus 754 to 803 for controls. The
development of asbestosis was also, documented. . The inci^-
dence of lung cancer was found to be greater in animals
- ^«,
surviving 600 days. There were 17 lung tumors, 6 in animals
with no evidence of asbestosis and 11 in rats with minimal
or slight asbestosis. Cancers at extrapulmonary sites were
also listed. Seven malignancies of ovary and eight of male
genito-urinary organs were observed in groups of approxi-
mately 350 rats. None were observed in groups of 60 male
and female controls. Incidence of malignancy at other sites
C-55
-------
TABLE 14
Number of Rats with Lung Tumors or Mesotheliomas After Exposure
to Various Forms of Asbestos Through inhalation
Form of asbestos
Amosite
Anthophyllite
Crocidolite
Chrysotile
(Canadian)
Chrysotile
(Rhodesian)
None
No. of Adenocarcinomas Squamous-cell Mesotheliomas
animals carcinomas
146
145
141
137
144
126
5
8
7
11
19
0
6
8
9
6
11
0
1
2
4
4
0
0
-From Wagner, et al. (1974)
TABLE 15
Numbers of Rats with Lung Tumors or Mesotheliomas After Various
Lengths of Exposure to Various Forms of Asbestos Through Inhalation
Length of
exposure
1
3
6
12
24
None
day
months
months
months
months
No. of No. with lung No. with pleural
animals carcinomas mesotheliomas
126
219
180
90
129
95
0
3b
8
7
35
37
0
2C
1
0
6
2
% of animals
with tumours
0.0
2.3
5.0
7.8
31.8
41.0
Wagner, et al. (1974)
2 exposed to Chrysotile and 1 to crocidolite
1 exposed to amosite and one to crocidolite
C-56
-------
was little different from that of controls. If controls
(
are included from other experiments in which ovarian and
genito-urinary tumors were present, the comparative incidence
:
in the exposure groups here lacks significance. No data
were provided, however, on the variation of tumor incidence
at extrapulmonary sites with asbestos dosage.
Wagner, et al. (1977a) also compared effects of inhala-
tion of a superfine chrysotile to a pure, non-fibrous talc.
One adenocarcinoma was found in 24 rats exposed to 10.8
mg/m of chrysotile for 37.5 hours/week for 12 months.
Finally, in a study similar to Wagner's, Davis, et
al. (1978) exposed rats to 2.0 or 10.0 mg/m of chrysotile.,
crocidolite, and amosite (equivalent to from 430 to 1950
f/ml). Adeno- and squamous-cell carcinomas were observ-
ed in chrysotile exposures, but not with crocidolite or
amosite (see Table 16). One pleural mesothelioma was observed
with crocidolite exposure, and extrapulmonary neoplasms
included a peritoneal mesothelioma. A relatively large
number of peritoneal connective-tissue malignancies were ;
also observed, including a leiomyofibroma on the wall of ,
the small intestine. The significance of these tumors is
speculative, however.
As discussed in the "Pharmacokinetics" section, inhala-
tion exposures result in concomitant gastrointestinal exposures
from the asbestos that is swallowed after clearance from
the bronchial tree. While all inhalation experiments focussed
on thoracic.tumors, those of Wagner, et al. (1974), Davis,
et al. (1978) and, to a limited extent, Gross, et al. (1967)
C-57
-------
TABLE 16
Experimental Inhalation Carcinogenesis in Rats'
Exposure Number of
Fiber
n
i
en
00
mass,
(mg/m )
Chrysotile 10
Chrysotile 2
Amosite 10
Crocidolite 10
Crocidolite 5
Control
fiber
(f 5 u/ml)
1950
390
550
860
430
animals
examined
40
42
43
40
43
20
Malignant tumors
6 adenocarcinomas
2 squamous-cell carcinomas
1 squamous-cell carcinoma
1 peritoneal mesothelioma
none
none
1 pleural mesothelioma
none
'Davis, et al. (1978)
-------
also included a search for tumors at extrathoracic sites.
A limited number of these were found, but no association
can be made with asbestos exposure.
One aspect of the inhalation experiments that is note-
worthy is the significant number of pulmonary neoplasms
that can be produced in the rat by inhalation as compared
to other species (Reeves, et al. 1971; Reeves, et al. 1974).
This points to the variability of species response to asbestos
and the need for an appropriate model before extrapolations
to man can be made with confidence. The absence of significant
gastrointestinal malignancy from asbestos exposure in animals,
in contrast to that found in humans, may be the result of
the use of inappropriate animal models.
Intrapleural Administration: Evidence that intrapleural
administration of asbestos would result in mesothelioma
was forthcoming in 1970 when Donna (1970) produced mesothe-
liomas in Sprague-Dawley rats treated with a single dose
of 67 mg of chrysotile, amosite or crocidolite. Reeves,
et al. (1971) produced mesothelial tumors in rats (1 of
3 with crocidolite and 2 of 12 with chrysotile) by intra-
pleural injection of 10 mg of asbestos. Two of thirteen
rabbits injected with 16 mg of crocidolite developed mesothe-
liomas.
Stanton & Wrench (1972), in a series of experiments,
demonstrated that major commercial varieties of asbestos,
as well as various other fibers, produced mesotheliomas
in as many as 75 percent of animals into which material
had been surgically implanted. Extension of these experi-
C-59
-------
raents were reported in 1973 (Stanton, 1973) . These results
are summarized in Table 17. The authors concluded that
the carcinogenicity of asbestos and other fibers is strongly
related to their physical size, those fibers of a diameter
less than 3 um being carcinogenic and those of a larger
diameter not. Further/ samples treated by grinding in a
ball mill to produce shorter length fibers were less likely
to produce tumors. While the authors attributed the reduced
carcinogenicity to a shorter fiber length, the question
has been raised as to the effect of the destruction of crystal-
linity and perhaps other changes in the fibers occasioned
by the extensive ball milling (Langer, et al. 1977).
Another comprehensive set of experiments was conducted
by Wagner (Wagner, et al. 1973; Wagner, et al. 1977b).
He, too, has produced mesothelioma from intrapleural admini-
stration of asbestos to CD Wistar rats and demonstrated
a strong dose-response relationship. Tables 18a and 18b
list the results of these experiments.
Pylev and Shabad (1973) and Shabad, et al. (1974) reported
mesotheliomas in 18 of 48 and in 31 of 67 rats injected
with three doses of 20 mg of Russian chrysotile. Other
experiments by Smith and Hubert (1974) have produced mesothel-
iomas in hamsters injected with 10 to 25 mg of chrysotile,
10 mg of amosite or anthophyllite, and 1 to 10 mg of crocidolite,
Various suggestions have been made that natural oils
arid waxes contaminating asbestos fibers might be related
to their carcinogenicity (Harington, 1962; Harington and
Roe, 1965; Commins and Gibbs, 1969). This, however, was
c-60
-------
TABLE 17
Dose-response Data Concerning the effects of
Intrapleural Implantation of ' - ?
Asbestos and Other Fibers in
n_ . _ci
Rats
Material Dose No. of rats
(rag) with
mesotheliomas
UICC-SRAS
crocidolite
Hand-cobbed
virgin
crocidolite
Special South African
crocidolite
Partically pulverized
crocidolite
UICC-SRAS
amosite
UICC-SRAS
chrysotile
Coarse
fibrous glass
Glass wool
Fine AAA fibrous glass
3u diameter
uncoated
coated
1
2
10
20
40
1
20
40
40
40
40
40
40
40
40
40
2
5
11
12
14
4
10
18
15
8
15
15
. 1
1
3
5
Total no. % of rats
of rats with
tumors
25
. - 23
27
25 :v
23
30
24
27
20
25*
'"<
25
26
24
25
26
28
8
22
41
48
61
13
42
67
75
32
60
58
4
4
12
18
Stanton and Wrench, 1972
C-61
-------
TABLE 18a
Percentage of Rats Developing Mesotheliomas After Intrapleural
Administration of Various Materials
Material % of rats
with mesotheliomas
SFA chrysotile (superfine
Canadian sample) 66
UICC crocidolite 61
UICC amosite 36
UICC anthophyllite 34
UICC chrysotile (Canadian) 30
UICC chrysotile (Rhodesian) 19
Fine glass fiber (code 100) ,
median diameter, 0.12 urn 12
Ceramic fiber, diameter,
0.5-1 umD 10
Glass powder 3
Coarse glass fiber (code 110) ,
median diameter, 1.8 urn 0
* Wagner, et al. (1977b)
.Wagner, et al. (1973)
c-62
-------
TABLE 18b
Dose-Response Data Following Intrapleural Administration of Asbestos to Rats'
Material Dose No. of rats with
(mg) mesotheliomas
SFA chrysotile 0.5
1
2
4
8
Crocidolite 0.5
1
2
4
8
1
3
5
4
8
1
0
3
2
5
Total no. % of rats Reference
of rats with tumors
12
11
12
12
12
11
12
12
13
11
8
27
42
33
62
Wagner, et al
(1973)
9
0
25
15
45
Wagner, et al. (1973)
C-63
-------
not borne out in the experiments described above by Wagner,
et al. (1973) or Stanton & Wrench (1972).
Intratracheal Injection: Intratracheal injection has
been used to study the combined effect of administration
of chrysotile with benzo(a)pyrene in rats or hamsters (see
"Synergism and/or Antagonism"). In rats given three doses
of 2 mg chrysotile (Shabad, et al. 1974) or hamsters given
12 mg of chrysotile (Smith, et al. 1970) no lung tumors
were observed. However, the co-administration of benzo(a)
pyrene did result in lung tumors.
