EPA-540/1-86-049
Agency
ce of Emergency and
nedial Response
Washington DC 204.60
Off'ce of Research and Development
Office of Health and Environmental
Assessment
Environmental Criteria and
Assessment Office
Cincinnati OH 45268
Superfund
&EPA
HEALTH EFFECTS ASSESSMENT
FOR ASBESTOS
Do not remove. This document
should be retained in the EPA
Region 5 Library Collection.
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EPA/540/1-86-049
September 1984
HEALTH EFFECTS ASSESSMENT
FOR ASBESTOS
U.S. Environmental Protection Agency
Office of Research and Development
Office of Health and Environmental Assessment
Environmental Criteria and Assessment Office
Cincinnati, OH 45268
U.S. Environmental Protection Agency
Office of Emergency and Remedial Response
Office of Solid Waste and Emergency Response
Washington, DC 20460
U S. Environmental Protection Agwe»
Region 5, library (PL-12J)
I* West Jackson Boulevard, 12th r»i
Chkago. »L 60604-3590
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DISCLAIMER
This report has been funded wholly or In part by the United States
Environmental Protection Agency under Contract No. 68-03-3112 to Syracuse
Research Corporation. It has been subject to the Agency's peer and adminis-
trative review, and It has been approved for publication as an EPA document.
Mention of trade names or commercial products does not constitute endorse-
ment or recommendation for use.
11
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PREFACE
This report summarizes and evaluates Information relevant to a prelimi-
nary Interim assessment of adverse health effects associated with asbestos.
All estimates of acceptable Intakes and carcinogenic potency presented In
this document should be considered as preliminary and reflect limited re-
sources allocated to this project. Pertinent toxlcologlc and environmental
data were located through on-Hne literature searches of the Chemical
Abstracts, TOXLINE, CANCERLINE and the CHEMFATE/DATALOG data bases. The
basic literature searched supporting this document Is current up to
September, 1984. Secondary sources of Information have also been relied
upon 1n the preparation of this report and represent large-scale health
assessment efforts that entail extensive peer and Agency review. The
following Office of Health and Environmental Assessment (OHEA) sources have
been extensively utilized:
U.S. EPA. 1980b. Ambient Water Quality Criteria for Asbestos.
Environmental Criteria and Assessment Office, Cincinnati, OH.
EPA-440/5-80-022. NTIS PB 81-117335.
U.S. EPA. 1983a. Reportable Quantity for Asbestos. Prepared by
the Environmental Criteria and Assessment Office, Cincinnati, OH,
OHEA for the Office of Solid Waste and Emergency Response, Wash-
ington, DC.
U.S. EPA. 1983b. Review of Toxlcologlc Data 1n Support of Evalua-
tion of Carcinogenic Potential of Asbestos. Prepared by the
Carcinogen Assessment Group, OHEA, Washington, DC for the Office of
Solid Waste and Emergency Response, Washington, DC.
U.S. EPA. 1983c. Technical Support Document on the Ranking of
Hazardous Chemicals Based on Carc1nogen1c1ty. Prepared by the
Carcinogen Assessment Group, OHEA, Washington, DC for the Office of
Emergency and Remedial Response, Washington, DC.
U.S. EPA. 1985. Drinking Water Criteria Document for Asbestos.
Prepared by the Environmental Criteria and Assessment Office,
- Cincinnati, OH, OHEA for the Office of Drinking Water, Washington,
DC. Final draft.
The intent in these assessments is to suggest acceptable exposure levels
whenever sufficient data were available. Values were not derived or larger
uncertainty factors were employed when the variable data were limited in
scope tending to generate conservative (i.e., protective) estimates. Never-
theless, the Interim values presented reflect the relative degree of hazard
associated with exposure or risk to the chemical(s) addressed.
Hi
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Whenever possible, two categories of values have been estimated for sys-
temic toxicants (toxicants for which cancer is not the endpoint of concern).
The first, the AIS or acceptable intake subchronic, is an estimate of an
exposure level that would not be expected to cause adverse effects when
exposure occurs during a limited time interval (i.e., for an interval that
does not constitute a significant portion of the lifespan). This type of
exposure estimate has not been extensively used or rigorously defined, as
previous risk assessment efforts have been primarily directed towards
exposures from toxicants 1n ambient air or water where lifetime exposure 1s
assumed. Animal data used for AIS estimates generally include exposures
with durations of 30-90 days. Subchronic human data are rarely available.
Reported exposures are usually from chronic occupational exposure situations
or from reports of acute accidental exposure.
The AIC, acceptable intake chronic, Is similar in concept to the ADI
(acceptable dally intake). It is an estimate of an exposure level that
would not be expected to cause adverse effects when exposure occurs for a
significant portion of the lifespan [see U.S. EPA (1980a) for a discussion
of this concept]. The AIC is route specific and estimates acceptable
exposure for a given route with the Implicit assumption that exposure by
other routes is Insignificant.
Composite scores (CSs) for noncarclnogens have also been calculated
where data permitted. These values are used for ranking reportable quanti-
ties; the methodology for their development is explained in U.S. EPA (1983d).
For compounds for which there is sufficient evidence of cardnogenicHy,
AIS and AIC values are not derived. For a discussion of risk assessment
methodology for carcinogens refer to U.S. EPA (1980a). Since cancer is a
process that is not characterized by a threshold, any exposure contributes
an increment of risk. Consequently, derivation of AIS and AIC values would
be inappropriate. For carcinogens, q-|*s have been computed based on oral
and Inhalation data 1f available.
1v
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ABSTRACT
In order to place the risk assessment evaluation In proper context,
refer to the preface of this document. The preface outlines limitations
applicable to all documents of this series as well as the appropriate Inter-
pretation and use of the quantitative estimates presented.
Human data clearly Indicate that asbestos exposure from Inhalation con-
tributes to excess risk for GI and lung cancer, and peritoneal mesothelioma
data 1n animals are corroborative. Evidence for the cardnogenidty of
asbestos following oral exposure is equivocal. Since the carcinogenic
potency of asbestos appears to be dependent upon fiber size and shape, a
carcinogenic potency estimate for "generic" asbestos is not proposed at this
time.
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ACKNOWLEDGEMENTS
The Initial draft of this report was prepared by Syracuse Research
Corporation under Contract No. 68-03-3112 for EPA's Environmental Criteria
and Assessment Office, Cincinnati, OH. Dr. Christopher DeRosa and Karen
Blackburn were the Technical Project Monitors and Helen Ball was the Project
Officer. The final documents In this series were prepared for the Office of
Emergency and Remedial Response, Washington, DC.
Scientists from the following U.S. EPA offices provided review "comments
for this document series:
Environmental Criteria and Assessment Office, Cincinnati, OH
Carcinogen Assessment Group
Office of Air Quality Planning and Standards
Office of Solid Waste
Office of Toxic Substances
Office of Drinking Water
Editorial review for the document series was provided by:
Judith 01 sen and Erma Durden
Environmental Criteria and Assessment Office
Cincinnati, OH
Technical support services for the document series was provided by:
Bette Zwayer, Pat Daunt, Karen Mann and Jacky Bohanon
Environmental Criteria and Assessment Office
Cincinnati, OH
v1
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TABLE OF CONTENTS
1.
2.
3.
4.
5.
6.
7.
ENVIRONMENTAL CHEMISTRY AND FATE
ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS . . .
2.1. ORAL . . '.
2.2. INHALATION
TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1. SUBCHRONIC
3.1.1. Oral
3.1.2. Inhalation. . . .•
3.2. CHRONIC
3.2.1. Oral
3.2.2. Inhalation
3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS. . . .
3.4. TOXICANT INTERACTIONS
CARCINOGENICITY
4.1. HUMAN DATA
4.1.1. Oral
4.1.2. Inhalation
4.2. BIOASSAYS
4.2.1. Oral
4.2.2. Inhalation
4.3. OTHER RELEVANT DATA
4.4. WEIGHT OF EVIDENCE
REGULATORY STANDARDS AND CRITERIA
RISK ASSESSMENT
6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS)
6.2. ACCEPTABLE INTAKE CHRONIC (AIC)
6.3. CARCINOGENIC POTENCY (q-j*)
6.3.1. Oral
6.3.2. Inhalation
REFERENCES
Page
1
4
. . 4
9
13
, . 13
. . . 13
13
15
. . . 15
15
. . . 18
18
, . . 21
, , . 21
. . . 22
, , . 24
29
. . . 29
33
. . . 38
39
. . , 42
, . . 43
. . . 43
. . . 43
43
. . . 43
, , , 44
. . . 45
APPENDIX: Summary Table for Asbestos ................. 59
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LIST OF TABLES
No.
1-1
2-1
2-2
4-1
4-2
4-3
4-4
4-5
Title
Selected Physical and Chemical Properties of Asbestos ....
Asbestos Levels In Rats Fed 1% Asbestos for 6 Weeks
Distribution of Fiber at the Termination of Exposure
Recent Studies of Cancers Related to Asbestos in
Drinking Water
Ep1dem1olog1cal Studies: Human Cancers Associated with
Inhalation of Asbestos
Deaths Among 17,800 Asbestos Insulation Workers in the
United States and Canada
Summary of Experiments on the Effects of Oral
Administration of Asbestos
Carc1nogen1c1ty of Asbestos 1n Animals Exposed by
Inhalation
Paqe
2
8
11
23
25
27
30
34
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LIST OF ABBREVIATIONS
ADI Acceptable dally Intake
AIC Acceptable Intake chronic
AIS . Acceptable Intake subchronic
BaP Benzo(a)pyrene
bw Body weight
CHO Chinese hamster ovary
CS Composite score
GI Gastrointestinal
TEH Transmission electron microscope
TLV Threshold limit value
TWA Time-weighted average
UICC International Union Against Cancer
1x
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1. ENVIRONMENTAL CHEMISTRY AND FATE
Asbestos Is a generic term applied to a variety of naturally formed
hydrated silicates containing metal cations such as sodium, magnesium,
calcium or Iron. The two major groups of asbestos are serpentine and amphl-
bole. Chrysotile 1s the only form of asbestos that belongs to the serpen-
tine group. The amphlbole group exists In five different classes: actlno-
Ute, amosHe, anthophylllte, croddollte and tremolHe. Only chrysotHe,
amoslte, croddolHe and anthophyllHe are of commercial Importance (IARC,
1973), and the first three varieties constituted a total of 99.9% of
asbestos, production 1n 1976 (Strelb, 1978). A few selected physical and
chemical properties of chrysotlle, amoslte and croddolHe asbestos are
shown In Table 1-1.
