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Thallium(I) sulfate
CASRN 7446-18-6
Contents
0116
Thallium(I) sulfate; CASRN 7446-18-6
Health assessment information on a chemical substance is included in IRIS only
after a comprehensive review of chronic toxicity data by U.S. EPA health
scientists from several Program Offices and the Office of Research and
Development. The summaries presented in Sections I and II represent a
consensus reached in the review process. Background information and
explanations of the methods used to derive the values given in IRIS are
provided in the Background Documents.
STATUS OF DATA FOR Thallium(I) sulfate
File On-Line 01/31/1987
Category (section) Status Last Revised
----------------------------------------- -------- ------------
Oral RfD Assessment (I.A.) on-line 09/01/1990
Inhalation RfC Assessment (I.B.) no data
Carcinogenicity Assessment (II.) on-line 09/01/1990
_I. CHRONIC HEALTH HAZARD ASSESSMENTS FOR NONCARCINOGENIC EFFECTS
__I.A. REFERENCE DOSE FOR CHRONIC ORAL EXPOSURE (RfD)
Substance Name -- Thallium(I) sulfate
CASRN -- 7446-18-6
Last Revised -- 09/01/1990
The oral Reference Dose (RfD) is based on the assumption that thresholds exist
for certain toxic effects such as cellular necrosis. It is expressed in units
of mg/kg-day. In general, the RfD is an estimate (with uncertainty spanning
perhaps an order of magnitude) of a daily exposure to the human population
(including sensitive subgroups) that is likely to be without an appreciable
risk of deleterious effects during a lifetime. Please refer to the Background
Document for an elaboration of these concepts. RfDs can also be derived for
the noncarcinogenic health effects of substances that are also carcinogens.
Therefore, it is essential to refer to other sources of information concerning
the carcinogenicity of this substance. If the U.S. EPA has evaluated this
substance for potential human carcinogenicity, a summary of that evaluation
will be contained in Section II of this file.
___I.A.1. ORAL RfD SUMMARY
Critical Effect Experimental Doses* UF MF RfD
-------------------- ----------------------- ----- --- ---------
No adverse effects NOAEL: 0.25 mg/kg/day 3000 1 8E-5
mg/kg/day
Rat Oral Subchronic LOAEL: None
Study
U.S. EPA, 1986
*Conversion Factors: None
___I.A.2. PRINCIPAL AND SUPPORTING STUDIES (ORAL RfD)
U.S. EPA. 1986. Subchronic (90-day) toxicity of thallium sulfate in Sprague-
Dawley rats. Office of Solid Waste, Washington, DC.
In a 90-day subchronic study, Sprague-Dawley rats (20/sex/group) were treated
by gavage with 0, 0.01, 0.05, and 0.25 mg/kg/day of an aqueous solution of
thallium sulfate (approximately 0.008, 0.04, and 0.20 mg Tl/kg/day). Data
generated from this study included body and organ weights, food consumption,
hematology and clinical chemistry parameters, neurotoxicologic examinations,
ophthalmologic examinations, and histopathology and neuropathology. No
mortality was observed, but apparent dose-related increases in the incidence
of alopecia, lacrimation, and exophthalmos were observed throughout the study.
No differences between the control groups and groups receiving thallium
sulfate were observed in body weights, body weight gains, food consumption, or
absolute and relative organ weights. Moderate dose-related changes were
observed in some blood chemistry parameters: increased SGOT, LDH, and sodium
levels, and decreased blood sugar levels. The only grossly observed finding
at necropsy thought to be treatment-related was alopecia, especially in female
rats; however, microscopic evaluations did not reveal any histopathologic
alterations. Based on the results of this study the 0.25 mg/kg/day thallium
sulfate is considered a NOAEL. By applying an uncertainty factor of 3000 to
this NOAEL, an RfD of 8E-5 mg/kg/day can be derived.
___I.A.3. UNCERTAINTY AND MODIFYING FACTORS (ORAL RfD)
UF -- The UF of 3000 includes factors of 10 to extrapolate from subchronic to
chronic data, 10 for intraspecies extrapolation and 10 to account for
interspecies variability, and a factor of 3 to account for lack of
reproductive and chronic toxicity data.