Intraperitoneal Administration: Intraperitoneal injec-
tions of 20 mg of crocidolite or chrysotile produced three
peritoneal mesotheliomas in 13 Charles River CD rats. Twenty
mg of amosite produced no tumors in a group of 11 (Maltoni
& Annoscia, 1974). They also injected 25 mg of crocidolite
into 50 male and 50 female 17-week old Sprague-Dawley rats
and observed 31 mesothelial tumors in males and 34 in females.
In an extensive series of experiments, Pott and Friedrichs
(1972) and Pott, et al. (1976) produced peritoneal meso-
theliomas in mice and rats injected with various commercial
varieties of asbestos and other fibrous material. These
results are shown in Table 19. As with the experiments
with intrapleural administration, the malignant response
was altered by ball-milling fibers for 4 hours. The rate
of tumor production was reduced from 55 percent to 32 percent
and the time from onset from exposure to first tumor was
lengthened from 323 to 400 days following administration
of four doses of 25 mg of UICC Rhodesian chrysotile. In
C-64
-------
Table 19
Tumors in Abdomen and/or Thorax After Intraperitoneal Injection of Glass Fibers,
Crocidolite or Corundum in Rats
Dust Form
I. p. Effective No. of days Average
dose number of before first survival time
Rats
with
Tumor type
(mg) dissected tumor of rats with tumors
rats tumors (days . (%)
after injection)
o
* Glass fibers
MN 104 f
Glass fibers
MN 104 f
Glass fibers
MN 104 f
Glass fibers
MN 112 f
Crocidolite f
Corundum g
"
2 73 421 703
10 77 210 632
2 x 25 77 194 367
20 37 390 615
2 39 452 761
2 x 25 37 545 799
t»
27.4
53.2
71.4
37.8
38.5
8.1
H
f-4
01
4J
O
m
01
X
17
36
47
12
12
1
01
u
i id
o> e
0 U
C U
an
co
3
4
6
1
3
_
H M KJ
§f3
o
10 C
EM -H
£,« u
r-t (0 M
O «
P< U
1
2
1
-
2
r-t
01
00
1 «t
e e
3 O
H O
3 M
u a
H M
4J
at
OS
1
3
-
2
2
u
c
en
rt
c
01
a)
1
-
-
1
1
2
-------
Table 19 (cont.)
Oust
UICC Rhodesian
n chrysotile
i
a\
<* UICC Rhodesian
chrysotile
UICC Rhodesian
chrysotile
UICC Rhodesian
chrysotile
UICC Rhodesian
chrysotile
UICC Rhodesian
milled
Palygorscite
Glass fibers
s + s 106
Glass fibers
S + s 106
Form
f
f
f
f
f
f
f
f
f
I. p.
dose
(mg)
2
6.25
25
4 x 25
3 x 25
s.c.
4 x 25
3 x 25
2
10
Effective
number of
dissected
rats
37
35
31
33
33
37
34
34
, 36
No. of days
before first
tumor
431
343
276
323
449
400
257
692
350
Average
survival time
of rats with
tumors (days
after injection)
651
501
419
361
449
509
.
348
692
530
Rats
with
tumors
(%)
a
Q
H
-»
0
in
01
16.2 4
77.1 24
80.6 21
54.5 16
3.0
32.4 9
76.5 24
2.9 1
11.1 2
Tumor type
^
-I
0) H
u H a
t a) e
0) 10 O <0 O
<- e i e c
DO e o *
c o So u
H U H U 1-4
&,<0 On) to
in in ft in u
2 - -
3
2 1 1
2
- 1
s.c.
3
2
_
2 - -
H
U
1
e
DO
sec
0 O Oi
-H O "*
4-* w C
01 iQ 01
H6 W ffl
1
- -
_ _
_ _
- -
_ _
-
-
1
-------
Table 19 (cont.)
n
Dust
Glass fibers
S t S 106
Gypsum
Henalite
Actinolite
Biotite
Haematite
(precipit. )
Haematite
(mineral)
Pectolite
Sanidine
Talc
NaCl (control)
Form
f
f
f
g
g
g
g
g
g
g
. - ' .
i. P.
dose
(mg)
4 x 25
4 x 25
4 x 25
4 x 25
4 x 25
4 x 25
4 x 25
4 x 25
4 x 25
> x 25
4 x 2ml
Effective
number of
dissected
rats
*
32
35
34
39
37
34
38
40
39
36
72
No. of days
before first
tumor
197
579
249
-
--
-
. - . -
569
579
587
Average
survival time
of rats with
tumors (days
after injection)
,
325
583
315
-
' - . '
-
- . -
569
579
587
..:
Rats
with
tumors
(%)
A
o
.^4
r-i
01
4J
O
n
01
s
71.9 20
5.7
73.5 17
-
-
-
_ _
2.5
2.6
2.8 1
-
Tumor type
" H
Si-t
H 10
i oi e
oi a u .o u
H U 1-1 tj M
0,10 o a a
CO 10 Oi (0 U
3
1 1
8 - -
- '. -
- ~
_
_ ..'
.
1
1
-., -'"
_
*
H
o)
U
1
6
3D
H (0
9 e
U 0
< u
41 U
v
H
c
01
A
_
-
-
-
-
-
-
1
-
--
-
-------
the case of the ball-milled fiber, 99 percent were reported,
to be smaller than 3 urn, 93 percent less than 1 urn, and
60 percent less than 0.3 urn.
A strong conclusion which can be drawn from the above
experimental data is that large-diameter fibers (greater
than 3 um) are significantly less carcinogenic than finer
fibers.. The origin of the reduced carcinogenicity of shorter,
ball-milled fibers is less clear as the relative contribu-
tions of shorter fiber length and the significant alteration
of the crystal structure by input of physical energy are
not, as yet, defined. Further, the extrapolation of data
developed on size-dependent effects, from intrapleural or
intraperitoneal administration to inhalation (where movement
of the fibers in airways and subsequently through body tissues
is strongly size-dependent) presents significant difficulties.
Finally, since the number of smaller fibers in an exposure
circumstance may be 100 times greater than those longer
than 5 um, the reduction of their carcinogenicity must be
demonstrated at a level 100 times less before their contribu-
tion can be neglected.
Carcinogenicity - Human Data
The modern history of asbestos disease dates from the
turn of the century, when two reports were published docu-
menting uncontrolled conditions in asbestos textile factories.
One, the testimony of H. Montague Murray (1907) at a hearing
concerning compensation, described severe pulmonary fibrosis
found at autopsy in 1900 in the last survivor of a group
ot" ten workers first employed 14 years previously in a carding
C-68
-------
room. The second was the description by Auribault (1906)
of deaths during, the early years of operation of an asbestos
weaving mill established at Conde-sur-Noireau, France/ in
1890. During this period, 50 men died, including 16 of
17 recruited from a cotton textile mill previously owned
by the factory director.
With time, however, the spectrum of disease associated
with asbestos exposure continued to expand. In 1935 two
clinical reports were published of lung cancer in asbestos
workers who had died with evidence of pulmonary fibrosis
(Lynch and Smith, 1935, Gloyne, 1935). while such reports
were not sufficient to causally relate asbestos exposure .
to the lung cancer, the possibility was raised. In 1947
it was confirmed by substantial data which showed that .13
percent of a group of individuals who died with asbestosis
in Great Britain also had bronchogenic carcinoma (Merewether,
1947). Mesothelioma, a rare tumor of the lining of the
abdomen or chest, was first described in an asbestos worker
in 1953 (Weiss, 1953) subsequently found to be frequently
associated with potential asbestos exposure (Wagner, et
al. 1960) , and unequivocally related to such exposure in
1965 (Newhouse and Thomson, 1965). Gastrointestinal cancer ,
also was found to be in excess among asbestos insulation
workerjs in the United States (Selikoff, et al. 1964).
i
Currently, all major commercial asbestos varieties,
chrysqtile, amosite, and crocidolite, have been found to
produce a significant incidence of asbestos-related disease
i
!
among Iworkers occupationally exposed in mining and milling,
C-69
-------
in manufacturing, and in the use of materials containing
the fiber. The predominant route of exposure has been inhala-
tion, although some asbestos may be swallowed directly or
after being brought up from the respiratory tract. Not
only has asbestos disease^ been found among individuals exposed
to the fiber directly as a result of excessive work exposures
in decades past, but asbestos-associated cancer has also
been identified, albeit less frequently, among those with
inhalation exposures of lesser intensity, including those
who had worked near the application or removal of asbestos
material, those with history of residing in the vicinity
of asbestos plants, and those who had lived in the house-
hold of an asbestos worker.
Water Ingestion: Four studies have considered the
relation.of asbestos ingested in drinking water to gastro-
intestinal cancer. As an outgrowth of the contamination
of Lake Superior by fibrous material in the tailings of
an iron ore processing plant, the mortality of the population
of Duluth was compared with that of Minnesota and Hennapin
County (Minneapolis) for quinquenia to 1969 (Mason, et al.
1974). The relative death rates for digestive cancer, lung
cancer and all neoplasm were elevated from 16 to 49 percent.
However, with the exception of colon/rectal cancer, which
was highly elevated, no trends with time or consistency
between male and female were clearly discernable. Mason,
et al. (1974) concluded that additional follow-up was necessary
to determine if a hazard exists. Levy, et al. (1976) conducted
C-70
-------
a similar study with equivalent results. However, the short
follow-up from the earliest possible exposure (1956) would
make it unlikely that any positive result would be found.
Furthermore, while the Reserve plant began production in
1956, current discharge levels did not begin until 1967
when a major plant expansion took place.
