TECHNICAL REPORT DATA
ffUat ft*d liuoueriOHS on tht rtvtrtt be fan complttiitg)
'< REP OUT NO.
EPA/600/8-88/018
3. RECIPIENT'S ACCESSION NO.
PB88-179445/AS
4. TITLE AND SU8TITLE
S. REPORT DATE
Health Effects Assessment for Antimony and Compounds
6. PERFORMING ORGANIZATION CODE
7. AUTHOR(S)
. PERFORMING ORGANIZATION REPORT NO
PERFORMING ORGANIZATION NAME AND ADDRESS
10. PROGRAM ELEMENT NO.
11. CONTRACT/GRANT NO.
12. SPONSORING AGENCY NAME AND ADDRESS
13. TYPE OF REPORT AND PERIOD COVERED
Environmental Criteria and Assessment Office
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati. OH 45268
14. SPONSORING AGENCY CODE
EPA/600/22
5. SUPPLEMENTARY NOTES
6. ABSTRACT
This report summarizes and evaluates information relevant to a preliminary interim
assessment of adverse health effects associated with specific chemicals or compounds.
The Office of Emergency and Remedial Response (Superfund) uses these documents in
preparing cost-benefit analyses under Executive Order ]2991 for decision-making under
CERCLA. All estimates of acceptable intakes and carcinogenic potency presented in
this document should be considered as preliminary and reflect limited resources
allocated to this project. The intent in these assessments is to suggest acceptable
exposure levels whenever sufficient data are available. The interim values presented
reflect the relative degree of hazard associated with exposure or risk to the
chemical(s) addressed. Whenever possible, two categories of values have been
estimated for systemic toxicants (toxicants for which cancer is not the endpoint of
concern). The first, RfD5 or subchronic reference dose, is an estimate of an exposure
level that would not be expected to cause adverse effects when exposure occurs during
a limited time interval. The RfD is an estimate of an exposure level that would not
be expected to cause adverse effects when exposure occurs for a significant portion
of the lifespan. For compounds for which there is sufficient evidence of
carcinogenicity, qi*s have been computed, if appropriate, based on oral and
inhalation data if available.
KEY WORDS AND DOCUMENT ANALYSIS
DESCRIPTORS
b.IDENTIFIERS/OPEN ENDED TERMS
c. COSATi Field/Croup
8. DISTRIBUTION STATEMENT
Public
19. SECURITY CLASS (This Rtport I
Unclassified
21. NO. Of PAGES
20. SECURITY CLASS (Thilpaftt
Unclassified
22. PRICE
EPA F«ra 2220-1 (R«i. 4-77) PREVIOUS BOITIOM i* OMOLKTB
-------
EPA/600/8-88/018
June. 1987
HEALTH EFFECTS ASSESSMENT
FOR ANTIMONY AND COMPOUNDS
ENVIRONMENTAL CRITERIA AND ASSESSMENT OFFICE
OFFICE OF HEALTH AND ENVIRONMENTAL ASSESSMENT
OFFICE OF RESEARCH AND DEVELOPMENT
U.S. ENVIRONMENTAL PROTECTION AGENCY
CINCINNATI, OH 45268
U.S. Environmental Protection Agency
Eo,i~ion 5, Library (SFL-lo)
230 S. De£,jto--n St -;,;-,, ,-.-)Q."3 1670
Chicago, IL 605CK
-------
DISCLAIMER
This document has been reviewed In accordance with the U.S.
Environmental Protection Agency's peer and administrative review policies
and approved for publication. Mention of trade names or commercial products
does not constitute endorsement or recommendation for use.
11
-------
PREFACE
This report summarizes and evaluates Information relevant to a prelimi-
nary Interim assessment of adverse health effects associated with antimony
and compounds. All estimates of acceptable Intakes and carcinogenic potency
presented In this document should be considered as preliminary and reflect
limited resources allocated to this project. Pertinent toxlcologlc and
environmental data were located through on-Hne literature searches of the
Chemical Abstracts, TOXLINE and the CHEMFATE/DATALOG data bases. The basic
literature searched supporting this document Is current up to Hay, 1986.
Secondary sources of Information have also been relied upon 1n the prepara-
tion of this report and represent large-scale health assessment efforts that
entail extensive peer and Agency review. The following Office of Health and
Environmental Assessment (OHEA) sources have been extensively utilized:
U.S. EPA. 1980a. Ambient Water Quality Criteria Document for
Antimony. Prepared by the Office of Health and Environmental
Assessment, Environmental Criteria and Assessment Office, Cincin-
nati, OH for the Office of Water Regulations and Standards, Wash-
ington, DC. EPA 440/5-80-020. NTIS No. PB81-117319.
U.S. EPA. 1983a. Reportable Quantity Document for Antimony and
Compounds. Prepared by the Office of Health and Environmental
Assessment, Environmental Criteria and Assessment Office, Cincin-
nati, OH for the Office of Emergency and Remedial Response, Wash-
ington, DC.
U.S. EPA. 1983b. Reportable Quantity Document for Antimony Potas-
sium Tartrate. Prepared by the Office of Health and Environmental
Assessment, Environmental Criteria and Assessment Office, Cincin-
nati, OH for the Office of Emergency and Remedial Response, Wash-
ington, DC.
U.S. EPA. 1983c. Reportable Quantity Document for Antimony Tr1-
oxlde. Prepared by the Office of Health and Environmental Assess-
ment, Environmental Criteria and Assessment Office, Cincinnati, OH
for the Office of Emergency and Remedial Response, Washington, DC.
U.S. EPA. 1985a. Health and Environmental Effects Profile for
Antimony Oxides. Prepared by the Office of Health and Environ-
mental Assessment, Environmental Criteria and Assessment Office,
Cincinnati, OH for the Office of Solid Waste and Emergency
Response, Washington, DC.
U.S. EPA. 1986a. Integrated Risk Information System (IRIS).
Reference dose (RfD) for oral exposure for antimony. Online.
(Verification date 11/6/85). Office of Health and Environmental
Assessment, Environmental Criteria and Assessment Office,
Cincinnati, OH.
111
-------
The Intent In these assessments 1s to suggest acceptable exposure levels
for noncarclnogens and risk cancer potency estimates for carcinogens
whenever sufficient data were available. Values were not derived or larger
uncertainty factors were employed when the variable data were limited In
scope tending to generate conservative (I.e., protective) estimates.
Nevertheless, the Interim values presented reflect the relative degree of
hazard or risk associated with exposure to the chemical(s) addressed.
Whenever possible, two categories of values have been estimated for
systemic toxicants (toxicants for which cancer Is not the endpolnt of
concern). The first, RfD$ (formerly AIS) or subchronlc reference dose. Is
an estimate of an exposure level that would not be expected to cause adverse
effects when exposure occurs during a limited time Interval (I.e., for an
Interval that does not constitute a significant portion of the llfespan).
This type of exposure estimate has not been extensively used, or rigorously
defined, as previous risk assessment efforts have been primarily directed
towards exposures from toxicants 1n ambient air or water where lifetime
exposure Is assumed. Animal data used for RFD$ estimates generally
The RfD (formerly AIC) 1s similar In concept and addresses chronic
exposure. It Is an estimate of an exposure level that would not be expected
to cause adverse effects when exposure occurs for a significant portion of
the Hfespan [see U.S. EPA (1980b) for a discussion of this concept]. The
RfD Is route-specific and estimates acceptable exposure for either oral
(RfD0) or Inhalation (RfOj) with the Implicit assumption that exposure
by other routes 1s Insignificant.
Composite scores (CSs) for noncarclnogens have also been calculated
where data permitted. These values are used for Identifying reportable
quantities and the methodology for their development 1s explained In U.S.
