United States
Environmental Protection
Agency March, 1988
Research and
Development
HEALTH AND ENVIRONMENTAL EFFECTS DOCUMENT
FOR THALLIUM AND COMPOUNDS
Prepared for
OFFICE OF SOLID HASTE AND
ENERGENCY RESPONSE
Prepared by
Environmental Criteria and Assessment Office
Office of Health and Environmental Assessment
U.S. Environmental Protection Agency
Cincinnati, OH 45268
DRAFT: DO NOT CITE OR QUOTE
NOTICE
This document Is a preliminary draft. It has not been formally released
by the U.S. Environmental Protection Agency and should not at this stage be
construed to represent Agency policy. It Is belna circulated for comments
on Us technical accuracy and policy Implications.
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DISCLAIMER
This report 1s an external draft for review purposes only and does not
constitute Agency policy. Mention of trade names or commercial products
does not constitute endorsement or recommendation for use.
11
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PREFACE
Health and Environmental Effects Documents (HEEOs) are prepared for the
Office of Solid Waste and Emergency Response (OSWER). This document series
Is Intended to support listings under the Resource Conservation and Recovery
Act (RCRA) as well as to provide health-related limits and goals for emer-
gency and remedial actions under the Comprehensive Environmental Response,
Compensation and Liability Act (CERCLA). Both published literature and
Information obtained for Agency Program Office files are evaluated as they
pertain to potential human health, aquatic life and environmental effects of
hazardous waste constituents. The literature searched for 1n this document
and the dates searched are Included 1n "Appendix: Literature Searched."
Literature search material 1s current up to 8 months previous to the final
draft date listed on the front cover. Final draft document dates (front
cover) reflect the date the document 1s sent to the Program Officer (OSWER).
Several quantitative estimates are presented provided sufficient data
are available. For systemic toxicants, these Include Reference doses (RfOs)
for chronic and subchronlc exposures for both the Inhalation and oral
exposures. The subchronlc or partial lifetime RfO, 1s 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 Hfespan. This type of
exposure estimate has not been extensively used, or rigorously defined as
previous risk assessment efforts hrave focused primarily on lifetime exposure
scenarios. Animal data used for subchronlc estimates generally reflect
exposure durations of 30-90 days. The general methodology for estimating
subchronlc RfDs 1s the same as traditionally employed for chronic estimates.
except that subchronlc data are utilized when available.
- . . _ >
In the case of suspected carcinogens, RfDs are not estimated. Instead,
a carcinogenic potency factor, or q-|* (U.S. EPA, 1980a) Is provided.
These potency estimates are derived for both oral and Inhalation exposures
where possible. In addition, unit risk estimates for air and drinking water
are presented based on Inhalation and oral data, respectively.
Reportable quantities (RQs) based on both chronic toxlclty and carcino-
gen 1 city are derived. The RQ Is used to determine the quantity of a
hazardous substance for which notification Is required 1n the event of a
release as specified under the Comprehensive Environmental Response, Compen-
sation and Liability Act (CERCLA). These two RQs (chronic toxlclty and
carclnogenldty) represent two of six scores developed (the remaining four
reflect 1gn1tab1l1ty, reactivity, aquatic toxlclty, and acute mammalian
toxlclty). Chemical-specific RQs reflect the lowest of these six primary
criteria. The methodology for chronic toxlclty and cancer based RQs are
defined 1n U.S. EPA, 1984 and 1986a, respectively.
111
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EXECUTIVE SUMMARY
Thallium exists 1n both stable unlvalent and trlvalent states. Prop-
erties of thallium compounds In the (I) valence state are similar to those
of both alkali metals and silver salts. The hydroxide, carbonate, oxide and
cyanide salts of thallium are water soluble like the corresponding alkali
metal salts, and Us hallde salts, with the exception of fluoride salts, are
Insoluble 1n water like the corresponding silver salts (Hul, 1983). Most
thallium (III) salts, particularly the salts of weak adds (e.g., sulflde,
carbonate, cyanide, acetate) are not stable 1n water and hydrolyze exten-
sively (Cotton and Wilkinson, 1980). Three chemical companies are currently
the principal domestic producers of thallium and compounds (Hu1, 1983; SRI,
1987). The U.S. demand for thallium was 2500 pounds In 1984 (USDI. 1986).
Thallium has limited commercial use because of Us toxldty. According to
USDI (1986), the U.S. consumption pattern for thallium In 1984 was agricul-
ture, OX; electrical, 70%; pharmaceutical, 4X; other, 26X.
Available Information regarding the fate and transport of thallium In
environmental media Is extremely limited. The principal sources of thallium
In the environment are cement factories, coal burning power plants and metal
smelters (Sharma et al., 1986; Brockhaus et al., 1980, 1981). In the atmo-
sphere, thallium may be present as elemental Tl, oxides of Tl, Tl.S and
T12S04. T12S 1s likely to be speclated to T12S04. and T120 will
be rapidly hydrolyzed to T10H by the moisture In the atmosphere. Because of
their water solubilities, both these compounds are likely to be removed from
the atmosphere by wet deposition; however, because It Is Insoluble In water,
T1203 may persist for a longer period In the atmosphere. T1o°3 1s
likely to be removed from the atmosphere by dry deposition. No estimate of
1v
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the half-life of thallium In the atmosphere was located In the available
literature cited In Appendix A. In water, most of thallium that enters the
medium 1n the Insoluble form may be found In the sediment (Mathls and
Kevern, 1975). Some thallium may be removed from the water by sorptlon onto
suspended solids 1n water (Kempton et al., 1987a,b). Host of the thallium
that enters natural waters In the soluble state will remain In the soluble
form because of the formation of soluble complexes with Inorganic and
organic Ugands, and these complexes will be more stable at higher pHs
(Stephenson and Lester, 1987a,b; O'Shea and Mancy, 1978). Thallium 1n water
may be transported to fish and vegetation (Wallwork-Barber et al., 1985).
The BCF of thallium In whole aquatic organisms ranges from 12-34 (ZUko and
Carson, 1975; Barrows et al., 1980). Based on Its transport In water,
leaching of thallium from soil, particularly from sandy soil, appears to be
likely. Up to 10X of thallium absorbed In plant roots from soil may .be
transported from the root to the shoot of the plant (Cataldo and Mlldung,
1983). . ^. ^. ... . . v .. '. ..,;....',
Inhalation of contaminated air and consumption of vegetables and fruits
grown near thallium emission sources are the major routes of human thallium
Intake (Sharma et al., 1986; Brockhaus et al., 1980, 1981). From the
limited air monitoring data available, U.S. EPA (1980b) estimated a dally
Inhalation absorption of 3.4 yg of thallium per day by an Individual 1n
the United States; however, the dally absorption may be higher for Individ-
uals who live 1n the vicinity of emission sources (Brockhaus et al., 1980,
1981). Thallium has been detected 1n surface waters that receive waste-
waters from certain mining and smelting operations (U.S. EPA, 1980b; Mathls
and Kevern, 1975; ZUko et al., 1975). Thallium was not detected 1n >99% of
tap waters sampled In the United States at a minimum detection limit of 0.3
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vg/l. U.S. EPA (1980b) estimated that >99% of U.S. adults would consume
<1 tig of thallium per day by Ingestlon of drinking water. From the
limited monitoring data on foods, U.S. EPA (1980b) estimated a maximum
dietary Intake of thallium by a U.S. adult as 3.8 yg/day. According to
Sharma et al. (1986), the average dietary Intake of thallium by an adult 1s
-2 jig/day.
There appeared to be considerable differences 1n the sensitivity of
different aquatic species to the toxlclty of thallium salts; however, there
did not appear to be marked differences 1n toxlclty between different salts
of thallium. The lowest concentration of thallium associated with acute
toxlclty was 1.142 mg/l, an LC5Q for Dabhnla maqna (Brlngmann and Kuehn,
1977). In a chronic study, a concentration of <0.04 mg/l was an MATC
determined 1n an embryo-larval test In the fathead minnow, Plmephales
promelas (U.S. EPA, 1978). A concentration of 0.008 mg/i was associated
with 50% plant damage to duckweed, Lemna minor (BroWn and Rattlgan, 1979).
Absorption or uptake of soluble thallium salts Is rapid and virtually
complete by any route of exposure (Smith and Carson, 1977; Venugopal and
Luckey. 1978; U.S. EPA, 19805; MoeschUn. 1980; Stoklnger, 1981; Hanzo et
al., 1983a). Distribution from the blood Is rapid and widespread, with
highest levels located 1n the kidney, heart and liver and lowest levels In
the nervous system and body fat (Manzo et al., 1983a,b; Rauws, 1974; Barclay
et al.. 1953, Lie et al.. 1960; Sabblonl et al.. 1980). The relative
concentrations In different tissues appear to be Independent of route of
administration (Lie et al., 1960), the valence of thallium administered
(Sabblonl et al., 1980). the time after administration (Lie et al.. 1960) or
the dosage (Gregus and Klaassen, 1986). Thallium translocates to the
placenta and fetus, but levels In the fetus are substantially lower than
v1
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those 1n maternal tissues (Gibson and Becker, 1970; Rade et al., 1982;
Zlskoven et al., 1983). The metabolism of thallium 1s not well understood,
but It Is hypothesized that thallium .In. vivo Is transformed to one oxidation
state (Sabblonl et al., 1980). The excretion of thallium appears to be
species-dependent, with fecal excretion predominating In the rat (Lie et
al., 1960; Rauws, 1974; Barclay et al., 1953; Gregus and Klaassen, 1986) and
urinary excretion predominating In humans (Barclay et al., 1953; Rlchelml et
al., 1980). Estimates of excretion half-lives In humans range from 2.15
days for tracer doses In ambulatory heart patients (Talas et al., 1983) to
21.7 days In a terminal cancer patient (Barclay et al., 1953; U.S. EPA,
1980b).
Thallium salts are potent poisons that cause acute toxlclty In humans.
Human poisoning has resulted from accidental Ingestlon of thallium salts
used as rodentlddes and Insecticides, from Internal and topical use as a
depilatory agent, and from cases of homicide and suicide (Gettler and Weiss,
1943; Mpeschlln, 1980). Symptoms In humans Include neurological and gastro-
intestinal effects. Death 1s usually due to respiratory failure (Gettler
and Weiss. 1943; Stoklnger, 1981). A threshold for acute toxlclty In
children appears to be -6 mg Tl/kg/day (Bedford, 1928). An average lethal
dose for adults Is -8-12 mg Tl/kg (Moeschlln, 1980). Acute oral LD™
values In rats and mice range from 16-35 mg Tl/kg, apparently Independent of
species or the Identity of the thallium salt.
Chronic oral exposure of humans appears to Increase the Incidence of
neurological and subjective symptoms, as observed In a population living In
the vicinity of a cement factory that discharged large quantities of
thallium Into the atmosphere (Brockhaus et al., 1980, 1981; Dolgner et al.,
a
1983). Exposure was primarily through Ingestlon of thallium from home-grown
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fruits and vegetables. Subchronlc oral exposure of laboratory animals Is
associated with hair loss, elevated kidney weights (Downs et al., 1960),
neurological and skeletal muscle effects (Manzo et al., 1983b; Deshlmaru et
al., 1977} and mortality (Downs et al., 1960). A NOAEL of 0.25 mg thallium
(I) sulfate/kg/day (0.20 mg Tl/kg/day) for these effects was Identified 1n a
90-day gavage study using rats (U.S. EPA, 1986b; MRI, 1986).
Inhalation animal toxlclty data consist of an unfinished rat study 1n
which Intermittent exposure to thallium (III) oxide at 0.5-2 mg/m3 was
associated with deteriorating health and Increased mortality (U.S. EPA,
1979). Adverse health effects were not reported In humans occupationally
exposed to thallium 1n a magnesium seawater battery plant (Marcus, 1985) or
In cement production (SenaHer et al., 1980; Ludolph et al., 1986).
Thallium salts have not been tested for cardnogenlclty In animals and
the NTP (1987) has not scheduled cancer and toxlclty testing. Cancer data
In humans are limited. Mixed results have been observed In genotoxlclty
testing. Negative results were obtained 1n reverse mutation tests
(Kanematsu et al., 1980; Singh, 1983) and 1n tests for effects on cell
division (Loveless et al., 1954). Positive results were obtained In a rec
assay (Kanematsu et al., 1980) and In several mammalian test systems Includ-
ing a dominant lethal test In male rats (Zasukhlna et al., 1983).
Thallium results In achondroplastlc malformations when Injected Into
developing chicken eggs (Karnofsky et al., 1950; Landauer, 1960; Ford et
al., 1968; Hall, 1972b; Skrovlna et al., 1973) or tested 1n mammalian whole
embryo cultures (Anschuetz et al.. 1981) or 11mb bud cultures (Neubert and
Bluth, 1985; Barrach and Neubert, 1985). Parenteral administration to
pregnant rats at high doses (>2 mg Tl/kg/day) resulted In reduced fetal body
weights, hydronephrosls and the absence of vertebral bodies (Gibson and
V111
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Becker, 1970). Oral administration to rats (>2 mg Tl/kg/day) and mice (>4
mg Tl/kg/day) during organogenesls resulted only In a slight Increase 1n
fetal loss 1n both species (Roll and Matthlaschk, 1981). Malformations of
the skeleton and Internal organs were not observed. In offspring of rats
and mice allowed to deliver, reduced survival at weaning (both species) and
reduced growth rate (mice) were observed. Adult offspring of dams treated
with thallium during gestation had significant learning deficits In a
lever-pressing behavior conditioning test (Bornhausen and Hagen, 1984).
Recent studies Indicate that thallium may have an adverse effect on male
reproduction. Adult male rats exposed to thallium In the drinking water at
0.74 mg/kg/day for 60 days had decreased sperm motllUy and hlstopatho-
loglcal alteration of the testes (Form1gl1 et al., 1986).
Thallium and Its salts were classified In EPA Group D, unable to be
classified as to cardnogenlclty In humans, because cancer data 1n animals
and humans are lacking. Lack of adequate data also precluded derivation of
RfDs for Inhalation exposure. Subchronlc. and chronic oral RfOs for thallium
and selected salts were derived from a NOAEL of 0.25 mg thallium (I) sulfate
(0.20 mg Tl/kg/day) In a 90-day gavage study using rats (U.S. EPA, 1986b;
MRI, 1986). The subchronlc RfD for thallium 1s 0.1 mg/day and the RfD for
selected salts Is 0.2 mg/day. The chronic oral RfD for thallium Is 0.01
mg/day and for thallium salts Is 0.02 mg/day. An RQ of 10 for thallium and
salts was based on Increased mortality In an Inhalation experiment 1n rats
(U.S. EPA, 1979).
1x
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TABLE OF CONTENTS
Page
1. INTRODUCTION 1
1.1. STRUCTURE AND CAS NUMBER 1
1.2. PHYSICAL AND CHEMICAL PROPERTIES 4
1.3. PRODUCTION DATA 4
1.4. USE DATA 5
1.5. SUMMARY 6
2. ENVIRONMENTAL FATE AND TRANSPORT 7
2.1. AIR 7
2.2. WATER 7
2.3. SOIL 9
2.4. SUMMARY 9
3. EXPOSURE 11
3.1. WATER 11
3.2. FOOD 11
3.3. INHALATION 12
3.4. DERMAL 13
3.5. SUMMARY 13
4. AQUATIC TOXICITY 14
4.1. ACUTE TOXICITY 14
4.2.-, CHRONIC EFFECTS. ..,..., 14
4.3. PLANT EFFECTS. 14
• 4.4. 'SUMMARY. ..:....;: ; . . /....... 19
5. PHARMACOKINETCS 20
5.1. ABSORPTION 20
5.2. DISTRIBUTION 22
5.3. METABOLISM 26
5.4. EXCRETION 27
5.5. SUMMARY 28
6. EFFECTS 30
6.1. SYSTEMIC TOXICITY 30
6.1.1. Inhalation Exposures 30
6.1.2. Oral Exposures 33
6.1.3. Other Relevant Information 38
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TABLE OF CONTENTS (cont.)
