United States
Environmental Protection
Agency
Office of Research and
Development
Washington, DC 20460
EPA-600/8-91/217
March 1992
&EPA
Health Assessment
Document for Talc
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EPA 600/8-91/217
March 1992
Health Assessment
Document for Talc
Environmental Criteria and Assessment Office
Office of Health and Environmental Assessment
U.S. Enviromental Protection Agency
Research Triangle Park, NC 27711
Printed on Recycled Paper
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DISCLAIMER
This document has been reviewed in accordance with U.S. Environmental Protection
Agency policy and approved for publication. Mention of trade names or commercial
I
products does not constitute endorsement or recommendation for use.
11
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CONTENTS
LIST OF TABLES
PREFACE . , .
AUTHORS, CONTRIBUTORS, AND REVIEWERS
1. SUMMARY
2. BACKGROUND INFORMATION
2.1 PHYSICAL AND CHEMICAL PROPERTIES
2.2 PRODUCTION AND INDUSTRIAL USES
2.3 SOURCES OF EMISSIONS
2.4 EXPOSURE
2.5 AMBIENT LEVELS
2.6 ENVIRONMENTAL FATE
2.7 ANALYTICAL METHODS .
3. TOXICOLOGY .
3.1 RETENTION AND BIODISPOSITION
3.2 ACUTE TOXICITY ,
3.3 SUBCHRONIC AND CHRONIC TOXICITY AND
CARCINOGENICITY
3.3.1 Inhalation Exposure
3.3.2 Intratracheal Administration
3.3.3 Intraperitoneal Administration
3.3.4 Other Administration . . .
3.3.5 Summary
3.4 DEVELOPMENTAL AND REPRODUCTIVE TOXICITY
3.5 MUTAGENICITY AND CYTOTOXITY
3.6 EFFECTS ON HUMANS
3.6.1 Cross-Sectional Studies, Clinical Evaluations,
and Case Reports
3.6.1.1 Respiratory Effects
3.6.1.2 Effects from Dermal Application
3.6.1.3 Effects from Intrapleural Instillation . . . .
3.6.1.4 Effects from Surgical Introduction
. 3.6.1.5 Effects from Intravenous Administration ..
3.6.2 Retrospective and Prospective Studies
v
vii
ix
1-1
2-1
2-1
2-2
2-3
2-4
2-10
2-10
2-10
3-1
3-1
3-5
3-6
3-6
3-7
3-9
3-10
3-10
3-10
3-12
3-13
3-13
3-13
3-20
3-22
3-22
3-22
3-23
111
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CONTENTS (continued)
3.7 QUALITATIVE AND QUANTITATIVE EVALUATION OF
TOXICOLOGICAL EFFECTS ASSOCIATED WITH EXPOSURE
TO TALC
3.7.1 Noncarcinogenic Effects
3.7.2 Carcinogenic Effects
4. REFERENCES
3-34
3-34
3-36
4-1
IV
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TABLES
Number
2-1 U.S. Production of Crude Talc and Pyrophyllite in 1984 e. 2-2
2-2 End Uses for Ground Talc and Pyrophyllite . 2-4
2-3 Airborne Concentrations of Talc Dust 2-5
3-1 Summary of Carcinogenicity Studies on Talc 3-11
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PREFACE
This health assessment on talc was prepared for the Office of Health and Environmental
Assessment to serve as a source document for EPA use. In the development of the
assessment document, the scientific literature has been inventoried, key studies have been
evaluated, and summary/conclusions have been prepared so that the chemical's toxicity and
related characteristics are qualitatively identified. Observed effect levels and other measures
of dose-response relationships are discussed, where appropriate, so that the nature of the
adverse health responses is placed in perspective with observed environmental levels. The
relevant literature for this document has been reviewed through early 1991.
Any information regarding sources, emissions, ambient air concentrations, and public
exposure has been included only to give the reader a preliminary indication of the potential
presence of this substance in the ambient air. While the available information is presented as
accurately as possible, it is acknowledged to be limited and dependent in many instances on
assumption rather than specific data. This information is not intended, and, therefore, should
not be used, as an exposure assessment by which to estimate risk to public health.
Vll
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AUTHORS, CONTRIBUTORS, AND REVIEWERS
This document was prepared by Dynamac Corporation under Contract No. 68-03-4140,
for the Environmental Criteria and Assessment Office, Research Triangle Park, NC; Dennis
J. Kotchmar, M.D., Project Manager.
The following Dynamac Corporation personnel were involyed in the preparation of this
document: Nicolas P. Hajjar, Ph.D. (Project Manager/Principal Author); Barrett N.
Fountos, Claire Kruger-McDermott, Ph.D., Patricia Turck, Mary E. Cerny, Dawn Webb,
Brion Cook, Nancy McCarroll, William McLellan, Ph.D., Christian Alexander, John Bruno,
Ph.D., Edward Flynn, Charles Rothwell, Ph.D., Janice Runge, and Sharon Segal, Ph.D.
(Authors); Karen Swetiow (Technical Editor); and Sanjivani Diwan, Ph.D., and Gloria Fine
(Information Specialists).
The following scientists reviewed an earlier draft of this document and submitted
comments:
Dr. K.P. Lee
Haskell Laboratory for
Toxicology and Industrial Medicine
E.I. du Pont de Nemours and Co.
Newark, DE
Dr. Friedrich Pott
Medical Institute for
Environmental Hygiene
Dusseldorf University
Dusseldorf, Federal Republic
of Germany
Dr. J.C. Wagner
MRC External Staff
Team on Occupational Lung
Diseases
Llandough Hospital
Penarthi Glamorgan, England
Mr. A. Morgan
United Kingdom Atomic Energy
Authority
Environmental and Medical
Sciences Division
Harwell, Oxfordshire, UK
Dr. Lorenzo Simonato
Unit of Analytical
Epidemiology
International Agency for
Research on Cancer
Lyon, France
Dr. Janet Hughes
Department of Biostatistics
and Epidemiology
Tulane Medical Center
New Orleans, LA
IX
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AUTHORS, CONTRIBUTORS, AND REVIEWERS
(continued listing of scientists who reviewed an earlier draft)
Dr. Jon Konjen
Medical and Scientific Committee
Thermal Insulation Manufacturers
Association
Stamford, CT
Dr. Gary M. Marsh
Department of Biostatistics
University of Pittsburg
Pittsburg, PA
Dr. Aparna Koppikar
U.S. Environmental Protection
Agency
Human Health Assessment Group
Washington, DC
Dr. Steven Bayard
U.S. Environmental Protection
Agency
Human Health Assessment Group
Washington, DC
Dr. Karen Milne
U.S. Environmental Protection
Agency
Office of Toxic Substances
Washington, DC
Dr. William J. Nicholson
Department of Community
Medicine
Mount Sinai School of
Medicine
New York, NY
Dr. Sheila Rosenthal
U.S. Environmental Protection
Agency
Human Health Assessment Group
Washington, DC
Mr. John Cherrie
Institute of Occupational
Medicine
Edinburgh, Scotland
Dr. William H. Maxwell
U.S. Environmental Protection
Agency
Office of Air Quality
Planning and Standards
Research Triangle Park, NC
Dr. David Coffin .
U.S. Environmental Protection
Agency
Health Effects Research
Laboratory
Research Triangle Park, NC
Dr. Vanessa T. Vu
U.S. Environmental Protection
Agency
Health and Environmental
Review Division
Office of Toxic Substances
Washington, DC
Dr. William Pepelko
U.S. Environmental Protection
Agency
Human Health Assessment Group
Washington, DC
Harlal Choudhury
U.S. Environmental Protection
Agency
Environmental Criteria and Assessment
Office-Cincinnati
Cincinnati, OH
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AUTHORS, CONTRIBUTORS, AND REVIEWERS
(continued listing of scientists who reviewed an earlier draft)
Dr. Bob Sonawane
U.S. Environmental Protection
Agency
Human Health Assessment Group
Washington, DC
Richard Walentowicz
U.S. Environmental Protection
Agency
Exposure Assessment Group
Washington, DC
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1. SUMMARY
Concern surrounding the adverse health effects of asbestos on the general population has
stimulated interest in the potential health effects of other natural and man-made fibers. The
health effects of talc, a nonfibrous silicate mineral with multiple consumer uses, are discussed
in this document. Additional concern over talc exposure is associated with the possible
presence of asbestos (i.e., tremolite) and/or crystalline silica as a contaminant in some
deposits of this mineral.
Talc (CAS No. 14807-96-6) is made up of pulverized, foliated hydrous magnesium
silicates from minerals with low crystalline silica content. Talc is a layered silicate, and both
talc crystals and fragments are commonly platey and nonfibrous. Its color can be white,
yellow, green, or gray depending on the number of impurities present. The chemical
composition of talc is 3MgO»4SiO2»H2O. Minerals commonly found in commercial talc
include MgO, TiO2, calcium silicate, iron oxide, carbonates, and aluminates. Talc is
insoluble in water and exhibits varying resistance to acids, alkalies, and temperature.
Approximately 1.25 million short tons (1.13 million metric tons) of talc were produced in the
United States in 1989. In 1990, talc production increased slightly, and apparent consumption
increased 7%. The largest end uses of talc are in ceramics and paint; only 5% is used in
cosmetics.
Estimates of environmental release of talc are not available. The National Occupational
Hazard. Survey (NOHS, 1976) conducted by the National Institute for Occupational Safety
and Health reports that 1,536,754 workers were potentially exposed to talc in 1972-74,
whereas the Institute's National Occupational Exposure Survey (NOES, 1984) estimated that
18,872 workers, including 5,244 females, were potentially exposed to talc in the workplace
in 1980.
Occupational exposure to talc dust has been measured at various mining and milling
facilities. The talc deposits have been found to differ in mineral composition. Average dust
exposure at a talc plant in Georgia prior to 1970 was reported to be 32 to 855 millions of
particles per cubic foot (mppcf) (mine) and 17 to 1,672 mppcf (mill). The talc dust was
reported to contain dolomite, tremolite, and little or no free silica. Talc dust from mining
1-1
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and milling operations in St. -Lawrence County, NY, was reported to contain tremolite and •
anthophyllite. The exposures ranged from 5 to 19 mppcf (mine) and from 7 to 36 mppcf
(mill) after 1945. Airborne fiber levels (>5 #m in length, 65% anthophyllite and 7%
tremolite) in the mine and mill gave mean exposures of 4.5 and 5.0 fibers >5 /an/cm3,
respectively. Mean concentrations of respirable dust in samples from three Vermont talc
fo ' ' * ' ' *
mines and mills ranged from 0.5 to 5.1 mg/m3 (mines) to 0.5 to 2.9 mg/m3 (mills).
Analysis of the dust showed talc, magnesite, and free silica; tremolite was reported but not
documented. Average talc dust exposure in Montana, Texas, and North Carolina was
I ij
reported in 1979 as 1.2, 2.6, and 0.3 mg/m , respectively. No fibers were found in samples
of Montana talc, fibrous tremolite and antigorite were reported in Texas talcs, and talcs from
North Carolina contained acicular cleavage fragments with particle length to diameter ratios
as high as 100:1, with some <0.1 /tm in diameter. Talc exposures in mines and mills in
Italy were reported after 1965 to be 0.8 to 3 mppcf and 2 to 8 mppcf, respectively; analysis
. ^ *
showed tremolite and silica fibers. Total dust exposure in a secondary-industry such as
rubber production was reported in 1972 as 5.4 to 199 mg/m3, with fiber exposures ranging
*3 f
from 4.7 to 19.2 fibers >5 /an/cm (fibers reported as silica).
The American Conference of Governmental Industrial Hygienists has recommended an
8-h threshold limit value-time weighted average (TLV-TWA) of 2 mg/m3 respirable dust for
talc containing no asbestos fibers, whereas the Occupational Safety and Health Administration
has recommended a total dust TWA of 201 mppcf.
Exposure to cosmetic grade talc, as used hi cosmetic and health care products, is
infrequent and of short duration. A simulated study, however, indicated that talc exposure
for an infant and mother during a 10-s dusting was 0.243 mppcf, which decreased to
0.124 mppcf during the next 65 s. The average respirable dust concentration was reported to
be 0.10 mg/min/m3. In a study of routine application of talcum powder, the calculated TWA
exposure separately for infants and adults indicated levels of 0.095 mg/min/m3 and
o
1.729 mg/min/m , respectively.
Estimates of airborne concentrations in ambient air are not available. Talc is not
expected to undergo chemical transformation when released into the environment. The
following analytical procedures are used to identify and quantitate talc: collection in an
impinger and counting by optical microscopy (used prior to 1970), phase-contrast optical
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microscopy, analytical electron microscppy and selected-area electron diffraction, and X-ray
diffraction.
Following single inhalation exposures, talc was retained in the lungs of exposed
hamsters. Talc was cleared slowly because it has a biological half-life of 7 to 10 days. The
talc content decreased to the detection levels found in control animals 4 mo after exposure.
Pulmonary deposition of talc following repeated exposures was dose dependent. Pulmonary
clearan.ce was facilitated by mucociliary activity, and talc was eliminated in the feces via the
gastrointestinal tract. Little, if any, talc was absorbed from the gastrointestinal tract of rats,
guinea pigs, mice, and hamsters following oral intubation. Most of the material was
eliminated in the feces within one to two days after dosing. No measurable transport of talc
was reported following intravaginal instillation into cynomolgus monkeys. In rats, however,
intrauterine or intravaginal instillation resulted in migration of talc particles into the ovaries.
No information was available on the acute toxicity of talc, although intratracheal
instillation of talc in hamsters resulted in pulmonary toxicity as shown by biochemical and
cellular changes. A study of talc-induced synovia! inflammation after injection (0.25 mL)
showed that the response in white rabbits was a local increase in temperature, hyperemia, and
venous congestion that facilitated anabolic cellular activity and increased production of
cartilage. Subchronic inhalation exposure (3 to 12 mo) in rats resulted in pulmonary fibrosis
that increased in severity as the exposure period increased. Intratracheal administration of
talc resulted in a typical granulomatous lesion consisting of dust-laden multinucleated foreign
body giant cells, as well as some fibrosis with collagen formation in several animal species.
In addition to the development of granulomas, intratracheal instillation of talc resulted in
moderate tissue destruction in hamsters, and intraperitoneal administration has been shown to
cause abdominal adhesions in rats and swine. Chronic exposure by the intratracheal route in
hamsters resulted in dust-laden macrophage aggregation with the accumulation of interstitial
cells and histiocytes with some accumulation of proteinaceous exudate within the alveoli. No
fibrosis or granulomas were observed. Talc alone caused moderate tissue destruction, slight
metaplasia in the tracheobronchial region, and moderate hyperplasia in the alveolar region.
Intraperitoneal injection of talc in another study resulted in foreign-body granulomas with
adhesions in rats after 12 weeks. The development of these granulomas has also been
reported in swine. Talc implanted surgically into the peritoneal cavity of rats produced
1-3
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extensive granulomatous peritonitis within two weeks that persisted until Week 13. Nodules
appeared and remained 52 weeks after exposure.