Of the 243,527 metric tons of asbestos discharged to the environment,
-1.5% Is discharged 1n the air (U.S. EPA, 1980b). Based on Its lack of
reactivity 1n aquatic media (Callahan et al., 1979), It 1s not Hkely that
asbestos will undergo any photochemical reaction or other chemical reactions
1n air. Both ralnouts and dry deposition may be primarily responsible for
the removal of asbestos from air. The lifetime of partlculate matter for
the physical removal mechanism 1s dependent on the particle size. The exact
particle size distribution of atmospheric asbestos 1s unknown, but It 1s
known that only a small fraction of atmospheric asbestos has particle
lengths of >5 Mm (U.S. EPA, 1980b). Based on the half-life of other atmo-
spheric metals (although the particle shape may be different from that of
asbestos), 1t 1s speculated that the half-life of submlcron asbestos parti-
cles may be several days. The aquatic fate of asbestos has been discussed
by Callahan et al. (1979). It appears from this report that asbestos
-1-
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TABLE 1-1
Selected Physical and Chemical Properties of Asbestos3
ISJ
I
Property
CAS No.
Idealized formula
Specific gravity
Approximate dlam-
Chrysotlle
12001-29-5
M
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remains chemically Inert 1n the aquatic environment. The only significant
mechanism of asbestos transfer from aquatic phase to sediment Is through
coagulation of asbestos or other processes of precipitation such as adsorp-
tion through clay and subsequent precipitation. Although the estimated
half-life of asbestos In the aquatic system 1s not known, It 1s expected to
be quite long.
Limited Information regarding the fate of asbestos 1n soil 1s available
1n the literature. Based on Us predicted Inability to undergo chemical
reactions, degradation and volatilization from water (Callahan et al.,
1979), none of these reactions are expected to be significant 1n soil.
Based on Us solubility 1n acidic and basic media, leaching of asbestos from
soils Is possible; however, the leaching process may destroy the crystalline
structure of asbestos by solubH1z1ng the element 1n the asbestos structure.
-3-
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2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS
2.1. ORAL
The weight of evidence suggests that the toxldty and cardnogenlcHy of
asbestos are associated with the nature of the asbestos fibers and their
actions upon the cells with which they come in contact or penetrate. Since
asbestos fibers are neither water nor I1p1d soluble, 1t seems unlikely that
absorption of asbestos fibers takes place either by passive diffusion or
active transport, but more likely as a result of the fibers mechanically
penetrating a tissue barrier, such as the epithelial lining of the GI tract
(persorption). Phagocytosis of asbestos fibers by macrophages, monocytes or
other phagocytic cells Is probably involved in absorption, or uptake, and
subsequent distribution of asbestos fibers to other tissues. Including the
lymphatic system or the bloodstream, resulting In widespread body distri-
bution.
The evidence for GI uptake of asbestos fibers In humans 1s highly sug-
gestive, but not absolutely conclusive. Fibers of amphibole asbestos (not
otherwise specified) were discovered in Duluth, MN, drinking water (Carter
and Taylor, 1980). The presence of amphibole fibers, which resembled those
found 1n the drinking water, were demonstrated in the liver, jejunum and
lung specimens from deceased Duluth residents. Among 96 tissue specimens
from 32 deceased Duluth residents, amphibole fibers were found In 60, with
concentrations ranging from 3-16xlOs fibers of all sizes/g of tissue. A
control cohort consisted of 61 tissue specimens from 21 deceased residents
of Houston, TX, and St. Paul, MN. Amphibole fibers were found 1n only two
tissue specimens in the control cohort. Since air sampling gave no evidence
of amphibole air concentrations In Duluth, these authors concluded that the
-4-
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presence of amphlbole fibers 1n these tissues Indicated transmucosal uptake
of fibers resulting from 1ngest1on of amph1bole-contam1nated drinking water
1n Duluth, MN.
Cook and Olson (1979) examined the urine sediment from humans who
Ingested drinking water 1n Ouluth, MN, contaminated with amphlbole asbestos
fibers. Measured concentrations of amphlbole fibers eliminated In the urine
averaged ~lxlO~3 times the concentration of amphlbole fibers 1n the drink-
Ing water. The authors noted that applying adequate filtration to the
drinking water removed the amphlbole fibers and resulted 1n a gradual
disappearance of amphlbole fibers from the urine. They concluded that these
observations provided direct evidence of the passage of asbestos fibers
through normal human GI mucosa. Furthermore, they emphasized that, since
some body retention of asbestos fibers undoubtedly occurs, urinary concen-
trations of asbestos are an underestimation of the actual uptake of asbestos.
Boatman et al. (1983) discovered that drinking water 1n the Puget Sound
area had unusually high levels of asbestos, with tap water from the homes of
seven Individuals containing 230-383x10° chrysotHe fibers/a. A control
group consisted of four residents from the Seattle/Bellevue area whose tap
water contained 1.2-3.1xl06 chrysotHe f1bers/s.. The content of chryso-
tlle fibers In the urine of long-term (>24 years) residents of the Puget
Sound area was significantly (p=0.05) higher than the content of chrysotlle
fibers 1n the urine of short-term (1.5-2.8 years) residents. There was no
significant difference, however, 1n the urinary content of chrysotlle for
Puget Sound compared to that from the Seattle/Bellevue residents. These
authors, however, reported some difficulties with their Nucleopore membrane
filters, which may have resulted 1n the lack of statistically significant
data generated 1n this study.
-5-
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In animals, a substantial body of evidence also exists that 1s highly
suggestive of GI uptake of asbestos fibers, but some Investigators doubt
that this phenomenon occurs. An early Investigation Indicated that fiber
uptake across the GI lining did not occur (Gross et al., 1974), but this
conclusion has been challenged by Cooper and Cooper (1978), who questioned
the sensitivity of the analytical procedure used.
Following 1ngest1on of chrysotHe or amoslte asbestos by rats, fibers
have been found 1n the colonlc mucosa (Westlake et al., 1965) or penetrating
the epithelial cells of the jejuna! mucosa (Storeygard and Brown, 1977).
Kidney cortical tissue of a neonatal baboon fed chrysotlle for 9 days was
found to contain a significant (p=0.005) excess of chrysotlle fibers
compared to the kidney cortical tissue from an untreated neonatal baboon
(Patel-MandHk and Hallenbeck, 1978).
Patel-Mandlik and Millette (1983a,b) treated 20 Sprague-Oawley rats with
50 mg chrysotile asbestos/kg by gavage 2 times/week until natural death or
sacrifice. A control group of rats was maintained. The test group of 20
rats was further divided into four groups of five rats, depending on age at
death or sacrifice. The four groups consisted of rats from <200, 200-400,
400-600 or >600 days of age when examined. There was a significant
(p<0.005) difference in the kidney cortical content of chrysotile between
the different treatment groups of rats, but the difference did not correlate
with duration of treatment. There was also a significant difference
(p<0.005) between the kidney cortical content of chrysotlle In treatment
rats (1.15 fibers/TEM grid) compared with control rats (0.05 fibers/TEM
grid).
-6-
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Following pretreatment, dietary regimens of 0 or 50 mg/day of UICC
chrysotlle A for 30 days, male MRC-hooded rats were given single oral doses
of 50, 30 or 1 mg or 10 or 0.1 pg of UICC chrysotlle A or "prepared"
chrysotHe (>90% of fibers <5 ym 1n length) (Welnzwelgh and Richards,
1983). Control rats were maintained. The portal hepatic vein was Ugated
and blood samples were drawn for analysis of chrysotlle at 2, 7 and 12 hours
after the single oral dose of asbestos. The occurrence of chrysotlle fibers
In the blood from control rats complicated Interpretation of the results.
Peak levels of chrysotlle 1n the blood seemed to occur ~7 hours after the
single oral dose was administered. In 6 of the 15 trials, the level of
chrysotHe In the blood of treated rats was significantly greater than that
of controls. Fibrils detected 1n blood were of small size (97% <1 urn).
These authors suggested that migration of larger asbestos particles probably
does not occur as a result of uptake Into the portal circulation.
Cunningham et al. (1977) fed diets containing 1% chrysotlle asbestos
(22% 0.3-1.0 wm; 59%, 1.1-3.0 vm; 9%, 3.1-5.0 vm; 10%, 5.1-10 vm;
10%, 10.1-50.0 pm) to 20 male Wlstar rats for 6 weeks. To reduce dust and
the likelihood of Inhalation of asbestos, corn oil or molasses was added to
the diet. Control rats were maintained. The rats were killed and tissues
were examined; the results are summarized In Table 2-1. In treated rats,
the greatest tissue content of chrysotlle was observed 1n the omentum,
followed by the brain and lungs. The fact that growth depression occurred
In all treated groups Implied that 1% chrysotlle 1n the diet "had some
biological effect." Food Intake figures were not reported.
-7-
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TABLE 2-1
Asbestos Levels In Rats Fed 1% Asbestos for 6 Weeks
(fibers x 106/g)a
Tissue
Blood
Omen turn
Lung
Kidney
Liver
Brain
Controls
0
1
0
0
0
.00
.08
.29
.17
.13
0.22
+
+
+
+
+
0.
0.
0.
0.
0.