A study by Harrington, et al. (1978) reviewed malig-
nancy in the Connecticut Tumor Registry from 1935 to 1973
to see if a correlation existed between the use of asbestos
cement (A/C) pipe for public water supply and the incidence
of gastrointestinal cancer. No association was found between
the age-adjusted, sex-specific incidence data for stomach,
colon, and rectal cancer and the use of A/C pipe. While
some water supplies reported A/C pipe that was 45 years
old in 1975, the majority (66 percent) of the population
studied received water through A/C pipes that were only
25 years old. while the majority (56 percent) of A/C pipe
systems in Connecticut have water which is considered aggres-
sive under the AWWA Standard for A/C transmission and pressure
pipe, fiber counts done on over 100 A/C pipe systems in
Connecticut showed 98 percent to be under 10 f/1 (J. Millette,
personal communication).
A report on an EPA grant to the University of Californ-
ia analyzed the 1969-1971 cancer incidence from 721 census
tracts of the five Bay Area Counties along with the chryso-
tile asbestos fiber concentrations in the drinking water
(Cooper, et al. 1978). For the census tracts the chrysotile
C-71
-------
asbestos fiber counts ranged from below detectable limits
to 36 x 10 fibers per liter.
The University of California investigators grouped
the census tracts on a gradient of low- to high-asbestos
counts and found significant dose-response gradients for
the incidence of several cancers. Statistically significant
positive trends were noted for white male lung and stomach
cancer and white female gall bladder, esophageal, and peri-
toneal cancer. The census tracts were cross-classified
using both asbestos count and tract socio-economic status
indicators of medium family income and medium school years
completed. The positive dose-response effect between cancer
incidence of certain sites and asbestos counts appeared
to be independent of the effect of socio-economic status.
The fact that the significant results are not restricted
to one body site is not surprising considering the know-
ledge that asbestos fibers are probably transported through-
out the body. For example, one study using rats has found
that ingested fibers are deposited in the lung. (Cunningham,
et al. 1977). An additional study (Cpoper, et al. 1979)
using six years of data showed a statistically significant
association between asbestos levels in Bay area, CA drinking
water and cancers of the digestive tract.
Insulation Application and Removal: A large study
by Selikoff, et al. (1979) best demonstrates the full spectrum
of disease from asbestos exposure. They studied the mortality
experience of 17,800 asbestos insulation workers from January 1,
1967, through December 31, 1976. These workers were exposed
primarily to chrysotile prior to 1940, and to a mixture
C-72
-------
of chrysotile and araosite subsequently. No crocidolite .
is known to have been used in U.S. insulation material (Selikoff/
' ' t;
1970). In this group, 2271 deathsVhave occurred/..-and. their
analysis provides important insights into, the nature of
asbestos disease. 'Table 20 lists the expected and observed
deaths by cause, and includes data on tumors less frequently
- , . i .' ' -
found. As in animal experiments, lung tumors are common
and account for about 20 percent of the deaths; 7 percent
are from mesothelioma of the pleura or peritoneum. Addition-
ally, though, cancer of the gastrointestinal tract is signifi-
cantly elevated; so, too, are cancer of the larnyx, pharynx,
and buccal cavity, and renal tumors. Other tumors are also
increased, but not to a statistically significant degree.
Comparing the deaths from cancer and asbestosis in this
group with those expected in the general population, nearly
40 percent of the deaths among insulators can be attributed
to their occupational exposure to asbestos fiber.
The large number of deaths allows an analysis to be
made of the onset of effects as related to time from first
exposure. Figure 4 depicts the excess asbestos-related
lung cancers and mesotheliomas according to time from onset
of exposure. It is seen that an important rise in broncho-.
genie carcinoma occurs only after 25 years and mesothelioma, :
after 30 years. This long-lapsed period is seen in individuals
exposed continuously to relatively high concentrations of
asbestos. At lower exposures, longer periods from exposure
onset to tumor development would be expected and, thus,
studies that do not provide adequate follow-up can be mis-
leading. Among other groups of insulation workers, high
C-73
-------
TABLE 20
Deaths Among 17,800 Asbestos Insulation Workers
in the United States and Canada
January lf.1967 - January 1, 1977a'b
Number of men: 17,
800
Man-years of observation: 166,853
Total deaths, all causes
Total cancer, all sites
Lung cancer
Pleural mesothelioma
Peritoneal mesothelioma
Cancer of esophagus
Cancer of stomach
Cancer of colon - rectum
Larynx
Pharynx, buccal cavity
Kidney
Cancer of pancrease
Liver, biliary passages
Bladder
Testes
Prostate
Leukemia
Lymphoma
Skin
Brain
All other cancer
Asbestosis
Chronic respiratory disease0
All other causes
a Selikoff, et al. (1979)
b _ . ,
Expected
1,660.96
319.90
105.97
7.01
14.23
37.86
4.84
8.58
8.08
17.46
7.50
9.34
1.95
19.98
12.95
20.21
6.58
10.34
27.02
__
58.58
1,282.48
Observed
2,271
994
485
66
109
18
22
59
11
21
20
22
5
8
2
30
15
19
12
14
56
162
66
1,049
i ff *
Ratio
1.37
3.11
4.58
2.57
1.55
1.56
2.27
2.45
2.48
1.26
0.67
0.86
1.50
1.16
0.94
1.82
1.35
2.07
1.12
0.82
mortality data of the U.S. National Center for Health
Statistics for 1967-1975 and extrapolation to 1976.
Other than asbestosis.
C-74
-------
CO
cr
LU
1
o
CO
LLl
CL
O
o
o
o"
CO
7 r~
LL!
.Q
so
80
70
60
50
40
50 h-
id
LUNG GANGER
MES07HEUOMA
10 20 30 40 50
TIME FROM ONSET OF EXPOSURE (YEARS)
Figure 4. The excess, Asbestos-related Mortality Rates for Lung Cancer and
Mesothelioma According to Time from Onset of Asbestos Disease.
C-75
-------
rates of cancer, particularly bronchogenic carcinoma and
pleural or peritoneal mesothelioma, have been reported in
the United Kingdom by Elmes and Simpson (1971).
Some data on exposure of U.S. insulation workers exist.
These have been reviewed by Nicholson (1976) and are summar-
ized in Table 21. Estimates of past average exposures were
made on the basis of current measurements by five labora-
tories of fiber concentrations during work activities thought
to be typical of those of past years and information on
product composition and usage. Time-weighted average concen-
trations of 10 to 15 f > 5 urn /ml and 15 to 20 f ? 5 urn/ml
were suggested for commercial construction and marine work,
respectively. It was noted that, while these average concentra-
tions were not extraordinary, peak concentrations could
often be very high and exceed 100 f/ml. Even though there
was good agreement between the results of several research
groups on current average concentrations, the extrapolation
to earlier years is highly speculative.
Factory Employment: An early study of workers from
an asbestos products factory (Mancusco and Coulter, 1963)
showed a significant excess in total mortality, with important
contributions to excess death rates from asbestosis, cancer
of the lung, bronchus and trachea, and neoplasms of the
digestive organs and peritoneum. In this latter group of
deaths, an important factor was peritoneal mesothelioma.
While in excess, increases in cancer of the esophagus, stomach,
colon and rectum did not have statistical significance.
C-76
-------
TABLE 21
Summary of Average Asbestos Air Concentrations during Insulation.Work
Average
Fiber Concentration f/ml
Light and heavy
Research group construction Marine work
Average concentrations of fibers longer than 5 um evaluated
by membrane filter techniques and phase-contrast microscopy
Nicholson (1975) 6.3
Balzer & Cooper (1968) 9 _ fi fi
Cooper & Balzer (1968) *'' °'°
Ferris, et al. (1971) 2.9
Harries (1971a,b) 8.9
Average concentrations of all visible fibers counted
with a konimeter and bright-field microscopy
Murphy, et al. (1971) 8.0
Fleischer, et al. (1946) 30-40
Estimates of past exposure based on current membrane-filter data
Nicholson (1976) 10-15
C-77
-------
TABLE 22
Observed Deaths and SMRs for Selected Causes of Death by Period of Follow-Up
for 1075 Males Retiring from a U.S. Asbestos Company from 1941-67
and Followed through 1973a
1941-1973
Cause of Death
All causes
Cancer (140-205) b
Digestive (150-159)
Respiratory (162-163)
All other cancers
Stroke (330-334)
Heart disease (400-443)
Respiratory disease
(470-527)
Pneumoconiosis and
pulmonary fibrosis
(523-525)
Asbestosis (523.2)
All other causes
Death certificates
not located
a Enterline, et al. (1972)
b
Observed
deaths
781
173
55
63
55
74
321
68
31
19
113
32
SMR
120.4
159.0
137.8
270.4
120.6
96.4
106.5
173.0
92.5
1941-1969
Observed
deaths
616
138
46
49
43
48
269
54
25
16
96
11
SMR
115.8
154.5
136.1
270.7
115.0
76.7
108.4
178.2
94.6
__
1970-1973
Observed
deaths
165
35
9
14
12
26
52
14
6
3
17
21
SMR
141.
179.
147.
269.
146.
183.
97.7
155.
82.5
_
6
5
5
2
3
1
6
c-78
-------
There was a consistent increase in the mortality rate with
increasing length of employment in the asbestos industry
for all causes of death and especially for malignant neoplasms
and asbestosis. . ... , .
A second study of factory employees is that of Enterline,
et'al. (Enterline, et al. 1972; Henderson and Enterline,
1978), who studied a group of retirees from several plants
of a major asbestos products manufacturing company. It
shows a similar pattern of mortality. Table 22 lists standard
mortality rates (SMR's) by cause in two time periods. The
usual asbestos cancers and asbestosis are seen as significant
causes of death. Here, too, a correlation was found between
total dust exposure and excess mortality for both malignant
and non-malignant disease. Table 23 lists the data for
lung cancer and shows a linear relationship with exposure.