Limited data suggest that talc is not carcinogenic following inhalation exposure or
intratracheal instillation in rats and hamsters. Similarly, no evidence of carcinogenicity was
noted following intrapleural, intraperitoneal, or oral administration in rats. The results of one
study suggest that talc may act as a cocarcinogen following intratracheal administration in
combination with benzo[#]pyrene once weekly for life, but the exact mechanism is not
known.
i
Limited data suggest that talc does not induce gene mutations in Salmonella or
,|
Saccharomyces at 200 mg/cm , chromosomal aberrations in rat bone marrow cells, or
dominant lethal mutations in the germinal cells of male rats; however, no details of these
studies were presented. Natural or acid-purified talc (particle size 0.2 to 20 jitm) exhibits
weak cytotoxicity in rat peritoneal and alveolar macrophages. Talc particles within the
respirable range were not cytotoxic to A549 alveolar human tumor cells or V79-4 Chinese
hamster lung cells.
i
Teratogenicity and reproductive effects studies were not available.
Several cross-sectional morbidity studies of miners and millers from the New York,
Montana, Texas, North Carolina, and Vermont mines indicate increased respiratory
symptoms, higher prevalence of pleura! thickening or calcification and pneumoconiosis, and
decreased pulmonary function in workers exposed to talc containing various amounts of
tremolite, anthophyllite, or silica fibers. These effects increased with age of workers,
intensity of smoking, and duration of exposure. However, exposure to talc free of
asbestiform fibers was associated with less pronounced effects. Increased incidences of
ovarian cancer are reported in a case-control study of 215 white females regularly using talc
as a dusting powder on the perineum or on sanitary napkins, or both, when compared with
controls. However, the purity of talc used was unknown. Additionally, other studies show
neither a strong nor a consistent association between genital talcum powder exposure and
ovarian cancer. Similar to the findings described above, several mortality studies indicate an
excess of respiratory cancer and nonmalignant respiratory disease (NMRD) among mining
and milling workers. Also, the talc was contaminated with asbestos, silicates, carbonates, or
radon. These studies had important limitations such as no smoking data and lack of
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dose-response data. Consequently, a direct relationship with talc exposure alone cannot be
established. One study that investigated the effects of worker exposure to very pure talc
showed no increase in mortality from lung cancer. An increase was seen in NMRD;
however, this was attributed to silica exposure.
The above findings indicate that the evidence for carcinogenicity of talc depends on the
presence of other contaminants, such as asbestos or crystalline silica. For talc without
asbestos contamination, the International Agency for Research on Cancer (IARC) has
concluded that the available epidemiological and animal toxicity data are inadequate to
demonstrate or refute the potential for carcinogenicity. The presence of asbestos in talc
would cause the talc to be viewed as a human carcinogen. In the case of crystalline silica,
the IARC views the human evidence as limited and the animal evidence as sufficient, which
classifies crystalline silica as a probable human carcinogen.
The U.S. EPA has not previously evaluated the data for talc or crystalline silica and has
not done so in this assessment. The IARC views on weight-of-evidence are useful as an
interim measure in considering the hazard perspective. The U.S. EPA and the IARC view
asbestos as a human carcinogen. The quantitative question arises as to how much crystalline
silica or asbestos contamination makes a difference in terms of potential risk, and this dose-
response issue has not been included in this assessment.
1-5
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2. BACKGROUND INFORMATION
2.1 PHYSICAL AND CHEMICAL PROPERTIES
Talc (CAS No. 14807-96-6) is composed of pulverized, natural, foliated hydrous
magnesium silicates originating from nonasbestiform minerals that are low in crystalline SiO2
content (Davies et al., 1983). It commonly exists as thin, tabular crystals up to 1 cm wide.
The crystals can be pale to dark green or greenish-gray, white, silvery-white, gray, or
translucent. Talc has a density of 2.58 to 2.83 g/cm3 (Roberts et al., 1974), has perfect
cleavage, is insoluble in water, and depending upon its purity, exhibits varying resistance to
acids, alkalies, and heat. Synonyms for talc include soapstone, steatite, and talcum
(International Agency for Research on Cancer, 1987; General Electric, 1978).
The structure of talc is characterized by hexagonal sheet arrangements of SiO4
tetrahydral groups linked in a common plane. Two such sheets are oriented so that the
unshared apical oxygen atoms face each other. The sheets are bonded by magnesium atoms,
which are coordinated by two oxygen and one hydroxyl group from each sheet. Talc crystals
are made up of stacks of these double-sheet units held together by Van der Waal's forces.
Platey crystals of talc slide past one another to produce the smoothness associated with talc
(Davies et al., 1983). The chemical composition of talc is 3MgO4SiO2«H2O (Johnson,
1991). When expressed in the standard oxide form, the ideal chemical composition is
31.7% MgO, 63.5% SiO2, and 4.8% H2O (Pooley and Rowlands, 1977).
Because talc is. formed by the alteration or metamorphosis of rocks, it is found
associated with many types of minerals. Minerals commonly found in commercial talc
include MgO, TiO2, calcium silicate, iron oxide (a color determinant), carbonates,
pyrophyllite, and aluminates. Tremolite and/or anthophyllite asbestos are also found as
contaminants of some talc deposits (National Research Council, 1984; Lockey, 1981; Rohl
and Langer, 1974).
The mineral composition of talc mined in Montana, for example, is essentially talc with
minor chlorite, dolomite, calcite, and quartz. In Texas, depending on the mining district,
associated minerals include quartz, magnetite, chlorite, tremolite, and anthophyllite. In
Vermont, magnesite, serpentine, chloride, and sulfides are associated with talc rock (Johnson,
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1991). The mineral compositions of various talcs from the United States and oilier parts of
i
the world have been listed by the International Agency for Research on Cancer (1987).
2.2 PRODUCTION AND INDUSTRIAL USES
i
Talc is derived by the alteration of mineral rocks, which sometimes include the
amphibole and serpentine groups of asbestos, after their exposure to specific temperatures,
pressures, and circulating liquid solutions or by the thermal metamorphism of silicon
dolomites (Hildick-Smith, 1976). The abundance of talc and the facility with which it can be
mined, combined with its many desirable functional properties, have made it an important
industrial mineral. Large-scale U.S. production of ground talc products began about 1880.
Talc is mined using hand tools, drilling, or blasting methods (Clifton, 1985).
Practices for refining talc ores vary greatly. Some operations initially sort the talc by
hand according to color and physical characteristics (Clarke, 1979). The latest technology,
however, employs flotation separation. Flotation techniques are especially prevalent in North
America, Norway, and Finland (Roe and Olson, 1983; Sinha, 1982). The amount of crude
talc and pyrophyllite (AlSi2O5(OH)) (a mineral that occurs commonly in talc deposits)
produced in the United States in 1984 is shown in Table 2-1.
TABLE 2-1. U.S. PRODUCTION OF CRUDE TALC AND
PYROPHYLLITE IN 1984 (thousand short tons)
State
California
Georgia (talc)
North Carolina
Oregon (talc)
Texas (talc)
Otherb
I Quantity
74
15
87
a
283
711
1 Total 1,170
"Less than one-half unit.
"Includes Arkansas, Montana, New York, Vermont, Virginia, and Washington.
Source: Clifton (1985).
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Recently, the U.S. Bureau of Mines reported that U.S. production of talc in 1989 was
1.25 million short tons (1.13 million metric tons). Actual sales of talc totaled 1.057 million
short tons (0.96 million metric tons) in 1987 and 1.070 million short tons (0.97 million
metric tons) in 1986 (Johnson, 1991). Approximately 23 talc-producing mines in 10 states
were in operation in 1990; Montana, Texas, Vermont, and New York collectively produced
88% of the domestic yearly total. The largest domestic producers of talc are as follows:
Cyprus Industrial Minerals Company; Dal Tile (Texas Talc Company); Gouverneur Talc
Company; Pfizer, Inc., Minerals, Pigments, and Metals Division; Vermont Talc Company;
and Windsor Minerals, Inc. (Johnson, 1991).
In 1990, talc production increased slightly and apparent consumption increased by 7%.
Canada, Japan, and Mexico were the major importers of talc produced in the United States,
whereas Australia and Canada supplied approximately 96% of the imported talc (Johnson,
1991).
Talc is one of the most versatile inorganic substances available to industries (Roe and
Olson, 1983). Technical products of talc are dependent upon the mineral character of the
refined ore and are sold in a multitude of grades, which have functional or physical
characteristics especially suited for certain applications (International Agency for Research on
Cancer, 1987). The end uses for ground talc and pyrophyllite are shown in Table 2-2. The
largest portion of ground talc is used in ceramics (37%), followed by paint (19%), paper
(10%), roofing (9%), other (9%), plastics (7%), cosmetics (5%), rubber (3%), and
insecticides (1%) (Clifton, 1985).
2.3 SOURCES OF EMISSIONS
Talc-milling processes do not usually alter the mineral composition of the talc mixture,
but rather produce a talc with different physical properties dependent on particle size.
Emissions of talc are associated with mining, crushing, separating, bagging, loading, and
end-use facilities. Because industrial talc is a mixture of various associated minerals,
occupational exposure involves exposure to a mixture of mineral dusts (International Agency
for Research on Cancer, 1987). Fiber intergrowths are often such that, even extensive
beneficiation may not yield a pure product. Thus, where fine-grained intergrowths of talc
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TABLE 2-2. END USES FOR GROUND TALC AND PYROPHYLLITE
(thousand short tons)
Use
Ceramics
Cosmetics11
Insecticides
Paint
Paper
Plastics
Refractories
Roofing
Rubber
Other0
Total
Talc !
358
44
8
189
100
67
4
86
29
85 ;
970
Phyrophyllite
29
b
14
1
,
1
21
6
11
83
Quantity
387
44
22
190
100
68
25
92
29
96
1,053
'Incomplete data; some cosmetic talc is known to be included with "other."
kNo data reported.
Includes art sculpture, asphalt filler and coatings, crayons, floor tile, foundry facings, rice polishing, stucco,
and uses not specified. ;
Source: Clifton (1985).
and tremolite occur, emissions of talc will probably contain residual tremolite fibers (Rohl
et al., 1976).
2.4 EXPOSURE
The greatest human exposure to talc dust is when it is used industrially or while it is
mined or milled. Occupational, consumer, and industrial exposure levels are given in
Table 2-3. Dreessen (1933) measured talc; exposure for workers involved in mining and
milling processes in a talc plant in Georgia. Average dust exposures for miners using
jackhammer drills were 1,440 million particles per cubic foot (mppcf) and those; for millers
were 52 mppcf. The talc was reported to contain 45% tremolite and 45% talc, with little or
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TABLE 2-3. AIRBORNE CONCENTRATIONS OF TALC DUST
Concentrations (mg/m3)
Gross
Respirable
Reference
Range of Range of Range of
Averages Concentrations Averages
Range of Type of
Concentrations Exposure
Boundy et al. (1979);
Wegman et al. (1982)
Dement and Zumwalde
(1979); Dement et al.
(1980); Selevan et al.
(1979a)
Dreessen and Dalla Valle
(1935); Dreessen (1933)
4.3-5.0
0.2-29.1
17-1,672"
0.5-5.1
0.86
Occupational
0.23-4.64 Occupational
Occupational
Fine et al. (1976)
Gamble et al. (1982); Greife
(1980)
Hildick-Smith (1976)
Hogue and Mallette (1949)
Kleinfeld et al. (1974, 1973,
1967, 1955); Messite et al.
(1959)
Rubino et al. (1976)
Russell et al. (1979)
Dement and Shuler (1972)
0,47-3.55
0.14-1.56
0.1752"
15-50"
69-l,227blCAe
12-798f
4.493
0.8-8h
0.106-3.52"
5.4-199
0.28-5.73 Industrial
0.07-2.54 Occupational
Consumer
Occupational
Occupational
Consumer
0.9-7.8 Industrial
"In mppcf.
bln mppcf; pre-1945 (for both mining and milling operations).
In mppcf; 1946-1965 (for both mining and milling operations).
dln mppcf; 1966-1969 (for both raining and milling operations).
eln mppcf; 1972 (for both mining and milling operations).
fo mppcf; to 1955.
EIn mppcf; 1956-1965.
"In mppcf; 1966-1972.
no free silica. Average dust concentrations in the mine were reported to range from 32 to
855 mppcf (six samples), whereas average mill exposures ranged from 17 to 1,672 mppcf
(14 samples). The dust was reported to contain 70% talc, 20 to 30% dolomite, 10%
2-5
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txemoKte, and occasional fragments of free silica. The dust morphology was described as
"bladed crystals." Highest exposures were in the bagging operation (Dreessen and Dalla
Valle, 1935). I
Occupational exposures to talc dust in mining and milling operations in St. Lawrence
County, NY, have been studied. Talc deposits in the state have been found to differ
significantly in mineral composition. Siegal et al. (1943) reported that talc in that area
contained tremolite, anthophyllite, and only traces of quartz, and described the particle
morphology as straight, needlelike fibers with a maximum length of 15 jam. Kleinfeld et al.
(1973) also reported the major fibrous components of these talcs to be tremolite and
anthophyllite. The mineral composition of other bulk samples of talc in the area revealed that
the samples contained 14 to 48% talc, 37 to 59% tremolite (fibrous and nonfibrous), 4.5 to
15% anthophyllite (fibrous and nonfibrous)1, and 0.25 to 26% free silica (Dement and
Zumwalde, 1979; Dement etal., 1980). ;
Kleinfeld et al. (1974) studied fibrous talc exposures in a mining and milling operation
in St. Lawrence County, NY, during the period from 1945 to 1972. Prior to dust control
measures such as wet drilling, average exposures to mine dust ranged from 120 to
[
818 mppcf; after 1945, these were reduced to 5 to 19 mppcf. Exposures in mills prior to
i
1945 ranged from 69 to 278 mppcf; average exposures in 1972 ranged from 7 to 36 mppcf.
In 1972, optical fiber counts revealed that exposures in mines were low (2 to 3 fibers
>5 /(m/cm3), whereas exposures in mills were severalfold higher, ranging from 25 to
62 fibers/cm3 (Kleinfeld et al., 1974).
Time-weighted average exposures to respirable dust ranged from 0.23 to 1.29 mg/m3
and from 0.25 to 2.95 mg/m3 for mining and milling operations, respectively, in upper
New York State (Dement et al., 1980). Analysis of the airborne samples revealed that 65%
> i
of the fibers hi the talc dust >5 /fm were anthophyllite fibers and 7% were tremolite fibers.
Airborne fiber levels gave mean exposures in the mine and mill of 4.5 and 5.0 fibers
i
>5 /im/cm3, respectively, with peak values as high as 29.1 fibers/cm3 in the mill (Dement
and Zumwalde, 1979; Dement et al., 1980).