Page
6.2. CARCINOGENICITY 43
6.2.1. Inhalation 43
6.2.2. Oral 44
6.2.3. Other Relevant Information 44
6.3. MUTAGENICITY 45
6.4. TERATOGENICITY 48
6.5. OTHER REPRODUCTIVE EFFECTS 51
6.6. SUMMARY 51
7. EXISTING GUIDELINES AND STANDARDS 54
7.1. HUMAN 54
7.2. AQUATIC 56
8. RISK ASSESSMENT 57
8.1. CARCINOGENICITY 57
8.1.1. Inhalation 57
8.1.2. Oral 57
8.1.3. Other Routes 57
8.1.4. Height of Evidence 57
8.1.5. Quantitative Risk Estimates 58
'8.2. SYSTEMIC TOXICITY. ;.".-. 58
8.2.1. Inhalation Exposure 58
8.2.2. Oral Exposure 59
9. REPORTABLE QUANTITIES 65
9.1. BASED ON SYSTEMIC TOXICITY 65
9.2. BASED ON CARCINOGENICITY 77
10. REFERENCES 79
APPENDIX A: LITERATURE SEARCHED 104
APPENDIX B: SUMMARY TABLES FOR THALLIUM AND COMPOUNDS 107
x1
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LIST OF TABLES
No. Title Page
1-1 Chemical Identity and Physical Properties of Thallium
and a Few Compounds 2
4-1 Acute Toxlclty of Thallium Salts to Aquatic Organisms .... 15
4-2 Chronic Toxlclty of Thallium Salts to Aquatic Organisms ... 16
4-3 Toxlclty of Thallium Salts to Aquatic Plants 17
5-1 Concentration of Thallium201 In tissues of Rats Following
Intraperltoneal Administration of Tl201 Salts 24
6-1 Experimental Protocol of Inhalation Study with Thallium
(III) Oxide 1n Groups of Male and Female 8-month-old
Wlstar Rats 31
6-2 Acute Oral 1059 Data for Thallium Salts 39
6-3 GenotoxIcHy Testing of Thallium Salts 46
7-1 Oral RfDs for Thallium Salts 55
8-1 Subchronlc Oral RfDs for Selected Thallium Salts 62
8-2 Chronic Oral RfDs for Selected Thallium-Salts 64
9-1 Systemic Toxlclty Summary for Thallium Salts Using the Rat. . 66
9-2 Composite Scores for Thallium Using the Rat '68
9-3 Thallium (and salts): Minimum Effective Dose (MED) and
Reportable Quantity (RQ) 70
9-4 ThaiI1um(III)ox1de: Minimum Effective Dose (MED) and
Reportable Quantity (RQ) 71
9-5 Thall1um(I)acetate: Minimum Effective Dose (MED) and
Reportable Quantity (RQ) 72
9-6 Thall1um(I)carbonate: Minimum Effective Dose (MED) and
Reportable Quantity (RQ) 73
9-7 Thall1um(I)chlor1de: Minimum Effective Dose (MED) and
Reportable Quantity (RQ) 74
9-8 Thall1um(I)n1trate: Minimum Effective Dose (MED) and
Reportable Quantity (RQ) 75
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LIST OF TABLES (cont.)
No., Title Page
9-9 Thal11um(I)su1fate: Minimum Effective Dose (MED) and
Reportable Quantity (RQ) 76
9-10 Thall1um(I)se]en1de (Tl2Se): Minimum Effective Dose
(MED) and Reportable Quantity (RQ) 78
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LIST OF ABBREVIATIONS
ATP Adenoslne tr1phosphate
BCF Bloconcentratlon factor
bw Body weight
CAS Chemical Abstract Service
CNS Central nervous system
CS Composite score
DNA DeoxyMbonuclelc add
EC5Q Concentration effective to 50% of recipients
EEG Electroencephalogram
LC5Q Concentration lethal to 50% of recipients
LOso Dose lethal to 50% of recipients
(and all other subscripted dose levels)
LDH Lactate dehydrogenase
MATC Maximum acceptable toxicant concentration
MED Minimum effective dose
NOAEL No-observed-adverse-effect level
NOEL No-observed-effect level
PEL Permissible exposure limit
ppb Parts per billion
ppm . , Parts per million
RfO Reference dose
RQ Reportable quantity
RV. Dose-rating value
RV Effect-rating value
SGOT Serum glutamlc oxaloacetlc transamlnase
STEL Short-term exposure level
TLV Threshold limit value
TWA Time-weighted average
x1v
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1. INTRODUCTION
1.1. STRUCTURE AND CAS NUMBER
Thallium (Tl), with an abundance of -0.3 ppm 1n the earth's crust. Is
not considered to be a rare metal (Hu1, 1983). There are numerous thallium
compounds, but only 18 of the most commonly used compounds have been
Included In this document. The synonyms, molecular formulas, molecular
weights and the CAS Registry numbers for thallium and these compounds are
given In Table 1-1. There 1s much confusion 1n the literature regarding the
correct chemical formula and the CAS registry number of thallium selenlde.
CAS (1983) lists the following four CAS numbers for thallium selenlde: Tl
(I) selenlde (Tl2Se), 15572-25-5; thallium (III) selenlde (Tl2Se3),
12039-58-6; a mixed thallium selenlde. 37189-37-0; and thallium selenlde
with a molecular formula of TISe and an ambiguous valence state (perhaps a
valence state of 2 1n which the compound 1s usually not stable), 12039-52-0.
In addition, both Sax (1984) and HSDB (1987) Incorrectly assigned the CAS
number1for thallium selenlde .(TTSe) (12039-52-0). to thallium (I) selenlte;
thallium selenlte, with a correct molecular formula of Tl-SeO^, 1s a
different compound than thallium selenlde (TISe) and should have a different
CAS number. In U.S. EPA (1985f), It Is not clear whether the risk assess-
ment was conducted for thallium selenlde or thallium selenlte because the
compound names and the CAS numbers were assigned Incorrectly. Since
thallium selenlte (Tl.SeO-) Is not a common chemical and of the three
thallium selenldes (Tl-S, Tl2Se3, TISe), T12S Is commonly used In
semiconductor and electrical switching devices (CAS, 1983). 1t 1s likely
that U.S. EPA (1985a) Intended to perform a risk assessment on this
compound, which has a CAS number of 15572-25-5.
0083d -1- 01/11/88
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TABLE 1-1
Chemical Identity and Physical Properties of Thai HUM and a Few Compounds*
§
en
Element/
Compound
Thallium
Thallium! I)
acetate
Thalllua(IIl)
acetate
Thalllua(I)
broalde
i
!' Thall lua( III)
i , bromide
Tballlua(l)
carbonate
Thallium! I)
chloride
Thai llua( 111)
chloride
Thallium! I)
ethoxlde
o Thalllua(III)
^ fluoride
^
co Thalllua(I)
00 formate
Synonyas
thalllua
acetic acid;
thall tua(l) salt;
thallous acetate
acetic acid;
thalllua! Ill) salt;
thai lie acid
thallous broalde;
thai HUB aonobro-
alde
thai lie broalde;
thalllua trlbro-
alde
dlthalllua carbo-
nate; carbonic
acid; dlthalltua
salt; thallous
carbonate
thallous chloride;
thalllua mono-
chloride
thai lie chloride;
thalllua tri-
chloride
thallous ethoxlde
thalllc fluoride
thalllua trl-
fluorlde
thallous formate
Atomic/
Molecular
Formula
Tl
T1C2H302
T1(C2H302)3
TIBr
T1Br3
T12C03
T1C1
T1C13
(T10C2H5)4
T1F3
T1HC02
Atoalc/
Molecular
Height
204.37
263.43
381.51
284.29
444.10
468.78
239.64
310.74
997.78
261.38
249.40
CAS .
Registry
Number
7440-28-0
563-68-8
2570-63-0
7789-40-4
13701-90-1
6533-73-9
7791-12-0
13453-32-2
20398-06-5
7783-57-5
992-98-3
Physical
Fora
: bluish-white
aetal
silky-white
deliquescent
solid
'solid
-
.yellow-white
solid
yellow
deliquescent
' solid
"colorless
solid
-
•
white solid
discolors In
air
white, hygro-
scopic solid
colorless
liquid
colorless
solid
colorless.
hygroscopic
Melting
Point
CC)
303.5
131
decomposes
at 182«C»
480
decoaposes
273
430
25
-3
327
101
Boiling
Point Density
<*C) (g/caVsp. gr.)
1457 11.85
NA 3.765
NA NA
815 7.557 at
17.3»C
NA NA
NA 7.11
720 7.004
decomposes NA
decoaposes 3.522
at 80*C
655 8.23 at 4*C
NA 4.967
Hater
Solubility
Insoluble
very soluble
•
NA
500 ag/t
at 2S*C
soluble
40,300 ag/t
at 15.5«C
2900 ag/t
at 15.6-C
very soluble
soluble but
decomposes
78.69/100 at
at 15-C
500.0 g/100
at at 10*C
Vapor
Pressure
10 am
1000'C
NA
NA
10 am
517«C
NA
NA
10 am
531 'C
NA
NA
NA
NA
at
•
at
at
solid
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TABLE 1-1 (cont.)
o
o
CO
s
CJ
1
Eleaent/
Coopound
Thalllua(I)
hydroxide
Thalltua(l)
Iodide
ThallliM(III)
nitrate
ThallliM(l)
nitrate
Thalllua(l)
oxide
ThallliMlIlI)
oxide
Thalllui(I)
sulfate
Thalllua(l)
selentde
Synonym
thallous hydroxide
thallous Iodide
thallous nitrate;
thalllui aono-
nltrate; nitric
acid. thalltua(I)
salt
thai lie nitrate;
thalllua trt-
nltrate; nitric
acid; thallliM(IIl)
salt
thallous oxide
thalllc oxide;
thalllui peroxide;
thai HIM
sesquloxlde;
thai HUB oxide
|T1203)
thallous sulfate;
sulfurtc acid;
thalllua(l) salt
thallous selentde
Atoaic/
Molecular
Foraula
T10H
Til
T1N03
T1|M03>3
T120
T1203
T12S04
T12Se
AtOMtC/
Molecular
Height
221.39
331.29
266.39
390.40
424.77
456.76
504.82
487.74
CAS
Registry
Nuaber
12026-06-1
7790-30-9
10102-45-1
13746-98-0
1314-12-1
1314-32-5
7446-18-6
15572-25-5
Physical
Fora
pale yellow
solid
yellow solid
<-)
red solid (B)
white solid
exists In a.
0 and T crys-
• talllne fora
colorless
solid
black
. deliquescent
solid
colorless
solid
colorless
solid
gray solid
Malting
Point
rc>
deconposes
at 139'C
transform
to B-fora
at 170*C
440
206C
NA
300
717
632
340
Soiling
Point
(•C)
NA
NA
823
430C
NA
loses
oxygen at
1080'C
loses two
oxygen
at 875*C
deconposes
NA
Density
(g/caVsp. gr.)
NA
7.29
7.098 at
14.7*C
NA
NA
9.52 at 16*C
9.65-10.19 at
21 »C
6.77
9.05 at 25/4*C
Water Vapor
Solubility Pressure
25.9 g/100 NA
•t at 0*C
6 «g/t at NA
20«C
Insoluble 1.0 MI
at 440*C
9.55 g/100 NA
M at 20*C
soluble NA
very soluble NA
but decomposes
Insoluble NA
48.700 ag/t NA
at 20*C
Insoluble NA
•Source: Ueast. 1985; HSDB. 1987; Hut. 1983; Ulndholz. 1983
°The aeltlng point Is for thalltiw(lll) acetate sesqulhydrate [T1(CH3COO)3>3/2H20] as given In Aldrtch (1986)
cThe physical properties are for the a-fora.
-------
1.2. PHYSICAL AND CHEMICAL PROPERTIES
Thallium exists In both stable unlvalent (I) and tMvalent (III) states.
Thallium compounds 1n the unlvalent states are called thallous salts and In
the trlvalent states thalUc salts.
The physical properties of thallium and Us selected compounds are given
In Table 1-1. Properties of thallium compounds 1n the (I) valence state are
similar to those properties of both alkali metal and silver salts. Like
alkali metal salts, the hydroxide, carbonate, oxide and cyanide of thallium
(I) salts are water soluble. The fluoride of thallium (I) Is very water
soluble, but the other halldes are Insoluble 1n water like the corresponding
silver salts. Thallium (III) salts' are easily reduced to the thallium (I)
salts by common reducing agents (Hu1, 1983). Most thallium (III) salts,
particularly the salts of weak adds (e.g., sulfldes, carbonates, cynldes,
acetates) are subject to extensive hydrolysis and do not exist In contact
with water (Cotton and Wilkinson, 1980). Both thallium (I) carbonate and
oxide also hydro!yze In water with the formation of T10H (Ueast, 1985; Hul,
1983).
1.3. PRODUCTION DATA
Noah Industrial Corp., Farmlngdale, NY. Harshaw/Flltrol Partnership,
Solon, OH, and Morton Thlokol, Inc., Danvers. MA, are currently the princi-
pal domestic producers of thallium and compounds since American Smelting and
Refining Co. discontinued Us operation In February of 1981 (Hu1, 1983; SRI,
1987). The current suppliers of thallium and Us salts In the United States
are as follows (OPD. 1986): AldMch Chemical Co., Inc., Milwaukee, WI; Alfa
Products, Morton Thlokol Inc., Toronto, Ont.; Atomerglc Chemicals Corp. and
Noah Industrial Corp., Farmlngdale, NY; R.P. Cargllle Laboratories. Inc..
Cedar Grove, NJ; Davos Chemical Corp., Fort Lee, NO; GFS Chemical, Columbus,
0083d -4- 01/20/88
-------
OH; Rhone-Poulenc Inc., Monmouth Juctlon, NJ; Sharpe Chemical Co., Burbank,
CA; and United Mineral and Chemical Corp., New York, NY.
According to the latest figure available from the USOI (1986). the U.S.
demand for thallium and compounds was 2500 pounds In 1984. In the same
year, 1000 pounds was produced 1n U.S. mines and 2535 pounds of thallium and
compounds was Imported Into the United States. The difference between the
U.S. supply and demand was used for export and Industry stock, but no data
were available regarding these uses (USOI, 1986). Thallium Is obtained
commercially from flue dusts of pyrlte (FeS_) burners, lead and zinc
smelters and refiners and as a by-product of cadmium production. If the
thallium content of flue dust Is water soluble, direct leaching with water
or dilute add separates thallium from other Insoluble compounds. For water
Insoluble thallium compounds In the dust or by-product, the material Is
solublUzed by oxidizing roasts, by sulfatlzatlon or by alkali treatment.
Thallium metal may be obtained either by electrolysis of carbonates,
sulfates or perchlorates; by precipitation- with Zn; or by reduction of
- " v .'.•.- ' • ' ' •'-••»• * '
thallium (I) oxalate or chloride (Stoklnger. 1981; Hu1. 1983).
1.4. USE DATA
Thallium has limited commercial applications because of Us toxldty.
Thallium Is used In alloy manufacture 1n bearings, contact points, anodes,
and switches and seals for equipment designed for use In polar regions or In
the stratosphere; manufacture of certain kinds of glass; In electronic
devices; In agriculture; and In medicine (Uallwork-Barber et al., 1985; Hu1,
1983). Because of Us toxlclty, the use of thallium compounds as a rodent1-
clde 1n agriculture was stopped 1n 1972 (Stoklnger, 1981). According to
USDI (1986), the U.S. consumption pattern for thallium In 1984 was agricul-
ture, OX; electrical. 70X; pharmaceutical, 4%; other, 26X.
0083d -5- 01/20/88
-------
1.5. SUMMARY
Thallium exists In both stable unlvalent and trlvalent states. Prop-
erties of thallium compounds 1n the (I) valence state are similar to those
of both alkali metals and silver salts. The hydroxide, carbonate, oxide and
cyanide salts of thallium are water soluble like the corresponding alkali
metal salts, and Us hallde salts, with the exception of fluoride salts, are
Insoluble 1n water like the corresponding silver salts (Hu1, 1983). Most
thallium (III) salts, particularly the salts of weak acids (e.g., sulflde,
carbonate, cyanide, acetate) are not stable In water and hydrolyze exten-
sively (Cotton and Wilkinson, 1980). Three chemical companies are currently
the principal domestic producers of thallium and compounds (Hul, 1983; SRI.
1987). The U.S. demand for thallium was 2500 pounds In 1984 (USDI, 1986).
Thallium has limited commercial use because of Its toxldty. According to
USOI (1986). the U.S. consumption pattern for thallium In 1984 was agricul-
ture, OX; electrical, 70%; pharmaceutical. 4%; other, 26%.