TABLE 23
Lung Cancer Mortality Rates According to Dust Exposure3
Cumulative dust exposure
(mppcf - years)
125
125 - 149
250 - 499
500 - 749
750
SMR
197.9
180.0
327.6
450.0
777.8
aHenderson and Enterline (1978)
Million particles per cubic foot
C-79
-------
These authors (Enterline and Henderson, 1973) suggested
earlier that crocidolite may have a higher carcinogenic
potential (for lung) than amosite or chrysotile. The later
analysis (Henderson and Enterline, 1978) shows that indivi-
duals in the textile departments of the company (chrysotile
only) have a lower lung cancer SMR than those in the pipe
department (chrysotile and crocidolite) for equal dust expo-
sures. However, no conclusions could be drawn from an analysis
of the mortality rates of all individuals exposed, or not
exposed, to crocidolite. Since the follow-up of this population
began only after the cohort members reached age 65, survivor
effects may be of importance. For example, those individuals
who smoke cigarettes and are thus at higher risk for lung
cancer may be preferentially excluded by virtue of death
before age 65 because of smoking-associated disease such
as myocardial infarction. Further, the limited number of
mesotheliomas (5 of 781 deaths) found in the latest follow-
up of this group could be due to the. high incidence of meso-
thelioma at age 50 to 65, 30 to 45 years from onset of first
employment (see Figure 4).
A study of the largest factory of the company studied
by Enterline, et al. (1972), but not limited to retirees,
shows a considerably different mortality pattern (Nicholson,
1976; Nicholson, et al. 1979a). All 689 maintenance and
production employees on January 1, 1959, who were first
employed at least 20 years earlier were followed through
1976. In this group, 274 deaths occurred, whereas 188.19
C-80
-------
were expected. Fourteen pleural and 12 peritoneal mesothe-
liomas accounted for nearly 10 percent of the deaths, most
occurring before age 65. A strong correlation with estimated
dust exposure was seen in deaths from,asbestosis, but not
with the asbestos-related malignancies. Gastrointestinal
cancer was especially high in the lowest of four dust categories
(11 o.bserved versus 3.15 expected) and only elevated slightly
in the higher exposure categories. In the highest dust
category, the textile mill, cancer was not dramatically
increased, but 40 percent of the deaths were from asbestosis.
Individuals in this department tended to die of non-malignant
disease before reaching the age of greatest risk for cancer.
. . A final significant U.S. factory study is that of Seidman,
efc al. (1979) which extends an earlier study (Selikoff,
etal. 1972) and documents, the experience of workers exposed
only to amos'ite asbesto^r In; the production of insulation
materials, primarily for/use aboard naval vessels. Overall
mortality shows- patterns similar to other heavily exposed
groups, with 59*4 deaths observed versus 368.62 expected.
Lung cancer was more than five times the number expected,
and 16 deaths from mesothelioma occurred. Of particular
importance in this study is the finding that individuals
employed for periods less than 6 months had significant
excess of lung cancer (see Table 24). Gastrointestinal
cancer was also elevated for those with exposures of less
than 6 months (15 observed versus 10.6 expected), but the
difference did not have statistical significance. Further,
C-81
-------
there was not an increasing risk with time of employment
as in the case with lung cancer.
TABLE 24
Expected and Observed Deaths
from Lung Cancer and Cancer of
the Esophagus, Stomach, Colon and Rectum
in Workers Exposed to Amosite Asbestos
(Followed 5 to 35 Years after Employment from 1941 to 1945)
Length of
employment
1 mo
1 mo
2 mo
3-5 mo
6-11 mo
1 yr
2+ yrs
Total
Lung cancer
expected
1.6
2.5
2.4
4.2
3.2
2.6
6.0
22.5
Observed
4
6
8
9
12
15
39
93
GI cancer
expected
1.4
2.4
2.6
4.2
3.2
2.5
6.4
22.7
Observed
2
2
3
8
1
5
7
28
aSeidman, et al. (1979)
Some data exist that would indicate the air concentra-
tions to which workers in this factory, which operated in
Paterson, New Jersey, from 1941 through 1954, were exposed.
Following cessation of operations there, two similar plants
were opened elsewhere, using the same equipment and manufac-
turing the same product with the same materials. As in
the Paterson factory, dust control was inadequate in the
newer plants. These continued operation through 1971 in
one case and 1975 in the second. During 1967, 1970, and
1971 asbestos fiber concentrations in the plants were measured
by the National Institute for Occupational Safety and Health
(NIOSH, 1972), and the results are presented in Table 25.
The overall arithmetic average exposure was 34.9 f/ml with
C-82
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TABLE 25
Asbestos Fiber Concentrations in Two Amosite Insulation Production Facilities3'
ASBESTOS INSULATION
Operation
Mixing
Forming
Finishing
Inspection
& Packing
Miscellaneous
Mean
107.
98.
32.
13.
1967
No. of
samples
0 3
9 12
2 4
3 2
Mean
27.7
24.1
16.8
13.0
21.0
ASBESTOS INSULATION
Operation
Mixing
Forming
Curing
Finishing
Inspection
& Packing
Miscellaneous
Mean
163.
33.
2.
44.
16.
1967
No. of
samples
0 5
3 18
5 1
6 3
7 7
Mean
36.2
25.7
31.0
34.8
17.9
13.8
PLANT Y
1970
NO. of
samples
2
13
2
8
14
PLANT X
1970
No. of
samples
3
3
1
4
3
2
Mean
46.3
25.2
15.0
11.. 0
2 .7
Mean
74.4
50.6
14.4
39.5
22.8
16.6
1971
No. of
samples.
7
32
17
19
5
1971
No. of
samples
11
39
5
26
15
24
a NIOSH (1972)
All samples expressed as f >5 urn/ml.
c-83
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a range from about 20 to 80. Using 40 f/ml, as an estimate
of the fiber count in the Paterson factory, one calculates
the average dose received by those employed for less than
6 months to be no more than 120 f/mi-months, the same dose
as would be received by a worker employed 20 years at an
exposure of 0.5 f/ml. Of significance, also, is that the
mesothelioma risk is less than that of insulators (3 percent
versus 7 percent). Since times from onset of exposure to
amosite are comparable for each group, the presence of amosite
in insulation materials cannot explain the high rate of
mesothelioma among insulators.
In Great Britain, a well-studied factory population
(Doll, 1955; Knox, et al. 1968) provides useful information
because of the availability of environmental information.
The mortality experience of this group has been recently
updated (Peto, et al. 1977). Workers exposed prior to 1933
(before dust concentrations were significantly reduced)
had a marked excess of lung cancer (25 observed versus 4.63
expected.) . Other cancers were elevated, but not greatly
so. Of significance, however, individuals employed after
1933, and even after January, 1951, were found to have an
excess risk of lung cancer. These data were analyzed by
Peto (1978) in relation to measured and estimated fiber
concentrations. Exposures averaged about 10 f/ml after
1933 and were virtually exclusively chrysotile. Using a
linear dose-response relationship for lung cancer and pleural
mesothelioma, he estimated that a 2 f/ml exposure for 50
C-84
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years would cause approximately 10 percent of male asbestos
workers to die from asbestos-related disease. It should
i *~ ' i .
be. noted that data available for analysis were very limited...
and the estimate was based on extremely small numbers (14
deaths from lung cancer, 4 from mesothelioma, and 17 from
I .'
non-malignant respiratory disease). Furthermore/ few individ-
uals in the cohort were more than 35 years from onset of
exposure and at a period of highest risk from asbestos disease.
Another factory population has been extensively studied
(Newhouse, 1969; Newhouse, et al. 1972; Newhouse and Berry,
1976; Newhouse and Berry, 1979). Exposures were to chrysotile,
crocidolite and amosite. Table 26 lists the mortality experi-
ence of both men and women according to estimates of fiber
exposure (no details are provided as to the method of estima-
tion) (Newhouse and Berry, 1979). Lung cancer, gastrointestinal
cancer and mesothelioma are significantly elevated in the
long-term ( 2 years) or severe exposure groups. It has
been estimated (Newhouse and Berry, 1976) that as much as
11 percent of this entire group will die of pleura! or peritoneal
mesothelioma. Among women, cancer of the breast and cancer
of the ovary were in excess at the 0.05 level of significance.
Mining and Milling: Three studies exist showing mortality
patterns in the mining and milling of pure chrysotile asbestos.
Among Canadian mine and mill employees a strong correlation
with total dust levels and lung cancer and gastrointestinal
cancer is seen. In studies of McDonald, et al. (1971) and
McDonald and Liddell, (1979) excess respiratory cancer was
seen and strongly correlated with dust index for individuals
c-85
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TABLE 26
Mortality Experience of Male and Female Factory Workers
Exposure (male)
a
Low to moderate (5-10 f/ml)
Cause of Exposed
Death Individuals:
O
All causes 118
Cancer of lung &
pleura (ICD 162 17
-163)e
G I cancer 10
(ICD 150-158)
Other cancers 6
Chr resp
disease 19
2 yrs
884
E
118.0
11.01
9.0
7.4
17.5
2 yrs
554
0 E
89 95.3
16 9.0
9 7.3
8 5.8
16 14.7
Severe (20+ f/ml)
2 yrs
937
O E
162d 122.2
31d 12.8
20C 9.5
16C 7.9
20 17.6
2 yrs
512
0 E
176d 102.5
56d 10.4
19C 8.2
16C 6.3
28 15.9
Exposure (female)
Low
Cause of Exposed
death Individuals:
O
All causes 34
Cancer of lung & .
pleura 3
(ICD 162-163)
G I cancer
(ICD 150-158) 3
Other cancers 4
Chr resp
disease 3
to moderate
(5-10 f/ml)
98
E
22.0
0.5
1.9
3.2
2.3
Severe (20+ f/ml)
2 yrs
396
O E
88° 65.6
15d 1.9
14C 5.7
16 11.9
6 6.8
2 yrs
199
0 E
78d 30.4
21d 0.8
9C 2.6
16d 5.3
10C 3.2
Newhouse and Berry (1979)
'P
0.05
0.01
0.001
e
Disease codes
C-86
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with 20 or more years employment, with a linear relationship
to dust exposure in mppcf-years providing the best fit (McDonald
and Liddell, 1979) (see Table 27).