58
08
03
06
11
Asbestos
0
9
1
0
0
1
.57 ±
.66 ±
.02 ±
.36 +
.62 +
.25 ±
Treated
0
3
0
0
0
0
.43
.18b
.20C
.03C
.30
.34b
aSource: Cunningham et a!., 1977
bp<0.02 using a t-test with each figure representing the average with
standard error for 10 rats.
cp<0.01
-8-
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Meek (1983), however, reported that no evidence for Intestinal mucosal
uptake could be found 1n rats treated with amoslte. This Investigator
Injected a 0.1 ma, suspension of amoslte In physiological saline Into the
wall of the Intact GI tract of male Wlstar rats to characterize the granu-
lomatous changes expected as a result of amoslte uptake. Dense accumula-
tions of macrophages were observed In the Injection site as a result of the
Injected amoslte. Subsequently, other rats were treated by gavage with 100
mg UICC amoslte for 5 days and then killed; their Intestinal tracts were
microscopically examined for the macrophaglc Invasion that was found to
characterize the response to amoslte. A lack of evidence of a macrophaglc
response or other pathological changes In the small Intestine of treated
rats was Interpreted to mean that the "gut wall of rats may present an
effective barrier to the penetration of asbestos " Meek (1983) acknowl-
edged the limitations of this study and suggested that further studies
should Involve electron microscopy of the mucosal cells.
According to Bolton et al. (1982), electron microscopic examination of
the Intestinal mucosa of male HAN spf Wlstar rats exposed to asbestos failed
to reveal any evidence of penetration or damage to gut tissues. Exposure
was to UICC amoslte, UICC croddollte or UICC chrysotHe A, at levels of 5
mg/g of margarine which was fed ad libitum for at least 25 months. Consump-
tion of asbestos was -250 mg/week. The result of the electron microscopic
examination of tissue residues Indicated no widespread penetration and/or
dissemination of asbestos fibers In treated rats.
2.2. INHALATION
Comparatively few data have been located on the absorption of asbestos
following Inhalation exposure. Whether Inspired asbestos fibers will be
deposited 1n the lung depends strongly upon their diameter. Timbrel! (1965)
-9-
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has shown that a fiber, Independent of Us length, behaves aerodynamlcally
like a particle having a diameter 3 times as great as Us actual diameter.
Brain and Valberg (1974) Indicated that 50% of particles with a median diam-
eter of <0.1 ym will be deposited on nonclllated pulmonary surfaces, as
determined by a model for aerosol deposition based on the aerodynamic char-
acteristics of particles. About 25% of particles with a diameter of 1 v»m
and 0% of particles with a diameter of 10 pm would be expected to deposit
on nondllated respiratory epithelium. Once Inhaled, a large fraction of
the Inhaled fibers Is rapidly cleared by mucodllary action, although some
fibers will remain 1n the lung and can be found there decades after exposure
(Pooley, 1973; Langer, 1974). Particularly large fibers trapped in the
lungs may become coated or calcified and form asbestos bodies.
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). Rats were exposed for 30 minutes to different varieties of UICC
standard asbestos samples, made radioactive by neutron bombardment, and
deposition and clearance from the respiratory tract was determined.
Subsequently, distribution among various tissues of the body was measured.
The results are presented In Table 2-2. These data Indicate the magnitude
of mucodllary clearance of asbestos fibers from the lungs.
A difference In the pulmonary retention of various forms of asbestos In
Wlstar rats exposed to 10.1-10.6 mg/m3 for 7 hours/day, 5 days/week for 24
months was reported by Wagner et al. (1974). These authors determined that
the amphlboles studied (amoslte, anthrophyllHe and crocldolHe) accumulated
1n the lungs ~7 times as heavily as the two chrysotlles (a Canadian and a
Rhodeslan sample).
-10-
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TABLE 2-2
Distribution of Fiber at the Termination of Exposure
('/. of Total Deposited)*'5
Fiber
Chrysotile A
Chrysotile B
Amos He
CrocidolHe
AnthophyllHe
Fluoramphibole
Nasal
Passages
9
8
6
8
7
3
± 3
± 2
i 1
± 3
i 2
i 2
Esophagus GI Tract
2 i 1 51
2 + 1 54
2 ± 1 57
2 + 1 51
2 ± 1 61
1 i 1 67
± 9
± 5
± *
± 9
± 8
± 5
Lower
Respiratory
Tract
38
36
35
39
30
29
± 8
± 4
± 5
± 5
± 8
± *
aSource: Morgan et al., 1975
bMean and SO
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More recently, Barry et al. (1983) found chrysotile fibers 1n the
alveolar macrophages, epithelium and Interstitial perlalveolar tissue of
rats exposed to 9.06 mg chrysotlle/m3 for 7 hours. After 3 month? of
exposure for 7 hours/day, 5 days/week, numerous fibers and cellular changes
were observed 1n the alveolar epithelium and 1nterst1t1um.
Phagocytosis by macrophages was considered to be the major method by
which chrysotHe fibers Inhaled by guinea pigs moved through the parenchyma
of the lungs to the pleura. Macrophages that disintegrated before complet-
ing the journey discharged their contents In the lymphatic system (Holt,
1983).
In an In vitro study of the toxldty of several Inhaled pollutants,
three forms of UICC standard reference samples of asbestos fibers (amosHe,
crocldollte and Canadian chrysotile B) were seen by electron microscopy to
be Ingested by human bronchial epithelial cells (Haugen et al., 1982).
-12-
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3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1. SUBCHRONIC
3.1.1. Oral. Pertinent data regarding toxldty associated with sub-
chronic oral exposure to asbestos In humans could not be located 1n the
available literature.
Jacobs et al. (1978) fed rats diets containing 0.5 or 50 mg of chryso-
tlle dally for 14 months, and subsequently examined the GI tract by both
light and electron microscopy. No effects were noted 1n the esophagus,
stomach or cecum, but "structural changes In the v1H1 of the Heum were
quite evident at both dosage levels."
3.1.2. Inhalation. Only one study of subchronlc Inhalation exposure of
humans to asbestos was located 1n the available literature. Harless et al.
(1978) discovered airflow abnormalities (not further specified) in 17/23
Individuals examined 1.5 and 8.0 months following an Intense 5-month
exposure to asbestos. Of the 17 affected Individuals, 12 were nonsmokers or
current light or ex-light smokers (<10 pack-years). The obstructive
abnormalities were usually observed during measurements of 1-m1nute forced
expiratory volume and of closing volume.
Male and female rats exposed to 9.06 mg chrysotlle/m3, 7 hours/day, 5
days/week for 3 months showed the presence of chrysotlle fibers and consid-
erable cellular change 1n the alveolar epithelial and Interstitial cells
(Barry et al., 1983). Most noteworthy was a 57% Increase 1n the number of
type II epithelial cells and a 90% Increase In their average cellular
volume. A 58% Increase 1n the number of Interstitial cells and a 40%
Increase 1n their average cellular volume were also observed. Infiltration
-13-
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with macrophages accounted for nearly all the Increase in Interstitial cell
numbers. Of cells that were observed to contain chrysotHe fibers, 88% were
macrophages. Eventually, calcification of these fibers occurred and cellu-
lar inclusions were thus formed.
Wagner (1963) exposed guinea pigs and vervet monkeys to chrysotlle and
amoslte dust at concentrations of 37,600 or 30,000 part1cles/m3, respec-
tively, for 8 hours/day, 5 days/week for 49 weeks. The technique of
asbestos analysis had the limitation of not being able to Identify "long"
asbestos fibers. Guinea pigs exposed to chrysotlle developed pulmonary
fibrosls, Interstitial pneumonitls, cuboldal metaplasia of the epithelium of
the alveolar ducts and cor pulmonale. Similar lesions but a more rapid
onset were noted In guinea pigs exposed to amoslte dust. Deaths occurred in
monkeys exposed to chrysotlle after 7, 10 and 22 months of exposure. Deaths
of the first two were due to gastroenteritis. Deaths occurred in monkeys
exposed to amoslte after 4, 12 and 14 months of exposure. Pathological
changes In both chrysotlle- and amosite-exposed monkeys included lung fibro-
sis and cor pulmonale. hlstologically consistent with slight to moderate
human asbestosis.
Subsequently, Wagner et al. (1974) exposed groups of -20-25 Wistar rats
to amoslte, anthophyllite, crocidolite and chrysotile to establish a dose
relationship between different asbestos dusts and pulmonary malignancies.
Exposure was for 7 hours/day, 5 days/week for 3, 6, 12 or 24 months to air
containing 10-11 mg/m3. Overall, the severity of asbestosis (fibrosis,
Increased numbers of type II pneumocytes) correlated with Increased length
of exposure.
-14-
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3.2. CHRONIC
Most studies of the chronic exposure of animals to asbestos by either
the oral or Inhalation route have been for the purpose of studying the abil-
ity of asbestos fibers to Initiate a carcinogenic response. Therefore, most
long-term studies of exposure to asbestos will be discussed In Chapter 4.
3.2.1. Oral. Bolton et al. (1982) fed margarine containing 5 mg UICC
amoslte, UICC croddollte or UICC chrysotHe A/g of margarine to groups of
23 HAN spf Wlstar rats. Negative control and vehicle control rats (fed
margarine without asbestos) were maintained. Margarine containing asbestos
was fed ad^ libitum, and asbestos Intake averaged -250 mg/rat/week. Rats
were treated for 25 months, and the majority were kept for the remainder of
their lifespan.
The animals tolerated the experimental diets well. Rats given access to
margarine with or without asbestos consumed -30% less standard laboratory
food and weighed consistently 25% more than rats not given access to marga-
rine. The resultant obesity had no obvious effect on morbidity or mortality
of the treated animals, with the majority surviving beyond 700 days of age.
Light and electron microscopic examination of many tissues was performed.
No penetration or damage to any of the gut tissues was observed. Although
occasional asbestos fibers were found in several tissue residues, no lesions
or effects of treatment were seen. Bolton et al. (1982) concluded that
there were no significant adverse effects of prolonged asbestos 1ngest1on 1n
healthy laboratory rats.
3.2.2. Inhalation. In humans, a chronic, progressive pneumoconlosls
(asbestosls) results from long-term Inhalation of asbestos fibers. It 1s
characterized by Hbrosls of the lung parenchyma, which usually becomes
radlographlcally discernible 10 years after the first exposure.