0083d -6- 01/20/88
-------
2. ENVIRONMENTAL FATE AND TRANSPORT
2.1.. AIR
The primary sources of anthropogenic thallium In the atmosphere are
likely to be emissions from cement factories, coal burning power plants and
metal smelters (Sharma et al., 1986; Brockhaus et al., I960, 1981). Infor-
mation regarding the fate and transport of thallium In the atmosphere 1s
extremely limited. Since thallium 1s collected In the form of oxide and
sulfate In the flue dust from metal smelters (Hu1, 1983), It Is likely that
the chemical form of atmospheric thallium originating from metal smelters,
coal burning power plants and cement plants will be elemental thallium,
oxides of thallium, Tl.SO. and T1~S (Smith and Carson, 1977). Like
other metals In the atmosphere chemical and photochemical Interaction of
thallium may change thallium from one species to another, but these
processes will not remove the metal species from the atmosphere. As Is the
case with lead, atmospheric Tl.S may be partially spedated to Tl-SO.
and any T1J) will be rapidly hydrolyzed to T10H. Both of these processes
will enhance the removal of atmospheric thallium by wet deposition because
of the higher water solubilities of the spedated products; however, 1f
T1?0 or elemental thallium 1s spedated 1n the atmosphere to Tl^O,, It
may persist 1n the atmosphere for a long time because of Its high chemical
stability and low water solubility. Dry deposition will be the likely route
of removal of the compound. No estimate of the atmospheric half-life of
thallium was found In the available literature cited 1n Appendix A.
2.2. HATER
Data regarding the fate and transport of thallium In water are avail-
able. Little Is known about the transformation of thallium In water by
either abiotic or blotlc processes. For example, thallium may undergo
0083d -7- 01/20/88
-------
methylatlon similar to Hg, Se, Pb and As, and this process may cause mobili-
zation of thallium from sediment Into the water column or from the water
column Into air (Helt and Klusek, 1985); however, there are no data In the
literature to confirm this process. The photolysis of the thallium (III)
salts of carboxyllc adds (e.g., acetic add, n-butyrlc acid, n-valerlc
add) In benzene solution at 254 and 350 nm was studied by Kochl and Bethea
(1968). At the higher wavelength, which 1s more relevant to environmental
conditions (cutoff wavelength of solar radiation Is "290 nm), Tl (I)
carboxylate, CO, and the corresponding alkanes were formed. Similar
photolytlc homolysls of other Tl (III) salts may be possible, but 1n aquatic
media the water soluble Tl (III) salts are likely to undergo more rapid
hydrolysis than photolysis. Pertinent data regarding the photolysis or
hydrolysis of environmentally relevant thallium salts (e.g.. sulfate, oxide,
sulflde) 1n water were not located In the available literature cited 1n
Appendix A.
Stephenson and Lester (1987a,b) reported that the removal of thallium
from water 1s due primarily to precipitation of Insoluble salts and not to
adsorption of the soluble metal compound onto water partlculates containing
high organic carbon such as sludge. In natural waters, both Inorganic
llgands (hydroxo- and carbonato-llgands) and organic llgands (humlc
materials) present 1n water will have a tendency to form complexes with
thallium and keep thallium 1n the water phase. The complexatlon with humlc
materials will be more Intense than with Inorganic llgands and the stability
of these complexes will be higher with Increase 1n pH (O'Shea and Mancy,
1978). Removal of thallium from the aquatic phase by adsorption onto non-
complexlng suspended solids Is likely to remove some thallium from solution
(Kempton et al., 1987a,b). In a study of the transport of thallium 1n
0083d -8- 01/20/88
-------
aquatic media, Uallwork-Barber et al. (1985) found that the concentration of
thallium 1n water decreased slowly and thallium was transported to vegeta-
tion, and fish but not to sand. This study also pointed out that most
thallium that enters water In the soluble form will not be found In the
sediment but 1n the aquatic phase. A mean concentration of 13.1 mg/kg of
thallium detected 1n the sediment of Lake Wlntergreen, MI, was attributed to
fallout of (Insoluble) airborne partlculate matter (Hathls and Kevern, 1975).
The bloconcentratlon of thallium 1n aquatic organisms 1s much less than
other heavy metals (Zltko and Carson, 1975). BCFs of 18.2 1n clams, Mya
aremaroa. and 11.7 In mussels. HytHus edulls have been reported (ZHko and
Carson, 1975). The BCF 1n muscle tissue of juvenile Atlantic salmon. Salmo
salar. was 130 (ZHko et al., 1975). In blueglll sunflsh, Lepomls macro-
chlrus. the maximum BCF was 34 (Barrows et al., 1980).
2.3. SOIL
Pertinent data regarding the fate and transport of thallium In soil were
not located In the available literature cited In Appendix A. with the excep-
tion of a study by Cataldo and Ulldung (1983). In this study, the authors
estimated that up to a maximum of 10% of thallium absorbed In the plant
roots from soil may be transported from root to shoot. Based on Its trans-
port characteristics 1n water (see Section 2.2.), leaching of thallium from
solil, particularly from sandy soil Is likely to occur.
2.4. SUMMARY
Available Information regarding the fate and transport of thallium 1n
environmental media 1s extremely limited. The principal sources of thallium
In the environment are cement factories, coal burning power plants and metal
smelters (Sharma et al., 1986; Brockhaus et al., 1980, 1981). In the
atmosphere, thallium may be present as elemental T1. oxides of Tl, T1.S
0083d -9- 01/11/88
-------
and T12S04. T12S Is likely to be spedated to T12S04. and T120
will be rapidly hydrolyzed to T10H by the moisture In the atmosphere.
Because of their water solubilities, both these compounds are likely to be
removed from the atmosphere by wet deposition; however, because It 1s
Insoluble In water, Tl-Og may persist for a longer period 1n the atmo-
sphere. Tl-O- 1s likely to be removed from the atmosphere by dry
deposition. No estimate of the half-life of thallium In the atmosphere was
located 1n the available literature cited In Appendix A. In water, most of
thallium that enters the medium In the Insoluble form may be found In the
sediment (Hathls and Kevern, 1975). Some thallium may be removed from the
water by sorptlon onto suspended- solids 1n water (Kempton et al.. 1987a,b).
Most of the thallium that enters natural waters In the soluble state will
remain In the soluble form because of the formation of soluble complexes
with Inorganic and organic Ugands, and these complexes will be more stable
at higher pHs (Stephenson and Lester, 1987a,b; O'Shea and Mancy, 1978).
Thallium In water may be transported to fish and vegetation (Wallwork-Barber
et al., 1985). The BCF of thallium In whole aquatic organisms ranges from
12-34 (Zltko and Carson, 1975; Barrows et al., 1980). Based on Us trans-
port In water, leaching of thallium from soil, particularly from sandy soil,
appears to be likely. Up to 10% of thallium absorbed In plant roots from
soil may be transported from the root to the shoot of the plant (Cataldo and
Ulldung, 1983).
0083d -10- 01/20/88
-------
3. EXPOSURE
3.1,. AIR
The concentration range of thallium In the air of six major U.S. cities
was reported to range from 0.02-0.1 ng/m3, with a typical concentration of
0.04 ng/m3 (U.S. EPA, 1980b). In another study, the concentration range
of thallium In Chadron, NB, was reported as 0.04-0.48 ng/m3 (U.S. EPA,
1980b). Given this value and the assumption that an Individual Inhales 20
m3 of air/day and that 35% of the Inhaled amount 1s retained. U.S. EPA
(1980b) estimated a maximum dally average absorption of 3.4 ng of thallium
per day by an Individual In the United States; however, the dally absorption
may be higher for Individuals who live 1n the vicinity of cement plants,
smelters and coal burning power plants, as Indicated by higher hair and
urinary thallium levels among a population living In the vicinity of a
cement plant In Germany (Brockhaus et al., 1980, 1981). The estimated
concentration of atmospheric thallium near a coal burning plant .was 0.7
yg/m3 (Smith and Carson, 1977). Assuming an Inhalation rate of 20
ma/day and and an absorption of 35X of the Inhaled amount, this air level
will amount to an absorption of 4.9 ^g/day by an Individual — an amount
more than twice the dally average dietary Intake (Section 3.3.) of thallium.
3.2. HATER
In a study that monitored metal runoffs to surface waters from several
mining and smelting operations 1n the United States, the highest concentra-
tions reported were 30 pg/l In a slag runoff near Kellog, ID, and 21
vg/l In water from the Colorado River just below the Big Williams River
which drained the Planet Nine (U.S. EPA, 1980b). Thallium was qualitatively
detected In samples of sediment/solI/water mixtures obtained from the Love
Canal, Niagara Falls, NY (Hauser and bromberg, 1982). Zltko et al. (1975)
0083d -11- 01/20/88
-------
detected thallium concentrations of 0.7-88.3 yg/8. In water from three
rivers that served as drains for mining operations 1n New Brunswick, Canada.
Hathis and Kevern (1975) reported concentrations of thallium 1n sediments of
Lake Wlntergreen, Kalamazoo, HI, In the range 2.1-23.1 mg/kg, with a mean
value of 13.1 mg/kg. The authors reported that fallout from airborne
participate matter was the source of this thallium. In their survey of
pollutant emission levels 1n wastewaters from the refining Industry, Snider
and Harming (1982) detected no thallium at minimum detection levels ranging
from 1-15 vg/l.
In a survey of tap waters from 3834 homes throughout the United States,
thallium was detected 1n only 0.68X of the samples at an average thallium
concentration of 0.89 »g/i (detection limit 0.3 yg/l) (U.S. EPA,
1980b). Based on the minimum detection limit and the assumption that an
Individual consumes 2 4 of water per day, U.S. EPA (1980b) estimated that
>99% of adults In the United States would consume <1 pg thallium/day.
3.3. FOOD
The levels of thallium In vegetables (lettuce, red and green cabbage,
leak and endive) and bread were reported to be 10 yg/kg wet weight and
0.75 yg/kg dry weight, respectively (U.S. EPA, 1980b). Given this value
for the level of thallium In vegetables and assuming that human thallium
Intake 1s primarily due to Ingestlon of vegetables and that the consumption
of vegetables per day by an Individual In the United States Is 0.38 kg, U.S.
EPA (1980b) estimated a maximum thallium Ingestlon of 3.8 yg/day by an
Individual 1n the United States. According to Sharma et al. (1986), Inhala-
tion of contaminated air and consumption of vegetables and fruits grown near
thallium emission sources are the major routes of human thallium Intakes.
The average dietary Intake of thallium by an adult Is estimated to be -2
pg/day (Smith and Carson, 1977; Sharma et al., 1986).
0083d -12- 01/20/88
-------
3.4. DERMAL
Dermal absorption of thallium may possibly occur as a result of bathing
with thallium-containing water, although no estimate of thallium Intake from
dermal absorption from this or any other source can be made.
3.5. SUMMARY
Inhalation of contaminated air and consumption of vegetables and fruits
grown near thallium emission sources are the major routes of human thallium
Intake (Sharma et al., 1986; Brockhaus et al., 1980, 1981). From the
limited air monitoring data available, U.S. EPA (1980b) estimated a dally
Inhalation 'absorption of 3.4 yg of thallium per day by an Individual 1n
the United States; however, the dally absorption may be higher for Individ-
uals who live 1n the vicinity of emission sources (Brockhaus et al., 1980,
1981). Thallium has been detected In surface waters that receive waste-
waters from certain mining and smelting operations (U.S. EPA, 1980b; Mathls
and Kevern. 1975; Zltko et al., 1975). Thallium was not detected In >99% of
tap waters sampled In the United States at a minimum detection limit of 0.3
vg/t. U.S. EPA (1980b) estimated that >99% of U.S. adults would consume
<1 yg of thallium per day by 1ngest1on of drinking water. From the
limited monitoring data on foods, U.S. EPA (1980b) estimated a maximum
dietary Intake of thallium by a U.S. adult as 3.8 ng/day. According to
Sharma et al. (1986), the average dietary Intake of thallium by an adult Is
-2 yg/day.
0083d -13- 03/08/88
-------
4. AQUATIC TOXICITY
4.1. ACUTE TOXICITY
Data regarding the acute tox1c1ty of several thallium salts to fresh-
water and saltwater aquatic species are presented In Table 4-1. Acute
LC5Q values for two species of freshwater fish ranged from 110-600 mg/kg
(Buccafusco et al., 1981; Oawson et al.t 1977; Juhnke and Luedemann, 1978);
a concentration of 0.030 mg/i was estimated as an Incipient lethal level
for the Atlantic salmon. Salmo salar (Zltko et al., 1975). An acute LC5Q
of 31 mg/l was estimated for the saltwater Inland sllverslde, Henldla
bervlllna (Oawson et al., 1977). LC5Q values In the water flea, Daphnla
roagna. ranged from 1.1-3.6 mg/l (Brlngmann and Kuehn, 1977; Leblanc,
1980); a concentration of 0.11 mg/l was an EC™ for Immobility 1n this
species (Brlngmann and Kuehn, 1982). The lowest concentration associated
with acute toxldty was 0.11 mg/l, the EC.Q for Immobility In Daphnla
roaqna (Brlngmann and Kuehn, 1977). Although the data were limited, It
appeared that the thallium salts tested had similar toxic potencies.
4.2. CHRONIC EFFECTS
The limited data available regarding the chronic toxldty of thallium
salts to aquatic organisms are presented In Table 4-2. The lowest concen-
tration associated with chronic toxldty 1n fish was <0.04 mg/l, an MATC
In the fathead minnow, Plmephales promelas. In an embryo-larval test (U.S.
EPA, 1978; LeBlanc and Dean. 1984). A 7-day LC5Q of 0.11 mg/i was
reported In the narrow-mouthed frog, Hlcrohyla carollnensis (B1rge, 1978).
4.3. PLANT EFFECTS
The limited data available on the toxldty of thallium salts to plants
are presented In Table 4-3. Considerable species variation was observed 1n
the toxic potency of thallium. A concentration of 1.43 mg/l depressed
oxygen output In the waterweed, Elodea canadensls (Brown and Rattlgan, 1979).
0083d -14- 01/11/88
-------
8
TABLE 4-1
Acute Toxlclty of Thai HIM Salts to Aquatic Organism
Species
Thai HIM Salt
Concentration
of ThallliM
(•g/t)
Effect
Coment
Reference
FISH
Blueglll, Lepoals aacrochlrus
Blueglll. lepoals aacrochlrus
Blueglll. lepoiils Mcrochlrus
Golden orfe, leuclscus Idus
Atlantic saloon. Salao salar
INVERTEBRATES
Uaterflea. Daphnla aaana
Uaterflea. Oaphnla aaana
Uaterflea. Oaphnla aaana
Uaterflea, Daphnla aaana
thai 1liM(l)sul fate
thall1iM(I)acetate
thalllwi(I)sulfate
tha111w(I)n1trate
NR
thalllM(I)n1trate
tha!1lui(I)sulfate
thall1ua(l)sulfate
tha11liM(I)nltrate
FISH
Inland stlverslde. Henldla bervlllna thall1u»(I)acetate
Sheepshead Minnow, CypMnodon varleaatus NR
INVERTEBRATES
FRESHWATER SPECIES
600
170
120
110
0.030
1.142
3.6
2.2
0.11
24-hour LCjQ
96-hour LC§o
96 -hour ICso
acute LCso
Incipient
lethal level
24-hour LCsQ
24-hour LCso
48-hour LCso
ECcn for
1 Mobility
S.U. Juvenile
S.U. 33-75 m
S.U. Juvenile
S.U. other details NR
Juvenile, other test
conditions NR
S.U
S.U. <24 hours old
S.U. <24 hours old;
no Mortality at 1.7 ag/ft
S.U
^ Nysld shrimp. Hvsldopsls bahIa
NR
SALTWATER SPECIES
31 96-hour LC50 S.U. 40-100 m
20.9 acute level. NOS S.U
2.130 acute level. NOS S.U
Buccafusco et al., 1981
Dawson et al.. 1977
Buccafusco et al., 1981
Juhnke and Luedeoann. 1978
Zltko et al.. 1975
Brtngnann and Kuehn. 1977
LeBlanc. 1980
LeBlanc. 1980
Brlngaann and Kuehn. 1982
Oawson et al.. 1977
U.S. EPA. 1978
U.S. EPA. 1978
oo S • Static test conditions; U - unoeasured concentration; NR - not reported; NOS » not otherwise specified
-------
§
00
TABLE 4-2
Chronic Toxtclty of Thallium Salts to Aquattc OrganlSMS
Species
Thai HIM Salt
Concentration
of Thallium
(•g/t)
Effect
Connent
Reference
FISH
Goldfish. Carasslus auratus
Rainbow trout. SalMO galrdnerl
FRESHWATER SPECIES
tha111uM(III(chloride 7
thall luMjUsulf ate 1.5
thallluB(III(chloride . 0.17
Rainbow trout. SalMO galrdnerl
AMPHIBIAN
Narrow-Mouthed frog. Hlcrohyla carolInensls thallIUM( 111(chloride
0.11
Fathead Minnow. Plaeohales oroaelas
SALTWATER SPECIES
thallium sulfate 0.04
Sheepshead Minnow. Cyprlnodon varleaatus NR
7-day LC§o S.N.A. eggs
10-day LCjo S.N. Juvenile
MATC
NR
E-L
E-L
Blrge. 1978
Craig and Beggs.