TABLE 27
Relative Risks for Respiratory Causes
Dust index 10 10-99 100-299 300-599 600
(mppcf-yrs)
Relative risk 1.0 1.1 1.2 1.8 2.9
aMcDonald and Liddell (1979)
These data, however, only compare various exposed groups.
*
In the initial publication of the mortality experience of
this cohort, it was seen that all dust categories had a
higher respiratory cancer rate than the rate of the neighboring
counties (McDonald, et al. 1971). Further, the use of a
dust index makes it difficult to separate time and intensity
of exposure (both of which, as seen, have considerable prog-
nostic influence), and it is not directly convertible into
fiber concentrations (Gibbs and LaChance, 1974) . High exposure
categories also showed an excess risk of cancer of the stomach
and esophogus. Mesothelioma was verified as the cause of
15 of 4,547 deaths, a rate much less than reported in factory
populations.
Separation of time and intensity is to some extent
achieved in a study by Nicholson (1979a), also of Canadian
mine and mill employees, all of whom had at least 20 years
from first exposure to asbestos at the time of enrollment.
C-87
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Asbestosis (14 percent of all deaths) and lung cancer (28
observed versus 11.1 expected) were the major sources of
excess mortality. One death (of 174) was from pleural mesothe-
lioma. ''"' ''
A Soviet study of the health effects of chrysotile
mining and milling is that of Kogan (1972). Overall excess
mortality of cancer of the respiratory or digestive tract
was seen, particularly in the groups aged 50 years or older
(and presumably 30 or more years from first exposure).
Among these, stomach cancer mortality in male miners is
increased 2.5 times and that of female workers by 3.6 times.
The corresponding increases for female and male mill workers
are 4.3 and 19.9 times expected. Additionally/ intestinal
cancer is elevated among the 50+ year group 4.3 times for
male miners, 6.9 times for female miners and 14.3 for women
mill employees. Unfortunately, data on the number of deaths
are not provided. No cases of mesothelioma are reported.
Anthophyllite mining has also been found to produce
a high risk of bronchogenic carcinoma (Meurman, et al. 1974) .
In a study of miners exposed to fibers of cummingtonite-
grunerite ore series (in which amosite is formed), Gillam,
et al. (1976) reported excess malignant respiratory disease
(10 observed versus 2.7 expected) at an average air concentra-
tion of 0.25 f/ml.
No cohort mortality studies exist for the mining or
milling of crocidolite or amosite.
In the above studies of chrysotile mining and milling,
mesothelioma was present to much less a degree than in the
C-88
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following three- irristance's: a factory :usirig chrysotil^"' exclus-
ively, (four percent of 20 + year employees) (Peto,. 1978);
the largest U.S. chrysotile using facility (ten percent)
(Nicholson, 1979); or insulation work using chrysotile and
amosite (seven percent) (Selikoff, et al. 1979). It appears
that as the fibers are manipulated through milling, processing,
and use, their carcinogenic potential increases. Whether
this is related to a reduction in fiber size or other factors
is yet to be definitively established, particularly in view
of animal data which indicates a reduction in carcinogenic
potential following ball-milling (see "Animal Inhalation"
section).
Because of its relevance to ingestion, a summary of
the available data on gastrointestinal cancer and peritoneal
mesothelioma is given in Table 28.
Indirect Occupational Asbestos Exposure: In 1968 it
was pointed out by Harries (1968) that shipyard workers
other than insulators were at risk from asbestos disease.
Among Devonport Dockyard employees, five cases of mesothelioma
were found among men who had not been "asbestos workers"
but had followed other trades in the yard. These men presum-
ably had been inadvertently exposed to asbestos merely by
working in the same shipyard areas where asbestos had been
used. Continuing to follow this group, Harries later docu-
mented 55 cases of mesothelioma .in this shipyard alone,
only two of which occurred in asbestos workers (Harries,
1976); and one, a man who had previously sprayed asbestos.
A study of the distribution of all verified cases of meso-
C-89
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TABLE 28
Gastrointestinal Cancer in Occupationally
Exposed Asbestos Workers
Reference Years of Causes Expected Observed
observation of de§th deaths deaths
(ICD)a
Selikoff, et al. (1979) 1967-77
Selikoff, et al. (1976) 1943-74
Kleinfeld, et al. (1967) 1945-65
Elmes and Simpson (1971) 1940-66
Henderson and Enterline
(1979) 1941-74
Nicholson, et al. (1979b) 1959-76
Seidman, et al. (1979) to 1977
(amosite only)
Newhouse and Berry (1979)
low-mod, exposure to 1975
severe exposure
McDonald- and Liddell (1979) to 74
"heavy exposures"
Kogan, et al. (1972)
age 50+ male miners
male millers
female miners
female millers
INSULATION WORKERS
150-154 59.10 99
150-154 13.63 43
150-159
150-154 4 12
FACTORY WORKERS
150-159 40.1 55
150-154 7.99 15
150-154 21.55 32
150-158 18.2 18
(excluding
mesothelioma) 26.0 42
MINING AND MILLING
150-151
150
Number of
Excess SMR peritoneal
deaths mesothelioma
39.9 168
29.4 315
390°
8+ 300+
15.1 137.8
7.0 188
10.5 149
15.8 99
16.0 162
289b
250b
430
360
1990
109
22
3
few
12
8
5
30
few
none.
reported
aDisease codes
no information on number of deaths
cproportionate mortality
-------
thelioma found in Scotland between the years of 1950 and
1967 is also revealing. Of 89 cases available for study,
55 were in shipyard employees, dockers or naval personnel.
Of the 55, again only one was an asbestos insulation worker
(McEwen, et al. 1977).
A study by Edge (1976) of men who had worked in a ship-
yard in Barrow, England, attempted to establish a risk of
low-level asbestos exposure on a population basis. .He select-
ed 235 shipyard workers with pleural plaques but no parenchy-
mal fibrosis on x-ray, and followed their mortality experience.
from 1970 through 1973. Seventy died, 17 of mesothelioma
and 13 from lung cancer, 2.6 times expected. However, the
relevance of these data have been called into question by
the possibility of bias in the selection of the 235 cases
(Edge, 197-9) .
The previously mentioned radiological evidence (see
"Indirect Occupational Asbestos Exposure" section) that
asbestos concentrations in general shipyard work (Selikoff,
et al. 1979) or maintenance activities in a chemical factory
(Lilis and Selikoff, 1979) are sufficient to produce fibrosis
points to the existence of a widespread carcinogenic problem
from indirect asbestos exposures.
Environmental Asbestos Disease: Wagner, et al. (1960)
reviewed 47 cases of mesothelioma found in the Northwest
Cape Province, South Africa in the previous five years.
Of this number, roughly half the cases were in people.who
had worked with asbestos. Virtually all the rest were in
individuals who had, decades before, simply lived or worked
C-91
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in an area of asbestos mining (one living along a roadway
in which asbestos fibers were shipped). This germinal obser-
vation demonstrated that asbestos exposure of limited intens-
ity, often intermittent, could cause mesothelioma. The
hazard was further pointed out by the findings of Newhouse
and Thomson (1965) , who showed that mesothelioma could occur
among people whose potential asbestos exposure consisted
of their having resided near an asbestos factory or in house-
holds of asbestos workers. Twenty of 16 cases from the
files of the London Hospital (1917 to 1964) were the result
of such exposure; 31 were occupational in origin, and asbestos
exposure was not identified for 25.
Synergism and/or Antagonism
"-'' Asbestos exposure and, cigarette smoking have been found
to act synergistically tp produce dramatic increases in
lung'; cancer over that from exposure to either agent alone.
In a study by Hammondv-et ;al. (1979) of 17,800 insulation
workers, smoking^ h:is;to fie s on 11,656 were obtained during
1966 prior to prospective observation. Of these workers,
1,457 reported they had never smoked, 607 had smoked only
a pipe and/or cigars, and 9,591 gave a history of cigarette
smoking. No information was available from the remaining
6,143. Using data of the American Cancer Society on age
and calendar year-specific cancer rates among smokers and
non-smokers in a prospective study of more than 1,000,000
people in the United States, it was possible to make smoking-
specific comparisons of the mortality experience of insulation
workers with nonasbestos exposed-individuals in the general
C-92
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population. Table 29 lists the relative risk of death from
lung cancer according to smoking habits and occupational
exposure to asbestos. Those insulation workers who claimed
never to have smoked cigarettes were found to have an increas-
ed risk of death from lung cancer compared with non-smokers
in the general population, although there were relatively
few deaths, eight observed versus 1.82 expected.. , Ho.wever,
among those with a history of cigarette smoking, the risk
was also increased and .its effect was large, .325 deaths ..,
being recorded versus 53.03 expected. Asbestos exposure
appears to multiply the risk of death of lung cancer by
four to six times, irrespective of smoking habits. When
that risk is already high, as in cigarette smokers, the '
result is catastrophic. An earlier study by Selikoff, et
al. (1968) .indicated that the risk of death from lung cancer -
in cigarette smoking asbestos workers was 92 times that
among individuals who were neither exposed to the fiber
nor smoked cigarettes.