-15-
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Radlographlc lesions are usually small, Irregular opacities, usually 1n the
lower and middle lung fields. Pleural flbrosis and thickening, often with
focal areas of calcification, are also found. Changes can occur more
rapidly 1f exposure 1s more severe. Shortness of breath Is the primary
symptom, cough Is somewhat less common, and signs such as rales, finger
clubbing and weight loss occur 1n more advanced stages of the disease. The
disease was first reported by Murray (1907), and has since been recognized
frequently among occupatlonally-exposed workers.
It has been estimated that 50-80% of workers exposed to asbestos >20
years have radlographlc evidence of asbestosls (Sellkoff et al. 1965; Mount
S1na1, 1976; Lewlnsohn, 1972). In many cases, the disease progresses
following cessation of exposure. In a group of workers employed 1n an
asbestos factory for varying lengths of time between 1941 and 1954, radio-
graphic changes were observed years after exposures as short as 1 week
(Sellkoff, n.d.).
Restrictive pulmonary dysfunction 1s also seen with asbestos exposure
and may be accompanied by dlffusional defects or airway obstruction (Bader
et al., 1961). In the early stages of asbestosis there is little correla-
tion between pulmonary function tests and radlographlc changes; as the
disease progresses, the degree of correlation between radlographlc changes
and pulmonary dysfunction Increases markedly (Bader et al., 1961).
Families of asbestos-exposed workers can also be affected. Anderson et
al. (1976) demonstrated that 36% of 626 family contacts of workers employed
sometime between 1941 and 1954 at an asbestos insulation manufacturing
facility had radlographlc evidence of exposure to asbestos.
-16-
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In addition to disease and disablement during life, asbestosls has
accounted for a large proportion of deaths among exposed workers. Early
Investigators (Aurlbault, 1906; Murray, 1907) attributed the death of entire
working groups to severe asbestosls. Since then, Improvement 1n dust
control has markedly reduced the Incidence of mortality due to asbestosls,
but workers 1n extremely dusty conditions, as 1n textile mills, stand a >40%
probability of death because of asbestosls (Nicholson, 1976). From 5-20% of
deaths may be attributed to asbestosls In groups of workers 1n occupations
where dust 1s controlled more satisfactorily (Mount Sinai, 1976; Sellkoff et
al., 1979).
The BOHS (1968) estimated that exposure to airborne asbestos for <50
years at an air level of 2 fibers (>5 vm In length)/cm3 would result In
asbestosls In 5 vm 1n length)/cm3 1n air experienced an
Increase 1n deaths due to respiratory malignancies (10 observed vs. 2.7
expected, p<0.005) and respiratory nonmallgnandes (8 observed vs. 3.2
expected, p<0.05). Simultaneous exposure to free silica dust also occurred,
but reportedly at levels below OSHA (Code of Federal Regulations, 1981)
standards, and these Investigators (GUlam et al., 1976) concluded that the
nonmallgnant respiratory disease was caused primarily by asbestos, possibly
assisted by low levels of silica dust.
The effects of chronic exposure of rats to asbestos fibers by Inhalation
was Investigated by Reeves et al. (1974), who exposed 207 rats to 47.9-50.2
mg chrysotHe, amoslte or croc1dol1te/m3 for 4 hours/day, 4 days/week for
-17-
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2 years. Only 0.08-1.82% of the dusts retained fibrous morphology as
assessed by light microscopy following completion of preparation procedures
for dust generation. A marked h1st1ocyt1c and giant cell response occurred
1n rats as a response to any of the forms of asbestos; pulmonary flbrosls
and hyperplasla were most severe In the croddollte-exposed group followed
by the amosHe-exposed group which was greater than the chrysotile-exposed
group. These Investigators also reported pulmonary flbrosls 1n mice,
gerblls, rabbits and guinea pigs exposed to asbestos by the same protocol.
Rats exposed to any of these asbestos dusts developed lung cancers and
mesotheHomas.
3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS
Pertinent data regarding the teratogenldty, fetotoxldty or effects on
reproduction In humans or animals associated with either oral or Inhalation
exposure to asbestos could not be located In the available literature,
although transplacental transfer of asbestos following oral exposure has
been demonstrated (Pontefract and Cunningham, 1973; Cunningham and
Pontefract, 1974).
3.4. TOXICANT INTERACTIONS
Asbestos exposure and cigarette smoking have been shown to act synergls-
tlcally to produce dramatic Increases 1n lung cancer over that from exposure
to either agent alone. In a prospective study of 17,800 Insulation workers
exposed to asbestos, smoking histories were taken, and a 10-year observation
period was begun (Hammond et al., 1979). Those Insulation workers who
claimed nonsmoker status experienced higher mortality (8) than expected
(1.3) based on age-, calendar- and year-specific cancer rate data among
smokers and nonsmokers compiled by the American Cancer Society. Insulation
workers who reported being smokers experienced 268 deaths compared to 4.7
-18-
-------
expected. These Investigators concluded that exposure to asbestos appeared
to multiply the risk of death by 4-6 times. The combination of exposure to
asbestos and the habit of smoking Increased the likelihood of death due to
lung cancer by >50 times. In an earlier study, Sellkoff et al. (1968) sug-
gested that the risk of death from lung cancer 1n cigarette smoking asbestos
workers was 92 times that of Individuals exposed to neither pulmonary Insult.
The study by Hammond et al. (1979) associated Increased deaths from
cancer of the larynx, pharynx, buccal cavity and esophagus among asbestos
workers who smoked cigarettes. Among asbestos workers 1n this study,
cancers of the pleura, peritoneum, stomach, colon and rectum were unrelated
to smoking habits. Shettlgara and Morgan (1975), however, found a much
stronger association of laryngeal cancer with asbestos exposure rather than
with cigarette smoking.
Berry et al. (1972) obtained retrospective smoking histories on a group
of asbestos workers and evaluated the causes of mortality over a 10-year
period. They concluded that the effects of cigarette smoking and exposure
to asbestos were multiplicative rather than additive 1n Increasing the
Incidence of lung cancers.
Some nonmallgnant effects of asbestos also appear to be synerglstlcally
enhanced by cigarette smoking. Among a cohort of factory workers exposed to
asbestos, Weiss (1971) found that radlographlcally-dlagnosed flbrosls was
Increased 1n cigarette smokers compared to nonsmokers. Hammond et al.
(1979) found that deaths due to asbestosls appeared to be Increased In
smokers compared with nonsmokers.
Simultaneous exposure to BaP and asbestos seems to provide convincing
data that these two agents may act synerglstlcally to produce malignant
tumors. Pylev and Shabad (1973) reported that Intratracheal Injection of
-19-
-------
6 mg chrysotHe, upon which 0.144 mg BaP had been adsorbed, and 2 mg chryso-
tlle simultaneously with 5 mg BaP resulted 1n malignancies In 29 and 54% of
the treated rats, respectively. Administration of 6 mg chrysotlle or 5 mg
BaP alone yielded no tumors.
Miller et al. (1965) showed that Intratracheal Injection of chrysotlle
with BaP Increased the tumor yield over that of BaP alone. In this study,
amoslte appeared to have IHtle effect.
-20-
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4. CARCINOGENICITY
4.1. HUMAN DATA
For an In-depth review of the literature the reader 1s referred to U.S.
EPA (1985). The modern history of asbestos disease dates from the early
1900s when two reports documented uncontrolled dust conditions 1n asbestos
textile factories. Murray (1907) described severe pulmonary flbrosls found
at necropsy In a cohort of deceased workers who had worked 10-14 years In a
carding room. Aurlbault (1906) discussed the deaths of 50 men In a short
period (unspecified) following the opening of an asbestos weaving mill In
France.
Two clinical reports associated lung cancer with exposure to asbestos
(Lynch and Smith, 1935; Gloyne, 1935). Merewether (1947) clearly related
lung cancer to asbestos exposure when he demonstrated that 13% of a group of
asbestos workers, who had died of asbestosis, also had bronchogenlc carci-
nomas. Mesothelloma, a rare tumor involving the pleura or peritoneum, was
first described in an asbestos worker in 1953 (Weiss, 1953), was subse-
quently found to be frequently associated with exposure to asbestos (Wagner
et al., 1960), and later, was unequivocally related to asbestos exposure
(Newhouse and Thomson, 1965).
Gastrointestinal cancer was also found to be related to asbestos
exposure among Insulation workers (Sellkoff et al., 1964), probably because
a large fraction of Inhaled asbestos is cleared from the respiratory tract
and subsequently swallowed (see Section 2.2.). Gastrointestinal cancers may
also result from Ingestion of asbestos fibers in food or drinking water. In
this document, the cardnogenlcity of asbestos associated with inhalation
will be considered separately from cardnogenlcity associated with oral
exposure, in spite of the fact that a substantial proportion of inhaled
asbestos fibers are ultimately swallowed.
-21-
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4.1.1. Oral. Historically, oral exposure of humans to asbestos fibers
has been through the drinking water, resulting either from contact with
asbestos deposits or transmission through asbestos cement water mains.
Several studies of carclnogenicity in humans associated with asbestos in
drinking water are summarized in Table 4-1.
Polissar et al. (1983) reported a slightly elevated Incidence of pharyn-
geal and stomach cancers in males living in the Everett, WA, area, whose
watershed is the Sultan River which reportedly contains unusually high
asbestos levels (~200xl06 fiber/a). Since only males seemed to be
affected, and since the population studied was small, these Investigators
concluded that the higher than expected incidence of stomach and pharyngeal
cancer was probably not related to asbestos intake.
Harrington et al. (1978) and Meigs (1983) investigated the incidence of
cancer of the 61 tract and peritoneum related to asbestos in drinking water
1n several Connecticut communities, resulting from the use of asbestos
cement pipe. No relationship was established between asbestos in the drink-
ing water and the incidence of GI or peritoneal tumors.
The incidence of death due to cancer of the digestive tract or lungs, or
tumors of all sites was elevated 16-49% in Duluth, MN residents compared
with residents of other Minnesota cities. Duluth drinking water originates
from Lake Superior, which is contaminated with fibrous tailings from
iron-ore processing in the area. More recently, Sigurdson (1983) observed
significant increases in deaths due to tumors of the peritoneum (p<0.05), 61
tract (p<0.01) or prostate (p<0.01) in Duluth residents compared with
residents of other Minnesota cities.