Concentrations of respirable dust in mass samples from three Vermont talc mines and
mills were surveyed in 1975 and 1976. Geometric mean exposures to respirable dust ranged
from 0.5 to 5.1 mg/m3 in the mines and fipm 0.5 to 2.9 mg/m3 in the mills; however,
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exposures in the mills were generally higher than those in the mines. Optical fiber counts of
as much as 60 fibers/cm3 were reported. Subsequent analyses of these samples by scanning
electron microscopy demonstrated rolled talc and elongated talc particles. X-ray diffraction
analyses showed that talc and magnesite were the major (20 to 100%) mineral components.
Trace amounts of free silica were found in 15% of the samples (Boundy et al., 1979;
Wegman et al., 1982). One closed mine was reported to contain tremolite microinclusions,
but its fibrosity was not documented (Selevan et al., 1979a,b).
The results of a cross-sectional study of occupational exposures in U.S. talc mines and
mills were reported by Gamble et al. (1982). Work histories and personal respirable dust
samples were compiled for 299 miners ami millers in Montana, Texas, and North Carolina.
The average time worked was 7, 6, and 10 years; and the average talc dust exposure was
1.2, 2.6, and 0.3 mg/m3 in Montana, Texas, and North Carolina, respectively. No fiber was
found in any sample of Montana talc; fibrous tremolite and antigorite were reported in Texas
talcs (0.5 to 3.0 /mi in diameter, 4 to 30 /mi in length); talcs from North Carolina contained
acicular cleavage fragments with particle length to diameter ratios as high as 100:1, with
some <0.1 /am in diameter (Greife, 1980; Gamble et al., 1982).
Analysis of 362 personal samples of respirable dust collected over a full shift by the
Mine Safety and Health Administration from talc mines and mills in the United States showed
the median dust exposure to be 1.20 mg/m3; 90% of all exposures were <2.78 mg/m3
(National Institute for Occupational Safety and Health, 1979).
Talc exposure in the Germanasca and Chisone Valleys (Piedmont), Italy, were reported
by Rubino et al. (1976). • Prior to 1955, talc dust exposures were approximately 442 mppcf
(range, 151 to 798 mppcf) in the mines and 23 mppcf (range, 19 to 35 mppcf) in the mills.
The free silica content was 6% (range, 1 to 14%) in the mines and 1% (range, < 1 to 2%) in
the mills. Between 1956 and 1965, the average exposures in the mines and mills were
21 mppcf (range, 4 to 49 mppcf) and 13 mppcf (range, 8 to 23 mppcf), respectively. As a
result of dust control measures, the average exposures dropped to 1.05 mppcf (range, 0.8 to
3 mppcf) and 5 mppcf (range, 2 to 8 mppcf) in the mines and mills, respectively, after 1965.
Sample analyses of these talcs showed that small amounts of tremolite and silica fibers were
present. Fiber counts >5 /mi in length were 0.01 fibers/cm3 for both the mines and mills.
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Limited information was available about exposures in secondary industries where talc
was used or processed further. Dement and Shuler (1972) collected personal air samples in a
rubber band production plant, where housekeeping, ventilation, and work practices were poor
and in which talc was used as an antistick agent. Time-weighted average respirable dust
concentrations were 2.5 to 7.8 mg/m3 (average, 4.8 mg/m3) for extruders, 5.3 to 6.1 mg/m3
for vulcanizers, and 0.9 to 1.3 mg/m3 for cutters. Total dust exposures were found to range
from 5.4 to 199 mg/m3. The talc was reported to contain 2 to 3% silica fibers. Fiber
exposures ranged from 4.7 to 19.2 fibers >5 /im/cm3.
Sable et al. (1990) characterized airborne dust in a soft-paper mill. Elongated
fragments of talc were identified on transmission electron microscopy (TEM) micrography,
structurally by electron diffraction, and compositionally by energy-dispersive X-ray
i
fluorescence spectroscopy (EDX) analysis.
Fine et al. (1976) measured respirable dust concentrations in two rubber-manufacturing
plants where Vermont talc was used as an antistick agent. Eighteen of 21 samples analyzed
for free silica contained less than 1 % by weight. In 12 samples analyzed for fibers, all
concentrations were less than 2 fibers >5 /an/cm3.
Hogue and Mallette (1949) studied two groups of specially selected workers for an
assessment of talc dust exposure in two rubber plants utilizing Vermont talc. Only those
workers who were exposed to the longest and heaviest concentration of dust were used. The
investigators found that tube machine operators had an average exposure of 20 mppcf; tube
"bookers," 35 mppcf; tube cure men, 15 mppcf; and "line rollers," 50 mppcf. The analyzed
talc was free from fibrous impurities.
The National Institute for Occupational Safety and Health conducted two workplace
exposure surveys. The National Occupational Hazard Survey (NOHS) conducted from 1972
to 1974 estimated the number of workers potentially exposed to chemical agents in the
workplace in 1970 (NOHS, 1976). These estimates were derived from observations of the
actual use of the agent, the use of trade nahie products known to contain the agent, and the
use of generic products suspected of containing the agent. The NOHS estimated that
1,536,754 people were exposed to talc, with 14% exposed to the actual product, 31%
exposed to trade name products containing! talc, and 56% exposed to generic products
suspected of containing talc.
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The National Occupational Exposure Survey (NOES), conducted from 1980 to 1983,
estimated the number of workers potentially exposed to chemical agents in the workplace in
1980 (NOES, 1984). Unlike NOHS, the NOES estimates were based only on observations
by the surveyor of the actual use of the agent. NOES estimated that 18,872 workers,
including 5,244 females, were potentially exposed to talc.
The American Conference of Governmental Industrial Hygienists has recommended an
8-h threshold limit value-time weighted average (TLV-TWA) of 2 mg/m3 respirable dust for
talc containing no asbestos fibers (American Conference of Governmental Industrial
Hygienists, 1991), whereas the Occupational Safety and Health Administration has
recommended a total dust TWA of 20 mppcf of air (International Agency for Research on
Cancer, 1987).
Exposure to cosmetic grade talc as used in cosmetic and health care products is
infrequent and of short duration (Hildick-Smith, 1976). However, due to the reported cases
of accidental aspiration of excessive amounts of talc by infants and children, a simulated
study was conducted to determine the amount of talc to which an infant and mother are
exposed. Analysis of the data indicated that during a 10-s dusting period, the total median
dust concentration is 0.243 mppcf, which decreases to an average of 0.124 mppcf during the
65 s required for the dust to settle. An estimated median exposure per application was
estimated at 0.1752 mppcf. A further study showed that the average respirable dust
<2
concentration was 0.10 mg/min/nr when dust samples were obtained during actual use of talc
by mothers (Hildick-Smith, 1976).
Russell et al. (1979) later conducted a study on the routine application of talcum powder
to infants and adults to determine the mass concentrations of potentially respirable particles.
The tests were conducted on 44 adults exposed to talc over the whole body area and on
48 infants exposed to talc in the diaper area only. The total exposure time, the amount of
powder used, and the average airborne talc concentration in the nasal region were measured.
For infant exposures, the TWA (± the standard deviation) was 0.095 ± 0.039 mg/min/m3.
For adult exposures, the TWA was 1.729 mg/min/m3. For a more accurate estimate of
exposure, .these values were converted to weekly exposure measurements. The average
values obtained were 0.055 and 0.20 nig/h/m3 for infants and adults, respectively.
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2.5 AMBIENT LEVELS
No information was found in the available literature concerning ambient levels of talc.
2.6 ENVIRONMENTAL FATE
Talc is not expected to undergo chemical transformation when released into the
environment. Its refractory nature precludes the effects of melting/boiling point, solubility,
vapor pressure, octanol/water partition coefficient, etc., on its transport. Terrestrial and
fluvial transport processes affecting talc are not well characterized.
2.7 ANALYTICAL METHODS
Because talc is frequently contaminated with a number of other mineral phases, some
known to be biologically active, an analytical protocol is often required that can distinguish
among these phases. As with most industrial exposures, nearly all measurements of talc
made prior to approximately 1970 were done by collecting particles in an impiiiger and
counting mem by optical microscopy (Dreessen, 1933; Dreessen and Dalla Valle, 1935;
Siegal etal., 1943; Kleinfeld et al., 1955j 1967, 1973, 1974; Messite et al., 1959; Rubino
et al., 1976; Hogue and Mallette, 1949). More recent studies, however, have used
gravimetric analysis followed by optical and/or electron microscopy fiber counts (Dement and
Zumwalde, 1979; Dement et al., 1980; Boundy et al., 1979; Greife, 1980; Gamble et al.,
1982; Dement and Shuler, 1972; Fine et al., 1976).
Phase contrast optical microscopy is a conventional technique for the identification of
minerals. A microscope equipped with bright-field illumination and polarized light optics
may be used to analyze talc powders (Hamer et al., 1976; Rohl and Langer, 1979). There
are, however, limitations to this technique( such as a restrictive resolution allowing large
numbers of small fibers to go undetected and indices of refraction that are difficult to
measure (Rohl et al., 1976). Analytical electron microscopy and selected-area electron
diffraction can be used to obtain morphological, structural, and chemical information on
single particles of talc and associated; minerals (Rohl et al., 1976).
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Quantitative mineralogical analyses by X-ray diffraction of bulk samples are sensitive to
1 to 2% talc (Pooley and Rowlands, 1977). The application of X-ray diffraction analysis,
both continuous and step-scan modes, for quantitative determination of contaminating
minerals in talc has been described. This includes the selection of talc and the reference
materials, the preparation of standard dilutions of fibers in talc to ensure sensitivity and
reproducibility, the selection of characteristic X-ray reflections to be scanned, and
instrumental technique. Tremolite, chrysotile, and anthophyllite impurities in talc can be
determined at levels as low as 0 to 1.2% (Rohl and Langer, 1974; Rohl et al., 1976).
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3. TOXICOLOGY
3.1 RETENTION AND BIODISPOSITION
This section provides a review of the information on retention of talc following
inhalation, oral, and vaginal administration. In addition, data on the biodisposition and
clearance of talc from the body are presented.
The pulmonary deposition, translocation, and clearance of inhaled talc (Johnson's Baby
Powder®) in Syrian Golden hamsters were studied by Wehner et al. (1977a,b). A group of
44 10-week-old female hamsters was exposed by nose only to neutron-activated talc aerosols
for 2 h. The mean aerosol concentrations during the two sampling periods (from 15 to
30 min and from 60 to 90 min during the 2-h exposure period) were 40 and 75 mg/m3.
After exposure, the urine and feces were collected. Groups of four animals were killed at
various times, and the lungs, liver, kidneys, ovaries, and skinned carcass were collected and
radioassayed by X-ray spectrometry. The counts were compared with those obtained from
nine unexposed control hamsters. Considerable variations in pulmonary deposition among
animals killed at the same period were attributable to variations in aerosol concentration at the
different tier levels for animal exposure and to differences in individual breathing patterns. It
was estimated that animals placed on tier levels 2 to 4 of the exposure chamber inhaled an
average of 360 /ig talc, whereas those on tier 1 inhaled an average of 570 /ig- Nonetheless,
the data indicated high talc levels in lung during the first 4 days after exposure, with mean
total measurements (+ standard deviation) of 33.1 + 31 /ig and 21.0 + 15.3 /ig at 15 min
and 4 days after exposure, respectively. Thereafter, talc content in the lungs dropped
gradually; mean values (3.7 + 1.4 /ig) were similar to those found in controls
(2.3 ± 0.4 /ig) after 4 mo. The "biological" half-life of the talc based on measurements of
radioactivity deposited in the lung was reported to be 7 to 10 days, and alveolar clearance
was complete within approximately 4 mo after exposure.
No significant differences were observed among mean radioactivity levels found in the
liver, kidneys, and ovaries of exposed and control animals (Wehner et al., 1977b).
Radioactive residues in carcasses were highest 4 h after exposure (455 + 338 /ig) and
decreased gradually to control levels (about 3.5 /ig) by Day 8. This activity was attributed to
3-1
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talc deposited on or about the nose and nares during exposure, as well as to talc passing
through the gastrointestinal tract after mucociliary clearance. Fecal samples contained
relatively high quantities of talc. The mean mass of talc excreted by 21 h after exposure was
106 ± 53 /ig; by Day 4, this value had increased by 3.5-fold (350 ± 292 /ig). The presence
!
of talc in the feces was attributed to mucociliary clearance from the lungs, probably together
with a fraction from licking the nose, lips; and so forth. Low levels of radioactivity found in.
the urine were attributed to 60Co leached from the lungs or absorbed in the gastrointestinal
tract.
i
Wehner et al. (1977c) exposed groups of 50 male and 50 female 4-week-old Syrian
Golden hamsters to talc aerosol (baby powder) for 3, 30, or 150 min/day, 5 days/week for
30 days. In a second study, 50 hamsters/sex (7-weeks-old) were exposed for 30 or
150 min/day either until they died naturally or, for a maximum of 300 days. Following
exposures, the animals were observed for the remainder of their lifespans. The mean
concentration of the respirable aerosol fraction was approximately 8 mg/m3, and the mass
mean aerodynamic diameter (MMAD) was 6 /tm. The estimated alveolar deposition-per-
exposure ranges were as follows: 0.04 to 0.06, 0.4 to 0.6, and 2 to 3 /ig talc for the 3-, 30-,
and 150-min exposures, respectively, in the 30-day study, and 0.86 to 1.15 and 4.3 to 5.8 /ig
talc for the 30- and 150-min exposures, respectively, in the 300-day study (Wehner et al.,
1977b).
Hanson et al. (1985) developed a method to determine the lung burden of talc in rats
and mice after repeated inhalation exposure to talc aerosols. This method was based on the
analysis of acid-insoluble magnesium (Mg), content in the lungs by atomic absorption
spectrQmetry. Magnesium was selected because it accounts for 19.2% of the composition of
talc, and most of the endogenous Mg present in the lung can be removed by dilute acids.
Whole-body exposures of 36 Fischer 344 (F-344) rats (sexes combined) and 27 B6C3FJ mice
(sexes combined) were performed 6 h/day, 5 days/week for a total of 20 exposures. The
mean lung burdens in rats were 77, 187, and 806 /ig talc/g lung tissue at exposure levels of
2.3, 4.3, and 17 mg talc/m3, respectively.' In mice, mean lung burdens were 114, 325, and
1,150 /ig talc/g lung tissue at exposure levels of 2.2, 6.3, and 20.6 mg talc/m3, respectively.
The higher contents of talc in mouse lungs; as compared to rats, were related to a difference
in initial deposition probably due to a greater minute volume respiration in mice.
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Pickrell et al. (1989) studied the relationship between the inhalation exposure
concentration of talc and the resulting lung burdens and histologic lesions using groups of
20 F-344/control rats and 20 B6C3F! mice (10 male and 10 female) exposed to one of three
concentrations of asbestos-free talc for 6 h/day, 5 days/week for 4 weeks. The mean
exposure concentrations for rats were 0, 2.3, 4.3, and 17 mg talc/m3. Lung burdens in rats
averaged 0, 0.07, 0.17, and 0.72 mg talc/g lung after the 20-day inhalation exposure; thus,
the amount retained in the lung per unit of exposure concentration increased with increasing
concentration. Similar results were obtained for mice. Lung burdens for this study were
used to project lung burdens that would result from longer exposure of rodents and humans.