Cancers of the larynx, pharynx and buccal cavity and
of the esophagus in insulators are also associated with
cigarette smoking (Hammond, et al. 1979). Among 50 deaths
due to tumors of these sites, none were among non-smokers
and three were among individuals who smoked only pipes or
cigars. Mesothelioma of the pleura or peritoneum and cancer
of the stomach, colon and rectum, however, were unrelated
to smoking habits. It is worth noting that in these studies
by Selikoff and Hammond over 200 excess deaths occurred
from peritoneal mesothelioma and gastrointestinal cancer
C-93
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Table 29
Ratios of Observed to Expected3 Deaths in Insulation
Workers According to Smoking Habits.
January 1, 1967 to December 31, 1976
No history of Current or past
cigarette smoking cigarette smokers
Control population 1.00 10.85
Asbestos insulation workers 5.17 53.24
(number of deaths) (8) (325)
Ratio of asbestos workers 5.17 4.90
to control population
aExpected deaths are calculated from observed age and smoking-specific
rates of death of a control population of 73,763 white, male workers
exposed on to job to dusts, fumes, vapors, chemicals, or radiation.
Hammond, et al. 1979.
C~94
-------
(excluding esophagus) in 2271 deaths of insulation workers.
Were smok-ing-related lung cancer not a factor, abdominal,::;
cancer deaths would dominate the mortality experience of
this group of asbestos workers.
Other studies have substantiated the synergistic effect
of cigarette smoking. Berry, et al. (1972) obtained retro-
spective smoking histories on a group of asbestos workers
and analyzed their mortality according to smoking habits
over a ten-year period of time. The results indicated that
the combined effect of cigarette smoking and asbestos exposure1
on the development of lung cancer is multiplicative rather .
than additive.
Although synergistic effects have been documented for
bronchogenic carcinoma, only cigarette smoking has been
investigated in the etiology of abdominal cancers. The
possibility exists, of course, that these tumors too could
have a multiple factor etiology and that other contaminants,
ingested with asbestos, may potentiate tumor development.
Additionally, some non-malignant asbestos effects are
related synergistically to cigarette smoking. Among a group
of factory employees it was found by Weiss (1971) that evidence
of fibrosis, as manifest on x-rays, was increased among
individuals who smoked cigarettes compared to non-smokers.
Deaths due to asbestosis appear also to be increased in
cigarette smokers compared to non-smokers (Hammond, et al.
1979) .
In animal experiments, exposure to benzo(a)pyrene (BP)
and asbestos may act synergistically. Pylev and Shabad
C-95
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(1973) reported that intratracheal injections of 6 mg of
chrysotile onto which was absorbed 0.144 mg of BP (from
a benzene suspension) and 2 mg of chrysotile co-administered
with 5 mg BP produced malignant tumors in 29 percent and
54 percent of rats, respectively. Administration of 6 mg
of chrysolite or 5 mg BP yielded no tumors. Miller, et
al. (1965) found intratracheal injection of chrysolite
with BP to increase tumor yield over that of BP alone while
amqsite appeared to have little such effect.
No data exist on antagonistic or prophylatic compounds
in relation to animal or human disease. In vitro experiments
by Schnitzer, (1974) have shown that hemolysis of red cells
can be inhibited by coating the fibers with ionic polymers
such as carbox-ymethylcellulose.
C-96
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CRITERION FORMULATION
Existing Guidelines and Standards
The current Occupational Safety and Health Administration
(OSHA) standard for an eight-hour time-weighted average
(TWA) occupational exposure to asbestos is 2 fibers longer
than 5 microns in length per milliliter of air (2 f/ml or
2,000,000 f/m ). Peak exposures of up to 10 f/ml are permit-
ted for no more than ten minutes (Fed. Reg., 1972). This stand-
ard has been in effect since July 1, 1976, when it replaced
an earlier one of 5 f/ml (TWA). In Great Britain, too,
a value of 2 f/ml is the accepted level, below which no
controls are required (BOHS, 1968); the British standard,
in fact, served as a guide for the OSHA standard (NIOSH,
1972) .
The British standard was developed specifically to
prevent asbestosis among working populations; data were
felt to be lacking that would allow a determination of a
standard for cancer(BOHS, 1968). Unfortunately, among occupa-
tional groups, cancer is the primary cause of excess death
among workers (see "Carcinogenicity" section). Three-fourths
or more of asbestos-related deaths are from malignancy.
This fact has led OSHA to propose a lower TWA standard of
0.5 f/ml (500,000 f/m3) (Fed. Reg., 1975). The Nation-
al Institute for Occupational Safety and Health (NIOSH),
in their criteria document for the hearings on a new standard,
have proposed a value of 0.1 f/ml (NIOSH, 1976) . In the .
discussion of the NIOSH proposal, it was stated that the
value was selected on the basis of the sensitivity of analyti-
C-97
-------
cal techniques using optical microscopy and that 0.1 f/ml
may not necessarily protect against cancer. Recognition
that no information exists that would define a threshold
for asbestos carcinogenesis was also contained in the preamble
to the OSHA proposal. The existing standard in Great Britain
has also been called into question by Peto (1978), who esti-
mates that asbestos disease may cause the death of ten percent
of workers exposed at 2 f/ml for a working lifetime.
The existing federal standard for asbestos emissions
into the environment prohibits "visible emissions" (U.S.
EPA, 1975). No numerical value was specified because of
difficulty in monitoring ambient air asbestos concentrations
in the ambient air or in stack emissions. (Time-consuming
and expensive electron microscopy is often required.) Some
local government agencies, however, may have numerical stand-
ards (New York, 27 ng/m for example).
No standards for asbestos in foods or beverages exist
even though the use of filtration of such products through
asbestos filters has been a common practice in past years.
Asbestos filtration, however, is prohibited or limited for
human drugs (FDA, 1976).
Current Levels of Exposure
As detailed in the "Exposure" section, asbestos is
a ubiquitous contaminant of our air and water. Air concentra-
tions over 24 hours in metropolitan areas usually are less
than 5 ng/m but can range up to 20 ng/m3. Values up to
50 ng/m are found during daytime hours in locations where
construction activities and traffic can be contributing
C-98
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sources. A significant fraction of the fibers inhaled can
be brought up from the respiratory tract and swallowed.
This leads to an ingestion exposure from air sources of .
up to 0.1 pg/day, although most of the population exposure
is from 0.02 to 0.05 jug/day.
Water concentrations of asbestos are usually less than
10 fibers of all sizes per liter although significantly
o
higher values ( 10 f/1) have been found in circumstances
where water systems have been in contact with asbestiform
minerals or where contamination of the water supply exists.
Fiber mass concentrations corresponding to fiber concentra-
tions are usually less than 0.01 jug/liter but could exceed
1 jug/1. Thus, direct water ingestion usually leads to exposures
of less than 0.02 jug/day.
Clearly, point source pollution can cause both air
and water concentrations to exceed the above values. Such
instances are discussed in the "Exposure" section.
Special Groups at Risk
Special groups at risk may include neonates and children;
however, no data exist on the relative sensitivity to asbestos
of infants and children undergoing rapid growth. Concern
exists because fibers deposited in the tissues of the young
may have an extremely long residence time during which malig-
nant changes could occur. In addition, risk could be influ-
enced by differential absorption rates which have not been
fully studied at this time.
Individuals on kidney dialysis machines may also be
at greater risk as fluids, potentially contaminated with
C-99
-------
asbestos fibers, can enter the blood stream directly or,
in selected instances, the peritoneal cavity (peritoneal
dialysis).
Although no synergistic effects have been identified
in the etiology of asbestos-related gastrointestinal cancer,
they cannot be ruled out. Thus, people exposed to other
carcinogens, initiators, or promotors could be at increased
risk.
An increased risk is also associated with increased
exposure to asbestos in water in municipalities such as
San Francisco or Seattle where asbestos occurs naturally
in water, in cities where there is an interaction between
aggressive water and asbestos-cement pipe, or in cities
whose water may be contaminated as a result of asbestos
operations. Also, the use of asbestos cement products for
the collection of water, such as in cisterns in the Virgin
Islands or in roof run-offs in tropical areas,.increases
exposure.
Basis and Derivation of Criterion
A substantial body of data exists which shows increased
incidence of cancer of the esophagus, stomach, colon, and
rectum or peritoneal mesothelioma in humans exposed to asbes-
tos occupationally. For several of these groups, 'data exist
on the approximate air-borne fiber concentrations to which
individuals were exposed (see "Effects" section). These
human data will serve as the primary basis for a standard
of asbestos in water. Experimental data ("Pharmacokine-
tics" section) indicate that a major fraction of the asbestos
C-100
-------
deposited in the lungs is subsequently swallowed. in this
section the dose to the gastrointestinal tract of four occupa-
tional groups will be calculated from knowledge of the air
concentrations to which the workers were exposed and follow
the assumption that all the asbestos inhaled subsequently
passed through the gastrointestinal tract and provided the
exposure that led to the observed increase in abdominal
cancer. The assumption that all inhaled asbestos is ingested
is an overestimate but not significantly. No account has
been taken.of the material that a worker may swallow directly,
»-'
and this quantity could be significant. However, for the
purposes of a criterion, our inability to quantitate direct
ingestion in the work place and to properly account for
it by the present approach provides some margin of safety
in the estimate of dose-response relations.
Table 30 lists the percentage of death from excess
gastrointestinal cancer and peritoneal mesothelioma in four
groups of asbestos workers. Calculations of this percentage
were made using expected numbers of death, rather than the
observed, because the latter was inflated by including other
asbestos-related deaths.