-22-
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TABLE 4-1
Recent Studies of Cancers Related to Asbestos tn Drinking Water
Watershed
Everett,
Washington
Various,
Connecticut
to
i
Eseambla
County,
Florida
Duluth.
Minnesota
Level of Duration of
Exposure Exposure
(fibers/4) (years)
-200x10* 23X; >30
"few hundred <5 to >30
thousand*
0.2-32.7x10* NR
1-65x10* NR
Target
Organ
Gl tract
peritoneum
Gl tract
several
peritoneum
Gl tract
prostate
Tumor Type
pharyngeal cancer
(males)
stomach cancer
(males)
peritoneal
mesothelloma
NR
several
total tumors
total tumors
total tumors
Number
of Tumors
Observed
NR
NR
NR
NR
NR
4.3/100.000
2.8/100,000
90.4/100.000
Number
of Tumors
Expected
NR
NR
NR
NS
NR
1.4/100,000
0.3/100,000
69.3/100,000
Relative
Risk
(positive)
p<0.05
p<0.05
NS
NS
p<0.05
p<0.01
p<0.01
Reference
Pollssar
et al., 1983
Helgs, 1983
Mlllette
et al.. 1983
Slgurdson,
1983
NR - Not reported; NS = not significant
-------
Cooper et al. (1978) reported on the Incidence of death due to cancer In
721 census tracts of the five Bay Area counties In California associated
with the chrysotile asbestos fiber concentrations 1n drinking water.
ChrysotHe content ranged from not detectable to 36xl06 fibers/8.. By
grouping population tracts according to a gradient of asbestos counts,
statistically significant dose-related trends were noted for white males
(lung and stomach cancer) and white females (gall bladder, esophageal and
peritoneal cancer).
4.1.2. Inhalation. Many ep1dem1olog1cal studies have clearly Implicated
asbestos as a cause of bronchogenlc cancers and pleural mesothellomas In
exposed workers (U.S. EPA, 1980b). The more significant ep1dem1olog1cal
studies are summarized 1n Table 4-2.
Without exception, the Incidence of deaths due to cancer 1s In excess of
the expected cancer-associated death rates for large control populations.
The occurrence of excess deaths due to cancer ranges from a low of 1.9 times
the expected rate for lung cancers and pleural mesothellomas 1n asbestos
factory workers In England (Peto et al., 1977), to a high of 28 times the
expected rate for lung and pleural cancers In women 1n asbestos textile
manufacturing 1n England (p<0.001) (Newhouse et al., 1972).
6111am et al. (1976) reported significant excess mortality from malig-
nancies Involving the respiratory tract 1n mine workers exposed to amoslte
at average concentrations of 4.82 fibers/cm3. The observed number of
deaths due to respiratory malignancies was 10/440, compared with an expected
Incidence of 2.7 (p<0.01).
A study of the incidence of mesothelloma and non-neoplast1c lesions in a
region of Turkey with very high environmental levels of naturally occurring
asbestos was performed by Baris et al. (1979). The occurrence of 148 cases
-24-
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TABLE 4-2
Epldemlologlcal Studies: Human Cancers Associated with Inhalation of Asbestos
in
i
Size of
Exposed
Population
165
557
239
126
440
143
963
632
370
Site of
Control
Population
Northern
Ireland
death rate
death rates
for England
and Wales
South
Dakota
general
population
national
death
rates
national
death
rates
U.S. death
rate data
U.S. death
rate data
Level of
Sex Exposure
N NR
F severe
F severe
F low to
moderate .
N 4.82
fibers/cm*
M 10-15a
fibers/cm'
H/F 2.9-13.3C
fibers /cm1
H NR
N NR
Duration of
Exposure
5-50*- years
<2 years
<2 years
any exposure
time
>60 months
>20 years
>10 years
>20 years
>20 years
Target Organ
lower
respiratory
system
lung and pleura
lung and pleura
lung and pleura
respiratory
system
lung
lung
lung, stomach,
colon, rectum
lung, stomach,
colon, rectum
Tumor
Type
cancer
cancer
cancer
cancer
malignant
cancer
cancer
cancer
cancer
cancer
cancer
Number of
Tumors
Observed
28
6
14
2
10
35b
36*>
42
29
47
14
Number of
Tumors
Expected
1.64
1.0
0.5
0.3
2.7
4.54
19.3
6.02
9.71
6.18
3.92
Relative
Risk
(p value)
NR
p<0.001
p<0.001
p<0.05
p<0.01
p<0.001
p<0.001
NR
NR
NR
NR
Reference
Elmes and
Simpson, 1971
Newhouse
et al., 1972
Gil lam et al..
1976
Peto et al.,
1977
Peto et al.,
1977
Sellkoff
et al., 1964
Sellkoff, 1976
aWorkers exposed prior to 1933. Exposure was estimated.
''Lung cancers and pleural mesothellomas
cWorkers exposed after 1933. Exposure measurements varied over the period measured. Actual measurements of asbestos dust were reported since 1951.
NR = Not reported
-------
of malignant pleura! mesothelioma (92 In males, 56 In females) was associ-
ated with the occurrence of asbestos fibers 1n the water, fields and streets
of this region. In 1 year, 11/18 deaths were due to malignant pleural
mesothelloma 1n a town of 604 Inhabitants.
An extensive study by Sellkoff et al. (1979) demonstrated the full spec-
trum of disease associated with asbestos exposure. The mortality experi-
ences of a cohort of 17,800 United States and Canadian asbestos workers,
which occurred over a 10-year period (1967-1976), were compared to those
expected based on data compiled by the U.S. National Center for Health
Statistics. Prior to 1940, these workers were exposed primarily to chryso-
tlle, and subsequently, to a mixture of chrysotlle and amosHe. During this
10-year period, 2271 deaths occurred. The causes of these deaths as deter-
mined from death certificates or from "best evidence" (clinical, surgical,
necropsy), and the expected Incidences of deaths from these cancers, are
detailed 1n Table 4-3.
Lung tumors were the most common cause of death and accounted for -20%
of the deaths. Pleural and peritoneal mesothellomas, ordinarily rare enough
so that expected deaths due to this cause have not been projected, accounted
for ~8% of the 2271 deaths. Considerable discrepancy exists between the
Incidences of mesothellomas as determined by "best evidence" compared with
the Incidence of mesothellomas reported on death certificates. Sellkoff et
al. (1979) judged that diagnosis based on "best evidence" 1s more likely to
be accurate, particularly 1n cases of rarely occurring tumors such as meso-
thellomas. Cancers of the GI tract also appeared to be strongly associated
with Industrial exposure to asbestos.
In addition to the Increase In lung cancers, mesothellomas and GI
cancers, recent case reports have associated exposure to asbestos with
-26-
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TABLE 4-3
Deaths Among 17,800 Asbestos Insulation Workers
1n the United States and Canadaa«b'c
(January 1, 1967 - January 1, 1977)
Observed
Underlying Cause of Death
Total deaths, all causes
Total cancer, all sites
Cancer of lung
Pleural mesothelioma
Peritoneal mesothelioma
Mesothelioma
Cancer of esophagus
Cancer of stomach
Cancer of colon-rectum
Cancer of larynx
Cancer of pharynx, buccal
Cancer of kidney
Deaths of less common
malignant neoplasms
Pancreas
Liver, biliary passages
Bladder
Testes
Prostate
Leukemia
Lymphoma
Skin
Brain
All other cancer
Expected
1658.9
319.7
105.6
NAd
NAd
NAd
7.1
14.2
38.1
4.7
10.1
8.1
17.5
7.2
9.1
1.9
20.4
13.1
20.1
6.6
10.4
25.5
BEd
2271
995
468
63
112
0
18
22
59
11
21
19
23
5
9
2
30
15
19
12
14
55
DCe
2271
922
429
25
24
55
18
18
58
9
16
18
49
19
7
1
28
15
16
8
17
92
Ratio
Observed/
Expected
BEd
1.37
3.11
4.60
NR
NR
NR
2.53
1.54
1.55
2.34
2.08
2.36
1.32
0.70
0.99
NR
1.47
1.15
0.95
1.82
1.35
2.16
DCe
1.37
2.88
4.06
NR
NR
NR
2.53
1.26
1.52
1.91
1.59
2.23
2.81
2.65
0.77
NR
1.37
1.15
0.80
1.22
1.63
3.61
-27-
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TABLE 4-3 (cont.)
Observed
Underlying Cause of Death Expected
Nonlnfectlous pulmonary
diseases total
Asbestosls
All other causes
59.0
NAd
1280.2
BEd
212
168
1064
oce
188
78
1161
Ratio
Observed/
Expected
BEd -
3.59
NR
0.83
DCe
3.19
NR
0.91
aSource: Adapted from Sellkoff et al.t 1979
bExpected deaths are based upon white male age-specific mortality data of
the U.S. National Center for Health Statistics for 1967-1975 and extrapola-
tion to 1976.
cHan-Years of Observation: 166,853
dRates are not available, but these have been rare causes of death 1n the
general population.
BE = Best evidence. Number of deaths categorized after review of best
available Information (autopsy, surgical, clinical)
i
DC = Number of deaths as recorded from death certificate Information only
NA = Not available; NR = not reported
-28-
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leukemia and myeloma (Kagan et a!., 1979; Haidak et al., 1979; Rouhler et
al., 1982). Kagan et al. (1979) and Haidak et al. (1979) reported cases of
Individuals with multiple myeloma and chronic lymphocytlc leukemia concur-
rent with pulmonary asbestosls. A third patient with multiple myeloma
developed a massive pleural mesothelloma (Kagan et al., 1979; Haidak et al.,
1979). Another patient, who had been occupatlonally exposed to asbestos for
30 years, developed malignant alpha-chain disease, and was found to have
malignant lymphoma (Rouhler et al., 1982). All of these cases showed
lesions of asbestosls 1n addition to the diagnosed malignancies.