EPA (1983).
For compounds for which there 1s sufficient evidence of carclnogenlclty
RfD§ and RfD values are not derived. For a discussion of risk assessment
methodology for carcinogens refer to U.S. EPA (1980b). Since cancer 1s a
process that 1s not characterized by a threshold, any exposure contributes
an Increment of risk. For carcinogens, q-|*s have been computed, If appro-
priate, based on oral and Inhalation data If available.
1v
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ABSTRACT
In order to place the risk assessment evaluation 1n proper context,
refer to the preface of this document. The preface outlines limitations
applicable to all documents of this series as well as the appropriate
Interpretation and use of the quantitative estimates presented.
RfOg values were derived for antimony and selected compounds based on
a LOAEL for antimony of 350 yg/kg/day associated with potassium antimony
tartrate In the drinking water of rats for lifetime exposure (Schroeder et
al., 1970). Reduced Hfespan was observed In both sexes and altered blood
biochemistries were observed 1n males. The only concentration tested was 5
ppm antimony. RfDg values for antimony of 24.5 yg/day, for antimony
potassium tartrate of 65.48 yg/day and for antimony tr1-, tetra- and
pentoxldes of 29.3, 30.9 and 32.5 yg/day, respectively, were calculated.
Because adequate subchronlc oral data were not located, an RfD$o value was
not developed. It should be noted that orally administered antimony has
been Inadequately tested for carclnogenldty.
RfD] and RfD$j values were not derived because of data suggesting
that antimony 1s carcinogenic In rats following Inhalation exposure.
However, the data were Inadequate for quantitative risk assessment (Watt,
1980. 1981, 1983; ASARCO, Inc., 1980).
Watt (1980, 1981, 1983) and ASARCO, Inc. (1980), In reports of the same
study, observed a statistically significant Increase In the Incidence of
lung tumors In rats exposed to antimony trloxlde by Inhalation. In addi-
tion, Wong et al. (1979) noted an Increased Incidence of lung cancer In rats
exposed by the Inhalation route to anlmony trlsulMde. This observation
coupled with Indications that occupational exposure to antimony processing
Is associated with lung cancers In humans (Oavles, 1973) Is qualitative
evidence for the carclnogenldty for antimony by Inhalation. However, the
Davles (1973) report Is only available In the form of a 2-page letter making
H Impossible to thoroughly evaluate this data. An earlier U.S. EPA (1983f)
analysis concluded that the animal data were Insufficient for quantitative
estimation of the carcinogenic potency of antimony.
-------
ACKNOWLEDGEMENTS
The Initial draft of this report was prepared by Syracuse Research
Corporation under Contract No. 68-03-3112 for EPA's Environmental Criteria
and Assessment Office, Cincinnati, OH. Or. Christopher OeRosa and Karen
Blackburn were the Technical Project Monitors and John Helms (Office of
Toxic Substances) was the Project Officer. The final documents In this
series were prepared for the Office of Emergency and Remedial Response,
Washington, DC.
Scientists from the following U.S. EPA offices provided review comments
for this document series:
Environmental Criteria and Assessment Office, Cincinnati, OH
Carcinogen Assessment Group
Office of A1r Quality Planning and Standards
Office of Solid Waste
Office of Toxic Substances
Office of Drinking Water
Editorial review for the document series was provided by the following:
Judith Olsen and Erma Durden
Environmental Criteria and Assessment Office
Cincinnati, OH
Technical support services for the document series was provided by the
following:
Bette Zwayer, Jacky Bohanon and K1m Davidson
Environmental Criteria and Assessment Office
Cincinnati, OH
v1
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TABLE OF CONTENTS
1.
2.
3.
4.
5.
6.
ENVIRONMENTAL CHEMISTRY AND FATE
ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS . . .
2.1. ORAL
2.2. INHALATION
TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1. SUBCHRONIC
3.1.1. Oral
3.1.2. Inhalation
3.2. CHRONIC
3.2.1. Oral
3.2.2. Inhalation
3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS. . . .
3.3.1. Oral
3.3.2. Inhalation
3.4. TOXICANT INTERACTIONS
CARCINOGENICITY
4.1. HUMAN DATA
4.1.1. Oral
4.1.2. Inhalation
4.2. BIOASSAYS
4.2.1. Oral
4.2.2. Inhalation
4.3. OTHER RELEVANT DATA
4.4. WEIGHT OF EVIDENCE
REGULATORY STANDARDS AND CRITERIA
RISK ASSESSMENT
6.1. SUBCHRONIC REFERENCE DOSE (RfDs)
6.1.1. Oral (RfDso)
6.1.2. Inhalation (RfDcr)
Paqe
. . . 1
. . . 5
. . . 5
, , . 5
. . . 7
7
. . . 7
. . . 9
9
. . . 9
. . . 10
. . . 13
. . . 13
. . . 13
. . . 14
. . . 15
. . . 15
. . . 15
. 15
. . . 15
. . . 15
. . . 16
. . . 18
. . . 18
. . . 20
. . . 21
, , . 21
. . . 21
. . . 21
V11
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TABLE OF CONTENTS
Page
6.2. REFERENCE DOSE (RfD) 21
6.2.1. Oral (RfD0) 21
6.2.2. Inhalation (RfDj) .... 23
6.3. CARCINOGENIC POTENCY (q^) 24
6.3.1. Oral 24
6.3.2. Inhalation 24
7. REFERENCES 26
APPENDIX: Summary Table for Antimony and Compounds 34
-------
LIST OF TABLES
No. Title Page
1-1 Selected Physical Properties of Antimony and Some of
Its Compounds 2
3-1 Summary Table for Subchronlc Tox1c1ty of Antimony
and Compounds 8
3-2 Summary Table for Chronic Toxldty of Antimony and
Compounds 11
4-1 Tumor Incidence 1n Female Rats Exposed by Inhalation to
Antimony Trloxlde 17
1x
-------
LIST OF ABBREVIATIONS
BCF
bw
CS
DNA
EGG
LOAEL
MED
NOAEL
PEL
ppm
RfD
RfD0
RfDs
RfOsi
RfDSO
RMCL
RVd
RVe
SNARL
TLV
TWA
B1oconcentrat1on factor
Body weight
Composite score
Oeoxyrlbonuclelc acid
Electrocardiogram
Lowest-observed-adverse-effect level
Minimum effective dose
No-observed-adverse-effect level
Permissible exposure limit
Parts per million
Reference dose
Inhalation reference dose
Oral reference dose
Subchronlc reference dose
Subchronlc Inhalation reference dose
Subchronlc oral reference dose
Recommended maximum contamination levels
Dose-rating value
Effect-rating value
Suggested-no-adverse-response level
Threshold-limit value
Time-weighted average
-------
1. ENVIRONMENTAL CHEMISTRY AND FATE
Antimony Is a metalloid that belongs to Group V-A of the periodic table
and has oxidation states of +3, +5 and -3; however, the -3 state Is not
stable In oxygenated water (U.S. EPA, 1980a). Antimony ore bodies are small
and scattered throughout the world. Well over a hundred minerals of
antimony are found In nature. Occasionally native metallic antimony Is
found, but the most Important source of the metal Is the mineral stlbnlte,
antimony trlsulflde (Carapella, 1978). Selected physical properties of
antimony and some of Its compounds are listed In Table 1-1.
Most of the available data concerning exposure to antimony substances do
not distinguish between antimony metal, antimony trloxlde and antimony tr1-
sulflde. Antimony 1s expected to exist as the trloxlde In the atmosphere,
however, since most of the atmospheric releases of antimony substances
result from high temperature Industrial processes, from the combustion of
petroleum, petroleum products and coal, and from the Incineration of
products that contain antimony. At the high temperatures used In these
processes, oxidation of the antimony substances occurs, resulting In the
formation of antimony trloxlde (and possibly also antimony tetraoxlde and
antimony pentoxlde) (U.S. EPA, 1985a).