1979
28-day LC5o S.N.A. eggs Blrge. 1978
7-day LCgo S.N.A. eggs Blrge. 1978
U.S. EPA. 1978;
LeBlanc and Dean.
1964
U.S. EPA. 1978
S • Static test conditions; N - Measured concentration; A - aerated tanks; E-L - embryo-larval test; NR - not reported
-------
TABU 4-3
Toxlclty of ThallliM Salts to Aquatic Plants
I*?
a.
Species Thai HUM Salt
Concentration
of Thalllua.
(•g/t)
Effect
Content
Reference
FRESHWATER SPECIES
i
-4
i
Uaterweed. thai 11ua(l)sulf ate
ilodea canadensls
Duckweed, Leona Minor, tha111ui(l)su1fate
Green algae. thal1lui(I)su1fate
Chlorelli vulgarls
Algae. NR
Chlaavdoaonas relnhardl
Algae. NR
Selenastrua caprlcornutm
Algae. NR
Selenastrua caprlcornutua
"1.43
0.008
0.016
40.8
0.110
0.100
Op production
reduced 90X
SOX plant damage
•axlmui concentra-
tion tolerated for
population growth
40X Inhibition of
oxygen evolution
96-hour ECsp for
chlorophyll a
Inhibition
96-hour EC5Q for
cell number
S.U. 24 hours; SOX plant
damage occurred at 2 *g/ft
S.U. 28 days
S.U, 3-4 Months exposure;
0.032 ag/t Inhibited
growth
NC
NC
NC
Brown and
Rattlgan. 1979
Brown and
Rattlgan. 1979
OeJong, 1965
Overnell. 1975a
U.S. EPA. 1978
U.S. EPA. 1978
SALTWATER SPECIES
88/1 I/ 10
Marine dlatoa.
Bltylim brlghtwelll
Algae.
Ounallella tertlolecta
Algae.
Dunallella tertlolecta
Algae.
Ounallella tertlolecta
thal11ui(l)ch1orlde
NR
tha111uMlH)salt
unspecified
thallliM(I)salt
unspecified
0.75
4.080
-1.0 nH
(-0.2 ng/l)
-0.5 i*
(-0.1 «g/l)
S-day alglstatlc S.U
SOX Inhibition of NC
photosynthesis
reduction In NC
culture growth
'reduction In NC
culture growth
Canter ford and
Canter ford. I960
Overnell. 1975b
Puddu et al.. 1985
Puddu et al.. 1985
-------
TABU 4-3 (cont.)
o
1
a.
i
CO
1
Species
Algae.
PhaeodactifltM trlcornutiM
Algae.
PhaeodactifliM trtcornutu»
Algae.
Phaeodact»ltM trtcornutua
S - Static test conditions;
ThalltiM Salt
NR
thal11u»(lll)salt
unspecified
thal1ti»|I)sa1t
unspecified
Concentration
of Thai HIM
SALTWATER
51.2
-1 .0 |M
(-0.2 •g/l)
-0.5 i*
(-0.1 ag/t)
U • unmeasured concentration; NC « no con
Effect Coment
SPECIES (cont.)
SOX Inhibition of NC
photosynthesis
reduction In NC
culture growth
reduction In NC
culture growth
Bent; NR « not reported
Reference
Overnell. 19756
Puddu et al.. 1965
Puddu et al.. 1985
-------
Concentrations of thallium (I) salts of -0.1 mg/i and thallium (III) salts
of -0.2 mg/i depressed culture growth 1n two species of marine algae,
Dunallella tertlolecta and Phaeodactylum trlcornutum (Puddu et al., 1985).
The duckweed, Lemna minor, appeared to be the most sensitive; 50% plant
damage was reported after 28 days of exposure to 0.008 mg/8. (Brown and
Rattlgan, 1979).
4.4. SUMMARY
There appeared to be considerable species differences In toxlclty to
thallium salts. Although the data were limited, there did not appear to be
marked differences 1n toxldty between different salts of thallium. The
lowest concentration of thallium associated with acute toxldty was 1.142
mg/l, an LC5Q for Daphnla maqna (Brlngmann and Kuehn, 1977). In a
chronic study, a concentration of <0.04 mg/l was an MATC determined 1n an
embryo-larval test In the fathead minnow, Plmephales promelas (U.S. EPA,
1978). In plants, a concentration of 0.008 mg/i was associated with 50X
damage to duckweed, Lemna minor (Brown and Rattlgan, 1979).
0083d -19- 01/20/88
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5. PHARMACOKINETICS
5.1. ABSORPTION
The conclusion of several studies regarding the pharmacoklnetlcs of
thallium Is that absorption of soluble salts occurs readily from any route
of exposure (Smith and Carson, 1977; Venugopal and Luckey, 1978; U.S. EPA,
1980b; Moeschlln, 1980; Stoklnger, 1981; Manzo et al.. 1983a). The best
documentation Is an experiment In which rats were administered thallium204
(I) nitrate by several routes (Figure 5-1). Body burden of radioactivity
expressed as a percent of the administered dose over time was nearly
Identical for all routes of administration Including the Intravenous route,
suggesting virtually complete and rapid uptake from all sites of adminis-
tration.
Manzo et al. (1983a) observed rapid and virtually complete uptake from
the gastrointestinal tract of rats. The uptake of single doses of 2 yg to
2 mg Tl* was measured In rats using an jri situ Intestinal loop clamped
method. By.l hour after administration, 50% of the dose was absorbed; by 3
hours 90X was absorbed. No evidence of saturation of the absorption mecha-
nism was observed within the dose range tested.
Data regarding gastrointestinal absorption In humans are limited to a
study 1n which a middle-aged woman with terminal osteogenlc carcinoma was
given a single oral dose of thallium204 (Barclay et al., 1953). A
dramatic rise In urinary radioactivity was noted, but fecal excretion over a
72-hour collection period accounted for only 0.5X of the dose, suggesting
virtually complete absorption.
Although data regarding absorption following Inhalation exposure were
not located, data following Intratracheal administration (Figure 5-1)
suggested that uptake through respiratory epithelium was rapid and complete
0083d -20- 01/20/88
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FIGURE 5-1
Body Burden of Thallium204 In Adult Hale Wlstar Rats
Source: Lie et al.. 1960
IV « Intravenous: 0.01 mg Tlao«/rat; IP • Intraperltoneal: 0.0375 mg
Tlao«/rat; SO - subcutaneous: 0.025 mg T1»°Vrat; IM > Intramuscular:
0.025 mg Tl«Vrat; IT • Intratracheal: 0.0315 mg Tl««/rat; 0 « oral:
0.20 mg Tl«Vrat
0083d
-21-
01/11/88
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(Lie et al., 1960). According to U.S. EPA (1980b), the deposition pattern
of Inhaled thallium salts would depend primarily on the aerodynamic size of
the particles and rate of clearance would depend primarily on solubility.
U.S. EPA (1980b) predicted that all salts of thallium except the oxide and
halldes would be cleared rapidly.
Quantitative data were not located regarding dermal absorption, but the
toxic signs observed In humans following application of a depilatory
containing thallium (Section 6.1.3.) suggest that dermal absorption may be
substantial, at least from a cosmetic preparation. U.S. EPA (1980b),
however, noted that dermal absorption 1s not likely to be significant under
ordinary exposure conditions to low concentrations 1n environmental media.
5.2. DISTRIBUTION
Distribution of thallium from the bloodstream appears to be rapid and
widespread (U.S. EPA, 1980b; Hanzo et al., 1983a; Rauws, 1974). Lameljer
and van Zwleten (1977a) described the disappearance of thallium204 (I)
sulfate from the blood of Intravenously treated rats by a two-compartment
model, with half-lives of 5 and 196 minutes, respectively. Using a small
(<2 tig) dose of thallium"" (I) chloride, Talas and Wellhoener (1983)
observed that plasma disappearance of radioactivity conformed to a three-
compartment model 1n rabbits, with half-lives of 2.1. 89 and 2758 minutes.
respectively. Higher doses (5.5 pinol/kg bw of thallium acetate) had
little Impact on the half-lives of disappearance from the plasma. In
humans, plasma disappearance of Tl * seemed to conform to a two-compart-
ment model, with half-lives of 3.9 and 3108 minutes, respectively (Talas et
al., 1983). Estimations of distribution volumes during the first and second
phases suggested that thallium translocated rapidly from extracellular
fluids to Intracellular space, and that large amounts of thallium were
concentrated In tissues.
0083d -22- 01/20/88
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The tissue distribution of thallium In rats has been studied by a number
of Investigators using different salts and different routes of administra-
tion. Highest levels were located 1n the kidney, somewhat lower levels were
located In the other parenchymatous organs and lowest levels were located 1n
the central and peripheral nervous system and body fat (Barclay et al.t
1953; Lund, 1956a; Lie et al., 1960; Schwetz et al., 1967; Kamerbeek et al.,
1971; Sabblonl et al., 1980; Rade et al., 1982; Ducket et al., 1983; Manzo
et al., 1983b; Gregus and Klaassen, 1986). Typical data from a distribution
experiment 1n rats are presented 1n Table 5-1.
The relative concentrations of thallium In different tissues appeared to
be Independent of the route of administration (Lie et al., 1960), the
valence state of thallium administered (Sabblonl et al., 1980), the length
of time after administration from 2 hours (Sabblonl et al., 1980; Gregus and
Klaassen. 1986) to 7 days (Lie et al., 1960; Schwetz et al., 1967) or after
thronlc administration (280 days) (Manzo et al., 1983b), or the dose admin-
istered (Gregus and Klaassen, 1986),. Expressed as a percent of total body
burden, greatest amounts of thallium were located In muscle, because this
tissue accounts for -30% of the body mass of rats (Lie et al., 1960).
Experiments using rabbits (Talas and Wellhoener, 1983) and mice (Andre
et al., 1960; Achenbach et al., 1980) suggested that tissue distribution In
these species was similar to that In rats, with highest concentrations
located 1n the kidney, particularly 1n the renal medula (Andre et al.,
1960). Gibson et al. (1967) noted that patterns of distribution 1n 1- and
7-day-old rats and mice were similar to patterns In adults; distribution was
widespread with highest concentrations In the kidneys. In dogs and goats,
highest tissue levels were located In heart, liver and kidney (Bradley-Moore
et al., 1975; Emara and Sollman, 1950).
0083d -23- 01/20/88
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TABLE 5-1
Concentration of Thallium201 1n Tissues of Rats
Following IntraperUoneal Administration of
Tl201 Saltsa»b
Tissue
Concentration
2 Hours
Post-Treatment
(ng/g fresh tissue)0
Concentration
40 Hours
Post-Treatment
(ng/g fresh tissue)0
Kidney
Liver
Small Intestine
Testls
Stomach
Pancreas
Salivary glands
LUng
.Heart .. ....
Thymus
Spleen
Brain
Cerebellum
Blood
97.2*17.3
14.8+1.7
21.6+5.3
6.4+0.9
22+2
32+16
30.1+5
15.5+1.4
25+6 .
14.4+6
16.3+1.2
0.4+0.1
4.7+0.6
1+0.2
167.7+16.5
6.5+0.65
NR
22+.S.9
14+0.98
21.2+4.8
28.1+12.9
12.7+1.3
14.5+1.5
14.3+5.1
9.2+1
4.1+0.5
7.4+2.2
1.6+1
aSource: Sabb1on1 et al.t 1980
bAdult male Sprague-Dawley rats were Injected with 2 jig thallium (I)
sulfate labeled with Tl20i (50 WC1).
cConcentrat1on as expressed 1s equivalent to parts per billion (ppb).
NR o Not reported
0083d
-24-
01/11/88
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Generally, administration of a single dose of thallium to rats resulted
In peak tissue concentrations within 24 hours (Rauws, 1974; Ducket et al.,
1983; Rade et al., 1982). Half-lives for depletion from several tissues In
rats were estimated at 2.7 days for the brain to 6.0 days for the spleen
(Ducket et al., 1983). Lie et al. (1960) estimated that total body clear-
ance In rats occurred exponentially In rats with a half-life of 3.3 days
(see Figure 5-1). No parenchymatous organ or tissue appeared to retain
thallium more than any other, although Rade et al. (1982) reported slower
decline from the brain and muscle than from other tissues of pregnant rats
treated with a single IntraperUoneal Injection, and Lie et al. (1960) noted
that the concentration 1n hair Increased with time.
Thallium has been shown to cross the placenta and locate In the fetus,
but, at concentrations substantially lower than those 1n maternal blood or
tissues. Gibson and Becker (1970) Intravenously Infused rats on day 20 of
pregnancy with thallium (I) sulfate and monitored the concentration of thal-
lium In 'maternal blood and 1n the whole fetus at several time points during
the 32-mlnute Infusion period. The concentration of thallium 1n maternal
blood and the fetus Increased with Increasing time and dose, but fetal
concentrations were -7% of those of maternal blood. Rade et al. (1982)
administered a single Intraperltoneal dose of thallium201 to rats on day
13 of gestation and monitored radioactivity In several maternal tissues,
placental tissue and the whole fetus for up to 192 hours (8 days). Levels
of radioactivity In maternal tissues (except blood) and the placenta always
exceeded those In the whole fetus. The decrease 1n concentration of
thallium In the whole fetus paralleled that In maternal tissues, with a
half-life for the terminal phase (of a two-phase model) of 64.2 hours.
0083d -25- 01/11/88
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Zlskoven et al. (1983) treated pregnant rats (gestation day 10) and mice
(gestation day 9) with single oral doses of thallium (I) sulfate and
measured levels of thallium In the maternal kidney and fetal tissues
(presumably whole fetus) at various times up . to 50 hours after treatment.
Concentrations In maternal kidney exceeded those In fetal tissues by a
factor of -10 throughout the study. There were no significant differences
between rats and mice. Using thallium204 (I) sulfate and a radlographlc
technique, Olsen and Jonsen (1982) showed that T1* crossed the placenta of
mice within 15 minutes of an Intraperltoneal Injection. Levels of radio-
activity In the placenta exceeded those 1n the fetus. Olsen and Jonsen
(1982) also administered single Intraperltoneal Injections of thallium204
(I) sulfate to mice on days 5-16 of gestation to measure uptake of radio-
activity by the embryo, fetus and placenta! membranes at different stages of
development. High concentrations of radioactivity were detected In the
embryo and fetus on or after day 8 and 1n the surrounding declduae on or
after day.5, Indicating early placental uptake of thallium.
5.3. METABOLISM
Little Information Is available regarding the metabolism of thallium.
Sabblonl et al. (1980) noted that the tissue distribution and retention of
radioactivity In rats following oral and Intraperltoneal administration of
201-thai 11 urn was quite similar for thallium (I) and thallium (III) sulfate.
These Investigators hypothesized that the different oxidation states were
transformed jjn vivo to a single valence. As supportive evidence they cited
similarities In the acute LD5Qs of thallium (I) and thallium (III) salts
(Section 6.1.3.), but concluded that data were Insufficient to determine
which oxidation state predominates In vivo.
0083d -26- 01/11/88
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5.4. EXCRETION
The route of excretion of thallium, which 1s strongly species-dependent,
has been studied most extensively 1n the rat. Lie et al. (1960) adminis-
tered thallium204 (I) nitrate to male Ulstar rats by a few natural or
parenteral routes and observed an exponential removal of thallium from the
body with an estimated half-life of 3.3 days, regardless of the route of
administration (see Figure 5-1). In female Wlstar rats treated Intraven-
ously with thallium204 (not otherwise specified), the estimated half-life
of 204-thallium 1n blood at steady-state was -4 days (Rauws, 1974). At the
end of a 72-hour collection period, fecal excretion accounted for 28.3% and
urinary excretion for 14.2% of the administered dose of thallium204.