MF -- None
___I.A.4. ADDITIONAL COMMENTS (ORAL RfD)
Groups of rats (5/sex/dose) were fed diets containing nominal concentrations
of thallium acetate of 0, 5, 15, or 50 ppm (Downs et al., 1960). An
additional group (30 ppm) was added after the study had been initiated (time
not specified). Animals were allowed ad lib access to these diets for 15
weeks. The 50 ppm level resulted in 100% mortality by week 5. The 30 ppm
level resulted in 100% mortality by week 9. By week 15, 4/10 control animals
died (2/sex), making interpretation of survival in remaining dose groups
difficult (15 ppm, 3/5 males and 1/5 females died; 5 ppm, 2/6 males and 0/4
females died). At termination, the only gross finding was alopecia in the 15
and 30 ppm groups. The authors stated that there was a slight increase in
kidney weight (doses not specified, data not shown). The authors reported
that histopathologic evaluations did not indicate treatment-related pathology.
Male Wistar rats (10/group) were administered drinking water containing 10 ppm
T1SO4 (approximately 0.7 mg T1/kg/day based on reported thallium consumptions
[270 ug T1/rat] and body weights [350-370 g] for 30 or 60 days; controls were
pair fed. After 60 days of treatment, the following testicular effects were
observed: disarrangement of the tubular epithelium, cytoplasmic vacuolation
and distention of the smooth endoplasmic reticulum of the Sertoli cells,
reduced testicular beta-glucuronidase activities, high concentrations of
thallium in the testes, and reduced sperm motility (Formigli et al., 1986).
Eighty female Sprague-Dawley rats were administered drinking water containing
thallium sulfate at a concentration of 10 mg Tl/L (approximately equivalent to
a dose of 1.4 mg T1/kg/day based on reported T1 intakes and an assumption that
the rats weighed 200 g). Mortality was 15 and 21% after 40 and 240 days of
treatment, respectively. Functional and histopathological changes were
observed in the peripheral nerves including changes in motor and sensory
action potentials and histopathological changes in the sciatic myelin sheath
and axonal destruction characterized by Wallerian degeneration, mitochondrial
degeneration, neurofilamentous clustering, and elevated lysozomal activity
(Manzo et al., 1983).
___I.A.5. CONFIDENCE IN THE ORAL RfD
Study -- Low
Data Base -- Low
RfD -- Low
Confidence in the critical study is rated low because of uncertainties in the
results (i.e., vehicle vs. control differences) and because supporting studies
show adverse health effects at doses slightly higher than the NOAEL. The data
base provided only one subchronic study and some anecdotal human data, thus, a
low confidence was assigned. Until additional chronic and reproductive
studies are available, confidence in the RfD is considered low.
___I.A.6. EPA DOCUMENTATION AND REVIEW OF THE ORAL RfD
Source Document -- This assessment is not presented in any existing U.S. EPA
document.
Other EPA Documentation -- U.S. EPA, 1986
Agency Work Group Review -- 05/20/1987, 07/16/1987, 08/05/1987, 04/21/1988
Verification Date -- 04/21/1988
___I.A.7. EPA CONTACTS (ORAL RfD)
Please contact the Risk Information Hotline for all questions concerning this
assessment or IRIS, in general, at (513)569-7254 (phone), (513)569-7159 (FAX)
or RIH.IRIS@EPAMAIL.EPA.GOV (internet address).
__I.B. REFERENCE CONCENTRATION FOR CHRONIC INHALATION EXPOSURE (RfC)
Substance Name -- Thallium(I) sulfate
CASRN -- 7446-18-6
Not available at this time.
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
Substance Name -- Thallium(I) sulfate
CASRN -- 7446-18-6
Last Revised -- 09/01/1990
Section II provides information on three aspects of the carcinogenic
assessment for the substance in question; the weight-of-evidence judgment of
the likelihood that the substance is a human carcinogen, and quantitative
estimates of risk from oral exposure and from inhalation exposure. The
quantitative risk estimates are presented in three ways. The slope factor is
the result of application of a low-dose extrapolation procedure and is
presented as the risk per (mg/kg)/day. The unit risk is the quantitative
estimate in terms of either risk per ug/L drinking water or risk per ug/cu.m
air breathed. The third form in which risk is presented is a drinking water
or air concentration providing cancer risks of 1 in 10,000, 1 in 100,000 or 1
in 1,000,000. The rationale and methods used to develop the carcinogenicity
information in IRIS are described in The Risk Assessment Guidelines of 1986
(EPA/600/8-87/045) and in the IRIS Background Document. IRIS summaries
developed since the publication of EPA's more recent Proposed Guidelines for
Carcinogen Risk Assessment also utilize those Guidelines where indicated
(Federal Register 61(79):17960-18011, April 23, 1996). Users are referred to
Section I of this IRIS file for information on long-term toxic effects other
than carcinogenicity.