The antimony released from high temperature processes condenses rapidly
onto suspended partlculate matter and will associate predominantly with
small diameter particles (e.g., 1 nm 1n size), which are not only difficult
to trap with conventional stack technology, but also tend to settle out less
rapidly and thus are transported greater distances through the atmosphere.
The estimated residence time of antimony partlculates 1n the atmosphere
ranges between <30 days to -40 days, which Is much longer than the atmo-
spheric residence time of most partlculates (<1 week) (U.S. EPA, 1985a).
0112h -1- 10/29/86
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In water, some photochemical reduction to metallic Sb and Sb-O,- of
both suspended prismatic and rhombic antimony trloxlde occurs upon Irradia-
tion at wavelengths >290 nm. The antimony metal from the rhombic form Is
readily oxidized back to antimony trloxlde 1n oxygenated waters, while the
prismatic form darkens because there 1s no facile oxidation of the dark
antimony metal 1n the crystal lattice. It appears that very Uttle of the
antimony oxides In water occurs In the dissolved state, and that which does
dissolve Is present as various hydrolysis products such as Sb(OH)_ and
H!sbO?. The vast majority of antimony species 1n water systems are In the
form of various suspended partlculates that tend to settle onto sediments
over time. The rate of removal from water by precipitation or by precipita-
tion and settling depends on such factors as salinity, changes In pH and
amount of current or turbulence present In the water systems. Antimony
associated with partlculates would therefore be expected to accumulate, for
example, where contaminated rivers flow Into reservoirs, lakes, delta areas
arid other areas where sediments are actively being deposited, such as Inside
of bends 1n rivers. The potential for this accumulation Increases as the
source(s) of the antimony material Is approached. B1oconcentrat1on of anti-
mony species other than metallic antimony has been shown to be Insignificant
for most aquatic species; however, a report of a BCF of 16,000 for fresh-
water and marine Invertebrates Indicates that bloconcentratlon may be
significant for some species; blomagnlfIcatlon of antimony materials was not
observed (U.S. EPA, 1985a).
In soil, trace metals Including amtlmony reportedly have been found as
water soluble species 1n the Interstitial water, precipitates and copreclpl-
tates as oxides, exchangeable species absorbed onto soil surfaces and organ-
ically bound species, and also within mineral crystal lattices; however, the
0112h -3- 02/13/87
-------
' amount of water soluble species 1s not expected to be significant for the
antimony oxides. Precipitation and coprec1p1tat1on as oxides (antimony
tr1-, Sb.O, and tetraoxlde) have been suggested as Important processes
4 0
by which antimony Is retained on soil surfaces.
Antimony trloxlde, and presumably tetra- and pentoxlde, 1s apparently
persistent 1n soil, which Is to be expected from Its low water solubility,
lack of reactivity, stability and low vapor pressure. It 1s expected that
antimony substances will accumulate 1n the soil and sediment near production
and processing facilities, as well as at or near disposal sites (U.S. EPA,
1985a).
0112h -4- 02/13/87
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2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS
2.1. ORAL
Fellcettl et al. (1974a) administered solutions of trl or pentavalent
"*Sb compounds by gavage to Syrian hamsters. Hamsters were whole body
counted dally until sacrifice on day 4 postexposure. Six hamsters were
dosed with 1 ml of solution containing 2 yCl/mt "*Sb. Two hamsters
were dosed with 2 ml of solution containing 2 yd/ml. The animals
dosed with the 2 ml volume received trlvalent 124Sb, two of the six
hamsters receiving a 1 ml volume received trlvalent 124Sb while the
remainder received pentavalent 124Sb. The two animals receiving 2 ml of
trlvalent 124Sb retained 15% and 9% of the Initial body burden by day 4,
of which 88 and 90%, respectively, was found In the GI tract. The median
values for retention of day 4 for the remaining animals was 1.6% for those
receiving the trlvalent compound and 2% for those receiving the pentavalent
ol: which 61 and 64% were found 1n the GI tract. The Investigators concluded
that "very IHtle" of these compounds were absorbed from the GI tract,
probably <1% (Fellcettl et al., 1974b).
U.S. EPA (1980a) noted that these forms were the relatively Insoluble
oxides and that water-soluble organic derivatives may be absorbed to a
greater extent. Ellnder and FMberg (1977) reported that -15% of a tartar
emetic (potassium antimony tartrate) was absorbed by the gastrointestinal
tract of mice. Further data were not available In the secondary source from
which this study was taken.
2.2. INHALATION
Belyaeva (1967) found detectable levels of antimony In the placenta,
amnlotlc fluids and cord blood of pregnant women working In antimony
0112h -5- 06/15/87
-------
smelters during pregnancy. These data Indicate that absorption does occur
from the human respiratory tract, but estimations of quantity or rate are
not possible.
Fellcettl et al. (1974a) exposed Syrian hamsters to aerosol of tr1- or
pentavalent 12*Sb antimony compounds and subjected the animals to whole
body scintillation counting until sacrifice on day 0 to day 32 postexposure.
The detection of radioactivity In several Internal organs, the pelt and the
urine suggest that absorption from the pulmonary tract occurred, but estima-
tion of the quantity of the dose absorbed 1s not possible. Based on the
data discussed In Section 2.1., 1t appears that gastrointestinal absorption
of radioactivity cleared from the pulmonary tract by mucoclllary action
should have contributed Uttle to the levels of radioactivity detected 1n
Internal organs.
Fellcettl et al. (1974b) exposed beagle dogs by nose only to aerosol of
124Sb from an antimony tartrate complex. Aerosol formation at three
different temperatures, 100, 500 and 1000°C, resulted In production of
particles with activity median aerodynamic diameters of 1.3, 1.0 and
0.3 ji, respectively. Regional body counting Immediately after exposure
Indicated that the 100°C aerosol had deposited In the nasopharynx and the
lung and that the smaller particles found at higher temperatures had
deposited mainly 1n the lungs. The detection of radioactivity In the pelt
and several Internal organs on sacrifice at 32-128 days postexposure
Indicated that absorption from the pulmonary tract did occur. It was not
possible to estimate the properties of the Inhaled dose that was absorbed or
the contribution to radioactivity In the tissues resulting from gastro-
intestinal absorption of antimony cleared from the pulmonary tract by
mucocllHary action.
0112h -6- 06/15/87
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3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1. SUBCHRONIC
3.1.1. Oral. Although the following two studies (Dunn, 1928; Monler-
U1ll1ams, 1934) reported acute poisoning Incidents In humans, they were
considered In the risk assessment (U.S. EPA, 1985a) and therefore are
reported here. Seventy people who drank lemonade from preparations left
overnight In white enamelware buckets (the enamel contained 2.88% antimony
trloxlde) became 111. Antimony trloxlde had been leached from the enamel by
the acidic lemonade. Fifty-six people were hospitalized, suffering from
burning stomach pains, colic, nausea and vomiting; most recovered within 3
hours. Analysis found that the lemonade contained 0.013% metallic antimony.
Each person Ingesting -300 ml lemonade would have received 36 mg antimony,
which Is similar to an emetic dose listed In the British Pharmacopoeia.
Several subchronlc and chronic oral studies with various forms of
antimony are briefly summarized 1n Table 3-1. Subchronlc oral studies
Include Sunagawa (1981), Bradley and Frederick (1941), Smyth and Carpenter
(11948), and Gross et al. (1955). However, 1n the Bradley and Frederick
study, effects for Individual exposure groups were not discussed.