Other experiments In rats Indicated that fecal excretion predominates
over urinary excretion (Barclay et al., 1953; Lund, 1956a; Schaefer and
Forth, 1980; Lehmann and FavaM, 1985; Gregus and Klaassen, 1986), and that
excretion half-lives vary from 3.3 (Schwetz et al., 1967) to >4 days (Gregus
and Klaassen, 1986). Gregus and Klaassen (1986) recovered only 0.150-0.160%
of an Intravenous 1-30 mg/kg dose of 204-T1* within 2 hours of treatment
In the bile of bile duct-cannulated rats, and concluded that biliary excre-
tion was not significant In this species. Lund (1956a) reached the same
conclusion using rats with 11 gated and sectioned bile ducts, and also
determined that thallium administered subcutaneously Is excreted Into all
sections of the gastrointestinal tract. Schaefer and Forth (1980)
determined that excretion Into the bowel occurred against a concentration
gradient.
Truhaut (1959) observed a fecal to urine excretion ratio of 0.75 In
rabbits In a 23-day collection period following treatment. Talas and
Uellhoener (1983) studied the excretion of T120U 1n rabbits treated
0083d -27- 01/11/88
-------
Intravenously. Generally, fecal excretion predominated over urinary excre-
tion; biliary excretion appeared to be Insignificant. Total body clearance
averaged 11 mi/ra1nute and appeared to be Inversely correlated with dose.
Available data Indicate that humans excrete thallium predominantly
through the urine. Barclay et al. (1953) studied the excretion of thallium
In a middle-aged woman with terminal cancer who was treated orally with 2.3
mg thallium204 followed by 5 doses of 45 mg thallium (I) sulfate every 3
days. Over a 5.5-day collection period, fecal excretion was described as
Inconsequential and urinary excretion accounted for -15.4% of the admin-
istered dose of thallium204. An excretion half-life of 21.7 days was
estimated from these data (U.S. EPA, 1980b). More recently. Talas et al.
(1983) estimated an average excretion half-life of 2.15 days In a group of
nine ambulatory patients treated with <10 yg thallium201 (I) chloride
Intravenously for myocardlal sdntlgraphy. These Investigators estimated
total body clearance at 80 ml/minute, -66% of the glomerular filtration'
rate. ..... .-.....-•'-.
Other routes of excretion may play a role In the elimination of thallium
from the body. Rlchelml et al. (1980) studied the concentration of thallium
In saliva and urine of a woman who attempted suicide by Ingesting thallium
sulfate. Levels 1n saliva were 5-15 times those In urine, but forced
diuresis Induced by Intravenous administration of glucose probably Increased
output of a less concentrated urine. Prick et al. (1955) Indicated that
thallium Is excreted 1n tears, respiratory secretion and milk as well as the
media discussed above.
5.5. SUMMARY
Absorption or uptake of soluble thallium salts 1s rapid and virtually
complete by any route of exposure (Smith and Carson, 1977; Venugopal and
0083d -28- 01/20/88
-------
Luckey, 1978; U.S. EPA, 1980b; Moeschlln, T980; Stoklnger, 1981; Hanzo et
a!., 1983a), although dermal absorption Is not likely to be significant In
environmental exposure. Distribution from the blood Is rapid and wide-
spread, with highest levels located 1n the kidney, heart and liver and
lowest levels In the nervous system and body fat (Hanzo et a!., 1983a,b;
Rauws, 1974; Barclay et al., 1953; Lie et al., 1960; Sabblonl et al., 1980).
The relative concentrations In different tissues appear to be Independent of
route of administration (Lie et al., 1960), the valence of thallium admin-
istered (Sabblonl et al., 1980), the time after administration (Lie et al..
1960) or the dosage (Gregus and Klaassen, 1986). Thallium translocates to
the placenta and fetus, but levels 1n the fetus are substantially lower than
those In maternal tissues (Gibson and Becker, 1970; Rade et al., 1982;
Zlskoven et al., 1983). The metabolism of thallium 1s not well understood,
but H Is hypothesized that thallium 1_n vivo 1s transformed to one oxidation
state (Sabblonl et al., 1980). The excretion of thallium appears to be
species-dependent, with fecal excretion predominating In the rat (Lie et
al., 1960; Rauws, 1974; Barclay et al., 1953; Gregus and Klaassen, 1986) and
urinary excretion predominating In humans (Barclay et al., 1953; R1chelm1 et
al., 1980). Estimates of excretion half-lives In humans range from 2.15
days for tracer doses 1n ambulatory heart patients (Talas et al., 1983) to
21.7 days 1n a terminal cancer patient (Barclay et al., 1953; U.S. EPA,
1980b).
0083d -29- 01/20/88
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6. EFFECTS
6.1. SYSTEMIC TOXICITY
6.1.1. Inhalation Exposures.
6.1.1.1. SUBCHRONIC — Pertinent data regarding the subchronlc Inha-
lation toxlclty of thallium salts were not located 1n the available litera-
ture cited 1n Appendix A.
6.1.1.2. CHRONIC — U.S. EPA (1979) described the protocol of an
Inhalation study with thallium (III) oxide In groups of 90 male and 90
female 8-month-old Wlstar rats. Rats were exposed In a stainless steel
chamber to concentrations of thallium (III) oxide dust adjusted from 0.5-2
mg/m3 according to clinical signs as shown In Table 6-1. Controls were
exposed to filtered air. Rats were exposed 7 hours/day, 5 days/week for 12
months, followed by a 4-month observation period, terminal sacrifice and
hlstopathologlcal examination. Interim sacrifices of 5 rats/sex/group were
scheduled for 6, 9 and 12 months. Rats that died or were sacrificed 1n a
moribund condition were necropsled. In addition to the clinical signs noted
In Table 6-1, alopecia was observed 1n exposed rats within 2 months. There
were no effects on body weights of males, but exposed females had slightly
reduced body weights at >26 weeks. Necropsy of dead rats and rats at
Interim sacrifices revealed pale or dark livers, granular appearance of the
kidneys and white or grey spots 1n the lungs of exposed rats. Hlstopatho-
loglcal evaluation of rats 1n this study has not been performed (Groth,
1987).
Human Inhalation data are limited. Marcus (1985) reported urinary
thallium levels up to 236 yg/l (median value 28.0 »g/l) In 1976 In a
group of 39 workers exposed to thallium In a magnesium seawater battery
0083d -30- 01/20/88
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TABLE 6-1
Experimental Protocol of Inhalation Study with
Thallium (III) Oxide In Groups of Hale and Female
8-month-old Ulstar Rats*
Concentration
(mg/ma)
Exposure Period
Clinical Signs
1
2
0
1
0.5
first 5 weeks of exposure
exposure weeks 6-18
week 19
weeks 20-30
weeks 31-52
no clinical signs
high mortality
NC
deteriorating health
NC
'Source: U.S. EPA. 1979
NC = No comment
00133d
-31-
01/11/88
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plant since 1970. These urinary concentrations suggested to the Investi-
gator that exposure levels exceeded the ACGIH TLV of 0.1 mg/m3, although
exposures were not quantified. The Institution of stringent Industrial
hygiene measures 1n 1977 led to a rapid decline In median urine thallium
concentrations to <0.6 wg/t by the end of 1978. Based on available
medical records, Marcus (1985) reported that there were no differences 1n 23
criteria of health (Including digestive, circulatory, CMS and mental health
problems) In a cohort of 86 exposed workers, compared with 79 unexposed
controls 1n the same factory. It Is unclear, however, whether the health
effects phase of the study Included workers exposed before Institution of
Improved hygiene. Furthermore, the length of employment of the exposed
cohort was not reported.
SenaHer et al. (1980) Investigated the effects of exposure to thallium
on the health of 128 male workers aged 16-62 years and exposed for 1-42
years (mean: 19.5 years) In three cement plants. Health evaluation
consisted of medical history and .a physical examination for symptoms of
thallium toxldty. Urinary levels of thallium ranged from <0.3-6.3
jig/4, compared with a normal upper limit of 1 jjg/l for unexposed
persons, suggesting that exposure to thallium above background levels had
occurred. The health evaluation revealed no evidence of an effect from
occupational exposure to thallium.
Ludolph et al. (1986) Investigated the effects of thallium exposure on
neurological health In 36 workers In cement production. The mean age of the
subjects was 47.6 years (range 26-62) and the mean duration of employment
was 22.9 years (range 5-44). The criteria for evaluating the neurological
health of workers Included subjective symptoms, neurological examination and
electrophyslcal parameters of nerve conduction, evoked potential and EEG.
0083d -32- 01/20/88
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Thallium levels were measured In blood, hair and urine. Although there was
no unexposed control group, the Investigators reported a high Incidence of
Impairment of the central and peripheral nervous system accompanied by a
high level of concurrent disease. Graphic presentation of levels of
thallium In blood, urine and hair Indicated that some Individuals had values
above a "critical border value." There was no correlation, however, between
levels 1n these biological media and the occurrence of clinical or electro-
physical evidence of neurological Impairment.
6.1.2. Oral Exposures.
6.1.2.1. SUBCHRONIC — Downs et al. (1960) Investigated the sub-
chronic toxldty of thallium (I) acetate and thallium (III) oxide In
weanling Wlstar rats. In the first experiment, groups of five male and five
female rats were fed diets containing 0, 0.0005, 0.0015 or 0.0050% thallium
(I) acetate for 15 weeks. After several weeks, additional groups of rats
were started on diets containing 0 or 0.003X thallium (I) acetate. These
groups were maintained on their respective diets for 63 days. Host rats on
the 0.005% diet died within 14 days; mortality rates of 80% for males and
60X for females occurred at 0.003X within 4-8 weeks. High mortality In the
control groups precluded meaningful Interpretation of mortality data at the
lower doses. Depression of growth rate occurred only In males at 0.003X.
Rats on the 0.005X diet probably died before an Impact on growth rate became
evident. The Investigators reported that relative weights of selected
organs from rats that survived to termination were within normal limits
except for a slight Increase 1n kidney weights; however, the significance of
the slightly Increased kidney weights 1s doubtful since small numbers of
rats were examined (3-5/group), and the authors did not specify which groups
were Involved. The only significant gross observation was moderate to
0083d -33- 01/11/88
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marked alopecia In rats on the 0.0015 and 0.003% diets that became notice-
able after 2 weeks of exposure and progressed to near halrlessness at termi-
nation. Hlstopathologlcal examination of 12 major organs and tissues
revealed no treatment-related lesions. The skin was not examined micro-
scopically.
In a second study, groups of five male and five female rats were fed for
15 weeks diets containing 0, 0.002, 0.0035, 0.005, 0.01 or 0.05% thallium
(III) oxide (Downs et al., 1960). All rats died at >0.005%, 4/5 males and
2/5 females died at 0.0035%, 2/5 females died at 0.002% and 1/5 males died
1n the control group. The authors did not attribute the death of 2/5
females at 0.0035% -to thallium (III) oxide, because the same number of
females died at 0.002%. Marked depression In growth rate, more evident In
males than In females, occurred at >0.0035%. Moderate depression In growth
rate occurred 1n males, but not females, at 0.002%. Progressive hair loss.
more apparent In the males-than 1n the females, occurred at >0.002%.
Elevated absolute (p<0.05) and relative kidney weights were observed at
>0.002% 1n rats that survived to termination. Apparently, statistical
analysis of relative kidney weights was not performed. Hlstopathologlcal
examination of the lung, liver, kidney and brain revealed no thallium (III)
oxide-associated lesions. Microscopic examination of the skin showed
atrophy of the hair follicles and degenerative changes In the sebaceous
glands.
The most adequate study of thallium toxlclty was a 90-day gavage experi-
ment In which groups of 20 male and 20 female Sprague-Oawley rats were
treated with thallium (I) sulfate at 0, 0.01, 0.05 or 0.25 mg/kg/day (U.S.
EPA, 19865; MRI, 1986). Parameters of toxlclty evaluated Included general
observation, mortality, body and organ weights, food consumption, hematology
0083d -34- 01/20/88
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and clinical chemistry, neurotoxlcology, ophthamology, gross and hlstopatho-
loglcal and neuropathologlcal examination. Effects possibly attributed to
thallium (I) sulfate Included alopecia, lacrlmatlon and exophthalmos,
although the Incidences and severity varied and did not clearly represent an
adverse effect of treatment with thallium (I) sulfate. Some moderate and
dose-related changes were observed In clinical chemistry parameters Includ-
ing elevated SGOT, LOH and blood sodium concentrations, and other subtle
changes In blood electrolyte concentrations were noted. The Investigators
suggested that these changes reflected a "possible" compromise of cardiac
and renal function, but that definitive Interpretation of the blood
chemistry changes required completion of the hlstopathologlcal examination,
which was not available for the Interim report of this experiment (U.S. EPA,
1986b). According to U.S. EPA (1987a) (presumably based on the final report
after hlstopathologlcal examination), there were no effects on mortality,
growth, organ weights, hlstopathologlcal .or neuropathologlcal morphology
(HRI. 1986), and the highest dose, 0.25 mg thallium (I) sulfate/kg/day, was
* ^ " . i '
judged to be a NOAEL.
A recent drinking water study using rats Indicates that the testls may
be an early sensitive target organ for the toxlclty of thallium salts.
Form1gl1 et al. (1986) provided drinking water containing 0 or 10 ppm
thallium from thallium (I) sulfate to groups of 10 mature male HI star rats
for 30 or 60 days. Food and water consumption were monitored, and thallium
Intake was estimated at 270 yg/rat/day. Using the starting average body
weight of 365 g, the only body weight data provided by the Investigators, a
dally dose of 740 ug/kg/day can be estimated. Treatment with thallium had
no effect on food or water consumption or body weight gain. There was no
•prominent" hair loss or clinical signs of neuropathy. Treatment for 30
0083d -35- 01/20/88
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days had no effect on biochemical parameters of the testls, apparently the
only parameters evaluated In rats exposed for 30 days. Exposure for 60 days
was associated with significantly decreased sperm motlllty, significantly
Increased testlcular content of thallium, significantly decreased testlcular
B-glucuronldase activity, the presence of Immature sperm cells In the
tubular lumen, altered microscopic appearance of the tubular epithelium and
altered ultrastructural appearance of the Sertoll cells. There were no
effects on relative testlcular weights, diameter of the seminiferous
tubules, plasma testosterone concentration or nonproteln thlol content of
the testls.
In an abstract from the Russian literature (Tlkhova, 1964, 1967).
rabbits dosed orally with thallium (I) sulfate at 0.35 mg/kg/day or with
thallium (I) carbonate at 0.25 mg/kg/day for 5-6 months exhibited behavioral
changes (aggressiveness, retardation, rear 11mb paralysis) and altered blood
protein profiles. Further data were not available.
In a report on neurological effects at higher dosages, 80 female
Sprague-Dawley rats Initially weighing 180-200 g were provided with drinking
water containing 10 mg Tl/l from thallium sulfate for up to 36 weeks
(Manzo et al., 1983b). A control group was maintained, but Us size and
handling were not reported. Effects were reported after 40 and 240-280 days
of treatment. The Investigators estimated dally Intake of thallium at
258.10 tig/rat at 40 days and 303.10 yg/rat at 240 days. Based on an
Initial average body weight of 190 g, the 40-day dosage may be expressed as
1.36 mg/kg/day. Based on a reference body weight for rats of 350 g (U.S.
EPA, 1985b), the dose at ,240 days may be expressed as 0.87 mg/kg/day. Hair
loss appeared as early as 32 days and affected -20% of the rats within a few
days. At termination, some rats were nearly hairless but some had no
0083d -36- 01/11/88
-------
evidence of hair loss. Cumulative mortality 1n treated rats was 15 and 21%
after 40 and 240-280 days, respectively, but control data were not
presented. Reduced motor action potential and sensory action potential were
observed In the caudal nerves of treated rats compared with controls after
240 days, but not after 40 days. Hlstopathologlcal and ultrastructural
examination of the sciatic nerves from six treated and three control rats
after 240 days revealed WalleHan degeneration and other changes 1n the
treated rats.