A model simulating chronic talc inhalation exposure of rats and mice predicted lung burdens
of 2 to 3 mg talc/g lung (wet wt.) if the animals were exposed to 17 mg talc/m3 for 2 years,
and deposition and clearance of talc were unchanged by continued exposure. The model
projected lung burdens that were significantly smaller than lung burdens that resulted from
experimental exposures to talc of 10.8 mg/m3 (Wagner et al., 1977). It is possible that the
model did not account for changes in alveolar lung clearance which exhibit progressive
inhibition starting at lung burdens >1 mg/gm lung. Humans exposed to aerosols of respirable
talc are projected to accumulate much higher lung burdens than would occur in rodents
exposed to the same aerosol, because humans have a higher estimated deposition fraction and
slower estimated clearance of the deposited talc dust. Equilibrium lung burdens of >2 mg
talc/g lung were predicted for human exposures at or near 2 mg talc/m3.
In two studies with humans (Churg, 1983; Churg and Warnock, 1980), talc constituted
approximately 16,0% of the nonasbestos fibers recovered from the lungs of 20 individuals
with no history of occupational dust exposure. All subjects (11 men and 9 women) were
selected from a general autopsy service. All were 40 years of age or older at the time of
death. The average number of nonasbestos fibers was 106 x 103 ± 87 X 103 fibers/g wet
lung, with no significant differences noted between men (96 x 103 fibers/g) and women
(115 x 103 fibers/g). Similarly, no significant differences were noted between the
15 smokers (93 x 103 fibers/g) and 5 nonsmokers (140 X 103 fibers/g). A total of
13 different mineral groups other than asbestos were identified, of which apatite, gypsum,
talc, silica, and attapulgite accounted for more than half the fibers. Silica was found in the
lungs of all 20 subjects and talc in 19 of 20. About 86% of all fibers (71 % for talc) were
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shorter than 5 /mi, and most had aspect ratios less than 15. In addition, the mean number of
nonasbestos fibers was similar to the number of asbestos fibers (102 x 103/g wet lung) found
in these subjects, with chrysotile accounting for more than 80% of the asbestos fibers (Churg,
1983; Churg and Warnock, 1980).
Several studies have been conducted to determine the metabolism of talc powder
following oral administration (Phillips et aj., 1978; Wehner et al., 1977a). Little, if any, is
absorbed from the gastrointestinal tract following oral intubation of rats, guinea pigs, mice,
and hamsters; most of the material is eliminated in the feces within 1 or 2 days after dosing.
These studies will not be discussed furtheri
Wehner et al. (1986) examined the migration of talc from the vagina in monkeys. Six
female exbreeder cynomolgus monkeys each received 30 intravaginal talc applications,
consisting of 125-mg neutron-activated powder per application, over a 45-day period. Doses
were equivalent to 29 to 52 mg talc/kg/day, depending on the animal's body weight. Six
untreated females served as controls. Animals were between 4 and 12 years of age and
weighed between 2.4 and 4.35 kg. The radioisotopes 46Sc, 60Co, 59Fe, and 51Cr were used
as tracers for the administered talc. Two days after the final application, abdominal lavage
fluid, ovaries, oviducts, uterus, and vagina with cervix were collected for X-ray analysis.
Only the vagina with cervix samples from dosed animals contained talc tracers. The authors
concluded that despite repeated applications to the fornix of cynomolgus monkeys, no
measurable quantities (i.e., greater than 0.5 g) of talc translocated to the uterus or beyond.
In contrast, Henderson et al. (1986) reported that talc particles introduced into the
uterus and vagina of the rat migrated to the ovaries. Eight female exbreeder (age 7.5 mo)
Sprague-Dawley rats each received an intravaginal dose of 250 #L of a talc-saline suspension
(100 mg talc/cm3). Four of the rats received additional uterine instillations on Days 6 and
15, and two of these rats were treated again on Days 22 and 30. .Ovaries were removed from
all animals at the time of sacrifice (Days 56, 20, and 49, respectively). In a separate
i
experiment, six Sprague-Dawley exbreedefs were given 250 jtiL of the same talc: suspension,
and an additional six rats received the saline vehicle only. Two animals from each of these
groups were sacrificed at 24, 49, and 96 hj after treatment; ovaries were removed as before.
Talc particles were recovered from the ovaries of all animals given intrauterine doses of the
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test material and from the two rats that were killed 96 h after intravaginal instillation. No
talc was found in the ovaries of the other treated or untreated animals.
In summary, the pulmonary deposition of talc following repeated exposure is dose
dependent. Following single inhalation exposures, alveolar clearance is slow, with a
biological half-life of 7 to 10 days. Talc is cleared by mucociliary action from the lungs and
eliminated in the feces via the gastrointestinal tract. Results of studies that investigated the
migration of talc from the vagina are equivocal.
3.2 ACUTE TOXICITY
There was no information in the available literature on the acute toxicity of talc.
However, intratracheal instillation of talc has been shown to result in pulmonary toxicity in
hamsters (Beck et al., 1987). Groups of six hamsters (sex and strain not specified) were
given single intratracheal injections of talc (mean diameter, 0.8 /zm) suspended in 0.9% saline
containing 13.3 g/cm3 rabbit surface active material (SAM) at concentrations of 0.15, 0.75,
or 3.75 nig/100 g body weight. Controls received saline plus SAM. The pulmonary
responses were quantified by measuring biochemical and cellular indicators of injury in the
bronchoalveolar lavage (BAL) fluid. One day after talc instillation, elevated enzyme levels,
pulmonary edema, and increased cell numbers in the BAL fluid (red blood cells,
macrophages, and polymorphonuclear leukocytes) were noted. Persistent elevation of enzyme
levels and inhibition of phagocytosis were also noted in a group of four hamsters receiving
3.75 mg/100 g body weight which were killed 1, 4, 7, and 14 days after administration.
The biochemical response of rabbit cartilage tissue to talc-induced synovitis was
investigated by Gershuni et al. (1981). In this study, approximately 0.25 cm3 of a talc-saline
suspension was injected into the right hip of 30 immature (age 1 mo) New Zealand White
rabbits (sex and weight not specified). Left hips and saline-injected animals served as
controls. Groups of rabbits were sacrificed 1, 2, 3, and 4 weeks after injection. Sections of
cartilage were removed, and levels of water, hexuronic acid, hexosamine, and collagen were
measured. Cartilage thickness was measured directly on corresponding hemisections from
left and right femoral heads. Significant (0.05 < p < 0.005) swelling of the medial joint
space of the right hip was apparent in treated animals at all sacrifice intervals. Water content
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was significantly (p < 0.05) increased at Weeks 1 and 2; hexuronic acid and hexosamine
content were decreased (p < 0.05), but only at the end of the first week. Collagen content
was not affected. The 15% increase in cartilage thickness (compared with control cartilage
thickness) could not be attributed solely to the 3% increase in hydration. The authors
concluded that the talc-induced synovia! inflammation caused a local increase in temperature,
hyperemia, and venous congestion that, in jturn, facilitated anabolic cellular activity and
increased production of cartilage.
3.3 SUBCHRONIC AND CHRONIC TOXICITY AND
CARCINOGENICITY
This section provides a review of the data on the systemic toxicity and carcinogenicity
of talc given by various routes of administration.
i
3.3.1 Inhalation Exposure
Wagner et al. (1977) exposed groups of male and female Wistar rats to a dust cloud
containing 10.8 mg/m3 talc (mean respirable concentration) for 3 mo (24/sex), 6 mo
(12/sex), or 12 mo (12/sex). Equal numbers of rats remained unexposed as cage controls or
were exposed to 10.8 mg/m3 chrysotile asbestos as positive controls. Exposure was for
7.5 h/day, 5 days/week. The test material (Italian 00000 grade) contained approximately
92% talc, 3% chlorite, 1% carbonate minerals, and 0.5 to 1.0% quartz by weight. The
remaining 3.0 to 3.5% was not defined. Particle size ranged up to 70 urn but averaged
25 fim; 40% of the talc cloud was respirable, and only 2% was fibrous. An unspecified
I
number of rats from each group was sacrificed at 10 days and 1 year after the end of each
exposure period, and the remaining rats were observed for life.
i
The severity of fibrosis produced was similar for the talc- and asbestos-exposed groups,
ranging from minimal to slight. Evidence of progression in severity was seen as the exposure
length increased and after the exposure was discontinued in animals exposed for 6 and 12 mo.
The severity of fibrosis was graded on a 7-point scale (1: nil, 2: minimal, 4: slight,
8: severe). The average scores were 2.2, 2.7, and 3.4, respectively, at the end of the 3-,
6-, and 12-mo exposure periods for talc, and 2.4, 3.4, and 4.6 by 1 year. Scores for
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controls ranged from 1.3 to 1.9. One of 48 rats exposed to talc developed a pulmonary
adenoma, and 7 of 48 asbestos-exposed rats developed pulmonary tumors. No pulmonary
tumors were noted in 48 control rats. These results suggest that exposure levels were near
the maximum tolerated dose (MTD); however, an inadequate number of animals was used.
Pickrell et al. (1989) report a study discussed in Section 3.1 indicating that for various
talc exposures, no clinical signs in rats or mice were seen prior to sacrifice at the end of the
20-day exposure. Also, histologic alterations in lung tissue consisted of only a modest,
diffuse increase of talc-containing free macrophages within alveolar spaces in both rat and
13
mouse groups exposed to the highest level of talc (17 to 20.4 mg talc/m ) for 20 days.
3.3.2 Intratracheal Administration
Trautwein and Helmboldt (1967) studied the pulmonary effects of talc after intratracheal
instillation into chinchillas. Groups of male and female chinchillas received intratracheal
instillations of 2 mL of a 2% suspension of talcum powder (purified Mg3Si4O11H2O; particle
size not specified) in saline. Controls were treated similarly to test animals and received
2 mL of saline per injection. The study consisted of three experiments. In the first,
14 chinchillas received injections on study Days 1, 20, 50, 70, and 90, and were killed
11 months after the last injection. A second group of 24 animals received a single
intratracheal injection; two animals were killed 24, 48, 72, and 120 h and 1, 2, 3, 4, 6, 17,
and 28 weeks, postdose. The last group of 18 animals received 11 weekly intratracheal
injections for 10 weeks, and chinchillas were killed 1, 2, and 3.5 mo after the last injection.
Several animals died during the study from the acute effects of talc exposure. All of
these animals exhibited some form of pneumonia caused by talc accumulation in the lungs.
Two animals from the first experiment died 3 days after the initial injection from acute
suppurative pneumonia. Five animals died from the third experiment: two from proliferative
and exudative pneumonia after 12 and 21 days (these animals received two and three
injections, respectively), and three from extensive granulomatous pneumonia between 41 and
46 days after the initial talc injection. Results indicated that talc caused exudative pneumonia
that developed into proliferative, granulomatous pneumonia. The granulomas consisted of
multmucleated foreign body giant cells that surrounded or engulfed the talc particles. Several
stages of transformation were noted in alveolar lining cells located only in areas of talc
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deposition or in close proximity to granulomas. Initially, swelling of alveolar epithelial cells
was noted. This was followed by hyperplasia and progressed to epithelialization. Finally,
columnar cells appeared, lining the affected alveoli and imparting an "adenomatous
appearance." No fibrosis was noted in talc-injected or control animals. Furthermore, single
or multiple injections resulted in the same Itissue reactions.
i
Stenback and Rowland (1978) treated two groups of 24 male and 24 female hamsters
with 18 intratracheal instillations, once webkly, of talc (3 mg) or talc plus benzo[«]pyrene
(B[«]P) (3 mg talc + 3 mg B[a]P); controls received saline only or were untreated. The
i
repeated instillation of talc plus B[a]P produced papillomas, squamous cell carcinomas, and
undifferentiated tumors of the larynx, trachea, and lungs. Talc alone produced only minor
respiratory disorders. In some cases, pulmonary congestion and interstitial fibrosis was
noted; however, there was no granuloma formation or signs of neoplastic transformation.
In a subsequent chronic study by Stenback et al. (1986), groups of 48 Syrian hamsters
received weekly intratracheal instillations of 3 mg talc alone or in combination with 3 mg
B[fl]P in saline for life. The talc sample consisted of 64 to 66% SiO2 and 34 to 36% MgO,
and 54% of the talc granules had a particle size of < 10 [im. Dust-laden macrophage
aggregation and accumulation of interstitial cells and histiocytes were noted in hamsters
exposed to talc alone. There were also increases in fibrillary material (elastic fibers)
surrounding alveolar and interstitial spaces i and some accumulation of proteinaceous exudate
within the alveoli. However, no fibrosis or granulomas were observed in talc-exposed
hamsters. Talc alone caused moderate tissue destruction, slight metaplasia, and no dysplasia
in the tracheobronchial zone; moderate hyperplasia was seen in the alveolar zone. Talc plus
B[<2]P resulted in moderate destruction, moderate metaplasia, and severe dysplasia in the
I
tracheobronchial zone, and severe hyperplasia and dysplasia in the alveolar zone. Talc alone
did not induce tumors in hamsters but, when given in combination with B[a]P, was found to
be an effective cocarcinogen, inducing an increased incidence of tumors in both the upper and
lower respiratory tract when compared to talc or B[a]P alone. There was a high incidence of
peripheral (alveolar) lung tumors, and adenocarcinomas were the predominant tumor type.
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3.3.3 Intraperitoneal Administration
In a study by Styles and Wilson (1973) that was designed to compare the in vitro
cytotoxicity with in vivo fibrogenesis of several synthetic and mineral fibers, a single
intraperitoneal injection of 50 mg/kg talc into Wistar rats (sex not specified) resulted in the
development of a granulomatous reaction that consisted of the aggregation of foreign body
giant cells containing talc particles 1 mo after administration. The lesions were still evident
3 mo after injection, but no fibrosis was evident. In this study, talc was found to have low
in vitro cytotoxicity, resulting in the death of less than 2% of peritoneal macrophages
following phagocytosis.
Kaiser et al. (1982) reported the development of foreign body granulomas, with
adhesions, in male and female Wistar rats 12 weeks after intraperitoneal injection of talcum
(dose and composition not specified). The development of foreign body granulomas has also
been reported in swine (Migaki and Garner, 1969). The lesions found in the inguinal canal
of four castrated male swine consisted of talc-containing epithelioid and giant cells,
lymphocytes, and fibrous tissue. The pigs were thought to have been exposed to talc during
castration, but the exposure period was not reported. ,
The tissue response to talc was also studied in rats by Felling and Evans (1986). Talc
(50 mg) was implanted surgically into the peritoneal cavity of 60 male Sprague-Dawley rats.