Smyth and Carpenter (1948) gave rats dietary antimony trloxlde at doses
ranging from 60-1070 mg/kg bw/day for 30 days and observed reduced growth
arid appetite as well as unspecified mkropathology of the liver, kidney,
spleen or testes at the highest dose. No effects were observed at 270
mg/kg/day. Sunagawa (1981), however, noted a significant decrease 1n
erythrocyte counts In rats fed diets containing 5000 ppm metal1c antimony
for 6 months. Assuming a food factor for rats of 0.05, an equivalent Intake
of 250 mg/kg/day Is estimated.
0112h -7- 06/15/87
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3.1.2. Inhalation. Several subchronlc Inhalation experiments with
antimony trloxlde dust In laboratory animals are summarized In Table 3-1.
These studies (Belyaeva. 1967; Gudzovskll, 1968; Dernehl et al., 1945; Watt,
1983; Gross et al., 1952) failed to Identify a NOAEL but Indicated that the
lung 1s the primary target organ by Inhalation exposure. At high levels of
exposure (250 mg/m3, 4 hours/day for 1.5-2.0 months), hlstopathologlcal
lesions were also noted 1n the liver, kidney, pancreas, uterus and ovary
(Belyaeva, 1967).
3.2. CHRONIC
3.2.1. Oral. Rats exposed to antimony showed a significant decrease In
longevity (p<0.001), which was defined as the mean survival time for the
last 10% of the surviving animals. Kanlsawa and Schroeder (1969) reported
similar results In mice.
Only two studies of the chronic oral toxlclty of antimony compounds were
located In the available literature. These experiments, summarized In Table
3-1 are a lifetime study with rats (Schroeder et al., 1970) and a lifetime
study with mice (Kanlsawa and Schroeder, 1969) In which drinking water
contained 5 ppm antimony from potassium antimony tartrate. The Kanlsawa and
Schroeder (1969) study was designed primarily as a cancer bloassay; there-
fore, other Indicators of toxldty were either not examined In detail or not
reported. Only visible tumors were sectioned, however. Body weights were
monitored and no significant differences found. The authors estimated that
the mice drank 7 ml water/100 g body weight, which corresponds to 35
tig/100 g or 350 yg/kg.
In the Schroeder et al. (1970) study, rats were exposed to 5 ppm anti-
mony 1n their drinking water. Endpolnts monitored Included body weights,
blood pressure, serum chemistries Including glucose, and urlnalysls.
0112h -9- 06/15/87
-------
Animals dying during the study were subjected to autopsy and grossly visible
lesions were examined hlstopathologlcally. Both males and females exhibited
significantly decreased longevity. Fasting serum glucose levels were not
significantly different from controls In either sex. Nonfastlng serum
glucose was depressed significantly In both sexes. No effects were seen on
blood pressure. Ur1nalys1s did not reveal statistically significant differ-
ences. The authors do not report water consumption In this study; however,
Kanlsawa and Schroeder (1969) report water consumption for rats of the same
strain handled 1n the same laboratory as 7.5 ml/100 g for females and 6.8
ml/100 g for males. These drinking rates would correspond to an estimated
dose of 350 yg/kg bw/day. The finding of reduced longevity appears to be
the most biologically significant finding. Failure to perform a complete
hlstopathologlcal workup Is seen as a major deficiency In this study along
with the single dose level and minimal reporting detail.
3.2.2. Inhalation. Chronic Inhalation studies Include a 2-year experi-
ment with rats using antimony trloxlde (Watt, 1983) and occupational studies
with antimony trloxlde (HcCallum, 1963, 1967; HcCallum et al., 1971) and
antimony trlsulflde (Brleger et al., 1954). These studies are summarized In
Table 3-2. Watt (1980, 1981, 1983) and ASARCO Inc. (1980) all report
portions of the results from apparently the same study. In this study 148
female CDF rats were divided Into three groups (numbers per group not
specified). Animals were exposed to antimony trloxlde dust at levels of
1.6+1.5 mg/ma or 4.2^3.2 mg/m3 (as antimony), 6 hours/day, 5 days/week
for 1 year. At baseline and following 3 months, 6 months and 1 year of
exposure hematology, serum enzymes and serum chemistries (endpolnts not
otherwise specified) were evaluated. Body and organ weights were evaluated
and "selected" tissues were examined hlstopathologlcally.
0112h -10- 06/15/87
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Suggestive elevations in BUN were seen; however, values were only
statistically different from controls In males after 6 months, but not 1
year of exposure. Lung weights showed a "consistent pattern" of being
heavier 1n exposed rats In a dose-related manner. Apparently Interim
sacrifices were conducted, although numbers of animals sacrificed are not
specified. The text states that the high-dose rats had statistically
Increased lung weights at the 9- and 12-month time points.
The primary findings at autopsy were both nonneoplastlc and neoplastlc
lung lesions. The nonneoplastlc lesions were described as focal Mbrosls,
adenamatous hyperplasla, multlnucleated giant cells, cholesterol clefts,
pneumonocyte hyperplasla and plgmented macrophages.
Neoplastlc changes In the lungs were seen In animals 18 months of age or
older with the majority seen In animals surviving 29 months. Apparently,
postexposure observations were conducted since exposure only lasted 1 year.
An unexplained figure suggests postexposure sacrifices "10 weeks and ~48
weeks postexposure (Watt, 1981). Lung neoplasms In general appeared to
arise from the alveolar epithelial lining. Tumor Incidences were reported
for six sacrifice times that appear to be 20, 33 and 53 weeks after the
start of exposure and 10 and 48 weeks postexposure. For all lung neoplasms
combined Incidences were significantly elevated In groups sacrificed at 10
weeks and at 53 weeks postexposure. The author states that there were
significant differences In both tte low- and high-dose groups; however, this
statement Is perplexing. At 10 weeks postexposure Incidences were 1/6, 0/5
and 5/7 for the control, low- and high-dose groups, respectively. After 53
weeks these same groups showed Incidences of 1/13, 1/17 and 14/18. The
predominant tumor type was sdrrhous carcinoma, which was reported at an
Incidence of 5/7 and 9/18 for the high-dose group at 10 and 53 weeks,
respectively, while the control and low-dose Incidence was zero.
0112h -12- 06/15/87
-------
This study 1s difficult to evaluate because of the fragmented reporting.
][n addition, there was apparently quite a lot of variability In exposure
concentrations.
An additional unpublished study (Wong et al., 1979; EPL, 1981) reported
1:he results of an Inhalation study 1n which rats were exposed to "5Q>40
ng/ma" antimony trloxlde for 1 year (7 hours/day, 5 days/week) and then
held for 1 year. Neoplastlc lesions were found In female rats but not
males. No further details were provided.
The lung and heart appear to be target organs for the toxic effects of
antimony compounds 1n humans. McCallum (1963, 1967) and HcCallum et al.
(1971) observed dermatitis and pneumoconlosls with no overt symptoms 1n
workers exposed to concentrations >0.5 mg/m3 antimony trloxlde, 40
hours/week for 5-35 years (see Table 3-1). Brleger et al. (1954) observed
altered ECG patterns In workers exposed to 0.58-5.5 mg/m3 antimony
trlsulflde for 2 years.
3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS
3.3.1. Oral. Limited data concerning the teratogenlc and reproductive
effects of antimony compounds were available. Rabbits given high oral doses
(15-55 mg every other day for 30-90 days) of metallic antimony had frequent
abortions (Boverl, n.d.). James et al. (1966) fed four yearling ewes a dose
of 2 mg/kg bw antimony potassium tartrate for 45 days or throughout gesta-
tion, and offspring of treated ewes were normal.