Deshlmaru et al. (1977) administered thallium (I) acetate at 2 mg/rat/
day (5.7 mg/kg/day, assuming a reference body weight of 350 g) for 6 months
and observed alopecia, but no neurological signs. Ultrastructural examina-
tion revealed degenerative changes, however, 1n muscle tissue and 1n the
cerebrum, thalamus and hypothalamus.
6.1.2.2. CHRONIC — Data were not located regarding the chronic oral
toxlclty of thallium 1n animals. Human data are limited to a series of
studies of health effects 1n persons living 1n the vicinity of a cement
factory In West Germany that discharged thallium Into the atmosphere
(Brockhaus et al., 1980, 1981; Dolgner et al.. 1983). Damage to plants and
domestic animals 1n the vicinity of the factory was observed and attributed
to exposure to thallium. Urine thallium concentrations of 1265 volunteers
living In the contaminated region ranged from <0.1-76.5 yg/t (mean = 5.2
tig/l), compared with mean values In two control populations of 0.4
vg/l (31 persons, rural area) and 0.3 yg/l (10 persons, urban area).
Concentrations In hair ranged from 0.6-565 ng/g (mean = 20.3 ng/g) In 1163
volunteers compared with a normal value of 10 ng/g. The Investigators
determined that thallium Intake by exposed persons was due largely to Inges-
tlon of fruits and vegetables grown near thallium emission sources, and was
not due to 1ngest1on through drinking water or Inhalation of ambient air.
0083d -37- 01/11/88
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WUhln the subgroup of exposed persons who consumed substantial amounts of
these fruits and vegetables, a positive correlation existed between
proximity to the factory and thallium levels 1n urine and hair. Health
effects, evaluated by questionnaire, were divided Into three broad cate-
gories: alteration of skin, hair or nails (Including alopecia); effects on
the oral cavity and gastrointestinal function; and neurological and subjec-
tive symptoms. There was no association between urine or hair levels of
thallium and effects In either of the first two categories. An effect on
neurological and subjective symptoms was observed; however, the Incidence
correlated positively with Increasing levels of thallium In hair or urine.
This category Included visual disturbances, hyperesthesla of the lower
extremities, tachycardia and extrasystoles, disturbed sleep and other
Indications of polyneuropathy, psychasthenla and psychic alteration.
6.1.3. Other Relevant Information. Acute oral LO~Q values for various
thallium salts In rats and mice expressed as mg Tl/kg bw are presented In
Table 6-2. Stoklnger (1981) evaluated the acute toxldty of several salts
of thallium administered orally and by various parenteral routes to five
different species and observed that toxlclty appeared to be Independent of
the anlon Involved, the species of animal and the route of administration.
Death In rats from acute exposure to thallium has been attributed to
respiratory failure (Hunch, 1928). Rats acutely poisoned with single high
(20-50 mg/kg) IntraperHoneal doses exhibited marked weight loss, anorexia,
diarrhea and lethargy (Herman and Bensch, 1967). Single Intraperltoneal
doses of 50-200 mg/kg were associated with ultrastructural and biochemical
changes 1n the liver consistent with Injury to the membranes of subcellular
organelles In the hepatocytes (Moods and Fowler, 1986). Lower Intraperl-
toneal doses (5-8 mg/kg/day) for up to 7 consecutive days resulted 1n
0083d -38- 01/20/88
-------
TABLE 6-2
Acute Oral 1059 Values for Thallium Salts
Species
Mouse
Mouse
Rat
Mouse
Mouse
Mouse
Mouse
Mouse
Rat
Thallium Salt
thallium (I) acetate
thallium (I) acetate
thallium (I) sulfate
thallium (I) sulfate
thallium (I) nitrate
thallium (I) nitrate
thallium (I) chloride
thallium (I) carbonate
thallium (III) oxide
LD50
(mg Tl/kg)
27.6
35
16
29
15
33
24
21
22
Reference
Jones et al., 1979
Sax, 1984
NIOSH, 1987a
NIOSH, 1987a
NIOSH, 1987b
Sax. 1984
Sax. 1984
Sax. 1984
Sax. 1984
0083d
-39-
01/11/88
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behavioral changes and ultrastructural and biochemical changes In the CNS
(Brown et al.t 1985; Hasan et al., 1977).
There are many reports of humans acutely poisoned with thallium com-
pounds. It Is beyond the scope or purpose of this document to review them
all. A brief overview of the subject taken largely from reviews 1s
presented here. Acute toxlclty In humans has resulted from the accidental
1ngest1on of thallium salts used as rodentlddes or Insecticides, from use
as a depilatory, both as an externally applied cream for cosmetic purposes
and Internally as an aid In the treatment of ringworm of the scalp In
children, and from cases of homicide and suicide (Gettler and Weiss, 1943;
Moeschlln, 1980).
The most commonly reported signs and symptoms of acute toxldty 1n
humans Involve the central and peripheral nervous systems and Include
paresthesla, particularly of the legs, other evidence of peripheral neuro-
pathy such as ptosls and Impaired vision from retrobulbar neuritis, ataxla,
tremors, delirium, hallucinations, convulsions and coma 1n severe cases,
'..-•••• ;...•..•;. •-..•-,..-_...•. . -' . -, - • -.-..-
culminating In death from respiratory failure (Stoklnger, 1981; Ginsberg and
Nixon, 1932; Chamberlain et al., 1958; L1111e and Parker. 1932; Munch et
al., 1933; Gettler and Weiss, 1943). Neurological signs were generally the
first to appear when relatively low doses were Ingested, and usually
occurred within 2-5 days (Stoklnger, 1981).
When high doses were Ingested, gastrointestinal signs and symptoms of
toxlclty Including gastroenteritis, diarrhea or constipation, vomiting and
abdominal pain occurred within 12-14 hours (Stoklnger, 1981). Gastrointes-
tinal symptoms were reported 1n a lesser number of cases Involving smaller
doses (Chamberlain et al., 1958). Alopecia occurred as a fairly constant
and often first symptom of toxlclty after prolonged exposure to lower doses
(Gettler and Weiss, 1943; Moeschlln, 1980).
0083d -40- 01/20/88
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When used as a depilatory to treat ringworm In children, dally oral
doses of 8 mg/kg/day (-6.2 mg Tl/kg/day) thallium acetate resulted In the
beginning of hair loss In -12 days; depllatlon was complete In -3 weeks
(Bedford, 1928). Toxic effects were observed In 3 of the 17 children
treated, and Included loss of appetite and pain and swelling 1n the legs.
Get.tier and Weiss (1943) estimated that 1.0 g of thallium (-14-15 mg/kg)
represented the minimal lethal dose for an average adult, based on acute
toxlclty data and organ concentrations of the metal In experimental dogs.
MoeschUn (1980) estimated that the average lethal dose for thallium sulfate
1s 1 g or 10-15 mg/kg for an adult (-810 mg Tl, or -8-12 mg Tl/kg), although
mortality occurred from a dose of thallium sulfate as low as 8 mg/kg/day
(-6.5 mg Tl/kg).
Thallium has been shown to Interact with potassium 1n biological systems
(U.S. EPA, 1980b), probably because of similarities In the chemical behavior
of Tlf and K* resulting from having nearly equivalent 1on1c radii
(Hughes et al., 1976). Nulllns and Moore (1960) observed similarities In
the Influx and efflux of thallium and potassium In frog muscle preparations.
Hughes et al. (1976) reported that Tl* and K* had qualitatively similar
effects when Injected Into In vitro rat heart preparations. Potassium has
been shown to Increase renal excretion of thallium (Lund, 1956b; Gehrlng and
Hammond, 1967), decrease the degenerative effects of thallium on eplphyseal
cartilage 1n mouse limb bud cultures (Neubert and Bluth, 1985; Barrach and
Neubert, 1985) (Section 6.4.), decrease placental transport of thallium
(Sabblonl et al., 1982) and Increase the LD.- of thallium 1n animals
(Gehrlng and Hammond, 1967). Equivocal results were obtained when potassium
was applied as an antidote 1n cases of human poisoning (U.S. EPA, 1980b).
0083d -41- 01/20/88
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Other attempts at treating thallium toxldty have centered around drugs
that accelerate elimination. Potent diuretics such as furosemlde and
ethacrynlc acid enhanced the urinary excretion of thallium In rats (Lehmann
and Favarl. 1985; Lameljer and van Zwleten, 1977a,b, 1978). These diuretics
accelerated excretion of water and electrolytes such as Na1", K* and
Cl~. No Increase In thallium excretion was observed with the diuretics
K-canrenoate or trlamterene, which Increased water excretion without
Increasing K* excretion (Lameljer and van Zwleten, 1979).
Oral administration of activated charcoal and Prussian blue accelerated
the elimination of orally administered thallium In rats (Lehman and Favarl,
1985; Lund, 1956b). These agents adsorb thallium In the gastrointestinal
tract and are themselves unabsorbed, thus reducing gastrointestinal absorp-
tion of thallium. Treatment with Prussian blue has been shown to reduce
both maternal and fetal tissue levels In rats poisoned with thallium (D1
Nucd et al., 1979).
In a study of the relative efficacy of several agents to accelerate the
-.-'•'' . ..-•-•'. • • ..•,.-.*..- ;. •--'..
elimination of thallium In rats, dlthlzone was reportedly the most efficient
(Lehmann and Favarl, 1985). In control rats treated orally with thallium
(I) sulfate at 10 mg Tl/kg and studied for 8 days, fecal excretion accounted
for 32% and urinary excretion for 21%, or total excretion of 53% of the
dose. Treatment with dlthlzone Increased total excretion to 99% of the dose
by the end of 8 days. Schwetz et al. (1967) demonstrated that both
dlphenylthlocarbazone (dlthlzone) and dlethyldlthlocarbamate (dlthlocarb)
enhanced excretion of thallium In rats, dlthlzone primarily by Increasing
fecal excretion and dlthlocarb by Increasing both fecal and urinary excre-
tion. Dlthlocarb, however, did Increase distribution of thallium to the
brains of treated rats (Rauws et al., 1969; Kamerbeek et al., 1971),
0083d -42- 01/20/88
-------
probably because the chelate formed 1s UpophlUc and readily crosses the
blood-brain barrier (Kamerbeek et al.t 1971).
Stavlnoha et al. (1959) Investigated the ability of a number of sulfur-
containing compounds to protect mice treated with thallium sulfate at 44.5
mg/kg, the ID-, for 1ntraper1toneal Injection. Greatest efficacy was
obtained with S-B-am1noethy11soth1uron1um*Br*HBr and S-f-amlnopropyl-
1soth1uron1um*Br*HBr. The Investigators theorized that these compounds
formed reversible bonds with the active sites of proteins, shielding them
from attack by thallium.
In other reports of Interactions, Hall (1972a) noted that cortisone
acetate exacerbated and vitamin C alleviated the achondroplastlc effect of
thallium on developing chick embryos (Section 6.4.). Levander and Argrett
(1969) observed that thallium (I) acetate Inhibited the pulmonary excretion
of volatile selenium compounds In rats Injected subcutaneously with sodium
selenlte. Thallium (I) acetate provided no protection against chronic
selenosls In rats.
6.2. CARCINOGENICITY
6.2.1. Inhalation. U.S. EPA (1979) described the protocol of an Inhala-
tion carclnogenlclty and toxlclty study In groups of 90 male and 90 female
Mlstar rats exposed to control air or thallium (III) oxide for 12 months,
followed by a 4-month observation period. Exposure concentrations ranged
from 0.5-2 mg/m3 and were administered 7 hours/day, 5 days/week. At the
termination of the exposure period, the Incidences of rats with nodules or
masses were 10 and 9 In control and exposed males, and 9 and 13 In control
and exposed females. The hlstopathologlcal evaluation of these rats has not
been performed and there are no Immediate plans to do so (Groth, 1987).
0083d -43- 01/20/88
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Human Inhalation data are limited. According to Marcus (1985) there was
no Increase In the Incidence of benign neoplasms (not otherwise specified)
In a group of 40 workers exposed to thallium 1n the manufacture of magnesium
seawater batteries, compared with controls. Health status evaluation was
limited tV> examination of current medical records, and was not adequate to
detect an oncogenlc response to thallium. Schaller et al. (1980) reported
on the health effects of 128 male workers exposed to thallium In three
cement factories (see Section 6.1.1.2.), but the health evaluation used
would not be expected to detect an oncogenlc response.
6.2.2. Oral. Pertinent data regarding the oncogenlcHy of thallium 1n
experimental animals were not located. NTP (1987) has not scheduled
thallium for toxlclty or cancer testing. The only human data available are
a series of Investigations of thallium levels and health effects 1n persons
living near a cement factory (Brockhaus et al., 1980, 1981; Dolgner et al.,
1983) (see Section 6.1.2.2.). These studies were not designed to detect an
oncogenlc response.
6.2.3. Other Relevant Information. Casto et al. (1979) demonstrated that
0.1 mM solutions of thallium (I) acetate and thallium (I) chloride signifi-
cantly enhanced Simian SA7 viral transformation of hamster embryo cells 1n
culture. Both thallium salts Increased the percentage of cells In the
cultures that were transformed as well as the number of transformed foci In
the affected cells.
Solutions of thallium salts have been tested for their abilities to
suppress tumor growth In experimental animals. Engman (1932) observed that
1ntraper1tonea1 Injection of an aqueous solution of thallium acetate 1n
single or repeated doses had no effect on the growth of Flexner-Jobllng
0083d -44- 01/20/88
-------
tumors subcutaneously Implanted Into young albino rats. Total doses ranged
from 12-44 mg/kg and often caused death from thallium toxlclty. More
recently, Intraperltoneal Injection with thallium (III) chloride at 2-5
mg/kg Increased the median survival time and number of long-term survivors
1n rats carrying the ascltlc form of Walker 256 cardnosarcoma (Hart and
Adamson, 1971). No effect was observed on the survival of mice carrying the
asdtlc form of leukemia L1210. Intraperltoneal administration had no
effect on the outcome of cancer 1n rats carrying the solid (subcutaneous)
form of Walker 256 cardnosarcoma, nor did subcutaneous Injection affect the
outcome 1n rats carrying the ascltlc form. Hart and Adamson (1971)
suggested that Intraperltoneal administration resulted In concentrations of
thallium too low at the subcutaneous tumor site to affect regression.
6.3. HUTAGENICITY
Data regarding the genotoxlclty testing, of thallium (I) salts are
presented In Table 6-3. Tl* was negative In reverse mutation tests In
prokaryotes (Kanematsu et al.,. 1980) and the reverse mutation and mltotlc
gene conversion tests In Saccharomyces cerevlslae (Singh, 1983). Tl* was
positive In the rec assay (Kanematsu et al., 1980; Kada et al., 1980), but
negative for effects on cell division 1n Escher1ch1a coll and S^ cerevlslae
(Loveless et al., 1954).
Positive results were reported for a number of tests 1n mammalian
systems. Depressed DNA synthesis was observed In Chinese hamster ovary cell
cultures (Garrett and Lewtas, 1983). Thallium (I) carbonate Induced
mutation of vaccinia virus and single strand DNA breaks In rat and mouse
embryo flbroblast cultures, and caused dominant lethal mutations In orally-
treated male white rats (Zasukhlna et al., 1983).
0083d -45- 01/20/88
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TABLE 6-3
Genotoxtclty Testing of Thai HUM Salts
o
00
G»
O.
o»
i
88/lL/LO
Assay
Reverse
•utatlon
Reverse
mutation
Reverse
mutation
Nilotic gene
conversion
Rec assay
Effects on
cell division
Effects on
cell division
Depressed DMA
synthesis
Vaccinia virus
•utatlon
Vaccinia virus
•utatton
Indicator
Organise
Salmonella
typhlmurlua
TA9B. TA100.
TA1535. TA1537.