__II.A. EVIDENCE FOR CLASSIFICATION AS TO HUMAN CARCINOGENICITY
___II.A.1. WEIGHT-OF-EVIDENCE CLASSIFICATION
Classification -- D; not classifiable as to human carcinogenicity
Basis -- Based on the lack of carcinogenicity data in animals and humans.
___II.A.2. HUMAN CARCINOGENICITY DATA
Inadequate. Medical records for 86 workers (sex and length of employment
not reported) occupationally exposed to thallium at a magnesium seawater
battery factory and 79 unexposed workers matched for age, length of
employment, shift pattern, and type of work were examined (Marcus, 1985). No
increase in incidence of benign neoplasms (site not specified) were observed.
This study is limited by the examination of medical records only, lack of
exposure quantitation, the small cohort, and unknown length of observation.
In another study, the health effects associated with exposure to thallium
in 128 men (age 16 to 62 years) exposed for 1 to 42 years (average=19.5 years)
in three cement manufacturing plants were reported (Schaller et al., 1980).
Analyses of roasted pyrites and electro-filter dust confirmed the presence of
thallium in various production areas in the plants. Urinary thallium was
elevated in the workers. The health evaluation, consisting of a medical
history and a physical exam, did not show any indication of thallium
poisoning. However, this health evaluation was not adequate to detect any
oncogenic response.
___II.A.3. ANIMAL CARCINOGENICITY DATA
None. Several subchronic and chronic animal studies on thallium and
compounds are available; however, they were not designed to examine
carcinogenic endpoints (reviewed in U.S. EPA, 1988).
___II.A.4. SUPPORTING DATA FOR CARCINOGENICITY
Thallium (I) salts were not mutagenic in reverse mutation assays using
Salmonella typhimurium strains TA98, TA100, TA1535,and TA1538 and Escherichia
coli strains B/r WP2 try and WP2 hcr try; use of hepatic homogenates was not
specified (Kanematsu et al., 1980). Positive results were obtained at 0.001M
for thallium nitrate in the Rec assay using Bacillus subtilis strains H17 and
M45; use of hepatic homogenates was not specified (Kanematsu\et\al., 1980;
Kada et al., 1980). Negative results were obtained in a screening of thallium
nitrate for induction of mitotic gene coversion and reverse mutation in the
yeast, Saccharomyces cerevisiae (Singh, 1983). Thallium nitrate produced
negative effects on cell division in S. cerevisiae and E. coli. (Loveless et
al., 1954). Cytotoxic levels (1000 ug/mL) of thallium acetate caused
depressed DNA synthesis in Chinese hamster ovary cells (Garrett and Lewtas,
1983). Single-strand DNA breaks occurred in mouse and rat embryo fibroblasts
exposed to thallium carbonate at E-6 to E-4M (Zasukhina et al., 1983).
Thallium carbonate (0.5-0.005 ug/kg/day) was positive in a dominant lethal
test in male white rats (Zasukhina et al., 1983).
__II.B. QUANTITATIVE ESTIMATE OF CARCINOGENIC RISK FROM ORAL EXPOSURE
None.
__II.C. QUANTITATIVE ESTIMATE OF CARCINOGENIC RISK FROM INHALATION EXPOSURE
None.
__II.D. EPA DOCUMENTATION, REVIEW, AND CONTACTS (CARCINOGENICITY ASSESSMENT)
___II.D.1. EPA DOCUMENTATION
Source Document -- U.S. EPA, 1988
The 1988 Health and Environmental Effects Document for Thallium and Compounds
is a preliminary draft and has not received Agency review.
___II.D.2. REVIEW (CARCINOGENICITY ASSESSMENT)
Agency Work Group Review -- 11/08/1989
Verification Date -- 11/08/1989
___II.D.3. U.S. EPA CONTACTS (CARCINOGENICITY ASSESSMENT)
Please contact the Risk Information Hotline for all questions concerning this
assessment or IRIS, in general, at (513)569-7254 (phone), (513)569-7159 (FAX)
or RIH.IRIS@EPAMAIL.EPA.GOV (internet address).