3.3.2. Inhalation. Belyaeva (1967) compared women working 1n an antimony
metallurgical plant with a similar group of women not exposed to antimony.
The exposed group had higher Incidences of spontaneous abortions (12.5 vs.
4.IX), premature births (3.4 vs. 1.2X) and gynecological problems (77.5 vs.
56X). The gynecological problems Included menstrual cycle disorders (61.2
Oll2h -13- 06/15/87
-------
vs. 35.7X). inflammatory disease (30.4 vs. 55.3X) and other reproductive
problems (8.4X of exposed women). These women were exposed to unspecified
amounts of antimony trloxlde, metallic antimony and antimony pentasulfldes.
Children born to these exposed women weighed significantly less after 1 year
when compared with children born to nonexposed women; there were no
statistically significant differences In weights at birth of the two sets of
children.
Alello (1955) observed a higher rate of premature deliveries and
frequent dysmenorrhea among female workers engaged In antimony smelting and
processing (U.S. EPA, 1980a).
Belyaeva (1967) exposed 24 female rats repeatedly to antimony trloxlde
dust by Inhalation for 1.5-2 months at doses of 250 mg/m3 for 4 hours/day
(NIOSH, 1978). Rats were treated In this manner 3-5 days before estrus and
then mated. Exposure to the dust was continued until 3-5 days before
delivery. Of the treated rats, 16/24 conceived whereas all of the 10
control rats became pregnant. Average litter sizes for treated rats were
6.2 and for control rats 8.3. No morphological changes were seen In the
fetuses. Resorptlon and fetal deaths were not discussed.
3.4. TOXICANT INTERACTIONS
Information concerning toxicant Interactions could not be located 1n the
available literature.
0112h -14- 06/15/87
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4. CARCINOGENICITY
4.1. HUNAN DATA
4.1.1. Oral. Data concerning the cardnogenldty of antimony by the oral
route could not be located In the available literature.
4.1.2. Inhalation. Davles (1973) conducted a retrospective epldemlo-
loglcal study In 1081 male and female antimony process workers. Of the 56
deaths reported for this cohort, 10 were attributed to lung cancer, and 9 of
these deaths occurred In workers engaged 1n antimony smelting and related
activities. The number of deaths expected was 5.7, based on community death
rates, yielding a relative risk of 1.75. Statistical analysis of these data
were not reported. Unfortunately, this study has only been reported 1n a
short letter making a critical analysis of the results unfeasible. Addi-
tional ep1dem1olog1cal studies are 1n progress (U.S. EPA, 1983f). The
available data are considered to be suggestive, but Inadequate to draw firm
conclusions.
4.2. BIOASSAYS
4.2.1. Oral. Schroeder et al. (1970) and Kanlsawa and Schroeder (1969)
gave rats and mice (see Section 3.2.1.) 5 ppm antimony as potassium antimony
tartrate In drinking water over the llfespan and observed no carcinogenic
effect. Tumors were located by gross Inspection at necropsy. Hlstopatho-
loglcal examination was performed only on grossly Identified tumors, grossly
observed lesions and sections of heart, lung, liver, kidney and spleen.
Decreased longevity was observed In rats of both sexes and 1n female mice,
but the Investigators did not feel that shortened Hfespan altered the
expression of the cardnogenlcHy of antimony. The authors felt that anti-
mony did not exhibit carcinogenic activity. This study was an Inadequate
rest of cardnogenlcHy for a number of reasons Including: 1) only one dose
0112h -15- 04/01/87
-------
level was employed; 2) no evidence was presented to Indicate the HTD was
approached; and 3) Inadequate hlstopathologlcal evaluations were conducted.
4.2.2. Inhalation. A statistically significant Increase 1n lung tumors
(Table 4-1) was observed 1n female rats exposed to 4.2 mg/m3 antimony from
antimony trloxlde for 6 hours/day, 5 days/week for 1 year (ASARCO, Inc.,
1980; Watt, 1980, 1981, 1983). A statistically significant Increase In lung
tumors was not observed 1n female rats exposed to 1.6 mg/m3 antimony.
Watt (1983) further reported that S-l miniature swine exposed by the same
exposure schedule did not develop exposure-related alterations.
Wong et al. (1979) exposed male and female rats to 50 or 40 mg/m3
antimony trloxlde or 50 or 40 mg/m3 antimony trlsulflde for 7 hours/day, 5
days/week for 1 year followed by a 1-year observation period. Neoplastlc
lesions developed 1n female rats exposed to either compound; nonneoplastlc
lesions developed 1n males.
U.S. EPA (1983e) stated that the Watt (1980, 1981, 1983) and Wong et al.
(1979) studies provided qualitative evidence of oncogenlc effects 1n rats,
but found these studies Inadequate for quantitative risk assessment because
only one sex was used In the Watt (1980, 1981, 1983) studies and only one
exposure level was used by Wong et al. (1979). No data exists concerning
the carclnogenlclty of metallic antimony. Since metallic antimony 1s oxi-
dized to antimony trloxlde during processing, there would be no significant
differences In the consequences of exposure to the two substances, and the
oncogenlc risk of exposure to metallic antimony should be "generally equiva-
lent" to exposure to antimony trloxlde (U.S. EPA, 1983f). Antimony potas-
sium tartrate has been scheduled for carclnogenlclty testing by the National
Toxicology Program (NTP, 1986) and Is currently being assigned to a labora-
tory for toxicology study.
0112h -16- 04/01/87
-------
TABLE 4-1
Tumor Incidence In Female Rats Exposed by
Inhalation to Antimony Tr1ox1dea»b
I:xposurec/Dose
(mg/kg/day)d
4. ,2 mg/m3
(0.48 mg/kg/day)
1 ,6 mg/m3
(0.18 mg/kg/day)
0
Duration of
Treatment
(days)
365
365
NA
Duration
of Study
(days)
730
730
730
Target
Organ
lung
lung
lung
Tumor Type
carcinoma
adenoma
carcinoma
adenoma
carcinoma
adenoma
Tumor
Incidence
15/17
1/17
1/13
aSource: ASARCO, Inc., 1980; Watt, 1981, 1983
bPur1ty of compound not reported
Exposures were for f> hours/day, 5 days/week
Calculated by assuming a respiratory rate of 0.223 mVday and a reference
body weight for rats of 0.35 kg, and expanding to continuous exposure.
NA = Not applicable
0112h
-17-
04/01/87
-------
4.3. OTHER RELEVANT DATA
Kanematsu et al. (I960) observed positive mutagenlc effects of antimony
trloxlde 1n the recomblnant DNA Bacillus subtlUs assay. Indicating that
antimony trloxlde damages DNA (U.S. EPA, 1979). Antimony trloxlde was nega-
tive for reverse mutation In Salmonella typhlmurlum strains TA1535, TA100,
TA98, TA1537 and TA1538 {Kanematsu et al., 1980). Antimony sodium tartrate
caused chromosomal aberrations In cultured human cells (Paton and Allison,
1972). Since differences In chemical and physical properties exist between
antimony tartrate and antimony oxides, the U.S. EPA does not consider these
data relevant to assessing the mutagenlclty of metallic antimony, antimony
trloxlde or antimony trlsulflde (U.S. EPA, 1983f).
4.4. WEIGHT OF EVIDENCE
Some data exist regarding Induction of lung tumors In female rats after
Inhalation exposure 1n a chronic study by Watt (1983), using dose levels
close to the present OSHA standard. U.S. EPA (1983f) reported that none of
the available studies. Including Watt (1983) and Wong et al. (1979). are
suitable for quantitative determination of carcinogenic risk and the
mutagenlclty studies are not conclusive. The deficiencies of these studies
were discussed 1n detail 1n previous sections of this report; however, the
deficiencies relate primarily to quantitative exposure-response estimates.