4.2. BIOASSAYS
4.2.1. Oral. Several studies of the cardnogenlcHy of asbestos adminis-
tered1 orally to animals have been found 1n the available literature (Table
4-4). These data have severe limitations: the numbers 1n each experimental
group were small; the doses of asbestos administered were limited; Important
Information on experimental procedures 1s lacking; and systemic hlstopatho-
loglcal examinations were performed only on a few experimental animals.
Smith (1973) discounted the significance of a single neoplasm of the
colonlc mesentery in 1 of 45 hamsters fed a diet containing 1% chrysotlle or
amoslte for an unspecified length of time because asbestos fibers were not
found 1n sections of the tumor. The finding of asbestos fibers 1n tumor
tissue seems unlikely, and, since mesenterlc tumors 1n hamsters are rare,
this result should not be disregarded arbitrarily.
The data summarized by Gross et al. (1974) were the results of unpub-
lished studies from three laboratories over a 10-year period. Lack of
Information about experimental detail and lack of systemic histopathologlcal
examination of all treated animals renders Interpretation of these limited
data difficult.
-29-
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1ABLE 4-4
Summary of Experiments on the Effects of Oral Administration of Asbestos
Species/Strain
Rats/Ulstar
Rats/Wlstar
Rats/Wlstar
Kats/W1star
SPF
(!o Rats/Wlstar
o SPF
Rats/Wlstar
SPF
Rats
Rats
"laboratory"
Rats/Wlstar
SPF
Rats/MUtar
SPF
Rats/Mlstar
SPF
Rats/Wlstar
SPF
No. /Sex
2SN, 25F
25H. 25F
25H, 25F
32/NR
32/NR
16/NR
10H
5/NR
31 /NR
33/NR
34/NR
24/NR
Material
Administered
asbestos filter
material containing
52.6* chrysotlle
talc
control
U1CC Canadian
chrysotlle In
malted milk powder
Italian talc
control
ball-milled chry-
sotlle mixed with
laboratory food
control
Rhodeslan
chrysotlle
0.2X-0.4X
croc Idol He In
butter 0.2-0.4X
mixture
croc Idol He In
butter 0.2-0.4X
mixture
control (butter)
Dosage
50 mg/kg bw/day
In the diet for
life
SO mg/kg bw/day
In the diet for
life
control
100 rag/day. 5
days /week for
100 days
100 rag/day. 5
days/week for
100 days
control
5X by weight of
feed mix for 21
months
control
10 nig weekly for
16 weeks
5 mg weekly for
for 16 weeks
10 mg weekly for
16 weeks
control
Animals Examined Findings
for Tumors (malignant tumors)
42 4 kidney carcinomas
3 retlculosarcomas
4 liver -cell carcinomas
1 lung carcinoma
45 3 liver-cell carcinomas
49 2 liver -cell carcinomas
32 1 gastric lelomyosarcoma
32 1 gastric lelomyosarcoma
16 none
10 none
5 none
31 less "a few* 2 mammary carcinomas
33 less "a few" none
34 less "a few" 1 lymphoma
(24?) 3 mammary carcinomas
1 thigh sarcoma
Average
Survival
lime (days)
441
649
702
618
614
641
sacrificed
sacrificed
NR
NR
NR
NR
Reference
Glbel
et al..
Glbel
et al..
Glbel
et al..
Wagner
et al..
Wagner
et al..
Wagner
et al..
Gross
et al..
Gross
et al..
Gross
et al.,
Gross
et al..
Gross
et al..
Gross
et al..
1976
1976
1976
1977
1977
1977
1974
1974
1974
1974
1974
1974
-------
TABLE 4-4 (cont.)
Species/Strain No. /Sex
Rats/Hlstar 35/NR
SPF
Rats/Wlstar 28/NR
SPF
Rats/MUtar 24/NR
SPF
Rats/Wlstar ION
Rats/W1star 10H
i
CJ
1 Rats/Wlstar 40N
Rats/Wlstar 40M
Hamsters/NR 45/NR
Material
Administered
NU Cape crocldo-
Itte In butter
(0.2-0.4X)
Transvaal crocldo-
llte In butter
(0.2-0.4X)
control (butter)
IX chrysotlle
control
1% chrysotlle
control
chrysotlle or
amosHe
Animals Examined findings
Dosage for Tumors (malignant tumors)
10 mg weekly for 35 less "a feu* none
18 weeks
10 mg weekly for 28 less "a few* none
for 18 weeks
control (24?) none
In diet 7 2 kidney
1 peritoneal
1 lymphoma
1 fibrosarcoma
1 brain
1 pituitary
NA 81 peritoneal
fibrosarcoma
In diet 36 3 thyroid
1 bone
1 liver
1 jugular body
2 leukemta/lymphoma
1 adrenal
1 large Intestine
anaplastlc carcinoma
1 small Intestine
fibrosarcoma
NA 38 1 thyroid
1 liver
2 adrenals
1 kidney
nephroblastoma
1 leukemia/ lymphoma
5 subcutaneous tissue
IX In diet for 45 1 mesenterlc neoplasm*
unspecified
period of time
Average
Survival Reference
Time (days)
NR Gross
et al., 1974
NR Gross
et al.. 1974
NR Gross
et al., 1974
NR Cunningham
et al.. 1977
NR Cunningham
et al.. 1977
NR Cunningham
et al.. 1977
NR Cunningham
et al., 1977
NR Smith. 1973
'From text, Impossible to state whether tumor was benign or malignant.
NA = Not applicable; NR = not reported
-------
Because of concern about the use of filter material containing asbestos
1n the purification of wine products, Gibe! et al. (1976) fed rats diets
containing asbestos filter material. Treatments continued throughout the
natural Hfespan of the animals; untreated controls were maintained. The
finding of four malignant kidney tumors 1n treated rats 1s accorded particu-
lar significance In view of the finding of an elevated risk of kidney cancer
among asbestos Insulation workers (Sellkoff et al., 1979} and a high excre-
tion of asbestos 1n the urine of humans exposed to asbestos-contaminated
drinking water (Cook and Olson, 1979). The presence of sulfated cellulose
and condensation resin In the filter material complicates Interpretation of
these results.
Cunningham et al. (1977) fed diets containing 1% chrysotlle to 10 male
Wlstar rats for up to 24 months. Control rats were maintained. In the
treated group, seven malignancies were fpund, while in the 10 control rats
only one malignancy was found. In a second trial, 40 treated and 40 control
male Wlstar rats were studied using the same experimental protocol. After
24 months of exposure, 11 malignancies were found 1n the treatment group and
11 malignancies were found 1n the control rats, which considerably reduces
the apparent relevance of the large number of malignancies 1n the earlier
study.
The U.S. EPA (1985) concluded a review of the available published animal
data with the following statement:
In animal populations, the majority of the experimental evidence
suggests that chronic, high-level 1ngest1on exposures to asbestos
fibers failed to produce any definite, reproducible, organ-specific
carcinogenic effect.
-32-
-------
In addition to the published literature, U.S. EPA (1985) presents a sum-
mary of the data from a draft NTP (1984) report. In this study no evidence
of carc1nogen1c1ty was found following feeding of short-range (98% <10 vm)
chrysotlle asbestos fibers to either male or female rats. In contrast, male
rats Ingesting Intermediate-range chrysotile fibers (65% >10 vm with -14%
>100 jjtn) at a 1% dietary level showed an Incidence of 3.6% for benign
epithelial neoplasms 1n the large Intestine. U.S. EPA (1985) quotes NTP
(1984) as follows:
Although not statistically significant (p=0.08) compared with
concurrent controls (0/85), the Incidence of these neoplasms was
highly significant (p=0.003) when compared with the Incidence of
epithelial neoplasms (benign and malignant combined) of the large
Intestine In the pooled control groups (male) of all the NTP oral
asbestos lifetime studies (3/524, 0.6%).
This study should be re-examined following peer review and final publication.
4.2.2. Inhalation. Several assays of the carclnogenldty of asbestos 1n
laboratory animals exposed via Inhalation have been conducted. Data from
some of the more pertinent studies are summarized 1n Table 4-5.
Lynch et al. (1957) administered chrysotHe dust (150-300xl06 parti-
cles/ft3, -5297-10,595xl06 part1cles/m3.) 8-12 hours/day, 5 days/week
for 19 months to AxC F, mice. Although a higher Incidence of pulmonary
adenomas was reported In the exposed group (58/127) than 1n controls
(80/222), these results were not statistically significant.
Exposure to 86 mg chrysotHe dust/m3 for 30 hours/week for 16 months
resulted 1n lung tumors 1n 24/72 rats (Gross et al., 1967). No lung tumors
were found 1n 39 control rats.
-33-
-------
TABLE 4-5
CarclnogenUUy of Asbestos In Animals Exposed by Inhalation
Species/
Strain
Mice
Mice
Rat/white
Rat/white
Rat/Charles
River CD
i
CO
» Rat/Charles
River CD
Rat/Charles
River CD
Rat/Charles
River CD
House/Swiss
House/Swiss
House/Swiss
Mouse/Swiss
Sex
H/F
H/F
M
M
H/F
H/F
H/F
M/F
M/F
M/F
M/F
M/F
Dose/Exposure
150-300xlO«a
particles/ft*
(B-12 hours/day;
5 days/week)
untreated
86 mg/m»c
0.0 rag
48.6 mg/ro*e
(4 hours/day;
4 days/week)
47.9 mg/m»c
(4 hours/day;
4 days/week)
50.2 mg/m»f
(4 hours/day;
0.0 rog/m»
48.6 mg/m*e
(4 hours/day;
4 days/week)
47.9 mg/m»h
(4 hours/day;
4 days/week)
50.2 mg/m*f
(4 hours/day;
4 days/week)
0.0 mg/m1
Duration
of
Treatment
19 months
NA
62 weeks
NA
24 months
24 months
24 months
24 months
24 months
24 months
24 months
24 months
Duration
of Study
19 months
19 months
>16 months
(lifetime)
lifetime
24 months
24 months
24 months
24 months
24 months
24 months
24 months
24 months
Purity of Vehicle or
Compound Physical
State
92.6-9B.8Xb dust
NA untreated
milled dust
NA untreated
NR dust
NR dust
NR dust
NA untreated
NR dust
NR dust
NR dust
NA untreated
Target
Organ
lung
lung
lung and
pleura
lung
lung and
pleura
lung and
pleura
lung and
pleura
no tumors
no tumors
no tumors
bronchial
bronchial
Tumor
Type
adenoma
adenoma
cancer
cancer
various
various
various
NA
NA
NA
carcinoma
carcinoma
Tumor
Incidence
58/127
(NS)
80/222
24/72d
0/39
3/46
3/43
5/469
0/5
0/17
0/19
2/18
1/6
Reference
Lynch
et al.,
Lynch
et al.,
Gross
et al..