Sham-operated rats served as controls. Animals were killed 2, 4, 8, 13, 26, and 52 weeks
after implantation and examined. Talc produced extensive granulomatous peritonitis within
2 weeks that persisted until Week 13. Numerous focal lesions described as discrete pale
nodules were observed in all animals receiving talc (100% incidence). These nodules were
still apparent 52 weeks after exposure. Both control and talc-exposed animals developed
adhesions. The animals receiving talc, however, had a significantly increased incidence
(p < 0.001) of adhesions over the entire time period when compared with control rats.
Histologically, the lesions consisted of granulomas containing dust-laden macrophages and
dust-laden multinucleated giant cells with some collagen formation.
No tumors were found after four intraperitoneal injections of 25 mg in 40 female Wistar
rats (Pott et al., 1974) or after a single intraperitoneal injection of 20 mg talc in 24 Swiss
mice (Oezesmi et al., 1985) when these animals were observed for life.
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3.3.4 Other Administration
Single intrapleural administration of 40tmg of talc to Osborne-Mendel rats (Stanton
et al., 1981) or 20 mg of talc to Wistar rats ((Wagner et al., 1977) did not result in tumor
induction after lifetime observation.
Ingestion of talc (100 mg/rat/day) for I'Ol days resulted in the development of
leimyosarcoma of the stomach in 1/32 Wistar rats observed for life (Wagner et al., 1977).
No controls developed tumors.
Hamilton et al. (1984) injected talc (10 mg) intrabursally on the surface of ovaries of
rats; the animals were observed for 18 mo. No tumors were found.
3.3.5 Summary
In summary, talc exposure generally results in a typical granulomatous lesion consisting
of dust-laden multinucleated foreign body giant cells, as well as some fibrosis with collagen
formation in several animal species. In addition to the development of granulomas,
intratracheal instillation of talc results in moderate tissue destruction in hamsters, and
intraperitoneal administration has been shown to cause abdominal adhesions in rats and swine.
Talc is not carcinogenic following inhalation exposure or intraperitoneal, intrapleural, or
intrabursal administration to rats, hamsters, and mice. However, these studies are not fully
adequate to evaluate the carcinogenic potential of talc. Oral administration of talc did result
in a leimyosarcoma of the stomach in 1/32 rats. Evidence from two studies suggests that talc
may be an effective co-carcinogen when administered intratracheally with B[«]P. A summary
of the carcinogenicity studies with talc appears in Table 3-1.
3.4 DEVELOPMENTAL AND REPRODUCTIVE TOXICITY
No information on the developmental or reproductive toxicity of talc was found in the
available literature.
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3.5 MUTAGENICITY AND CYTOTOXITY
The mutagenicity of talc has been studied in gene mutation assays involving Salmonella
or Saccharomyces, in addition to chromosomal aberration in rat bone marrow cells and
dominant lethal mutation assays. This section also reviews the cytotoxicity data from in vitro
assays, intratracheal instillation of talc, monolayer cultures of tracheal epithelial cells,
suspensions of sheep erythrocytes, and preparations of phospholipid-cholesterol vesicles.
Lord (1978) reported that Litton Bionetics, Inc., evaluated talc for mutagenicity in
1973. There were no increases in gene mutation in Salmonella or Saccharomyces at
200 mg/cm3, and no increase was reported for chromosomal aberrations in rat bone marrow
cells or for dominant lethal mutation in the germinal cells of male rats exposed to 30, 300, or.
3,000 mg/kg. Study details were not available.
In vitro cytotoxicity assays conducted with natural or acid-purified talc (diameter from
0.2 to 20 jwn) indicate low-level cytotoxic activity in peritoneal and alveolar macrophages
from Wistar rats (Styles and Wilson, 1973), which corresponded to the minimal toxicity
exhibited by talc in vivo. It is noteworthy that within 1 h of exposure, approximately 50% of
the treated macrophages contained talc particles. Other investigators have reported that talc
particles (50 /fg/mL) within a respirable range were not cytotoxic to V79-4 or A549 cells
(Chamberlain and Brown, 1978).
In contrast, intratracheal instillations of asbestos- and quartz-free Vermont talc (0.15,
0.75, or 3.75 mg/100 g body weight; median aerodynamic diameter 7.5 jam, calculated using
known relationships) produced a dose-related cytotoxic effect in hamsters, as evidenced by
elevated lactate dehydrogenase, j3-N-acetylglucosaminidase, and peroxidase levels in BAL
(Beck et al., 1987). Cellular damage was also indicated at 1-day postexposure by
significantly increased BAL albumin levels in high-dose animals when compared with
controls.
The effects of silica and talc on cellular and artificial membranes were examined using
three test systems: monolayer cultures of tracheal epithelial cells, suspensions of sheep
i
erythrocytes (sRBCs), and preparations of phospholipid-cholesterol vesicles (Woodworth
et al., 1982). Each mineral preparation was; at least 99% pure, and approximately 60 to 70%
of the talc or silica fibers were 3.0 /2m or smaller.. Particles were suspended in veronal-
buffered 0.95% sodium chloride and added to the test systems at concentrations ranging from
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0.003 to 20.0 mg/cm3. Activity was monitored via radiolabeled sodium chromate (specific
activity of 51Cr, 200 to 500 Ci/g). At the end of a 24-h incubation period, both minerals
were cytotoxic to the trachea! epithelial cells. Phagocytosis of talc and silica particles was
evident within 4 h, and cells containing talc or silica demonstrated retraction of lamellipodial
extensions, surface blebbing, and morphological changes. Release of 51Cr by trachea!
epithelial cells was higher for cells exposed to 0.1 mg/cm3 silica (20%) and talc (35%) than
•3
for nonexposed cells. As talc and silica concentrations increased from 1 to 20 mg/cm ,
percent hemolysis of sRBC increased steadily from approximately 5 to 90% following a
60-min incubation period. Membrane distortion and sRBC ghosts were observed. Percent
spontaneous leakage of [51Cr]chromate from liposomes and liposomes exposed to 10 mg
o
silica particles/cm3 was approximately 4 to 6%; following a 1-h exposure to 10 mg talc/cm ,
chromate release rose to about 20%, suggesting an increased permeability of the liposomes.
In conclusion, limited evidence suggests that there is no mutagenicity from talc in
Salmonella or Saccharomyces, no chromosomal aberrations in rat bone marrow cells and no
dominant lethal mutation in germinal cells of male rats. Low-level cytotoxicity was reported
in rat alveolar macrophages but not in V79-4 or A549 cells. Intratracheal instillation of talc
produced a dose-related cytotoxic effect. Cytotoxicity was also observed in cultures of
trachea! epithelial cells, sRBCs, and phospholipid-cholesterol vesicles.
3.6 EFFECTS ON HUMANS
3.6ol Cross-Sectional Studies, Clinical Evaluations, and Case Reports
The health effects of talc in humans, studied in cross-sectional studies, clinical
evaluations, and case reports, are reviewed in this section with reference to the consequence
resulting from pulmonary, dermal, intrapleural, surgical, intravenous administration, and
ingestion.
3.6.1.1 Respiratory Effects
In general, most silicates such as talc were considered harmless until Dreessen and Dalla
Valle (1935) studied the health effects of exposure to talc at two mining milling operations in
Murray County, GA. Analysis of the talc deposits showed them to consist of talc as fibrous
3-13
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splinters, fibrous aggregates, and foliated masses (70%), dolomite as broken rhombs (20 to
30%), and tremolite in two samples as bladed crystals (10%). No quartz was found except
for occasional fragments. Physical examinations were performed on 66 talc workers; 33 mill
workers were exposed to >300 million particles per cubic foot (mppcf), 13 miners were
exposed to an average of 135 mppcf, and 20 additional workers were exposed to an average
of 17 mppcf. Twenty-nine workers (44%) had worked less than 5 years, 18 (27%) worked
5 to 9 years, 13 (20%) worked 10 to 14 years, and 6 (9%) worked 15 years or more.
Sixteen of the 33 mill workers in the higher dust groups were diagnosed as having
pneumoconiosis: eight were classified as Stage I, five were Stage n, and three were
Stage m. Five persons in this group were diagnosed as having pneumoconiosis plus
tuberculosis. The miners showed no evidence of advanced pneumoconiosis, although 6 out of
13 men were Stage I. Workers in the lowest exposure category were negative for
pneumoconiosis.
In a study designed to investigate the health effects associated with exposure to pure
talc, Hogue and Mallette (1949) examined two groups of workers from two rubber plants:
One group was composed of 20 men exposed to talc alone (21 + 10 mppcf) for periods
ranging from 10 to 36 years, whereas the second group consisted of 20 men with a major
exposure to whiting and minor exposure to pyrophyllite and talc (58 + 24 mppcf) ranging
from 10 to 25 years. Physical examinations and chest roetgenograms of men from the group
exposed to talc alone were normal. Workers in the second group were also normal, with the
exception of one man with Stage El pneumoboniosis who had the highest dust exposure of the
two groups (150 mppcf) and a previous occupational history of 5 years in mining. The study
suggested that exposure to talc alone does not produce pathological changes in the lungs.
Negri et al. (1989) noted an increased relative risk (RR) for pleural cancer in a northern
Italian cohort of rubber workers. The authors considered a possible link to fibers containing
talc in tire manufacturing and storage, but also considered possible asbestos exposure related
to prior work experience or to the mechanical maintenance job category that had the highest
RR by job category. The data do not allow any conclusions.
Fine et al. (1976) conducted pulmonary function tests, performed chest X rays, and sent
i
respiratory questionnaires to 80 talc workers and 189 controls (nonexposed rubber workers)
from three rubber tire manufacturing plants. ; There were no important differences between
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the exposed and control groups with regard to age, cigarette smoking, past occupational
exposure, and socioeconomic and ethnic factors. Environmental sampling indicated that
exposure for the majority of jobs was under lmg/m3. The maximum lifetime exposure was
estimated to be below 60 mppcf-years, and the average lifetime exposure was estimated as
less than 20 mppcf-years. The talc was characterized by a low content of silica and fiber
(18 in 21 samples contained less than 1% free silica). The 12 samples counted for fibers
showed less than 2 asbestos fibers/cm3. None of the workers had severe dyspnea or talc
pneumoconiosis; however, the talc workers had a significantly (p < 0.05) greater prevalence
of productive cough and positive criteria for chronic obstructive lung disease than control
workers. Workers with greater than 10 years of exposure had impaired' ventilatory function.
The forced expiratory volume in 1 s (FEVj 0) was significantly decreased (p < 0.02).
Multiple regression analysis of FEV1 0 in talc workers suggested that for each year of
exposure, a talc worker suffers a 26 cm3 loss of FEVj 0 in excess of that related to age and
cigarette smoking.
The results of a study of 93 New York miners and millers exposed to talc containing
tremolite and anthophyllite fibers indicated increased respiratory symptoms, abnormalities
detected by X-ray examinations, and decreased pulmonary function when compared with a
population of potash miners (Gamble et al., 1979). Among the talc workers, higher
respiratory symptom rates were found for those who had worked for less than 15 years than
for those with 15 years or more of employment. However, most of the workers with
symptoms were either smokers or ex-smokers. Mean pulmonary function values (FEVj 0,
forced vital capacity, and maximum respiratory flow at 50 and 75% of VC) of talc workers
were significantly decreased in comparison to those of the potash workers. These decreases
remained after controlling for age, height, smoking, and number of years of employment.
An association was found between decreased pulmonary function and fiber and particulate
n
exposure and the number of years worked. The prevalence of pleura! calcification and
pneumoconiosis in talc workers with 15 or more years of employment was higher than in
potash miners. The greatest difference between the two groups was the increased prevalence
of pleura! thickening in talc workers. Among the talc workers, pleural thickening occurred in
1.6% of workers with less than 15 years of employment and in 31% of those with more than
3-15
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15 years employment. Corresponding values for potash miners were 0.5% and 4,(
respectively.
Fitzgerald et al. (1991) conducted a case history study of radiographic chest
I
abnormalities in a talc-mining.region of upstate New York. Chest X rays taken between
April 1, 1982, and March 31, 1983, for 4,280 male and 5,160 female residents (age 40 and
above) of St. Lawrence or Jefferson Counties were examined. The prevalence rate of
confirmed pleural changes and/or parenchymal fibrosis was 3.8% (i.e., 355 of 9,442
patients). Men were 12 times more likely to exhibit parenchymal abnormalities and 5 times
more likely to show pleural changes than were women. Of the 355 patients whosie
i
radiographs were confirmed positive by the beta-reader, 306 (or their next-of-kin) were
interviewed. Occupational distribution of the cases was compared to that for men in both
counties according to the 1960 U.S. Census.; Two-thirds of the cases were at least age 60,
and 86.5% were men; approximately 70% had smoked cigarettes at some time during their
lives. Sixty percent reported occupational exposure to asbestiform minerals for at least
1 year. More than one-third of the cases had worked in talc mining and milling industries,
and one-quarter had been employed in construction trades. In contrast, the U.S. Census
indicated that only 2.4% of men in these counties engaged in such employment in 1960. The
results also suggest no evidence of widespread radiographic abnormalities resulting from
ambient dust exposure.
A cross-sectional study of 299 workers from Montana, Texas, and North Carolina, who
were exposed to talc containing low levels of silica and tremolite and antigorite fibers, was
conducted by Gamble et al. (1982). The mean age of the study population was 40, and the
mean duration of exposure to talc dust was less than 10 years. The average concentration of
airborne dust ranged from 0.28 to 2.64 mg/m3. Respiratory symptoms did not show any
consistent association with years worked or cumulative exposure. There were no significant
increases in pneumoconiosis among the study group or significant reductions in lung function.
An increased prevalence in bilateral pleural thickening was found in some exposed workers.
The prevalence was related to age and smoking habits and was greater (23%) in those
i
employees working 10 years or more when compared with those working less than 10 years
(2.5%). Moreover, workers with bilateral pleural thickening had higher average and
3-16
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cumulative exposures than those with no pleural thickening. All pulmonary function values
of these affected workers were reduced when compared with those of unaffected workers.
Evidence of fibrosis in workers exposed to talc containing minimal amounts of
crystalline silica and asbestiform minerals was reported in a pulmonary pathology study by
Vallyathan and Craighead (1981). Pulmonary tissue from seven deceased Vermont talc
workers exhibited various degrees of pulmonary fibrosis. The severity of the fibrosis
increased with duration of employment and concentration of heavy mineral deposits in fibrotic
lesions of the lung. X-ray crystallographic studies of lung digestates revealed that the
predominant mineral in the lungs was talc.
A study of 202 talc (purity not specified) workers in India showed a significant increase
(p < 0.001) in respiratory symptoms among the workers when compared to 101 matched
control subjects of the same socioeconomic status but not engaged in any dusty trade (Bachani
and Agarwal, 1985; Bachani, 1984). Exposure levels were not reported. Signs and
symptoms included pain and burning of the nose and throat, increased phlegm production,
difficulty in breathing, and chest pain. Clinical examinations revealed a higher number of
workers with nasal and pharyngeal mucosal congestion and scattered rhonchi. Over 13% of
the workers and 9% of the controls had clinical evidence of chronic airflow limitation (CAL).