These studies are considered to represent adequate qualitative evidence of
carcinogen-city In experimental animals following Inhalation exposure.
Increased Incidence of lung cancer-related mortality has been reported In
workers associated with smelting operations (Davles, 1973). However, this
report was' limited to a 2-page letter making It Impossible to adequately
evaluate this study. Applying the criteria for weight of evidence proposed
by EPA (U.S. EPA, 1986b), antimony 1s most appropriately classified 1n
0112h -18- 04/01/87
-------
Group B2, Possible Hunan Carcinogen, based on sufficient animal data. Human
data, while suggestive, are considered Inadequate because of reporting
deficiencies. This classification w111 require revaluation pending more
complete reporting of existing human studies or new reports of human
exposures. The B2 classification currently can be applied only to Inhaled
antimony. Current data are Inadequate to assess the potential carcino-
gen 1c1ty of Ingested antimony. This would result In an EPA classification
of D for orally administered antimony.
0112h -19- 04/27/87
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5. REGULATORY STANDARDS AND CRITERIA
U.S. EPA (1986a) derived an RfD of 0.0004 mg/kg/day for antimony based
on a rat chronic oral bloassay (Schroeder et al., 1970). U.S. EPA (1980a)
derived an ambient water quality criterion of 145 yg/i, or 45 mg/l 1f
consumption Is from fish and shellfish alone, for antimony [also based on
Schroeder et al. (1970)]. U.S. EPA (1985a) derived RfDs for a 70 kg man of
29.3, 30.9 and 32.9 yg/day for antimony trloxlde, tetraoxlde and pent-
oxide, respectively, based on Schroeder et al. (1970). NAS (1980) suggested
a chronic SNARL based on a LOAEL of 0.0025 mg/kg reported by Arzamastsev
(1964). U.S. EPA (1985b) did not propose an RHCL for antimony because
"preliminary analysis Indicated limited potential for. drinking water
exposure causing a significant risk from these substances.*
OSHA (1985) adopted a PEL of 0.5 mg/m3 for antimony and compounds.
NIOSH (1978) recommended a TWA concentration limit of 0.5 mg/m3 based on
exposure-associated cardiac and respiratory changes and Irritation of the
skin and mucous membranes. ACGIH (1986) recommended a TLV-TWA of 0.5
mg/m3 as antimony for antimony and compounds.
0112h -20- 04/01/87
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6. RISK ASSESSMENT
6.1. SUBCHRONIC REFERENCE DOSE (RfD$)
6.1.1. Oral (RfOgg). Subchronlc oral data are not adequate for quanti-
tative risk assessment because the available studies, with one exception, do
not define thresholds for toxlclty. The study by Smyth and Carpenter (1948)
could be used to derive an RfDso» however, but 1t was considered
Inadequate because small numbers of animals were tested and no controls were
maintained. RfD_ values for selected antimony compounds are derived In
Section 6.2.1.
6.1.2. Inhalation (RfDCT). Several subchronic Inhalation studies were
ol
reviewed In Section 3.1.2., but these studies do not define either Individ-
ually or collectively the thresholds for toxldty. The data, therefore, are
Insufficient for derivation of an RfOCT. In addition, bloassay data
dl
suggest that antimony 1s carcinogenic by the Inhalation route (see Section
6,2.2.).
6.2. REFERENCE OOSE (RfD)
6.2.1. Oral (RfD.,). Many of the EPA documents on antimony and com-
pounds have based risk assessment for Individual members of a class by a
particular route of exposure on the most toxic compound of the class to
provide the greatest margin of safety (U.S. EPA, 1980, 1985a, 1986a). ACGIH
(1986), NIOSH (1978) and OSHA (1985), however, have reported a single value
when considering antimony as a class. Observations from a limited database
Indicate that the target organs for the toxic effects of antimony and
compounds by the oral or Inhalation routes Include the heart, lung, liver
and kidney (see Table 3-1).
OH2h -21- 06/15/87
-------
The approach to derivation of RfD_ values taken In this document
Incorporates previous U.S. EPA (1980a, 1985a, 1986a) analyses. U.S. EPA
(1980a) calculated an RfD for antimony from the LOAEL of 5 ppm antimony
(from potassium antimony tartrate) 1n the drinking water of rats exposed for
their lifetimes (Schroeder et al., 1970). This treatment was associated
with reduced Hfespan 1n both sexes and blood biochemistry alterations 1n
males. U.S. EPA (1980a) assumed a water Intake of 0.025 l/day and
estimated an average body weight for the rats of 0.3 kg (presumably based on
the tabular data provided by the Investigators) to compute a dose of 417
vg/kg/day. Application of an uncertainty factor of 100 resulted In an RfD
of 4.17 vg/kg/day or 292 yg/day for a 70 kg human. An uncertainty
factor of 100 rather than 1000 was used, because It was felt that this LOAEL
approximates the 'no-effect* level for antimony Induced effects on growth
and longevity."
In a more recent analysis (U.S. EPA, 1985a, 1986a), a dally dose of 350
vg/kg/day was estimated for the 5 ppm level of antimony In drinking water
In the Schroeder et al. (1970) experiment with rats. Although mg/kg/day
doses were not reported for this experiment, this value Is consistent with
consumption rates reported by these Investigators for the same strain of rat
and similar experimental protocols utilizing different metals (Kanlsawa and
Schroeder, 1969).
The more recent U.S. EPA (1985a, 1986a) analysis chooses an uncertainty
factor of 1000 rather than 100, as was chosen In the earlier (U.S. EPA,
1980a) report. The choice of the larger uncertainty factor seems more
appropriate when applied to a LOAEL associated with reduced longevity,
regardless of effects on growth, and 1s, therefore, used In this analysis.
0112h -22- 06/15/87
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Application of an uncertainty factor of 1000 to a dose of 350 jig/kg/day
results In an RfDQ for antimony of 0.350 yg/kg/day or 0.024 mg/day (24.5
vg/day) for a 70 kg human (U.S. EPA, 1986a). By correcting for differ-
ences In molecular weights, RfD- values for other antimony compounds are
as follows: antimony potassium tartrate, 65.4 tig/day; antimony trloxlde,
29.3 vg/day; antimony tetroxlde, 30.9 yg/day; antimony pentoxlde, 32.5
yg/day (U.S. EPA, 1985a). RfD values for more soluble salts and
organic compounds of antimony are not calculated because virtually nothing
1s known about the subchronlc or chronic toxldty of these substances.
U.S. EPA (1983b) derived an oral CS of 38 for antimony potassium
tartrate based on the endpolnt of decreased longevity In rats exposed to 5
ppm antimony (equivalent to 13.7 ppm of antimony potassium tartrate) In
drinking water over a lifetime (Schroeder et al., 1970).
6,.2.2. Inhalation (RfD.). Qualitative evidence strongly suggests that
antimony 1s a possible human carcinogen. A retrospective epldemlologlcal
study suggested that deaths from lung cancers Increased In antimony workers
(Davles, 1973). An Increased Incidence of lung cancers was observed In rats
exposed to 4.2, but not to 1.6 mg ant1mony/m3, 6 hours/day, 5 days/week
for 1 year and observed for another year (Watt, 1980, 1981, 1983; ASARCO,
Inc., 1980). U.S. EPA (1983f) evaluated these data and determined them
Inadequate for quantitative assessment of carcinogenic risk. Further
carclnogenlclty testing was recommended. Pending the outcome of these
tests, and based upon the qualitative evidence for carclnogenlclty, an
RfD. Is not derived.