Gross
et al..
Reeves
et al.,
Reeves
et al.,
Reeves
et al.,
Reeves
et al..
Reeves
et al..
Reeves
et al..
Reeves
et al..
Reeves
et al..
1957
1957
1967
1967
1974
1974
1974
1974
1974
1974
1974
1974
-------
TABIf 4-5 (cont.)
Species/
Strain
Rat/
nonspecific
Rat/
nonspecific
Rat/
nonspecific
Rat/Wlstar
Rat/Wlstar
Rat/Hi star
co
en
1 Rat/Wlstar
Rat/Wlstar
Rat/Wlstar
Rat/Wlstar
Rat/Wlstar
Rat/Wlstar
Rat/Wlstar
Sex
H/F
H/F
H/F
H/F
H/F
H/F
H/F
H/F
H/F
H/F
H/F
H/F
H/F
Duration
Dose/Exposure of
Treatment
47.4-47.9 ng/m»l 2 years
(4 hours/day;
4 days/week)
48.2-48.6 mg/m*J 2 years
(4 hours/day;
4 days/week)
48.7-50.2 mg/m** 2 years
(4 hours/day;
4 days/week)
14.1 mg/m* 1 day
7 hours/day6
12.8 mg/m* 1 day
7 hours/day™
12.5 mg/m* 1 day
7 hours/day'
9.7 mg/m» 1 day
7 hours/day0
14.7 mg/in* 1 day
7 hours/day"
0.0 mg/m* NA
7 hours/day
12.4 mg/m* 3 months
7 hours/day
5 days/week6
13.5 mg/m* 3 months
7 hours/day
5 days/week1"
12.6 mg/m* 3 months
7 hours/day
5 days/week''
12.1 mg/m* 3 months
7 hours/day
5 days/week0
Duration
of Study
2 years
2 years
2 years
804 days
806 days
795 days
763 days
753 days
803 days
771 days
823 days
817 days
790 days
Purity of Vehicle or Target
Compound Physical Organ
State
NR dust lung and
pleura
NR dust lung and
pleura
NR dust lung and
pleura
NR dust lung
NR dust lung
NR dust lung
NR dust lung
NR dust lung
NA untreated lung
NR dust lung
NR dust lung
NR dust lung
NR dust lung
Tumor
Type
various
various
various
various1!
various1
various^
various1
various1
adenoma
various1
various1
various1
various1
Tumor
Incidence
3/54
3/61
7/50
3/45
2/44
6/43
1/42
5/45
4/44
10/37
6/37
14/36
18/34
Reference
Reeves,
Reeves,
Reeves,
Wagner
ct al.,
Wagner
et al.,
Wagner
et al..
Wagner
et al..
Wagner
et al.,
Wagner
et al.,
Wagner
et al..
Wagner
et al.,
Wagner
et al..
Wagner
et al..
1976
1976
1976
1974
1974
1974
1974
1974
1974
1974
1974
1974
1974
-------
TABLE 4-5 (cont.)
Species/
Strain
Rat/Wlstar
Rat/Utstar
Rat/Wlstar
Rat/Wlstar
Rat/Wlstar
o? Rat/Wlstar
i
Rat/Mlstar
Rat/Wlstar
Rat/Wlstar
Rat/Wlstar
Rat/Wlstar
Rat/Wlstar
Sex
H/F
M/F
H/F
H/F
H/F
H/F
H/F
H/F
H/F
H/F
H/F
H/F
Dose/Exposure
12.3 mg/m»
7 hours/day
5 days/week"
0.0 mg/m»
11.2 mg/m*
7 hours/day
5 days/week*
10.9 mg/m*
7 hours/day
5 days/week1"
10.7 mg/m*
7 hours/day
5 days/week'
10.2 mg/m*
7 hours/day
5 days/week0
10.7 mg/m*
7 hours/day
5 days/week"
10. 8 rng/n*
7 hours/day
5 days/week6
11.4 mg/m'
7 hours/day
5 days/week™
10.6 mg/m*
7 hours/day
5 days/weekf
10.7 mg/n*
7 hours/day
5 days/weekc
10.9 mg/m1
7 hours/day
5 days/week"
Duration Duration
oF of Study
Treatment
3 months 857 days
NA 793 days
6 months 763 days
6 months 686 days
6 months 788 days
6 months 669 days
6 months 766 days
12 months 692 days
12 months 759 days
12 months 776 days
12 months 778 days
12 months 826 days
Purity of
Compound
NR
NA
NR
NR
NR
NR
NR
NR
NR
NR
NR
NR
Vehicle or
Physical
State
dust
untreated
dust
dust
dust
dust
dust
dust
dust
dust
dust
dust
Target
Organ
lung
lung
lung
lung
lung
lung
lung
•
lung
lung
lung
lung
Tung
Tumor
Type
various1
adenoma
various1
various1
various1
various1
various1
various1
various1
various1
various1
various1
Tumor
Incidence
16/36
3/40
2/18
6/18
4/18
5/17
8/19
10/25
20/28
18/26
11/23
19/27
Reference
Wagner
et al..
Wagner
et al.,
Wagner
et al..
Wagner
et al..
Wagner
et al..
Wagner
et al..
Wagner
et al..
Wagner
et al.,
Wagner
et al..
Wagner
et al..
Wagner
et al..
Wagner
et al.,
1974
1974
1974
1974
1974
1974
1974
1974
1974
1974
1974
1974
-------
TABLE 4-5 (conl.)
Species/
Strain Sex Dose/Exposure
Rat/Histar N/F 10.6 rag/m*
7 hours/day
5 days/week6
Rat/Ulstar H/F 10.6 mg/m»
7 hours/day
5 days/week1"
Rat/Ulstar N/F 10.3 mg/ra*
7 hours/day
5 days/week'
Rat/Utstar H/F 10.1 mg/m»
7 hours/day
S days/week0
Rat/Ulstar N/F 10.1 mg/m*
7 hours /day
i S days/week"
CO
T' Rat/Utstar N/F 0.0 mg/n»
Duration Duration
of of Study
Treatment
24 months 807 days
24 months 778 days
24 months 756 days
24 months 585 days
24 months 758 days
NA 754 days
Purity of Vehicle or Target Tumor
Compound Physical Organ Type
State
NR dust lung various1
NR dust lung various1
NR dust lung < various1
NR dust lung various1
NR dust lung various1
NA untreated lung various1
Tumor
Incidence Reference
13/21 Uagner
et al.,
16/18 Uagner
et al.,
13/18 Uagner
et al..
10/21 Uagner
et al.,
11/17 Uagner
et al..
0/42 Uagner
et al.,
1974
1974
1974
1974
1974
1974
aChrysot11e (very fine, low fiber content: Canadian)
°S102 (37.12-43.36X). HgO (39.54-43.90X). H20 (12-15X), FeO (0-6X). Fe203 (1-5X), A1203 (0.2-1.5X), CaO (0-0.3X). Pure chrysotlle . 3NgO-2S102-
cChrysot11e (Canadian)
dExcluslve of lymphoblastomas, since this tumor type Is known to occur spontaneously In those rats.
2H20
eAmos1te
Crocldollte
94 carcinomas of the lung; 1 adenocarclnoma of the lung
Chrysotlle
Chrysollle - fiber count measured as 54 million fibers/in1
^ Amos He - fiber count measured as 864 million flbers/m3
Crocldollte - fiber count measured as 1105 million fibers/in'
Adenoma, adenomatosls, adenocarclnoma, squamous carcinoma
mAnthophyl11te
"Chrysotlle (Rhodeslan)
NR = Not reported; NA = not applicable; NS « not statistically significant
f
-------
Reeves et al. (1974) tested the carclnogenlclty of various forms of
asbestos 1n rats, mice, rabbits, guinea pigs and gerblls. Dusts of chryso-
tHe, crorldolHe and amoslte were prepared by ban-milling, a process noted
for destroying much of the fibrous character of asbestos. Exposures were up
to 24 months to air concentrations of 47.9-50.2 mg/m3. Fiber counts were
54 fibers/ma (chrysotHe), 864 fibers/ml (amoslte) and 1105 fibers/ml
(croddolHe). Neoplasms were detected only In rats and mice. Rats exposed
to crocldolHe, chrysotHe and amoslte developed lung tumors 1n 5/46, 3/43
and 3/46, respectively. Papillary carcinomas developed In mice (2/18)
exposed to crocldolHe. Subsequently, Reeves (1976) exposed rats to chryso-
tlle, crocldolHe and amoslte, using the protocol previously described for a
2-year treatment period. Fiber counts were as reported previously (Reeves
et al., 1974). CrocldolHe, with the highest fiber count, also Induced the
highest Incidence of tumors (7/50), while chrysotlle (3/54) and amoslte
(3/61) were associated with fewer tumors 1n treated animals.
Wagner et al. (1974) exposed CO Wlstar rats to amoslte, croddolHe,
anthophylllte, Canadian chrysotHe or Rhodeslan chrysotlle at concentrations
of 9.7-14.7 mg/m3 for 1 day, 3, 6, 12 or 24 months for 7 hours/day, 5
days/week. Exposure to all forms of asbestos was associated with an
Increased Incidence of lung carcinomas and mesotheHomas after 3 months of
exposure. No mesotheHomas were found 1n rats exposed to Rhodeslan chryso-
t1le for any length of time.
4.3. OTHER RELEVANT DATA
MutagenlcHy testing of chrysotHe, amoslte, anthophylllte or superfine
chrysotHe gave negative results 1n several strains (unspecified) of Esche-
rlchla coll and Salmonella typhlmurlum assay systems (Chamberlain and Tarmy,
1977). The authors recognized that since prokaryotlc cells do not phago-
cytlze particles as do eukaryotlc cells, a positive response was not likely.