TA1538
Escherlcnla coll
B/r WP2 try and
UP2 her try
Saccharoayces
cerevlslae. 07
Saccharoavces
cerevlslae. D7
Bacillus subtllls
H17 and N45
I- coll
strain B
S. cerevlslae
Chinese hamster
ovary cells
vaccinia virus
vaccinia virus
Thallium Salt
thalllu* (1)
nitrate
thalllu* (1)
nitrate
thai HIM (I)
nitrate
thalllui (1)
nitrate
thalllui (I)
nitrate
thai Hun (I)
nitrate
thall liui (1)
nitrate
thallium (I)
acetate
thalllu* (1)
carbonate
thallium (IJ
carbonate
Application Concentration
or Dose
spot test NR
spot test NR
plate 0.1 N
Incubation.
central well
plate . 0.1 N
Incubation,
central well
plate 0.001 H
Incubation
liquid medium 250 yg/mfc
Incubation
liquid medium NR
Incubation
cell culture 1000 tig/ml
mouse embryo 10~« H
flbroblast
cell culture
rat embryo 10'« N
flbroblast
cell culture
Response Convent
NC
NC
NC
NC
» Stronger response In
N45
Concentration tested
decreased cell growth
No effect on cell
growth
» Cell viability was
reduced and ATP and
protein synthesis
were reduced
«• Greater response In
C57B1/6 than In C8A
strain cells
» NC
Reference
Kanematsu et al.,
I960
Kanematsu et al..
1980
Singh. 1983
Singh. 1983
Kanematsu et al..
1980; Kada et
al.. 1980
Loveless et al..
1954
Loveless et al.,
1954
Garrett and
Lewtas. 1983
Zasukhlna et al..
1983
Zasukhlna et al.,
1963
-------
TABLE 6-3 icont.)
o
8 Assay
Q.
Single strand
DMA breaks
Single strand
DMA breaks
Dominant
lethal test
Indicator
Organise
•ouse enbryo
flbroblasts
rat entry o
flbroblasts
•ale white rats
Thai HUB Salt
thai HIM (1)
carbonate
thai lira (I)
carbonate
thalltua (1)
carbonate
Application
cell culture
cell culture
dally oral
treatment
for 8 aonths
Concentration Response
or Dose
10~» to 10'« N »
10"« to 10~« M »
5xlO~* to »
5xl(T«
•g/kg/day
Coonent
Positive response In
cells fro* C57B1/6.
but not CBA strain
•tee
Magnitude of response
was dose-related
Magnitude of response
was dose-related
Reference
Zasukhlna et al..
1983
Zasukhlna et al..
1983
Zasukhlna et al..
1983
•C • No cooMent; MR • not reported
ce
CO
-------
6.4. TERAT06EMICITY
A number of Investigations have demonstrated that thallium compounds
Injected Into developing chicken eggs were associated with embryolethallty
and the development of achondroplastlc dwarfs (Karnofsky et al.t 1950;
Landauer, 1960; Ford et al.. 1968; Hall, 1972b; Skrovlna et al., 1973).
These experiments and a more recent in vitro study with cultured chick
tibiae (Hall, 1985) revealed that the chondrogenlc cells In the long bones
underwent degeneration and necrosis when exposed to thallium.
Recent experiments with whole embryo and organ cultures Indicated that
chondrocytes 1n the long bones of mammals are also sensitive to thallium.
Neubert and Bluth (1985) and Barrach and Neubert (1985) reported that
thallium concentrations of 15 yM caused minimal effects and 50 yM caused
clearly adverse effects on growth of the forellmb using 11-day-old 11mb buds
from mice. Neubert and Bluth (1985) concluded that thallium concentrations
>10-15 yM (2.0-3.1 yg/mi) 1n tissues of mammalian embryos may
adversely affect fetal development, but that these levels are not likely to
occur In environmentally exposed humans. In another study, thallium concen-
trations of 3-100 yg/ml produced a dose-dependent retardation of growth
In cultured whole rat embryos (Anschuetz et al., 1981). Hlstopathologlcal
examination also revealed cytotoxlc effects 1n the CNS.
Nogaml and Terashlma (1973) evaluated effects of thallium on the long
bones of neonates and fetuses by hlstopathologlcal examination and by
quantltatlng uptake of "SO. by mucopolysaccharldes as a measure of
cartilage growth within the bone. When thallium (I) sulfate was adminis-
tered by Intraperltoneal Injection to SO rats at 6 days of age (20 yg/kg)
or at 9 days of age (40 yg/kg), the hlstopathologlcal appearance of
0083d -48- 01/11/88
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cartilage 1n the long bones Indicated retarded growth, and mucopolysac-
charlde uptake of "SO. had decreased to 50% that of controls. Effects
were less severe 1n fetuses and term offspring from rat dams treated with
thallium (I) sulfate (doses and route of administration not reported).
Hlstopathologlcal lesions were not observed 1n the cartilage of the long
bones of the fetuses; however, cartilaginous uptake of "SO. was reduced
50% In term offspring from the treated rats.
Gibson and Becker (1970) administered thallium (I) sulfate by IntrapeM-
toneal Injection to groups of 4-7 mated Sprague-Dawley rats maintained on
standard laboratory animal diets at doses of 0 or 2.5 mg/kg on days 8, 9 and
10 or on days 12, 13 and 14 of gestation. Additional groups were treated on
days 12, 13 and 14 of gestation at 10.0 mg/kg. All treatments resulted In
significantly reduced fetal body weights but did not significantly alter the
frequency of fetal resorptlon from that observed 1n controls. An Increased
Incidence of hydronephrosls and the absence of vertebral bodies In fetuses
was also observed. Both defects were produced by administration of thallium
sulfate during gestation; the effects were also produced during early
gestation, although the Increase was not statistically significant In every
treated group. The authors concluded that the failure of thallium sulfate
to produce the severe teratogenlc effects In rats compared with chickens 1s
the result of placental restriction of thallium transfer.
The only oral developmental toxldty Information located was an abstract
of a study 1n VMstar rats and NHRI mice. Roll and Hatthlaschk (1981) admin-
istered thallium chloride or thallium acetate to rats and mice by gavage on
days 6-15 of gestation. Gravlda were examined on gestation days 18 (mice)
or 21 (rats), and some dams were allowed to deliver. Offspring were killed
and examined at 21 days of age to evaluate the occurrence of late developing
abnormalities. The only effects reported In mice were a slight Increase 1n
0083d -49- 03/08/88
-------
postlmplantatlon fetal loss at 6 mg thallium chlor1de/kg/day and a slight
effect on birth weights at upper (unspecified) dose levels. Effects In rats
were limited to slightly Increased postlmplantatlon loss at 3 mg/kg/day
thallium acetate. Higher doses could not be tested because of acute
maternal toxlclty. Malformations of the skeleton and Internal organs were
not observed.
Bornhausen and Hagen (1984) treated Wlstar rats with thallium sulfate by
gavage on days 6-9 of gestation at doses of 0, 0.1, 0.5 or 2.0 mg Tl/kg to
Investigate the effect of prenatal exposure to thallium on learning ability
of the adult female offspring. The test was described as a conditioning
program 1n which lever pressing was rewarded with a food pellet. Pre-
natal ly-exposed offspring were apparently tested at 3 months of age.
Prenatal exposure to thallium resulted In significant Impairment of learning
at all doses. H1s.topatholog1cal examination of brain, liver and kidney
revealed no lesions.
Dolgner et .al. (1983) Investigated the Incidence of birth defects In
children born between January 1, 1978 and August 31. 1979 to 297 mothers
living in the vicinity of a cement factory that emitted large quantities of
thallium Into the atmosphere. Data were obtained from questionnaires and
urine samples. The study revealed that 19 children had possible congenital
malformations; pedlatrlc and anemnestlc evaluation eliminated all but 5 from
consideration. Based on the expected rate of birth defects 1n a population
of 297 births (0.8), an observed:expected ratio of 6.25 was calculated.
Generally, thallium levels In the urine of mothers of children with birth
defects were near the lower limits of the general population, and the Inves-
tigators concluded that exposure to thallium was not likely to have caused
the malformations.
0083d -50- 03/08/88
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6.5. OTHER REPRODUCTIVE EFFECTS
Roll and Hatthlaschk (1981) reported a slight Increase 1n overall
mortality up to weaning, and slightly decreased growth rate In offspring of
mice treated by gavage with thallium chloride at 6 mg/kg/day for an
unspecified period of time 1n breeding experiments. These effects were not
observed with thallium chloride at 3 mg/kg/day. When similarly administered
to rats, thallium chloride and thallium acetate at 3 mg/kg/day resulted 1n a
slight Increase 1n overall mortality of the offspring.
Since changes 1n testlcular biochemistry may precede other signs of
toxic damage, for example hair loss and peripheral nervous system disorders
(Manzo, et al., 1983b), Investigations were extended to selected testlcular
enzyme (0-g1ucoron1dase) activities considered as Indicators of testlculae
function 1n the rat.
In a 30- to 60-day drinking water study using rats (Form1gl1 et al.,
1986), rats treated with thallium [from thallium (I) sulfate] at 10 ppm
thallium (270 yg/rat/day) for 60 days had significantly decreased sperm
motnity, significantly Increased testlcular content of thallium, signifi-
cantly decreased testlcular B-glucuron1dase activity, the presence of
Immature sperm cells 1n the tubular lumen, altered microscopic appearance of
the tubular epithelium and altered ultrastructural appearance of the Sertoll
cells (see Section 6.1.2.1.). There were no effects on relative testlcular
weights, diameter of the seminiferous tubules, plasma testosterone concen-
tration or nonproteln thlol content of the testls. No abnormalities In
testlcular morphology or biochemistry were seen 1n 30-day treated rats. In
contrast, both the ubiquitous add phosphatase and sorbUol dehydrogenase,
which are normally associated with postmelotlc spermatogenlc cells (Mills
and Means, 1972) 'did not differ from controls. Degenerative changes In
0083d -51- 03/11/88
-------
Sertoll cells are associated with disarrangement of the seminiferous
epithelium and premature release of 2 developing germ cells. In this study
both the biochemical and morphological findings are consistent with
thallium-Induced teslcular damage.
6.6. SUMMARY
Thallium salts are potent poisons that cause acute toxldty 1n humans.
Human poisoning has resulted from accidental 1ngest1on of thallium salts
used as rodentlcldes and Insecticides, from Internal and topical use as a
depilatory agent, and from cases of homicide and suicide (Gettler and Weiss,
1943; MoeschUn, 1980). Signs of toxldty 1n humans Include neurological
and gastrointestinal effects. Death Is usually due to respiratory failure
(Gettler and Weiss, 1943; Stoklnger, 1981). A threshold for acute toxldty
In children appears to be ~6 mg Tl/kg/day (Bedford, 1928). An average
lethal dose for adults 1s -8-12 mg Tl/kg (Hoeschlln, 1980). Acute oral
LD50 values 1rt rats and mice range from 16-35 mg Tl/kg, apparently
Independent of species or the Identity of the thallium salt.
Chronic oral exposure of humans appears to Increase the Incidence of
neurological and subjective symptoms, as observed In a population living In
the vicinity of a cement factory that discharged large quantities of
thallium Into the atmosphere (Brockhaus et al., 1980, 1981; Dolgner et al.,
1983). Exposure was primarily through Ingestlon of thallium from fruits and
vegetables grown near thallium emission sources. Subchronlc oral exposure
of laboratory animals Is associated with hair loss, elevated kidney weights
(Downs et al., 1960), neurological and skeletal muscle effects (Manzo et
al.. 1983b; Deshlmaru et al., 1977), body weight loss and mortality (Downs
et al., 1960). According to U.S. EPA (1986b) the highest dose (0.25
mg/kg/day) did not produce any effects on mortality, growth and target organ
0083d -52- 03/11/88
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toxlclty; therefore this dose (0.25 mg/kg/day thallium sulfate or 0.20
mg/kg/day thallium) was Identified as the NOAEL 1n the 90-day gavage study
1n rats.
Inhalation animal toxldty data consist of a study 1n which rats were
exposed Intermittently to thallium (III) oxide at 0.5-2 mg/m3 was
associated with deteriorating health and Increased mortality (U.S. EPA,
1979). Adverse health effects were not reported 1n humans occupationally
exposed to thallium 1n a magnesium seawater battery plant (Marcus, 1985) or
In cement production (Schaller et a!., 1980; Ludolph et al., 1986).
Thallium salts have not been tested for cardnogenlclty 1n animals, and
the NTP (1987) has not scheduled 1t for cardnogenlclty testing. Cancer
data 1n humans Is very limited. Mixed results have been observed In geno-
toxldty testing. Negative results were obtained In reverse mutation tests
(Kanematsu et al., 1980; Singh, 1983) and In tests for effects on cell
division (Loveless et al., 1954). Positive results were obtained 1n a rec
assay '(Kanematsu et al., 1980) and 1n several mammalian test systems.
Including a dominant lethal test in male rats (Zasukhlna et al., 1983).
Thallium results 1n achondroplastlc malformations when Injected Into
developing chicken eggs (Karnofsky et al., 1950; Landauer, 1960; Ford et
al., 1968; Hall, 1972b; Skrovlna et al., 1973) or tested In mammalian whole
embryo cultures (Anschuetz et al., 1981) or 11mb bud cultures (Neubert and
Bluth, 1985; Barrach and Neubert, 1985). Parenteral administration to
pregnant rats at high doses (>2 mg Tl/kg/day) resulted 1n reduced fetal body
weights, hydronephrosls and the absence of vertebral bodies (Gibson and
Becker, 1970). Oral administration to rats (>2 mg Tl/kg/day) and mice (>4
mg Tl/kg/day) during organogenesls resulted only 1n a slight Increase 1n
fetal loss In both species (Roll and Matthlaschk, 1981). Malformations of
0083d -53- 03/11/88
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the skeleton and Internal organs were not observed. In offspring of rats
and mice allowed to deliver, reduced survival at weaning 1n both species and
reduced growth rate 1n mice were observed. Adult offspring of dams treated
with thallium during gestation had significant learning deficits In a
lever-pressing behavior conditioning test (Bornhausen and Hagen, 1984).
Recent studies Indicate that thallium may have an adverse effect on male
reproduction. Adult male rats exposed to thallium In the drinking water at
0.74 mg/kg/day for 60 days had decreased sperm motHUy, Inhibition of
8-glucoron1dase activity and hlstopathologlcal alteration of the testes.
These changes were not observed 1n animals sacrificed at the end of the
30-day thallium exposure. These findings therefore suggest that the male
reproductive system Is a susceptible target site to toxic effects of
thallium under chronic exposure.
0083d -54- 03/11/88
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7. EXISTING GUIDELINES AND STANDARDS
7.1. HUNAN
ACGIH (1987) adopted a TWA-TLV of 0.1 mg Tl/m3 for soluble compounds
of thallium based predominantly on analogy to other toxic heavy metals,
because data on thallium and Us salts were not sufficient for derivation of
a TLV (ACGIH, 1986). No STEL was recommended. OSHA (1985) adopted 0.1 mg
Tl/m3 as the occupational standard PEL for soluble compounds of thallium.
U.S. EPA (1980b) recommended an ambient water quality criterion of 13
yg Tl/l for protection of human health, assuming consumption of 2 I
water and 6.5 g of fish and shellfish/day. A concentration of 48 yg/l
was calculated for consumption of edible aquatic products alone. These
recommendations were based on an RfO of 37.3 yg Tl/day for a 70 kg man,
calculated from the NOEL of 0.0005% (5 ppm) thallium (I) acetate (equivalent
to 4 ppm Tl) 1n the subchronlc study by Downs et al. (1960), and a BCF of
119. Details of the derivation of this RfD are presented 1n Section 8.2.2.2.
In an update of quality criteria for water, U.S. EPA (1987a) presented
an RfD for thallium of 3.9xlO~4 mg/kg/day, which would be equivalent to
27.3 yg/day for a 70 kg human. Using an RfD of 27.3 yg/day, ambient
water quality criteria of 9.8 yg/l for consumption of drinking water and
aquatic products and 35 yg/l for consumption of aquatic products alone
can be calculated.
Verified oral RfDs for a number of thallium salts are listed 1n Table
7-1. The values listed 1n Table 7-1 were derived by analogy to thallium
based on a NOEL of 0.39 mg Tl/kg/day 1n a 15-week study by Downs et al.
(1960) In which rats were fed diets containing 0-500 ppm thallium acetate.
A more recent oral RfD for thallium (I) sulfate of 0.25 yg/kg/day was
derived and verified by the U.S. EPA (1987b) based on the 90-day gavage
0083d -55- 03/11/88
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TABLE 7-1
Oral RfDs for Thallium Salts
Thallium
Salt
Thalllc oxide
Thallium
Thallium
Thallium
Thallium
Thallium
Thallium
(I)
(I)
(I)
(I)
acetate
carbonate
chloride
nitrate
selenlte
(I)
sulfate
Oral RfD
(yg/kg/day)
0.
0.
0.
0.
0,
0.
0.
4
5
4
4
5
5' '
5
U.
U.
U.
U.