The prevalence of CAL was related to age and smoking history. A positive correlation was
found between the prevalence of CAL and duration of exposure to talc dust. In addition, the
presence of eosinophils in sputum samples of 13 of 38 workers and none in the control
subjects suggested that talc exposure may induce an allergic-type pathology.
Changes in ventilatory functions in response to industrial grade talc dust exposure (no
levels given) were investigated in 202 workers (Damodar et al., 1983). Smoking habits were
graded by duration in years times frequency per day. Forced vital capacity, FEVX 0, and
FEV% were measured. All indices decreased with increasing age, intensity of smoking, and
duration of exposure. A significant decrease in pulmonary function was found for workers
who smoked compared with control subjects who smoked. No significant difference was
found between workers and control subjects who did not smoke. The authors postulated a
complementary effect of smoking on talc-induced changes in lung function.
A cross-sectional study of the respiratory function of 116 Vermont miners and millers of
talc ore, free from asbestos and silica, was performed by Wegman et al. (1982). Exposure
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levels were found to be below 3.0 mg/m3 respirable dust with a geometric mean exposure of
1.8 mg/m3 respirable dust. In addition, a 1-year followup evaluation of pulmonary function
was performed on 103 workers. A significant reduction in pulmonary function was found in
workers who smoked. After adjusting for smoking, the effect of exposure to talc was not
statistically significant, although there was evidence of an exposure-related effect in workers
with an annual dust exposure of 1.5 mg/m3. Effects on pulmonary function in nonsmokers
were not associated with exposure. Talc exposure was also associated with small, rounded,
and irregular opacities seen on chest X rays. t An annual loss in pulmonary function occurred
in the workers at a rate greater than expectetj. However, the loss did not correlate with
exposure to talc dust.
A microscopic analysis of the lung and lymph node dust samples from 12 deceased
Austrian workers occupationally exposed to talc dust revealed a slightly increased
concentration of real fibers and elongated particles in comparison to normal individuals
(Friedrichs, 1987). The ratio of length to diameter was inconsistent throughout the diameter
range examined and was not comparable to that found in asbestos workers with
mesothelioma. It was concluded that the carcinogenic potential of the fibers was not very
high, because neither of the two factors postulated to be important in assessing the
carcinogenic hazard of a fiber (i.e., increased numbers of very fine fibers <0.01 m in
diameter and high numbers of fibers in the Stanton range) appeared to be related to the
disease state.
Talc is considered to be hazardous when inhaled in large quantities. The hazard is acute
in cases of accidental inhalation and chronic in cases of industrial exposure or prolonged use
of commercial products. However, since talc is not always a uniform substance, the
association between talc exposure and adverse health effects may be related in some instances
to the presence of contaminating minerals such as asbestos and silica. Most reports
describing acute and chronic effects of talc exposure include little characterization of the talc
involved. j
Infants and small children have died from cardiorespiratory arrest, pulmonary edema,
and pneumonia within hours after inhaling talcum powder (Cotton and Davidson, 1985;
Motomatsu et al., 1979; Gould and Barnardo, 1972; Anonymous, 1969). The powder dries
the mucous membranes of the bronchioles, thus disrupting pulmonary clearance and clogging
3-18
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the small airways. Victims usually display dyspnea, tachypnea, tachycardia, cyanosis, and
fever. Bronchopulmonary lavage is not effective, since talc is insoluble in water. Gould and
Barnardo (1972) described the case of a 7-year-old girl who survived a massive aspiration of
powdered talc and later developed bronchiectasis of the left lung.
Hollinger (1990) states that if talc is taken in via the airway, it acts as a pulmonary
•\
irritant producing acute symptoms, typically including cough, dyspnea, sneezing, vomiting,
and cyanosis. Inhalation of talc can lead to complete obstruction of the small airways,
resulting in respiratory distress syndrome. Hollinger (1990) states that in view of the
questionable efficacy of talc and its potential for producing pulmonary toxicity, there are no
compelling indications for use of talc-based topical powders for infants. A more desirable
alternative would be the substitution of appropriate creams and lotions.
Lund and Feldt-Rasmussen (1969) described the case of a child who survived a massive
aspiration of talc but only after exhibiting cyanosis, tachypnea with intercostal retractions,
and tachycardia. There was fine crepitation over the lungs, and X rays revealed signs of
bronchitis and peribronchitis with atelectases. Clinical treatment provided a gradual
regression back to normal.
In addition to the effects of a massive acute inhalation, cases of talc pneumoconiosis or
chronic sarcoidosis characterized by foreign body granulomas and interstitial fibrosis have
been reported as a result of chronic use of cosmetic talcum powder (Tukiainen et al., 1984;
Wells et al., 1979). Signs and symptoms included dyspnea, productive cough, and weakness.
Abnormal chest radiographs and decreased pulmonary function were also observed.
Increased respiratory symptoms, higher prevalence of pleura! thickening or calcification
and pneumoconiosis, and decreased pulmonary function have been reported in workers
exposed to talc containing various amounts of tremolite, anthophyllite, or silica fibers. The
extent of these effects increased with age of workers, intensity of smoking, and duration of
exposure. These effects were less pronounced with exposure to talc free of asbestiform
fibers. In cases of accidental inhalation of large quantities of talc, victims usually display
dyspnea, tachypnea, tachycardia, cyanosis, and fever. Signs of bronchitis and peribronchitis
with atelectases are noted. Chronic use of cosmetic talcum powder can result in talc
pneumoconiosis or chronic sarcoidosis with foreign body granulomas and interstitial fibrosis.
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3.6.1.2 Effects From Dermal Application
An analogy between asbestos-induced mesotheliomas and talc-induced ovarian cancers
was originally based upon the close relationship between talc and asbestos. Additional
supporting evidence for this analogy is derived from the similarity in origin and histology
between mesotheliomas and ovarian cancers (Longo and Young, 1979).
In a case-control study of 215 white females with epithelial ovarian cancers and
215 controls from the general population, 92 in 215 (42.8%) cancer cases regularly used talc
either as a dusting powder on the perineum or on sanitary napkins compared with 61 in
215 (28.4%) of controls (Cramer et al., 1982). The relative risk adjusted for parity and
menopausal state was 1.92 (p < 0.003). A'total of 32 in 215 (14.9%) of cancer cases
regularly used talc both on the perineum and on sanitary napkins compared with 13 in
215 (6.0%) of the controls. Women with both exposures, therefore, had the greatest adjusted
relative risk of 3.28 (p < 0.001).
An extraction-replication technique (Griffiths et al., 1973; Henderson, 1972; Henderson
et al., 1973; Henderson ,and Griffiths, 1975) was used to examine tissue from patients with
ovarian tumors. No asbestos particles were found in any of the tissues studied (Efenderson
et al., 1971). Particles of talc were identified in approximately 75% (10 in 13) of the
ovarian tumors. Talc particles were found localized deep within the tumor tissue; some were
as small as 1,000 A in size, but they were generally within a range from 1,000 A to 2 /wn.
In a letter to the editor, Hartge et al. (1983) refuted the association between talc use and
ovarian cancer. The data collected were part of a case-control interview study of epithelial
ovarian cancer conducted on 197 women with pathologically confirmed primary epithelial
ovarian cancer from 1974 to 1977. The control population consisted of 197 women treated at
the same hospital for conditions other than gynecologic, psychiatric, or malignant diseases or
pregnancy. Questions about talc were added to the questionnaire after the study began so that
135 cases and 171 controls were questioned about talc exposure. No increase was found in
the relative risk to women who used talc as a body powder or on diaphragms. A reliable
estimate of relative risk in women who used talc specifically on sanitary napkins, underwear,
or the genital area was not possible, however, because of the small numbers of women
involved.
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Harlow and Weiss (1989) report a case control study of borderline ovarian tumors and
the influence of perineal exposure to talc. Borderline ovarian tumors differ from epithelial
malignant ovarian tumors described in the other studies in that borderline tumors are lesions
of low malignant potential that are usually noninvasive. The authors interviewed 116 female
residents of western Washington state with serous and mucinous borderline ovarian tumors
diagnosed between 1980 and 1985 and questioned them on their use of hygienic powders.
A sample of 158 control women from the same counties was identified through random digit
dialing. These women were interviewed as well. The authors reported 18 RR calculations
with number of subjects for cases in the subset analysis ranging from 4 to 49 of the total
*
116 cases. Neither the perineal application of baby powder (RR of 0.8 with 95% confidence
interval [CI] at 0.4 to 1.9; 18 cases, 31 controls) nor talc (RR of 1.0 with 95% CI of 0.4 to
2.4; 13 cases, 19 controls) was associated with appreciably altered risk of borderline ovarian
tumors. Women who used deodorizing powder alone or in combination with other talc-
containing powder had RR at 2.8 (95% CI of 1.1 to 11.7; 14 cases, 7 controls). The authors
suggest caution in interpreting the results of the study, because the elevated risk among
women who specifically used deodorizing powders could have been due to chance or
applicable only to borderline, not malignant, ovarian tumors. Additionally, they note that the
risk of ovarian tumors in women who apply deodorizing powder to the perineum may not
relate to talc per se, but rather to asbestos contamination or a substance or substances used
specifically for deodorization.
Whittemore et al. (1988) reported a study on exposure to talcum powder and epithelial
ovarian cancer in 188 women in the San Francisco Bay area diagnosed in 1983-1985 and in
539 control women. To investigate the roles of blood-borne environmental exposures on
ovarian cancer risk, they assessed lifetime consumption of coffee, tobacco, and alcohol in
these women. Ninety-seven (52%) of the cancer patients habitually used talcum powder on
the perineum, compared with 247 (46%) of the controls. Adjusted for parity, the RR equals
1.4, p = 0.06. There were no statistically significant trends with increasing frequency or
duration of talc use. Thus, the results of this study show neither a strong nor a consistent
association between genital talcum powder exposure and ovarian cancer. While these data do
not exonerate talc as an ovarian carcinogen, neither do they provide strong evidence to
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implicate it. Further epidemiologic studies are needed to clarify the role of talc as a
i :
carcinogen, cocarcinogen, or promoter of epithelial ovarian carcinogenesis.
Granulomas of the skin postulated to be caused by entrance of talc through the skin at
sites of draining or incised furuncles were reported by Tye et al. (1966).
3.6.1.3 Effects From Intrapleural Instillation
Adverse systemic effects, including dyspnea followed by acute respiratory failure and
bilateral pleura! effusion with interstitial infiltrates, was reported in a patient a few hours
after talc pleurodesis (Bouchama et al., 1984). The patient improved with corticosteroid
th'erapy.
A total of 210 cases of patients who had undergone pleurodesis with iodized talc or
kaolin 14 to 40 years previously were traced, and the numbers of deaths from all causes and
cancer of the lung and pleura were compared with a control death rate derived from age- and
i
year-specific tables from England and Wales (Research Committee of the British Thoracic
Association and the Medical Research Council Pneumoconiosis Unit, 1979). No increase was
found in the incidence of lung cancer in these patients, and no cases of mesothelioma were
reported.
3.6.1.4 Effects From Surgical Introduction
Inadvertent introduction of talc into the body has been shown to produce granulomas.
A granuloma that completely obstructed the ureter of a 53-year-old woman was attributed to
the introduction of talc as a glove powder 20 years previously during a hysterectomy
operation (Joannides, 1978). However, the granuloma may also have been produced by
either starch granules or Lycopodium spores^ Sahi et al. (1967) reported that granuloma
formation on the bowel and peritoneum was believed to be the result of talcum powder use
during a previous surgical intervention. Fienberg (1937) reported two cases of granuloma
formation caused by talc introduced during surgical procedures.
3.6.1.5 Effects From Intravenous Administration
Intravenous abuse of stimulant drugs intended for oral administration can lead to the
embolization of insoluble tablet fillers such as talc to the pulmonary vasculature. The
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vasculature acts as a filter in most cases, thereby restricting talc-induced pathologic lesions to
the lungs. Blockage of pulmonary perfusion by the passage of intravenously injected talc
particles can result in pulmonary hypertension with the formation of arterio-venous shunts.
The venous blood can then bypass the lungs and enter the arterial system, lodging particles in
various organs such as the eye. The resulting peripheral retinal neovascularization has been
noted after injection of talc emboli (Lederer and Sabates, 1982). Particles smaller than 7 mm
can travel to the retina via the pulmonary capillary bed. Bilateral intraretinal talc emboli
were reported in 23 patients by Tse and Ober (1980). A case of talc retinopathy that
included vitreous hemorrhage and retinal detachment was reported by Bluth and Hanscom
(1981). In this case the effects of talc particle injection resulted in blindness.
Granulomatous lesions found in lungs, liver, spleen, bone marrow, and systemic lymph
nodes as a result of systemic talc embolization were reported by Mariani-Costantini et al.
(1982). Larger talc crystals (10 to 17 urn) remained localized in the lungs; small crystals
(2 to 10 /zm) spread systemically. No crystals were found in numerous sections of the central
nervous system, and only a few were present in the myocardium, retina, optic nerve, and
kidneys. The talc particles were present in urine, demonstrating that they may have been
able to pass through the glomerular capillary bed. Self-induced pulmonary granulomatosis
was described by Waller et al. (1980). Cases of intravenous talc granulomatosis (Tao et al.,
1984), liver talc granulomas (Molos et al., 1987), and systemic talc granulomatosis (Lewis
et al., 1985) have been reported in association with intravenous drug abuse.
Kehrer (1990) comments that talc has not been shown to produce any toxic effects when
ingested orally. As a result, the use of talc in various tablet formulations is not considered
hazardous for the ingestion route. However, Hollinger (1990) notes that during drug abuse
oral medication containing talc may be crushed, solubilized, and injected intravenously. The
terminal pulmonary arterioles and capillaries serve as a sieve for the talc crystals.
Granulomas develop in the arteries, and vascular endothelial proliferation and secondary
thrombosis may lead to pulmonary hypertension and cor pulmonale.
3.6.2 Retrospective and Prospective Studies
Several studies have been conducted to identify potential relationships between exposure
to talc and nonmalignant respiratory disease (NMRD). However, except in one study,
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workers were simultaneously exposed to talc containing asbestos (i.e., tremolite), silicates,
carbonates, or radon.
Kleinfeld et al. (1967) conducted a proportionate mortality study of 220 talc miners and
millers employed between 1940 and 1965 who had achieved at least 15 years of exposure to
talc dust. In addition to talc, exposure also included tremolite and anthophyllite (asbestiform
I
and nonasbestiform fibers), carbonate dusts,| and a small amount of free silica. Data for this
cohort concerning employment and health histories as well as deaths were obtained from a
number of sources, including plant records, death certificates (when available), private
physician records, state health department files, hospital records, and autopsy records
(procured for 35 of 91 deaths). The degreejof completeness for disease ascertainment of the
study population and the criteria for classifications of morbidity and mortality were not
specified. The reference population used for calculating expected mortality was U.S. white
i
males for the year 1957, which was the median year of death for the 91 total deaths
i
occurring out of 220 workers. An analysis of the 91 deaths by cause yielded a significant
increase in the proportional mortality of the total observed deaths from cancer of the lung and
pleura (11 observed, 3.2 expected, proportionate mortality ratio [PMR] = 344, p < 0.01).