-38-
-------
Slncock and Seabrlght (1975) reported finding chromosomal aberrations In
CHO cells cultured In a medium containing 0.01 mg/m2. of either chrysotlle
or croddolHe. In a more extensive series of experiments, both morphologic
transformation and positive genetic responses resulted from the Inclusion of
several chrysotHe or croddolHe samples In the culture medium of CHO cells
(Slncock, 1977). Very fine glass fibers produced the same abnormalities,
but chemically leached asbestos produced fewer abnormalities than did
unleached asbestos.
4.4. WEIGHT OF EVIDENCE
Evidence Indicates that Ingested asbestos fibers may cause an excessive
incidence of cancers of the 61 tract. Pollssar et al. (1983) found a slight
but significant (p<0.05) Increase 1n the Incidence of pharyngeal and stomach
cancers 1n males drinking asbestos-contaminated water from the Sultan River,
considered to be one of the most highly contaminated water supplies In the
country. Slgurdson (1983) reported a significant Increase 1n the Incidence
of peritoneal tumors (p<0.05) and tumors of the GI tract (p<0.01) 1n resi-
dents of Duluth, MM, whose drinking water contained l-65x!06 fibers/8,.
Other Investigators failed to find a positive association between
Ingested asbestos and cancer 1n humans. Harrington et al. (1978) and Melgs
(1983) Investigated the Incidence of GI and peritoneal cancers In several
Connecticut communities 1n which concrete-asbestos water mains are used. No
relationship was established between asbestos 1n the drinking water and the
Incidence of these tumors.
Cooper et al. (1978) failed to find a dose-related trend In the Inci-
dence of cancer 1n 721 census tracts of five Bay Area counties of California
by examining the mortality data and ranking the census tracts according to
the level of asbestos 1n the drinking water.
-39-
-------
Evidence for a carcinogenic role for asbestos 1n orally exposed animals
Is also not convincing. The data generated have severe limitations: the
numbers of animals tested were small, the doses of asbestos used were
limited, and systematic histopathologlcal examination of all animals was not
always performed. The most convincing data suggesting a carcinogenic role
for orally-administered asbestos were provided 1n the study by G1bel et al.
(1976), who fed rats diets containing asbestos filter material which Is used
to clarify wine products. The finding of four kidney carcinomas among 50
rats treated throughout their lifetimes was considered a significant finding
In view of the fact that Selikoff et al. (1979) found an Increased risk of
kidney cancer associated with asbestos Insulation workers. The presence of
sulfated cellulose and condensation resin 1n the filter material fed to the
test rats complicates Interpretation of these results. Additional data are
available in the form of a draft NTP (1984) report (see Section 4.2.1.).
The case for cardnogen1c1ty of asbestos 1n humans exposed by Inhalation
Is considerably more convincing. Many ep1demolog1cal studies have demon-
strated significant Increases in the Incidence of deaths due to cancer
associated with inhalation (particularly occupational) exposure to asbestos
(see Table 4-2). Peto et al. (1977) and Newhouse et al. (1972) have clearly
shown that exposure to asbestos in the workplace is related to a significant
(p<0.001) increase In the likelihood of death due to cancers of the lung and
pleura. GiUam' et al. (1976) associated malignancies of the lung with
exposure to asbestos mining operations. Selikoff (1976) and Selikoff et al.
(1964, 1979) have shown that working with asbestos insulation may dramati-
cally elevate the likelihood of death due to cancer of the lung, pleura,
peritoneum and GI tract.
-40-
-------
The animal data substantiate the observation of cancers In humans asso-
ciated with Inhalation exposure to asbestos. Although several bloassays
strongly suggest the cardnogenldty of Inhaled asbestos fibers, the data of
Wagner et al. (1974) best Illustrate this phenomenon. This complex study,
which employed five forms of asbestos and treatment times of from 1 day to 2
years followed by varied post-exposure times, Is presented 1n tabular form
In Section 4.2.2. This study did not present statistical analysis of the
tumor Incidence data.
In light of the sufficient evidence Indicating cardnogenldty of
asbestos 1n humans exposed by Inhalation, which Is well corroborated by the
animal bloassay data, asbestos 1s most appropriately classlfed as a Group A
substance by application of the classification criteria devised by the
Carcinogen Assessment Group of the U.S. EPA {Federal Register, 1984).
-41-
-------
5. REGULATORY STANDARDS AND CRITERIA
The OSHA standard for asbestos fibers (defined as fibers >5 vm In
length) In workplace air was set In 1972 at 5 fibers/cm3 TWA for an 8-hour
day. In 1976, this standard was reduced to 2 fibers/cm3 for an 8-hour
TWA. A celling concentration of 10 fibers/cm3 was set (Code of Federal
Regulations, 1981).
The AC6IH (1980) recommended TWA-TLVs for asbestos as follows: amosHe,
0.5 fiber/cm3; chrysotHe, 2.0 fibers/cm3; croddolHe, 0.2 fiber/cm3;
other forms, 2.0 fibers/cm3. In Great Britain, the BOHS (1968) also
suggested a TWA of 2.0 fibers/cm3, although Peto (1978) suggested that
exposure to this level may result 1n the death of 10% of workers exposed for
a lifetime.
Standards for asbestos 1n foods or beverages could not be located 1n the
available literature.
The U.S. EPA (1980b) has recommended criteria for ambient water based on
estimated levels of asbestos that would result 1n increased lifetime cancer
risks of 10~5, 10~« and 10~7 as 300,000, 30,000 and 3000 fibers,
respectively. These criteria were derived from the association of GI cancer
with occupational exposure to asbestos dusts and by applying several assump-
tions. Primary among these assumptions is that virtually all of the asbes-
tos 1s ultimately swallowed, and Is therefore capable of causing lesions,
including neoplasms, in the GI tract. Estimates of occupational exposure
levels were matched with observed incidence of death due to GI cancers from
several epidemiological studies. A linear relationship between increased
cancer risk and exposure level was also assumed.
-42-
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6. RISK ASSESSMENT
6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS)
Asbestos Is a substance that Is known to be carcinogenic. Although the
U.S. EPA (1983c) determined that H 1s Inappropriate to derive a potency
factor for asbestos because Us carcinogenic potency 1s related to specific
fiber shapes, sizes and air concentrations, the U.S. EPA (1980b) estimated
unit carcinogenic risks for asbestos based on human epidemologlcal data. It
1s Inappropriate, therefore, to consider an oral or Inhalation AIS for
asbestos.
6.2. ACCEPTABLE INTAKE CHRONIC (AIC)
Asbestos 1s a substance that 1s known to be carcinogenic. The U.S. EPA
(1983c) determined that 1t 1s Inappropriate to derive a potency factor for
asbestos because Us carcinogenic potency Is related to specific fiber
shapes, sizes and air concentrations.
6.3. CARCINOGENIC POTENCY (q^)
6.3.1. Oral. As reviewed In Section 4.1.1., oral exposure of humans to
asbestos 1n drinking water has not been conclusively shown to result In
Increased risk of cancer. Pollssar et al. (1983) associated an Increased
Incidence of stomach and pharyngeal cancers with a high concentration of
asbestos fibers 1n drinking water in the Everett, WA area. Epldemlologlc
evaluations of cancer Incidence 1n residents of the five Bay Area counties
of California (Cooper et al., 1978) Indicated a dose-related trend In the
Incidence of lung and stomach cancer (males) and gall bladder, esophageal
and peritoneal cancer (females). Other epldemiologlc studies (Melgs, 1983;
MUlette et al., 1983) have failed to relate increased risk of cancer with
exposure to asbestos.
-43-
-------
Animal bloassays have not clearly established a carcinogenic role for
asbestos administered by the oral route (see Section 4,1.2.}.
The U.S. EPA (1980b) used human Inhalation data to derive a risk esti-
mate 1n order to develop ambient water quality criteria for asbestos. In a
later evaluation, the U.S. EPA (1983c) suggested that 1t may not be appro-
priate to calculate a potency factor for asbestos because Us carcinogenic
potency is related to the size and shape of asbestos particles as well as
Its concentration 1n the air. This Issue Is currently undergoing review
(U.S. EPA, 1985). The risk assessment portion of U.S. EPA (1985) Is not as
yet final. When completed, U.S. EPA (1985), as a more extensive evaluation
of the asbestos Issue, should supercede any recommendations 1n this document.
6.3.2. Inhalation. The carclnogenlcHy of asbestos for humans exposed by
the Inhalation route has been well established (Elmes and Simpson, 1971;
Newhouse et al., 1972; Glllam et al., 1976; Peto et a!., 1977; SeHkoff et
a!., 1964, 1979; Sellkoff, 1976).
Animal bloassays confirm the carclnogenlcHy of asbestos administered by
Inhalation (Gross et al., 1967; Reeves et al., 1974; Reeves, 1976; Wagner et
al., 1974). According to U.S. EPA (1983c), H 1s Inappropriate to derive a
potency factor for asbestos because the carcinogenic potency of asbestos Is
related to specific fiber shapes, sizes and air concentrations.
-44-
-------
7. REFERENCES
ACGIH (American Conference of Governmental Industrial Hygienists). 1980.
Documentation of the Threshold Limit Values, 4th ed. (Includes Supplemental
Documentation, 1981, 1982, 1983). Cincinnati, OH. p. 27-30.
Anderson, H.A., R. LIHs, S.M. Daum, A.S. Fischbein and 1.3. Selikoff.
1976. Household-contact asbestos neoplastic risk. Ann. NY Acad. Sd.
271: 311-315. (Cited 1n U.S. EPA, 1980b)
Aurlbault, M. 1906. Sur 1'hygiene et la securlte des ouvriers. Jji:
Bulletin de 1'Inspection du Travail, p. 120-132. (Fre.) (Cited in U.S.
EPA, 1980b)
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' •',,.*.
APPENDIX
Summary Table for Asbestos
Carcinogenic
Potency
Species
Experimental
Dose/Exposure
Effect
-------
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