U.S. EPA (1985a) based an Inhalation CS for the antimony oxides on the
Watt (1983) observation of flbrotlc lung changes 1n female rats at a dose of
0.18 mg/kg/day, which corresponded to a chronic human MED of 2.2. An RV.
0112h -23- 06/15/87
-------
of 5.0 was calculated, and an RVg of 6 was1 assigned for the flbrotlc lung
changes. Multiplying the RVd of 5 by an RVg of 6, a CS of 30 was
obtained. Watt (1983) used a 1-year exposure period In rats which arguably
should be considered subchronlc and the converted dose should be divided by
an additional factor of 10; thus, a chronic human MED of 0.2 mg/day would be
obtained, corresponding to an RV. of 6.5. Multiplying an RV. of 6.5 by
an RV of 6 would result 1n a CS of 39.
e
U.S. EPA (1983a) based an Inhalation CS of 46 on BMeger et al. (1954)
who observed altered ECG patterns In workers exposed to concentrations of
antimony trlsulflde >0.58 mg/m3 (0.2 mg/m3 as antimony). This CS was
not adopted because of lack of control data. Additionally, the workers had
been exposed to mixtures of chemicals.
U.S. EPA (1983c) derived an Inhalation CS of 18 for antimony trloxlde.
(For a discussion of the Inadequacies of this value see U.S. EPA, 1985a.)
The CS of 39 associated with flbrotlc and hyperplastlc changes In the lungs
of rats exposed to antimony trloxlde by Inhalation for 1 year (Watt, 1980,
1981. 1983; ASARCO, Inc., 1980) 1s chosen as most stringently representing
the toxlclty of antimony.
6.3. CARCINOGENIC >OTENCY (q^)
6.3.1. Oral. No data concerning the oral cardnogenldty of antimony and
compounds 1n humans was available. Available animal studies suggested that
antimony and compounds were not carcinogenic by the oral route (Schroeder et
al., 1970; Kanlsawa and Schroeder, 1969).
6.3.2. Inhalation. Davles (1973) suggested that occupational exposure to
antimony may lead t) lung cancer In humans. Davles (1973) reported that 10
deaths from lung cancer were observed 1n occupatlonally exposed workers.
The expected number of deaths attributed to lung cancer was 5.7, yielding a
relative risk of 1.75.
0112h -24- 04/01/87
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Watt (1983) observed a statistically significant Increase In lung tumors
(see Table 4-1) In female rats exposed to 4.2 mg/m* antimony from antimony
trloxlde for 6 hours/day, 5 days/week for 1 year followed by a 1-year
observation period.
Wong et al. (1979) observed lung tumors In male and female rats exposed
to 5Q>40 mg/m3 antimony trloxlde for 7 hours/day, 5 days/week for 1 year.
U.S. EPA (1983f) considered these studies Inadequate for quantitative
risk assessment, but stated they that provided qualitative evidence of an
oncogenIc effect.
-------
7. REFERENCES
ACGIH (American Conference of Governmental Industrial Hyglenlsts). 1986.
Documentation of the Threshold Limit Values and Biological Exposure Indices,
5th ed. Cincinnati. OH. p. 32.
Alello, G. 1955. Pathology of antimony. Folia Med. (Naples). 38: 100.
(Cited 1n U.S. EPA, 1980a)
Arzamastsev, E.V. 1964. Experimental substantiation of the permissible
concentrations of trl- and pentavalent antimony In water bodies. Hyg.
Sanlt. 29: 16-21. (Cited In NAS, 1980}
-------
Matt (1983) observed a statistically significant Increase In lung tumors
(see Table 4-1) In female rats exposed to 4.2 mg/m* antimony from antimony
tr1 oxide for 6 hours/day, 5 days/week for 1 year followed by a 1-year
observation period.
Wong et al. (1979) observed lung tumors In male and female rats exposed
to 50^40 mg/m3 antimony trloxlde for 7 hours/day, 5 days/week for 1 year.
U.S. EPA (1983f) considered these studies Inadequate for quantitative
risk assessment, but stated they that provided qualitative evidence of an
oncogenlc effect.
0112h -25- 04/01/87
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7. REFERENCES
ACGIH (American Conference of Governmental Industrial Hyglenlsts). 1986.
Documentation of the Threshold Limit Values and Biological Exposure Indices,
5th ed. Cincinnati, OH. p. 32.
Alello, G. 1955. Pathology of antimony. Folia Med. (Naples). 38: 100.
(Cited In U.S. EPA, 1980a)
Arzamastsev, E.V. 1964. Experimental substantiation of the permissible
concentrations of tr1- and pentavalent antimony 1n water bodies. Hyg.
Sanlt. 29: 16-21. (Cited In NAS, 1980)
ASARCO, Inc. 1980. TSCA 8(e) submission 8EHQ-0580-0342. B1o/tox data on
antimony trloxlde. OTS, U.S. EPA, Washington, DC.
Belyaeva, A.P. 1967. The effect of antimony on reproduction. Gig. Truda.
Prof. Zabole. 11: 32. (Cited In NIOSH, 1978)
BoveH, P.A. n.d. No title provided. (Cited 1n Bradley and Frederick.
1941)
Bradley, U.R. and W.G. Frederick. 1C41. The toxlclty of antimony Animal
studies. Ind. Med. (Ind. Hyg. Sec.). 2: 15-22.
Brleger, H., C.W. Semlsch III, J. Stasney and D.A. Pratnlk. 1954. Indus-
trial antimony poisoning. Ind. Ned. Surg. 23: 521-523.
i
0112h -26- 04/01/87
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Carapella, S.C. 1978. Antimony and antimony alloys. Iri: K1rk-0thmer
Encyclopedia of Chemical Technology, 3rd ed., N. Grayson and D. Eckroth, Ed.
John Wiley and Sons, Inc., New York. 3: 96.
Davles, T.A.L. 1973. The health of workers engaged In antimony oxide
manufacture -- A statement. Dept. Employment, Employment Medical Advisory
Serv., London. 2 p. (Cited In NIOSH, 1978)
Oernehl, C.V., C.A. Nau and H.H. Sweets. 1945. Animal studies on the
toxlclty of Inhaled antimony trloxlde. J. Ind. Hyg. Toxlcol. 27: 256-262.
Dunn, J.J. 1928. A curious case of antimony poisoning. Analyst. 53:
532-533.
EUnder, C.G. and L. Frlberg. 1977. Antimony. In_: Toxicology of Metals,
Vol. II. Prepared by the Subcommittee on the Toxicology of Metals,
Permanent Commission and International Association of Occupational Health In
cooperation with the Swedish Environmental Protection Board and the
Karollnska Institute. NTIS PB-268324. (Cited In U.S. EPA, 1985a)
Fe11cett1, S.A., R.G. Thomas and R.O. McClellan. 1974a. Metabolism of two
valence states of Inhaled antimony. Am. Ind. Hyg. Assoc. J. 355: 292-300.
Fel1cett1, S.M., R.G. Thomas and R.O. McClellan. 1974b. Retention of
Inhaled antlmony-124 In the beagle dog as a function of temperature of
aerosol formation. Health Phys. 26: 525-531.
0112h -27- 04/01/87
-------
Gro^s, P., J.H.U. Brown and T.F. Hatch. 1952. Experimental endogenous
Upold pneumonia. Am. J. Pathol. 28: 211.
Gross, P., J.H.U. Brown, M.L. Westrlck, R.P. Srslc, N.L. Butler and T.F.
Hatch. 1955. Toxlcologlcal study of calcium halophosphate phospher and
antimony trloxlde. I. Acute and chronic toxlclty and some pharmacological
aspects. Arch. Inc. Health. 11: 473.