»<' .
Table 31 lists the fiber concentration estimates (see
"Carcinogenicity" section) and an exposure index for each
cohort (years of exposure x fiber concentration). This
index will be used to calculate the number and mass of asbes-
tos fibers ingested during a working lifetime. As the observ-
ed mortality is, to a large extent, after 20 years from
first exposure, the intermixing of time and exposure does
not present significant problems.
C-101
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TABLE 30
Percentage of Excess Gastrointestinal Cancers and
Peritoneal Mesothelionias in Four Groups of Asbestos Workers
Exposed group
Number of Excess Deaths
(from Table 28)
G.I. cancer
Peritoneal
mesothelioma
Expected
Number of
deaths in
cohor t
Excess deaths as a
percentage of expected
deaths in cohort
GI
Per. meso. Total
Insulation workers'*
(chrysotile and amosite)
Insulation workers"
(chrysotile and amosite)
Factory employment1
(amosite)
Factory employment"
(chrysotile, crocidolite
and amosite)
39.9 109
(ICD 150-154)e
29.4 22
(ICD 150-154)
10.5 8
(ICD 150-154)
15.8 35
(ICD 150-154 ex meso)
1660.96 2.4
305.20 9.6
368.62 2.9
556.0
2.8
6.6
7.2
2.2
6.3
9.0
16.8
5.1
9.1
aSelikoff, et al. (1979)
bSelikoff, et al. (1976)
cSeidman, et al. (1979)
Newhouse and Berry (1979)
ePublic Health Service (1967-69)
-------
TABLE 31
Exposure Indices for Asbestos Worker Groups
Person-weighted Exposure index
average exposure (years x f/mlj
time (yrs.)
Exposed group
Air fiber concentration
(f/ml)
U.S. insulators .,',
Selikoff, et al. (1979) 15
NY/NJ insulators
Selikoff, et al. (1976) . . . 15
Amosite factory workers
Seidman, et al. (1979) 40
34
40
1.9
510
600
76
British factory workers
Newhouse and
Berry (1979)
10-30
See Table 32
180
: ;The average length of exposure for the insulation workers
; in.:fthe first group was calculated, from data on employment
time at? eiltry into the cohoirt.'in 1967. Forty years was
used as the working lifetime; ifoir the smaller group of New
York and New Jersey .insulators', virtually all of whom are
deceased or retir-ed=: The estimate of the person-weighted
exposure index for the amosite factory is simply the average
employment time multiplied by 40 f/ml. Data from Table
32 were used to estimate a person-weighted exposure index
for the Newhouse and Berry group.
(Person-weighted exposure index = (No. at risk x exposure x time)
(No. at risk)
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TABLE 32
Exposure Estimates for Workers in a British Factory3
Exposure group No. at risk Exposure (f/ml) Time of exposure
(years)
Severe 2 years 711
2 years 1333
Low to Moderate 2 years 503
2 years 933
30
30
10
10
20
2
20
2
aNewhouse and Berry (1979)
A detailed calculation of the daily intake of asbestos
to produce a lifetime risk of 10 is given in Appendix
I. Data of the occupational risk of both gastrointestinal
cancer and peritoneal mesothelioma were used (Table 30).
Account was taken of the fact that occupational exposures
took place over a 5-day work week and that the ingestion
exposure may encompass a lifespan of 70 years. It was assumed
that a worker breathes at the rate of 1 m /hr during work
exposure for the purpose of calculating total asbestos intake
per day. Using a linear dose-response relationship, and
a specified risk of 10~ , the calculated 70-year daily intake
V\
resulting from these calculations are give.in Table 33.
The data from Seidman, et al. were not used because it was
exclusively from amosite exposures. Assuming that two liters
o£ water are ingested per day, this would correspond to
a concentration of 300,000 fibers of all sizes/liter of
water.
C-104
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TABLE 33
Calculated intake for 10~ lifetime Risk of Death from
gastrointestinal cancer and peritoneal mesothelioma
Exposure Group
Estimate of intake/day
for 10 risk (fibers
of all lengths/day)
Selikoff, et al. (1979)
Selikoff, et al. (1976)
Newhouse and Berry, (1979)
Average
900,000
600,000
400,000
600,000 fibers of all
lengths/day
.A criterion for a mass concentration of asbestos can
also be calculated using the conversion value of 30 ug/m /f/ml
derived from the data of Table 2 for predominantly chrysotile
exposures. A value of 150 ug/m /f/ml for amosite appears
more appropriate, based on the finding of Davis, et al.
(19,78) that amosite has approximately a three time greater
conversion factor than chrysotile. A detailed calculation
is given in Appendix II and the results summarized in Table
34, Assuming that two liters of water are ingested per
day, a risk of 10~ would be produced from ingesting water
containing 0.05 ug/liter. As mentioned in the "Exposure"
section, the variability in the data used to convert optical
fiber counts to mass (Factor D in Appendix II) leads to a
large uncertainty in the above estimate.
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TABLE 34
Calculated Intake for 10" lifetime Risk of Death from
gastrointestinal Cancer and peritoneal mesothelioma
Estimate of intake/day
Exposure Group for 10~ risk (ug/day)
Selikoff, et al. (1979) 0.14
Selikoff, et al. (1976) 0.09
Seidman, et al. (1979) 0.11
Newhouse and Berry, (1979) 0.05
Average 0.1 ug/day
Considering chrysotile and depending on the source
of the asbestos in water, 0.05 ug/liter corresponds to from
10 to 20x10 fibers of all lengths per day. Such estimates
are considerably higher than those derived previously and
are most likely a reflection of the differences in- the sizes
of the fibers found in water, as compared to those found
in air. Because of these uncertainties, high priority should
be given to obtaining accurate size and mass distribution
of typical fibers found in different circumstances (air
and water) which would allow appropriate conversions to
be made between fiber concentrations in air and water.
The majority of samples analyzed for the EPA to date
were characterized by a concentration of all microscopic
visible fibers per liter of water (See "Exposure" section).
Further, techniques for the determination of fiber concentra-
tions (as opposed to mass concentrations) have been published
as interim EPA procedures (Anderson and Long, 1978). Thus,
C-106
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a criterion for the concentration of fibers of all sizes
5
in water corresponding to a 10 risk will be calculated
directly from the concentrations of fibers greater than
5 yon measured in the occupational circumstances that produced
disease. Unfortunately, the data currently available relating
concentrations of fibers longer than 5 ^um, counted by optical
microscopy, jdetermined by electron microscopy, are extremely
limited. These include those by Wallingford (1978) , 15:1;
Millette (personal communication), 400:1; and Winer and
Cossett (1978), 1000:1 and are only for chrysotile asbestos.
Using the geometric mean of 200 for this factor from all
available data, a total fiber concentration corresponding
to a 10 risk can be calculated from the data of Tables
30 and 31.
In making the calculation, one tacitly assumes the
same fiber size distribution in water as in occupational
air samples. Some data show that water fiber size distri-
butions vary (Millette, et al. 1979c), and occupational-air
distributions have been shown to be so variable that the
fraction of fibers longer than 5 microns can range over
a factor of 10 depending on sampling circumstances (Nicholson,
et al. 1972). Although sizing of airborne and waterborne
fibers have not been done using the same methods, qualitative-.
ly, water appears to have fiber distributions with more
smaller fibers than in occupational air samples (Millette,
J., personal communication). Thus, an estimate assuming
the same fiber size distribution in water as in air will
yield a conservative criterion (from the point of view of
health).
C-107
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Although positive animal experiments had various experi-
mental limitations, such data as existed were treated in
the model of EPA. The data are presented in Table 35.
TABLE 35
Estimated 10~5
Effect dosage (jug/1)
4/42 Kidney carcinomas 3.2
0/49 control
12/42 Malignancies 1.1
2/49 control
aGibel, et al. (1976)
Considering the large number of experimental uncertainties,
these values provide reasonable support for the concentration
deprived from human exposure data.
This document was concerned with the estimation of
that concentration of asbestos in water which will produce
a lifetime risk of 1 in 100,000 in a population exposed
continuously. The risk estimate was made using a linear
extrapolation from existing human data and would appear
to constitute a conservative extrapolation. However, in
the case of asbestos the risk factor of 1/100,000 is not
conservative. If we were concerned with intermittent or
localized contamination incidents of some carcinogen that,
once identified, could be abated, such a value would have
utility. With asbestos, however, we are concerned with
a ubiquitous contaminant in the environment to which large
populations are continuously exposed for decades. Further,
C-108
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the estimated value has a high degree of uncertainty associated
with it, based upon the data from which it was derived.
Under the Consent Decree in NRDC v^ Train, criteria
are to state "recommended maximum permissible concentrations
(including where appropriate, zero) consistent with the";
protection of aquatic organisms, human health, and recreation-
al activities." Asbestos is suspected of being a human
carcinogen. Because there is no recognized safe concentration
for a human carcinogen, the recommended concentration of1
asbestos in water for maximum protection of human health
is zero.
Because attaining a zero concentration level may be"
infeasible in some cases and in order to assist the Agency
and States in the possible future development of water quality
regulations, the concentrations of asbestos corresponding
i
to several incremental lifetime cancer ri'sk levels have
been estimated. A cancer risk level provides an estimate
of the additional incidence of cancer that may be expected
in an exposed population. A risk of 10 for example, indi-
cates a probability of one additional case of cancer for
every 100,000 people exposed, a risk of 10 indicates -
one additional case of cancer for every million people exposed,
and so" forth.
In the Federal Register notice of availability of draft
ambient water quality criteria, EPA stated that it is consid-
ering setting criteria at an interim target risk level of
10~5, 10~6, or 10~7 as shown in the table below.