_VI. BIBLIOGRAPHY
Substance Name -- Thallium(I) sulfate
CASRN -- 7446-18-6
Last Revised -- 08/01/1991
__VI.A. ORAL RfD REFERENCES
Downs, W.L., J.K. Scott, L.T. Steadman and E.A. Maynard. 1960. Acute and
subacute toxicity studies of thallium compounds. Am. Ind. Hyg. Assoc. 21:
399-406.
Formigli, L., R. Schelsi, P. Poggi, et al. 1986. Thallium-induced testicular
toxicity in the rat. Environ. Res. 40(2): 531-539.
Manzo, L., R. Scelsi, A. Moglia, et al. 1983. Long-term toxicity of thallium
in the rat. Proceed. 2nd Int. Conf., Chem. Toxicol. Clin. Chem. Met. p. 401-
405.
U.S. EPA. 1986. Subchronic (90-day) toxicity of thallium sulfate in
Sprague-Dawley rats. Office of Solid Waste, Washington, DC.
__VI.B. INHALATION RfC REFERENCES
None
__VI.C. CARCINOGENICITY ASSESSMENT REFERENCES
Garrett, N.E. and J. Lewtas. 1983. Cellular toxicity in Chinese hamster
ovary cell cultures. I. Analysis of cytotoxicity endpoints for twenty-nine
priority pollutants. Environ. Res. 32: 455-465.
Kada, T., K. Hirano and Y. Shirasu. 1980. Screening of environmental
chemical mutagens by the Rec-assay system with Bacillus subtilis. In:
Chemical Mutagens: Principles and Methods for Their Detection, F. deSerrres
and A. Hollaender, Ed. 6: 149-173.
Kanematsu, N., M. Hara and T. Kada. 1980. Rec assay and mutagenicity
studies on metal compounds. Mutat. Res. 77: 109-116.
Loveless, L.E., E. Spoerl and T.H. Weisman. 1954. A survey of effects of
chemicals on division and growth of yeast and Escherichia coli. J. Bacteriol.
68: 637-644.
Marcus, R.L. 1985. Investigation of a working population exposed to
thallium. J. Soc. Occup. Med. 35(1): 4-9.
Schaller, K.H., G. Manke, H.J. Raithel, G. Buhlmeyer, M. Schmidt and H.
Valentin. 1980. Investigations of thallium-exposed workers in cement
factories. Int. Arch. Occup. Environ. Health. 47(3): 223-231.
Singh, I. 1983. Induction of reverse mutation and mitotic gene conversion
by some metal compounds in Saccharomyces cerevisiae. Mutat. Res. 117:
149-152.
U.S. EPA. 1988. Health and Environmental Effects Document for Thallium and
Compounds. Prepared by the Environmental Criteria and Assessment Office,
Cincinnati, OH, for the Office of Solid Waste and Emergency Response,
Washington, DC.
Zasukhina, G.D., I.M. Vasilyeva, N.I. Sdirkova, et al. 1983. Mutagenic
effect of thallium and mercury salts on rodent cells with different repair
activities. Mutat. Res. 124(2): 163-173.
_VII. REVISION HISTORY
Substance Name -- Thallium(I) sulfate
CASRN -- 7446-18-6
-------- -------- --------------------------------------------------------
Date Section Description
-------- -------- --------------------------------------------------------
03/31/1987 I.A.6. Documentation corrected
03/01/1988 I.A. RfD changed - new study
03/01/1988 I.A.6. Verification date changed
06/30/1988 I.A. RfD withdrawn
09/07/1988 I.A. Revised oral RfD summary added
09/01/1990 I.A. Text edited
09/01/1990 I.A.7. Secondary contact changed
09/01/1990 II. Carcinogen assessment on-line
09/01/1990 IV.F.1. EPA contact changed
09/01/1990 VI. Bibliography on-line
08/01/1991 VI.C. Kada et al. citation corrected
01/01/1992 IV. Regulatory actions updated
VIII. SYNONYMS
Substance Name -- Thallium(I) sulfate
CASRN -- 7446-18-6
Last Revised -- 01/31/1987
7446-18-6
C.F.S.
CSF-Giftweizen
Dithallium Sulfate
M7-Giftkoerner
Rattengiftkonserve
Sulfuric Acid, Dithallium(1+) Salt
Sulfuric Acid, Thallium(1+) Salt
Thallium(I) sulfate
Thallium Sulfate
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0116.HTM
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