When the cohort was analyzed by age group; (<40, 40 to 59, 60 to 79, > 80 years), a
significant increase in cancer of the lung and pleura occurred in the subgroup 60 to 79 years
old (17 observed, 3.9 expected, PMR = 436, p < 0.01). The authors expressed concern
that this finding was at variance with the results from asbestos workers who had a similar
duration of exposure during a similar period; Increased respiratory cancer incidence was
i
found in both the 40 to 59 and 60 to 79 age groups of asbestos workers. A possibility exists
that the discrepancy in these findings could be due to a greater carcinogenic potential and/or
greater exposure levels in the case of asbestos workers. However, since the power to detect a
carcinogenic risk in the 40 to 59 age group of talc workers was inadequate (21%), no definite
conclusions could be drawn. An analysis of individuals with carcinoma of the lung or pleura,
by duration of exposure, found that all these individuals were initially exposed prior to the
institution of wet drilling (a period of heavy exposure before 1945), with an average duration
of exposure of 14.6 years. Environmental dust exposure concentrations before 1945 ranged
from 120 to 818 mppcf for mines and 69 to 1,227 mppcf for mills, and concentrations
between 1946 and 1965 ranged from 5 to 9 mppcf for mines and 25 to 73 mppcf for mills.
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No direct relationship was observed, However, between the duration of exposure before wet
drilling and the occurrence of pulmonary carcinoma.
Of the 91 total deaths, 28 were attributed to pneumoconiosis or complications or both.
Nineteen of the 28 were due to cor pulmonale, which was reported as a major cause of death
among talc workers. Because of the absence of adequate data, the role of smoking in the
causation of pulmonary carcinoma could not be ascertained in this study.
Findings from an update of this previous study through 1969 further supported the
increased incidence of cancer of the lungs and pleura (Kleinfeld et al., 1974). The criteria
for inclusion in the cohort remained the same for the followup study. The total number of
workers studied was 260, and the analysis used was a comparison of observed proportional
mortality rates from specific causes with expected rates. Expected mortality for the total
group represented the proportion of deaths among white men in the United States due to
specific causes in 1955 (median year of death among the total 108 deaths). For each of the
5-year periods, median years 1942, 1947, 1952, 1957, and 1962 were selected. Data for the
cohort were obtained from the same sources as those in the previous study. The total number
of deaths out of 260 workers was 108, and an analysis of these deaths by cause yielded
results consistent with the previous study; there was a significant increase in proportional
mortality from respiratory cancer in the 60 to 79 age group (16.6 observed, 3.6 expected,
PMR = 461, p < 0.05).
Insufficient power to detect an increase in other age groups was still a confounding
problem in this analysis. An analysis of carcinoma of the lung and pleura as related to six
5-year periods (1940-44, 1945-49, 1950-59, 1960-64, and 1965-69) revealed significant
increases in the observed proportional mortality for respiratory cancer for three periods:
1945-49 (observed = 11.7, expected = 3.1, PMR = 377, p < 0.05); 1950-54
(12.5 observed, 4.3 expected, PMR = 291,p < 0.01); and 1955-59 (observed = 20.0,
expected = 5.7, PMR = 351, p < 0.05). Investigators found no differences in mortality for
respiratory cancer occurring after 1960 and no correlation between respiratory cancer deaths
and age or years of exposure. Ten of the 13 deaths from respiratory tract cancer occurred in
the period between 15 and 24 years of exposure to talc dust. However, a prolonged exposure
of more than 25 years did not produce any additional risk. Although they remained major
causes of death, deaths attributable to pneumoconisis and its complications decreased by more
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than 50% in the last 5-year period studied (decrease from nine to four deaths). A firm
conclusion of an elevated lung cancer risk is difficult to make for this study because of the
lack of a dose-response relationship and the lack of smoking information.
The only mortality study conducted with very pure talc was reported by Rulbino et al.
i
(1976). The cohort consisted of 1,514 talc miners and 478 talc millers, who began work in
i
the years between 1921 and 1950, and who had been employed for at least 1 year in talc
operations of the Germanasca and Chisone Valleys in Italy. Because millers were exposed to
very pure talc, while miners' exposures included a certain amount of inhalable silica particles,
miners and millers were analyzed separately, Data for each worker were obtained from
payrolls and records of a mining company of Pinerolo. Age-matched control subjects were
chosen from the population of the town of Alba, which represented similar ethnic, social, and
economic conditions. Followup for the study cohort was 88.9% complete for miners and
91.6% complete for millers. The cause of death was obtained from death certificates for
exposed and control persons and was coded according to the 8th Revision of the International
Classification of Deaths (LCD). For both internal and external controls, an age-adjusted
modified life-table technique was used to compute expected deaths. The age intervals used
were <30, 30 to 50, 51 to 70, and >70, and the latency periods were 1 to 10, 11 to 20,
21 to 30, 31 to 40, 41 to 50, and >50.
Cumulative exposure was computed by, multiplying dust level for a period by number of
years exposed and summing the resulting values for each period. Three exposure levels were
then classified for miners (Exposure Level 1 = 566 to 1,699; Exposure Level 2 = 1,700 to
5,665; Exposure Level 3 = 5,666 to 12,750) and millers (Exposure Level 1 = 25 to 141;
Exposure Level 2 = 142 to'424; Exposure Level 3 = 425 to 906). Analysis of mortality
data indicated a significantly lower mortality! for talc miners and millers than expected
(miners = 704 observed, 791.2 expected, SMR = 89, p < 0.01; millers = 227 observed,
258.4 expected, SMR = 88, p < 0.01). When the overall mortality was subdivided by
cause of deaths, deaths from all NMRD in miners were significantly higher than in controls
(140 observed, 101.8 expected, SMR = 138, p < 0.01). Among malignant diseases, deaths
from lung cancer were significantly lower than in controls (9 observed, 19.7 expected, SMR
= 46, p < 0.01). An analysis of cause of death by exposure levels in miners showed a
trend of increasing deaths with increasing exposure from NMRD (Exposure Level 1 =
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26 observed, 36.9 expected, SMR = 70, p < 0.05; Exposure Level 2 = 38 observed,
36.3 expected, SMR = 105, not significant, Power ='85.8%; Exposure Level 3 =
76 observed, 67.1 expected, SMR = 113, p < 0.05). No clear trends, by exposure level,
were observed for deaths from any other cause in miners or millers. When mortality by
cause of death was analyzed by latency, the only significant increase found was for NMRD
after 20 to 40 years of latency (76 observed, 54.4 expected, SMR = 140, p < 0.01); and
after >40 years of latency (36 observed, 23.9 expected, SMR = 151, p < 0.01). No
significant increase in observed deaths by latency was found for millers.
The choice of the control population was discussed by the authors as a confounding
factor that could contribute to the observed differences. It was not possible to verify the
appropriateness of this reference group. In addition, smoking data were unavailable;
therefore, it was assumed that the control and exposed groups were similar in this respect.
An internal comparison of groups of workers by increasing dose and latency period produced
a pattern of excess mortality for respiratory causes of death in miners. This trend, plus the
different incidence of silicosis in miners (62 observed, 30.9 expected, SMR = 201,
p < 0.01), led the authors to conclude that the increased risk of death from NMRD was due
to silica rather than talc. The lack of increased risk from any cause of death in talc-exposed
millers led the authors to conclude that no evidence from the study supported the role of pure
talc in carcinogenesis. It should be noted, however, that the power to detect lung cancer in
the study population of millers was inadequate.
Brown et al. (1979) conducted a mortality study involving 398 white males initially
employed some time between January 1, 1947, and December 31, 1959, at a talc mine and
mill in upper New York State (Gouverneur region). Vital status for cohort members as of
June 30, 1975, was determined through government records including the Social Security
Agency, state vital statistics offices, and the state motor vehicle registration office. Death
certificates were obtained and causes of death were interpreted by a qualified nosologist and
converted to the 7th Revision of the ICD. A modified life-table technique was used to obtain
person-years at risk of dying by 5-year time periods, 5-year age groups, duration of
employment, and number of years since initial employment. The reference population used
was U.S. white males. Vital status was determined for 96% of the exposed cohort.
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No significant difference in overall mortality was observed. However, a significantly
higher mortality from all malignant neoplasms was detected (19 observed, 10.6 expected,
SMR = 180, p < 0.01). This was ascribed, in part, to the significant increase in deaths due
to bronchogenic cancer (9 observed, 3.3 expected, SMR = 270, p < 0.05). la addition,
investigators found an increase in deaths from NMRD, excluding influenza, pneumonia,
bronchitis, and acute upper respiratory infection (5 observed, 1.3 expected, SMR = 380,
p < 0.05). An analysis of the association between bronchogenic cancer and latency revealed
a significant increase in the interval 20 to 28 years since onset of employment (6 observed,
1.3 expected, SMR = 460, p < 0.01).
The study of mortality patterns in workers'exposed to talc from the Gouvernour mining
i
area demonstrated an excess in mortality from both NMRD and bronchogenic caincer. This
study had the confounding variables of smoking and exposure to asbestiform tremolite and
i
anthophyllite. The authors postulated that the exposure to asbestiform tremolite and
anthophyllite may have been responsible for the results observed. Another problem with the
study cohort was the relatively short duration of employment for many of the workers: 50%
were employed less than 1 year, and less than 25% were employed more than 10 years. Of
the 10 deaths from bronchogenic cancer, 4 occurred in workers employed less than 1 year.
Only two of these four were known to have been previously exposed to talc containing
asbestiform minerals.
Stille and Tabershaw (1982) conducted a mortality study of 655 white male workers
employed between January 1, 1948, and December 31, 1977, at one talc mine and mill
(TMX) in upper New York State. Exposure data were not included. Due to small numbers
and lack of talc exposure, women were excluded from analysis. The cohort was followed
until December 12, 1978. Data on the workers were retrieved from employment records.
Vital status was unknown for 36 members (5.5%) of the cohort. Death certificates were
obtained and coded according to the 8th Revision of the ICD by a trained nosologist.
Expected values were based on the U.S. white male population by means of a modified life-
table method. ,
The mortality analysis of the cohort revealed no significant increases in deaths from all
causes, from cancer of the respiratory tract and lung, from NMRD, or from other causes of
death. The cohort was divided into workers with a prior work history before TMX
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employment and workers with no known prior work experience. Investigators found no
significant difference in mortality rates for all disease categories in workers without prior
employment. However, workers with prior work histories did show significant increases in
deaths attributable to a number of causes including respiratory cancer (9 observed,
4 expected, SMR = 228, p < 0.05) and NMRD (9 observed, 2.9 expected, SMR = 307,
p < 0.01). The authors postulated that the observed mortality cancer was from exposures
that occurred in the workers' previous jobs.
An analysis of the dose-response relationship of the lung cancer cases observed in the
entire cohort and cumulative dose as measured by years of exposure resulted in an inverse
dose-response relationship. Investigators found a clustering of 9 out of 12 cases within the
first 5 years of employment at TMX. In addition, a calculation of the average latency time
for lung cancer among TMX workers was 19.9 years. The authors cited the lack of a dose-
response relationship and the short latency period as evidence that the prior occupational
exposures and not exposures at TMX may have been responsible for subsequent cancers.
Confounding variables in the study included the small cohort size and inclusion of short-
term (< 1 year) employees. Although the U.S. white male population was used as a
reference group, the authors pointed out that the New York State cancer death rate is
substantially higher (199.24 compared to 174.04). Lack of data concerning smoking histories
and incomplete work histories were also limitations of this study.
Reger and Morgan (1990) discuss the implication of an updated data and analysis of the
original cohort of talc workers from upstate New York. Eight more years of followup were
added plus an exposure by latency analysis, and a nested case-control study to account for
possible confounding by smoking and other occupational exposures. When the data were
stratified by smoking, the odds ratio decreased with tenure and the trend analysis was
significant. The analysis showed a strong association between lung cancer and cigarette
smoking. These results were considered to provide an argument against a causal relation
between lung cancer and exposure to nonasbestiform tremolite.
Selevan et al. (1979b) conducted a mortality study of 392 white male talc workers who
had been radiographed as part of the Vermont Health Department annual surveys. The
workers were employed by five companies in the Vermont talc industry for at least 1 year
between January 1, 1940, and December 31, 1969. Followup was begun from the initial
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radiograpMc examination, when 1 year of employment was achieved, or January 1, 1940,
^ ' '
whichever was later, and was continued through December 31, 1975. Vital status
ascertainment was performed through government records including those from the Social
Security Administration, state vital statistics offices, and state motor vehicle registration files.
Vital status was unknown for 1% (4 of 392 workers) of the cohort. Death certificates were
i
obtained, and causes of death were classified by a qualified nosologist and converted to the
7th Revision of the ICD. A modified life-table technique was used to obtain person-years of
observation by 5-year time periods, 5-year age groups, 5-year exposure groups, ;and 5-year
latency groups. The study cohort was divided into two groups: milling (225 workers) and
mining (163 workers). A minimum of 1 year of employment in the work area was required
for inclusion; 47 workers (12% of the total population) qualified for inclusion in both groups.
United States rates were used for calculation of expected values. In addition, Vermont rates
were used for comparison in the cases of NMRD and respiratory cancer deaths, since
Vermont rates are higher for these causes. An analysis of exposure revealed that both
airborne dust and bulk samples of talc from the mines and mills were similar in composition:
i
No asbestos was detected; free silica was below 0.25% for nearly all samples; and the
minerals magnesite, chlorite, and dolomite were present in significant quantities. Although
no cumulative exposures could be calculated, it was not uncommon for past levels to exceed
the OSHA and Mine Safety and Health Administration standard of 20 mppcf. Miners, but
not millers, may also have been exposed to serpentine rock and radon.
The mortality analysis of the total cohort showed that the only significant excess
occurred from NMRD (excluding influenza and pneumonia) (11 observed, 1.79 expected,
SMR = 615, p < 0.01), particularly among millers (7 observed, 0.89 expected,
SMR = 787, p < 0.01). A significant increase in respiratory cancer mortality was observed
only among miners (5 observed, 1.15 expected, SMR = 435, p < 0.05). These two
significant excesses were maintained when expected numbers of deaths from the Vermont
population were used (NMRD, 1.33 expected, p < 0.01; respiratory cancer, 1.22 expected,
p < 0.05). To confirm that the excess of NMRD deaths in millers was from talc exposure,
chest radiographs for 8 of the 11 men who died from this disease were examined for
pneumoconiosis. Of the eight radiographs, six (75%) had indications of pneumoconiosis.
When 2 of the 11 workers with prior dust exposure were included, five of the six (83.3%)
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radiographs were read as having pneumoconiosis. Qualitative radiograph readings by the .
Vermont Health Department provided information on three deaths with missing radiographs;
all three had evidence of pneumoconiosis, which provided a total of 9 of 11 deaths with
readings consistent with pneumoconiosis. This supported the association between talc
exposure and NMRD.