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Exposure Assumption Risk Levels and Corresponding Criteria
0 10~7 10"6 10"5
2 liters of drinking water 3,000 f/1* 30,000 f/1 300,000 f/1
Consumption of fish and
shellfish only. No Criterion
*f = fibers
(1) Calculated by applying a modified "one-hit" extrapo-
lation model described in the Methodology Document
to the human epidiomological data presented in Appen-
dix III. Since the extrapolation model is linear to
low doses, the additional lifetime risk is directly
proportional to the water concentration. Therefore,
water concentrations corresponding to other risk
levels can be derived by multiplying or dividing
one of the risk levels and corresponding water
concentrations shown in the table by factors such
as.10, 100, 1,000, and so forth.
Concentration levels were derived assuming a lifetime
exposure to various amounts of asbestos occurring from the
consumption of drinking water only.
Although total exposure information for asbestos is
discussed and an estimate of the contributions from other
sources of exposure can be made, this data will not be factor-
ed into ambient water quality criteria formulation until
additional analysis can be made. The criteria presented,
therefore, assume an incremental risk from ambient water
exposure only.
C-110
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APPENDIX I
Sample calculation (using Selikoff, et al. (1976)
exposure data) of intake in fiber_s^day
corresponding to a risk of 10
(Linear dose response)
600 f/ml-yrs x 5/7 x 200 x 1/70 yrs x 106ml/m3 x 8 m3/day
A BCD E F
x 10~5/(16.8 x 10~2) = 600,000 fibers of all sizes/day
A = Exposure index.
B = Exposure was concentrated in 5 days rather than in 7
days/week.
C = Conversion from optical counts (fibers>5 pm) to electron
microscopic counts (all fibers).
D = 70-year exposure is assumed.
E = Factor for converting ml to m .
F = Exposure took place for 8 hours and the worker was assumed
to breathe 1 m /hour.
G = A risk of 10 is calculated from data on an observed
risk of 16.8 x 10~2.
fFrom the study of Selikoff, et al. (1976)]
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APPENDIX II
Sample calculation of intake in jug/day corresponding
to a risk of 10 (Linear dose resonse)
600 f/ml-yrs x 5/7 x 1/70 yrs x 30 jug/m x 8 M /day
f/ml
A BCD E
x 10~5/(16.8 x 10~2) = 0.09 jug/day.
F
A = Exposure index.
B = Exposure was concentrated in 5 days rather than in 7
days/week.
C = 70-year exposure is assumed.
D = Average conversion factor for chrysotile (Table 2).
E = Exposure took place for 8 hrs. and the worker was assumed
to breathe 1 m /hr.
F = A risk of 10 is calculated from data on an observed
_2
risk of 16.8 x 10 .
[From the study of Selikoffr et al. (1976)]
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APPENDIX III
Summary and Conclusions Regarding the
Carcinogenicity of Asbestos*
Asbestos is a collective mineralogical term referring
to naturally occurring minerals which have crystalized in
the form of masses of long fibers which can be easily separat-
ed. This term also commonly refers to certain mineral occur-
rences in which fibrous silicate mineral can be extracted
and used commercially for insulation, textiles, brake linings,
asbestos cement, construction products, etc. Chrysotile,
the fibrous form of serpentine, provides over 95 percent
of the approximately 900,000 tons of asbestos consumed each
year in the United States. The remaining asbestos used
consists of. the fibrous amphibole minerals crocidolite,
amosite (fibrous grunerite) and anthophyllite. Fine dusts
produced from the mining, milling, manufacturing, and use
of these asbestos minerals contain discreet microscopic,
elongated mineral particles or "fibers" which when inhaled
by man are known to cause bronchogenic carcinoma and pleural
and peritoneal mesothelioma.
Asbestos particles and other inorganic fibers introduced
into the pleura, peritoneum and trachea of rodents have
induced malignant tumors in numerous studies reported in
the literature. Limited and contradictory data exist for
the carcinogenicity of asbestos administered to animals
*This summary has been prepared and approved by the Carcino-
gens Assessment Group of EPA on June 23, 1979.
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by ingestion. One study in wtiich asbestos filter material
was fed to rats (Gibel, et al. 1976) reports 12 malignant
tumors in 42 exposed animals versus only 2 liver-cell carcino-
mas in 49 control animals. Electron microscope analysis
of animal tissues for asbestos indicates that ingested fibers
can accumulate at many sites following hematogenous or lympha-
tic transport of ingested fibers which pass through the
gastrointestinal mucosa.
The strongest evidence for the carcinogenicity of ingest-
ed asbestos is provided by epidemiology of populations occupa-
tionally exposed to high concentrations of airborne asbestos
dust. Inhalation exposure to asbestos dust is accompanied
by ingestion exposure because high percentage of inhaled
fibers are removed from the respiratory tract by mucociliary
clearance and swallowed. Peritoneal mesothelioma/ often
in great excess since it is very rarely observed in the
absence of asbestos exposure, and modest excesses of stomach,
esophagus, colon-rectum, and kidney cancer have been observed
associated with occupational exposure.
The influence of long-term chrysotile fiber contamination
of San Francisco Bay area water supplies on cancer incidence
has recently been studied by the University of California
under an EPA grant. Significant dose-response gradients
for the incidence of several cancers, including white male
lung and stomach and white female esophageal and peritoneal
cancer, were noted independent of the effect of socio-economic
status. Other water supply studies are of limited value
due to factors such as very low exposure and insufficient
time elapsed since initial exposure of the population.
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Observation in human urine of mineral fibers previously
ingested with drinking water has established that ingested
asbestos can pass through the human gastrointestinal mucosa
and migrate to various tissues.
Asbestos is a known carcinogen when inhaled. The demon-
strated ability of asbestos to induce malignant tumors in
different animal tissues, the passage of ingested fibers
through the human gastrointestinal mucosa, and the extensive
human epidemiological evidence for excess peritoneal, gastro-
intestinal, and other extrapulmonary cancer as a result
of asbestos exposure suggests that asbestos is likely to
be a human carcinogen when ingested.
The water quality criterion for asbestos particles
is derived from the substantial data which exists for the
increased incidence of peritoneal mesothelioma and gastroin-
testinal tract cancer in humans exposed occupationally to
asbestos. This derivation assumes that much or all of this
increased disease .incidense is caused by fibers ingested
following clearance from the respiratory tract. Several
studies, including one of 17,800 insulation workers, allow
the association of approximate air-borne fiber concentrations
to which individuals were exposed with observed excess perito-
neal and gastrointestinal cancer. All of the inhaled asbestos
is assumed to be eventually cleared from the respiratory
tract and ingested.
The water concentration, calculated to keep the indivi-
dual lifetime cancer risk below 10~5, is 300,000 fibers
of all sizes/liter. The corresponding mass concentration
for chrysotile asbestos is approximately 0.05 jug/liter.
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Derivation of the Water Quality Criterion for Asbestos
The criterion for asbestos particles in water is derived
from the substantial data which exists for the increased
incidence of peritoneal mesothelioma and gastrointestinal
tract cancer in humans exposed occupationally to asbestos.
This derivation assumes that much or all of this increased
I
disease incidence is caused by fibers ingested following
clearance from the respiratory tract. Several studies,
including one of 17,800 isulation workers, allow the associa-
tion of approximate air-borne fiber concentrations to which
individuals were exposed with observed excess peritoneal
and gastrointestinal cancer. All of the inhaled asbestos
is assumed to be eventually cleared from the respiratory
tract and ingested.
Excess deaths due to peritoneal mesothelioma and gastro-
intrestinal cancer (ICD 150-154) equal approximately 12
per-cent of the expected number of deaths for asbestos workers
in three different cohorts studied. An average exposure
index of 430 years x fibers >S jam/ml is calculated for these
workers by multiplying average air fiber concentration esti-
mates by average years of exposure time.
Since water measurement for asbestos requires electron
microscope analysis for fibers (asbestos particles with
length to width ratios >3.0) of all sizes, the occupational
exposure index must be converted from fibers >5 jm (optical
microscope) to fibers of all sizes (electron microscope).
A ratio of 200 electron microscope identifiable fibers to
one optical microscope identifiable fiber is used for chryso-
tile asbestos in workplace air samples. A much smaller
ratio is expected for amphibole fibers.
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Assuming a linear dose response, occupational exposure
of 5 days/week and 8m air inhaled/workday, and 70 years
for ingestion of drinking water, the criterion is calculated
as follows:
(430 f>5 urn/ml - years) (5/7) (200 f/f ?5 pm) (1/70 years)
A BCD
(106ml/m3) (8m3/day) (10~5/l-2 x
E F G
600,000 fibers of all sizes/day
A = Exposure index in years x fibers>5 pm/ml from
Selikoff, et al. (1976, 1979) and Newhouse and Berry (1979)
B = Occupational exposure for 5 days versus 7 days for water
exposure
C = Conversion from optical counts (F >5jum) to TEM counts
(all fibers) in fibers/fibers Sum
D = 70-year exposure is assumed for drinking water
E = Conversion from ml to m
F = Occupational exposure for 8 hours while breathing 1m /I hour
_c
G = A risk of 10 is calculated from data on an average
observed risk of 1.2 x 10 from Selikoff, et al.
(1976,1979) and Newhouse, Berry (1979)
Based on these parameters and an average ingestion
i
exposure of 2 liters of water per day, the water concentration
calculated to keep the individual lifetime cancer risk below
10" is 300,000 fibers of all sizes/1. The corresponding
mass concentration for chrysotile asbestos based on occupation-
al data is approximately 0.05 /ag/1.
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