GudzovskM, G.A. 1968. Development of I1p1d focal pneumonia during anti-
mony dust Inhalation. Sb. Nauch. Rab. K1rg. Nauch.-Issled. Inst. Tuberk.
5: 82-87. (Rus.) (CA 71:24549c)
James, L.F., V.A. Lazar and W. B1nns. 1966. Effects of sublethal doses of
certain minerals on pregnant ewes and fetal development. Am. J. Vet. Res.
27: 132-135. (Cited In U.S. EPA, 1979)
Kanematsu, N., S. Kara and T. Kada. 1980. Rec assay and mutagen1c1ty
studies on metal compounds. Hutat. Res. 77(2): 109-116.
Kanlsawa, M. and H.A. Schroeder. 1969. Life term studies on the effects of
trace elements of spontaneous tumors In mice and rats. Cancer Res. 29:
892-895.
McCallum, R.I. 1963. The work of an occupational hygiene service In
environmental control. Ann. Occup. Hyg. 6: 55-64. (CUed In NIOSH, 1978;
U.S. EPA, 1980a, 1981)
0112h -28- 04/01/87
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MeCallurn, R.I. 1967. Detection of antimony In process workers' lungs by
x-rad1at1on. Trans. Soc. Occup. Ned. 17: 134-138. (Cited In U.S. EPA,
1980a, 1981)
McCallum, R.I., N.J. Day, J. Underbill and E.G.A. Alrd. 1971. Measurement
of antimony oxide dust 1n human lungs In vivo by x-ray spectrophotometry.
In: Inhaled Particles-Ill, Vol. 2, W.H. Walton, Ed. Proc. Int. Symp.
Organized by the British Occupational Hygiene Society, London, September
14-23, 1970. Unwln Brothers Ltd., Gresham Press, England, p. 611-619.
(Cited 1n NIOSH, 1978)
Mon1er-W1ll1ams, G.W. 1934. Antimony In enamelled hollow-ware. Report on
Public Health and Medical Subjects, No. 73, Ministry of Health, London.
18 p. (Cited 1n NIOSH, 1978)
NAS (National Academy of Sciences). 1980. Drinking Water and Health. Vol.
III. Problems of Risk Estimation. NAS, Washington, DC. p. 77-80.
NIOSH (National Institute for Occupational Safety and Health). 1978.
Criteria for a Recommended Standard...Occupational Exposure to Antimony.
U.S. DHEW, PHS, CDC, Rockvllle, MD. Publ. No. 78-216.
NTP (National Toxicology Program). 1986. Management Status Report. Dated
6/8/86.
OSHA (Occupational Safety and Health Administration). 1985. OSHA Safety
and Health Standards. Code of Federal Regulations. 29 CFR 1910.1000.
0112h -29- 04/01/87
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Paton, G.R. and A.D. Allison. 1972. Chromosome damage In human cell
cultures Induced by metal salts. Hutat. Res. 16: 332-336.
Schroeder, H.A., H. Kitchener and A.P. Nason. 1970. Zirconium, nlobHum,
antimony and lead In rats: Life-time studies. J. Nutr. 100: 59-69.
Smyth-, H.F. and C.P. Carpenter. 1948. Further experience with the range
finding test In the Industrial toxicology laboratory. J. Ind. Hyg. Toxlcol.
30: 63-68.
Sunagawa, S. 1981. Experimental studies on antimony poisoning. Igaku
Kenkyu. 51(3): 129-42. (Japanese with English abstract)
U.S. EPA. 1979. Fourth report of the Interagency Testing Committee;
receipt of the report and request for comments. Federal Register. 44:
31866-31880.
U.S. EPA. 1980a. Ambient Water Quality Criteria Document for Antimony.
Prepared by the Office of Health and Environmental Assessment, Environmental
Criteria and Assessment Office, Cincinnati, OH for the Office of Water Regu-
lations and Standards, Washington, DC. EPA 440/5-80-020. NTIS PB81-117319.
U.S. EPA. 1980b. Guidelines and Methodology Used In the Preparation of
Health Effect Assessment Chapters of the Consent Decree Water Criteria
Documents. Federal Register. 45(231): 79347-79357.
0112h -30- 04/01/87
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U.S. EPA. 1983a. Reportable Quantity Document for Antimony and Compounds.
Prepared by the Office of Health and Environmental Assessment, Environmental
Criteria and Assessment Office, Cincinnati, OH for the Office of Emergency
and Remedial Response, Washington, DC.
U.S. EPA. 1983b. Reportable Quantity Document for Antimony Potassium
Tartrate. Prepared by the Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, Cincinnati, OH for the Office
of Emergency and Remedial Response, Washington, DC.
U.S. EPA. 1983c. Reportable Quantity Document for Antimony Tr1ox1de.
Prepared by the Office of Health and Environmental Assessment, Environmental
Criteria and Assessment Office, Cincinnati, OH for the Office of Emergency
and Remedial Response, Washington, DC.
U.S. EPA. 1983d. Methodology and Guidelines for Reportable Quantity Deter-
minations Based on Chronic Toxlclty Data. Prepared by the Office of Health
and Environmental Assessment, Environmental Criteria and Assessment Office,
Cincinnati, OH for the Office of Solid Waste and Emergency Response,
Washington, DC.
U.S. EPA. 1983e. EPA National Revised Primary Drinking Water Regulations.
Federal Register. 48(194): 45502.
U.S. EPA. 1983f. Antimony metal, antimony trloxlde and antimony sulflde
response to the Interagency Testing Committee. Federal Register. 48(4):
717-725.
0112h -31- 04/01/87
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U.S. EPA. 1985a. Health and Environmental Effects Profile for Antimony
Oxides. Prepared by the Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, Cincinnati, OH for the Office
of Solid Waste and Emergency Response. Washington, DC.
U.S. EPA. 19855. National Primary Drinking Water Regulations. Synthetic
Organic Chemicals, Inorganic Chemicals and Microorganisms. Federal Register.
50(219): November 13, 1985.
U.S. EPA. 1986a. Integrated Risk Information System (IRIS). Reference
dose (RfO) for oral exposure for antimony. Online. (Verification date
11/6/85). Office of Health and Environmental Assessment, Environmental
Criteria and Assessment Office, Cincinnati, OH.
U.S. EPA. 1986b. Guidelines for Carcinogenic Risk Assessment. Federal
Register. 51(185): 33992-34003.
Watt, W.O. 1980. Chronic Inhalation toxldty of antimony trloxlde and
validation of the TLV. Progress report Suirmary of results. TSCA 8(e)
submission 8#HQ-0980-0342. Study submitted by ASARCO, Inc., New York.
Microfiche No. OTS0204846
Watt, W.O. 1981. FYI submission TY-OTS-COOf,l-0121 regarding pathology
report on rat Inhalation study on antimony trloxlde. OTS, U.S. EPA,
Washington. DC. (Cited In U.S. EPA, 1985a)
0112h -32- 04/01/87
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Uatt, M.D. 1983. Chronic Inhalation toxlclty of antimony trloxlde:
Validation of the threshold limit value. 01ss. Abstr. Int. B 1983. 44(3):
739-740.
Weast. R.C., Ed. 1983. CRC Handbook of Chemistry and Physics, 64th ed.
CRC Press, Inc., Boca Raton, PL. p. B70-B71.
Wong, L.C.K.. et al. 1979. Study of cardnogenlcHy and toxlclty of
Inhaled antimony trloxlde, antimony ore concentrate and thalUc oxide In
rats. Midwest Research Institute, Kansas City, MO. (Cited 1n U.S. EPA,
1983f) r.
.S. Environmental Protect:en
0112h -33-
V04/01/87
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