The authors stated that the possibility of a selection bias was small because workers who
were missed by the radiographic surveys were mostly short-term workers. An examination of
NMRD mortality by latency resulted in a pattern of significant excess after 15 years
(2 observed, 0.31 expected, SMR = 645, p < 0.05), and after 30 years (5 observed,
0.41 expected, SMR = 1,220, p < 0.01), but not before 15 years. This suggested that no
selection bias toward less healthy workers existed. No data were available on the smoking
histories of workers. In addition, the small cohort size resulted in a lack of adequate power
to detect increased risk in many of the disease categories.
Thomas and Stewart (1987) and Thomas (1990) conducted a mortality study of
2,055 white males employed for at least 1 year between January 1, 1939, and January 1,
1966, at three plants of a ceramic plumbing fixture company. More than 60% of the cohort
was employed for 10 or more years. Nonwhite males and females were excluded from the
cohort because their group was small. Vital status was determined from company, Social
Security Administration, credit bureau, and department of motor vehicle records. As of
January 1, 1981, 1,394 (67.8%) of the 2,055 cohort members were alive; 578 (28.1%) had
died; and 83 (4.0%) were lost to followup. Death certificates were obtained for all but 1.7%
of the decedents and coded by a qualified nosologist using the 8th Revision of the ICD.
Expected numbers of deaths were calculated using rates for U.S. white males rather than
local mortality rates. Because exposure data for talc dust were unavailable, exposure
classifications were based on the potential exposure to silica dust (none, low, or high). All
jobs involving talc exposure had high silica exposure and were further classified into no talc,
nonfibrous talc, and fibrous talc exposures; no talc was the lowest exposure, and fibrous talc
was the highest exposure. No information on smoking patterns was known for this cohort.
The mortality analysis showed a significant increase in deaths from lung cancer
(52 observed, 36.3 expected, SMR = 143) and NMRD (64 observed, 37.0 expected,
SMR = 173, p < 0.05). The increase in NMRD deaths was mainly from respiratory disease
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other than pneumonia or emphysema, which included 23 deaths nosologically classified as
pneumoconiosis from silica and silicates (41 observed, 14.1 expected, SMR = 290,
p < 0.05). An analysis of lung cancer and NMRD by year of hire showed a significant
increase in lung cancer among workers hired between 1940 and 1949 (22 observed,
11.4 expected, SMR = 193, p < 0.05) ancl a significant increase in NMRD among workers
hired before 1940 (55 observed, 24.5 expected, SMR = 224, p < 0.05). Analysis of
i
mortality by exposure category for lung cancer and NMRD revealed a significant excess only
in workers in the high silica exposure category (44 observed, 24.3 expected, SMR = 181,
p < 0.05), particularly among those exposed to nonfibrous talc (21 observed, 8.3 expected,
SMR = 254, p < 0.05). In addition, a significant increase in NMRD was found among
those exposed to high silica with no talc exposure (36 observed, 13.7 expected, SMR = 264,
p < 0.05) and to nonfibrous talc (16 observed, 7.3 expected, SMR = 220, p < 0.05). An
analysis by duration of exposure and years since first silica exposure revealed an increase in
NMRD mortality by duration of exposure (15 to 29 years: 21 observed, 12.1 expected,
SMR = 173, p < 0.05; 30+ years: 36 observed, 12.8 expected, SMR = 281, p < 0.05);
and years since first exposure (50 observed,! 22.0 expected, SMR = 227, p < 0.05). Lung
cancer mortality did not increase with duration of exposure, but there was an increase in
years since first exposure (30+ years: 32 observed, 20.6 expected, SMR = 156, p < 0.05).
The analysis by duration of exposure and y^ars since first exposure to nonfibrous talc,
revealed an increased mortality from lung cancer with duration of exposure (5 to 14 years:
11 observed, 4.0 expected, SMR = 276, p < 0.05; and 15+ years: 8 observed,
2.2 expected, SMR = 364, p < 0.05) and with years since first exposure (5 to 14 years:
8 observed, 2.9 expected, SMR = 281, p < 0.05; and 15+ years: 13 observed,
4.7 expected, SMR = 275, p < 0.05). Mortality from NMRD was not affected by duration
or time since first exposure to nonfibrous talc.
The excess NMRD was elevated among workers with exposure to high levels of silica,
regardless of nonfibrous talc exposure. This risk decreased over time, suggesting a reduction
in silica exposure. Risk of NMRD was also unaffected by duration or time since first
exposure to nonfibrous talc. The authors concluded an association between silica dust rather
than talc exposure with this disease. The excess in lung cancer found in this study, however,
occurred primarily in workers exposed to both nonfibrous talc and silica. Risk of lung cancer
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occurred only among those hired after 1940 and increased with increasing duration of
exposure to nonfibrous talc but not with duration of silica exposure. This suggested that
exposure to nonfibrous talc was related to lung cancer risk.. However, the confounding
problem of simultaneous silica exposure prevented any conclusions as to their respective roles
in the disease. The possibility that silica acts as a co-factor or promoting agent cannot be
ruled out. • -.
In Norway, Wergeland et. al. (1990) studied cancer incidence and cause-specific ,
mortality in a male cohort of 94 talc miners and 295 talc millers exposed to nonasbestiform
talc with low quartz content. All'employees from the mine in the years 1944-1972 with at
least 1 year of employment in talc-exposed jobs and all employees from the mill in the years
1935-1972 with at least 2 years of employment in talc-exposed jobs were included.
Information about the miners was gathered from company payrolls, lists of union
membership, and the central registry of silica-exposed workers of the National Board of
Occupational Safety and Health. Information about smoking habits was available for 63 of
the 94 miners.. No information was available on smoking habits of the millers. Information
on date and main cause of death was obtained from the death certificate registry of the
Central Bureau of Statistics. Information on cancer cases was provided by the Cancer
Registry. Dust exposure was determined by samples collected in 1980-1982 and varied
greatly by job category. Air samples were analyzed for fiber concentration, which varied
from iess than 0.2 up to 0.9 fibers/mL and consisted of tremolite, antophyllite, and talc
particles.
No excess risk was found compared with national age-specific incidence, SMR of 75,
with 117 observed deaths and 155.2 expected. :Six cases of lung cancer occured versus
6.49 expected. Three deaths were due to NMRD against 10:9 expected. Both the healthy
population and survivor population effect may be factors here. The mortality from NMRD
may increase with further follow-up time, as any impact of "healthy worker" selection
becomes less prominent. The probability of detecting an increased mortality from NMRD
(a = 0.05, one-sided) is 83% for a true RR of 2.0 and 100% for RR = 3.0, assuming a ,
Poisson1 distribution.
In both groups the numbers are too small to form inference on particular cancer types.
The International Agency for Research on Cancer (1987) found sufficient evidence for
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carcinogenicity of crystalline silica to experimental animals and limited evidence for
i ..
carcinogenicity to humans. They found inadequate evidence for carcinogenicity of talc to
either experimental animals or humans. The result of this low quartz content talc exposure is
i
compatible. The possibility of detecting an increased lung cancer incidence during the
follow-up period in this study (a = 0.05, one-sided) assuming a Poisson distribution is 65%
for a true RR = 2.0 and 97% for RR = 3:0. This study does not show an association
between lung cancer morbidity or respiratory disease mortality and exposure to
nonasbestiform talc with low quartz contenjt in the one mine and one mill studied. Further
follow-up time is needed, however, to lessen any impact of "healthy worker" selection.
The American Thoracic Society (Weill et al., 1990) review examines the carcinogenicity
of talc and tremolite and concludes that the talc studies do not convincingly demonstrate an
increased cancer risk reliably attributed to talc exposure and further do not support a role for
tremolite as a lung carcinogen in talc mining whether the tremolite is an asbestiform or not.
However, the authors do state further that, from all studies considering tremolite "fibers",
they have been demonstrated in both humans and animals to cause health effects identical to
those produced by other forms of asbestos.
3.7 QUALITATIVE AND QUANTITATIVE EVALUATION OF
TOXICOLOGICAL EFFECTS ASSOCIATED WITH EXPOSURE
TO TALC
This section summaries and evaluates noncarcinogenic effects and carcinogenic effects.
3.7.1 Noncarcinogenic Effects
Data from animal studies indicate that talc exposure generally results in a granulomatous
lesion consisting of dust-laden multinucleated foreign body giant cells, as well as some
fibrosis with collagen formation. Systemic effects in humans after inhalation exposure
include increased respiratory symptoms, higher prevalence of pleura! thickening or
calcification and pneumoconiosis, and decreased pulmonary function. These effects were
more pronounced in those exposed to talc containing asbestiform fibers than to pure talc.
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Humans chronically exposed to talc exhibit pneumoconiosis or chronic sarcoidosis with
foreign body granulomas and interstitial fibrosis.
A review of the chronic toxicity data of talc in animals by the International Agency for
Research on Cancer (1987) indicated the appearance of foreign body giant-cell granulomas,
fibrosis, and chronic inflammatory changes eventually leading to emphysema. Toxic effects
in humans after inhalation include pneumoconiosis, restrictive or obstructive breathing
disorders, and decreased vital capacity. There was an association between the severity of the
pneumoconiosis and the presence of asbestiform fibers. x
The following three studies were considered for the development of a no-observed-
adverse-effect level (NOAEL) and a lowest-observed-adverse-effect level (LOAEL): two
inhalation studies in animals and one epidemiolbgical study. However, the data were limited,
and a NOAEL or LOAEL cannot be determined. In the study by Wehner et al. (1977a,b),
Syrian Golden hamsters were exposed to 8 mg/m3 (respirable fraction) cosmetic talc for 30 or
150 min/day, 5 days/week for 300 days; the animals were observed until death. The
estimated alveolar deposition/exposure range was 0.86 to 1.15 and 4.3 to 5.8 /Jg talc for the
30- and 150-min exposures, respectively; the exposure concentration for continuous exposure
would be 0.12 and 0.6 mg/m3/day, respectively. No effects were seen on body weight,
clinical signs, or microscopic pathology. These levels represent a rather low exposure and
help confirm that the NOAEL is greater than 8 mg/m3 (i.e., 0.6 mg/m3/day).
Wagner et al. (1977) exposed Wistar rats to talc from northern Italy at 10.8 mg/m3 for
7.5 h/day, 5 days/week for 3, 6, or 12 mo. The talc did not contain asbestos minerals of
either the tremolite or chrysotile varieties. The exposure concentration for continuous
exposure would be 2.4 mg/m3/day. The lung burdens at the end of the 3-, 6-, and 12-mo
exposure periods were 2.5, 4.7, and 12.2 mg talc/rat. The severity of fibrosis was minimal
to slight, and there was a progression in severity as the exposure length increased, as well as
after the exposure had been discontinued. These levels represent a rather high exposure and
help confirm that a NOAEL is lower than 10.8 mg/m3 (i.e., 2.4 mg/m3/day).
In the epidemiological study conducted by Rubino et al. (1976) data were collected for
workers in talc mines and mills in the Germanasca and Chisone Valleys (Piedmont) in Italy.
The talc in the mines was described as pure; no amphibole or chrysotile was detected. Some
tremolite microinclusions were detected; however, no other fibrous mineral was reported.
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Environmental data-were available for the mines and mills since 1948. Prior to 1950,
exposures were reported to be approximately 800 mppcf in the mines and 25 mppcf in the
mills. Exposures in both areas were reduced to less than 10 mppcf after 1965. Other than
some rather crude estimates that could be devised for human exposure from the data
presented, quantification of the human exposure to talc was not possible.
3.7.2 Carcinogenic Effects
Talc was not shown to be carcinogenic following inhalation exposure or intratracheal
instillation to rats and hamsters. No evidence of carcinogenicity was noted following
intrapleural, intraperitoneal, or oral administration in rats. However, these studies are
inadequate to evaluate the carcinogenic potential of talc. Several mortality studies on mining
and milling workers involving exposure to talc contaminated with asbestiform fibers indicated
an excess of respiratory cancer and NMRD. However, these studies had important
limitations such as lack of smoking data and lack of dose-response data. Recent updates seem
to indicate that the talc studies do not convincingly demonstrate an increased lung cancer risk
reliably attributable to exposure and as such do not support a role for tremolite as a lung
carcinogen in talc mining whether the tremolite was asbestiform or not. A study of worker
exposure to very pure talc showed no increase in mortality from lung cancer.
Consequently, the weight of evidence from human health effects and animal toxicity
data are inadequate to characterize the carcinogenic potential of talc.
The evidence for carcinogenicity of talc has several aspects depending upon the nature
of the contamination with other mineral substances. Of particular note is contamination with
asbestos and crystalline silica.
The presence of asbestos in talc would cause the contaminated talc to be viewed as a
human carcinogen from a weight-of-evidence perspective. In the case of crystalline silica,
the International Agency for Research on Cancer (1987) views the human evidence for
crystalline silica as limited and the animal evidence as sufficient, which places crystalline
silica in lARC's "probable" human carcinogen classification. By inference, then, talc with
crystalline silica would be viewed as inheriting the carcinogenic hazard potential of the
crystalline silica.
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In the case of talc without asbestos contamination, the International Agency for
Research on Cancer (1987) found the available human and animal evidence to be inadequate
to demonstrate or refute the potential for carcinogenicity. Some animal studies are
nonpositive, but it is not clear that these are adequate to'properly evaluate talc's
s
carcinogenicity with and without the low content of crystalline silica.
The U.S. EPA has not previously evaluated the talc or the crystalline silica data and has
not done so in this assessment. The International Agency for Research on Cancer views on
weight-of-evidence are useful as an interim measure in considering the hazard perspective.
The U.S. EPA and the International Agency for Research on Cancer view asbestos as a
human carcinogen. The quantitative question arises as to how much crystalline silica or
asbestos contamination makes a difference in terms of potential risk, and this dose-response
issue has not been included in this assessment.
In a similiar evaluation, the American Thoracic Society (Weill et al., 1990) discusses
the health effects of tremolite and reviews studies of talc health effects. With regard to
tremolite asbestos, the American thoracic Society (Weill et al., 1990) concludes the
following after a review of other tremolite studies beyond those of contaminated talc:
1. Unquestioned health effects of tremolite asbestos have been demonstrated in
both humans and animals. These effects are identical to those produced by
other forms of asbestos.
2. There may be important physicochemical distinctions between asbestosform and
nonasbestosform tremolite dust particles. However, there appears to be considerable
controversy in applying these mineralogic definitions to specific samples of
minerals, particularly individual particles viewed microscopically after collection by
air sampling or found in human lungs or when used experimentally.
3. At present, the prudent public health policy course is to regard appropriately sized
tremolite "fibers", in sufficient exposure dose (concentration and duration), as
capable of producing the recognized asbestos-related diseases, and they should be
regulated accordingly.
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Several rebuttals have since been published for tremolite and its presence in talc
addressing physicochemical distinctions: OSHA's analytical procedures and definitions,
results of animal studies, etc. (Reger and Morgan, 1991, 1990; Case, 1991; Langer et al.,
1991). However, this information is beyond the present scope of this document,,
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