U.
U.
U.
Reference
S.
S.
S.
S.
S.
S.
S.
EPA,
EPA,
EPA,
EPA,
EPA,
EPA.
EPA,
1985c
1985d
1985e
1985f
1985g
1985a
1985h
0083d
-56-
03/11/88
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study exposing rats to thallium (I) sulfate (MRI, 1986} 1n which the highest
dose tested (0.25 mg/kg/day) was a NOAEL. Details of the derivations of
these RfDs are discussed 1n Section 8.2.2.2.
The U.S. EPA (1987c) listed thallium as a chemical requiring regulation
under the Safe Drinking Mater Act amendments of 1986, but regulations are
not currently available.
7.2. AQUATIC
U.S. EPA (1986c) reported that data were Insufficient for derivation of
ambient water quality criteria for protection of aquatic life. The follow-
ing discussion was taken from that document:
The available data for thallium Indicate that acute and chronic
toxldty to freshwater aquatic life occurs at concentrations as low
as 1400 and 40 yg/l, respectively, and would occur at lower
concentrations among species that are more sensitive than those
tested. Toxldty to one species of fish occurs at concentrations
as low as 20 yg/t after 2600 hours of exposure.
The available data for thallium Indicate that acute toxldty to
saltwater aquatic life occurs at concentrations as low as 2130
vg/a and would occur at lower concentrations among species that
are more sensitive than those tested. No data are available
" concerning = the. chronic toxUHy of thaUtum -to...sensitive saltwater .
aquatic life.
0083d -57- 03/11/88
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8. RISK ASSESSMENT
8.1. CARCINOGENICITY
8.1.1. Inhalation. Inhalation cancer data In animals are limited to an
unfinished study with thallium (III) oxide 1n which rats were exposed Inter-
mittently for 12 months and the number of rats with masses and nodules was
reported but hlstopathologlcal examinations were not performed (U.S. EPA,
1979). Human data consist of occupational studies of workers exposed to
thallium 1n magnesium seawater battery manufacture (Marcus, 1985) and cement
manufacture (Schaller et al.t 1980); these studies were Inadequately con-
ducted to discern an oncogenlc effect. Marcus (1985) reported no Increased
Incidence of benign neoplasms 1n workers 1n a magnesium seawater battery
factory.
8.1.2. Oral. The oncogenlclty of thallium has not been tested In animals
and NTP (1987) has not scheduled any thallium salts for testing. A series
of health Investigations of persons living 1n proximity to a* cement factory
that contaminated the area, with thallium (Brockhaus et al.. 1980, 1981;
Dolgner et al., 1983) were not designed to detect an oncogenlc effect. In
these studies 1t was determined that exposure was predominantly oral.
resulting from Ingestlon of thallium-contaminated home-grown fruits and
vegetables.
8.1.3. Other Routes. Pertinent data regarding the oncogenlclty of
thallium administered by other routes were not located In the available
literature cited 1n Appendix A.
8.1.4. Weight of Evidence. The studies reviewed 1n Sections 8.1.1. to
8.1.3 above constitute "no data" In both animals and humans that are useful
for evaluating the overall weight of evidence for the carclnogenldty of
0083d -58- 03/11/88
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thallium 1n humans. Applying- the U.S. EPA (1986c) guidelines, thallium and
Us salts are designated EPA Class D substances: unable to be classified as
to human carclnogenlclty.
8.1.5. Quantitative Risk Estimates. The lack of adequate data precludes
derivation of quantitative risk estimates for thallium salts for either
Inhalation or oral exposure.
8.2. SYSTEMIC TOXICITY
8.2.1. Inhalation Exposure.
8.2.1.1. LESS THAN LIFETIME EXPOSURES (SUBCHRONIC) — Pertinent data
regarding the toxlclty of subchronlc Inhalation exposure were not located 1n
the available literature cited 1n Appendix A, hence derivation of subchronlc
Inhalation RfDs for thallium salts 1s precluded.
8.2.1.2. CHRONIC EXPOSURES — Animal data are limited to an unfin-
ished study In which rats were exposed to thallium (III) oxide at levels of
0.5-2 mg/m3, 7 hours/day, 5 days/week for 12 months. Reported effects
were limited to clinical signs, mortality, effects on body weight and
necropsy observations of dead rats and rats subjected to Interim sacrifice.
Hlstopathologlcal examination has not been performed. Human data are
restricted to occupational Investigations of workers 1n a magnesium seawater
battery manufacturing plant (Marcus, 1985) and 1n cement manufacture
(Schaller et al., 1980; Ludolph et al., 1986) that associated no effects
with exposure to thallium. Although Marcus (1985) concluded that the ACGIH
(1987) TLV of 0.1 mg/m3 was adequately protective, exposures were not
quantified and these data are Inadequate for estimation of Inhalation RfDs
for thallium or Us salts.
0083d -59- 03/11/88
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8.2.2. Oral Exposures.
8.2.2.1. LESS THAN LIFETIME EXPOSURES (SUBCHRONIC) — Downs et al.
(1960) fed weanling rats diets containing 0, 0.0005, 0.0015, 0.003 or
0.0050% thallium (I) acetate for 63 days to 15 weeks. The lowest dietary
concentration tested, 0.0005X (5 ppm) was a NOEL; hair loss, depressed body
weight gain, elevated kidney weights and mortality occurred at higher
dietary concentrations. Downs et al. (I960) fed weanling rats diets
containing thallium (III) oxide at 0, 0.002, 0.0035, 0.005, 0.01 or 0.05%
for 15 weeks. Hair loss and elevated kidney weights were observed at all
dietary levels. Increased mortality was reported at >0.0035%. The NOEL of
5 ppm dietary thallium (I) acetate 1s equivalent to 0.5 mg/kg/day, assuming
weanling rats consume food equivalent to 10X of their body weight/day. The
equivalent dose of thallium 1s 0.39 mg/kg/day.
In a more recent study, rats were treated by gavage with thallium (I)
sulfate at 0, 0.01, 0.05 or 0.25 mg/kg/day for 90 days In a comprehensive
and well controlled subchronlc toxlctty test (U.S. EPA, 1986b; MRI. 1986).
Effects possibly attributed to exposure to thallium Included alopecia,
1acr1mat1on, exophthalmos and some moderate changes In clinical chemistry
parameters. There were no histopathologlcal alterations, however, and the
highest dose. 0.25 mg/kg/day was considered a NOAEL (U.S. EPA, 1987a).
A brief abstract from the Russian .literature reported behavioral changes
1n rabbits treated orally with thallium (I) carbonate at 0.25 mg/kg/day or
with thallium (I) sulfate at 0.25 mg/kg/day for 5-6 months (Tlkhova, 1964,
1967). Because a full report of the conduct and results of this study were
not available for evaluation, these data are not adequate for consideration
1n risk assessment. Neurophyslologlcal effects and degeneration of periph-
eral nerves were reported In rats provided with drinking water containing
0083d -60- 03/11/88
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thallium sulfate at 10 mg Tl/l for °40 days (Manzo et al., 1983b). The
dose of Tl was estimated at 0.87 mg/kg/day (see Section 6.1.2.1.). Degen-
erative changes 1n skeletal muscle and different regions of the brain were
reported 1n rats treated with thallium (I) acetate at 5.7 mg/kg/day for 6
months. Oral administration of thallium acetate at 3 mg/kg/day (2.3 mg
Tl/kg/day) to rats during organogenesls resulted In slightly Increased post-
Implantation loss and reduced survival of offspring at weaning (Roll and
Matthlaschk, 1981). Rats treated with thallium (I) sulfate at 0.74 mg
Tl/kg/day In drinking water for 60 days had reduced sperm motllUy and
hlstopathologlcal alteration of the testes (Form1gl1 et al., 1986).
Benchmarks of toxlclty available for consideration for derivation of a
subchronlc RfD for oral exposure to thallium and Us salts Include the NOEL
of 0.39 mg Tl/kg/day 1n the Downs et al. (1960) dietary experiment with
thallium (I) acetate In rats and the NOAEL of 0.25 mg thallium (I) sulfate/
kg/day 1n the 90-day gavage experiment reported by U.S. EPA (1986b) and MRI
(1986). Because tha>l1um (I)- sulfate contains 80.97% thallium (Wlndholz,
1983), this NOAEL corresponds to a dose of thallium of 0.20 mg/kg/day. The
NOAEL of 0.20 mg Tl/kg/day Is chosen as the basis for subchronlc RfDs for
thallium and Us salts, primarily because of the higher quality of the
90-day gavage study (U.S. EPA, 1986b; MRI, 1986); this study used larger
numbers of rats/group than the Downs et al. (1960) study. Furthermore, 1n
the Downs et al. (1960) study there was high mortality In all groups Includ-
ing controls, rendering questionable the Interpretation of the results. The
dose of 0.20 mg Tl/kg/day 1s substantially below doses associated with
fetotoxlclty (Roll and Matthlaschk, 1981) and effects on male reproduction
(Formlgll et al., 1986).
0083d -61- 03/11/88
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Application of an uncertainty factor of 100, 10 each for Inter- and
Intraspecles variation, results In an RfD of 0.002 mg/kg/day, or 0.1 mg/day
for a 70 kg human for subchronlc oral exposure to thallium 1n thallium
salts. Subchronlc oral RfDs can be calculated for specific thallium salts,
assuming their toxlclty depends entirely on the thallium moiety, by correct-
Ing for the proportion of thallium 1n each salt. This approach 1s 1n
keeping with an earlier Agency analysis, as explained In Section 8.2.2.2.
Subchronlc oral RfDs for thallium and selected salts are presented In Table
8-1. Confidence 1n the critical study 1s rated medium because Interpreta-
tion of the biological significance of some of the reported effects was
unclear. Confidence In the data base and RfDs are also rated medium.
8.2.2.2. CHRONIC EXPOSURES — Chronic exposure data are limited to a
series of Investigations of health effects 1n persons living In the vicinity
of a cement factory that discharged thallium Into the atmosphere (Brockhaus
et al., 1980, 1981; Dolgner .et al., 1983). An Increase In the Incidence of
neurological and subjective symptoms was reported that correlated positively
with distance from the factory. Exposure was shown to result from con-
sumption of home-grown fruits and vegetables that were contaminated with
thallium. Exposures were not quantified, however, and these data are
Inadequate for use In risk assessment.
U.S. EPA (1980b) derived an RfD for thallium based on the NOAEL of 5 ppm
thallium (I) acetate, equivalent to 4 ppm thallium, 1n the subchronlc
dietary study 1n weanling rats by Downs et al. (1960). U.S. EPA (1980b)
assumed that the rats consumed 10 g of food/day, and estimated body weight
at 0.075 kg to calculate an equivalent dose of 533 yg Tl/kg/day. Applica-
tion of an uncertainty factor of 1000 and multiplication by the reference
human body weight of 70 kg resulted In an RfD of 37.3 yg/day. In more
0083d -62- 03/11/88
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TABLE 8-1
Subchronlc Oral RfDs for Selected Thallium Salts3
Thallium Salt
Thallium
Thallium (III) oxide
Thallium (I) acetate
Thallium (I) carbonate
Thallium (I) chloride
Thallium (I) nitrate
Thallium selenlde (TISe)
Thallium (I) selenlde (Tl2Se)f
Thallium (I) sulfate
Thallium
Content
(*)
100
89.49b
77.59e
87.206
85.22e
76.72e
72.13&
83.816
80.976
Subchronlc
(mg/kg/day)
0.002
0.002C
0.003C
0.002C
0.002C
0.003C
0.003C
0.002C
0.002C
Oral RfD
(mg/day)
0.1
0.2d
0.2d
0.2d
0.2d
0.2d
0.2d
0.2d
0.2d
aSubchron1c oral RfDs were calculated for those thallium salts for which
the Agency has calculated chronic oral RfOs.
Calculated from molecular formula and atomic weights
cCalculated by dividing the subchronlc oral RfD for thallium of 0.002
mg/kg/day by the fraction of the salt that Is thallium, and rounding to
one significant figure.
Calculated by dividing the subchronlc oral RfD for thallium of 0.002
mg/kg/day by the fraction of the salt that 1s thallium, multiplying the
result by 70 kg and rounding to one significant figure.
eW1ndholz, 1983
flt 1s likely that U.S. EPA (1985a) Intended to derive an oral RfD for
this compound rather than for TISe (see Section 1.1.).
0083d -63- 03/11/88
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recent analyses the U.S. EPA (1985a,c,d,e,f,g,h) derived oral RfDs for a
number of thallium salts (see Section 7.1.) from the NOEL of 5 ppm thallium
(I) acetate In the Downs et al. (1960) study, by assuming that weanling rats
consume food equivalent 1n amount to 10% of their body weight, resulting In
a transformed dose of 0.5 mg/kg/day for thallium (I) acetate. Oral RfDs for
the other thallium salts were calculated by correcting for differences 1n
molecular weights and molarUy of thallium, 1f necessary.
U.S. EPA (1987b) derived a new oral RfD for thallium (I) sulfate of 0.25
vg/kg/day or 17.5 yg/day (verified by the Agency-wide RfD Work Group on
07/16/87) for a 70 kg human by applying an uncertainty factor of 1000 to the
NOAEL'of 0.25 mg/kg/day In the 90-day gavage study by U.S. EPA (1986b) and
MRI (1986). As discussed 1n Section 8.2.2.1., this gavage study Is a more
sound basis for risk assessment than the dietary study by Downs et al.
(1960). Therefore, new oral RfDs for thallium salts are calculated from the
NOAEL of 0.25 nig thallium (I) sulfate/kg/day, equivalent'to 0.20 mg Tl/kg/
day. Application.of an uncertainty factor of 1000, 10 for estimation of a
chronic NOAEL from a subchronlc NOAEL, and 10 each for Inter- and 1ntra-
specles variation, results In an oral RfD for thallium of 0.2 yg/kg/day or
14 yg/day for a 70 kg human. Oral RfDs for selected thallium salts are
calculated In Table 8-2. Confidence levels In the critical study, data base
and RfDs are all rated medium, as discussed 1n Section 8.2.2.1.
0083d -64- 03/11/88
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TABLE 8-2
Chronic Oral RfDs for Selected Thallium Salts3
Thallium Salt
Thallium
Thallium (III) oxide
Thallium (I) acetate
Thallium (I) carbonate
Thallium (I) chloride
Thallium (I) nitrate
Thallium selenlde (TISe)
Thallium (I) selenlde (Tl2Se)f
Thallium (I) sulfate
Thallium
Content
(%)
100
89.49b
77.59e
87.20s
85.22e
76.72e
72.13b
83.816
80.97
Subchronlc
(yg/kg/day)
0.2
0.2C
0.3C
0.2C
0.2C
0.3C
0.3C
0.2°
0.3«
Oral RfD
(mg/day)
0.01
0.02d
0.02d
0.02d
0.02d
0.02d
0.02d
0.02d
0.029
.aQral RfDs were .calculated, for those thallium, salts for which the Agency
had previously'calculated oral RfOs.
^Calculated from molecular formula and atomic weights
cCalculated by dividing the oral RfO for thallium of 0.2 yg/kg/day by
the fraction of the salt that 1s thallium and rounding to one significant
figure.
Calculated by dividing the oral RfD for thallium of 0.2 yg/kg/day by
the fraction of the salt that 1s thallium, multiplying the result by 70 kg
and rounding to one significant figure.
eW1ndholz, 1983
flt 1s likely that U.S. EPA (1985a) Intended to derive an oral RfD for
this compound rather than for TISe (see Section 1.1).
QCalculated by rounding the U.S. EPA (1987a) estimate to one significant
figure.
0083d -65- 03/11/88
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9. REPORTABLE QUANTITIES
9.1. BASED ON SYSTEMIC TOXICITY
Data relevant to the derivation of an RQ based on the systemic toxlclty
of thallium salts Include an uncompleted subchronlc Inhalation toxldty
study and a number of subchronlc oral studies (see Chapter 6). Pertinent
data from these studies are summarized 1n Table 9-1. Although the effects
reported by U.S. EPA (1979), Downs et al. (1960), and U.S. EPA (1986b) and
MRI (1986) were observed In both male and female rats, the smaller body
weights of the females resulted In the lower equivalent human doses, and
therefore only data for the females are tabulated. All doses were expressed
In terms of mg Tl/kg/day, because thallium 1s the toxic moiety In the
thallium salts and toxic potency appears to be Independent of the salt
selected (see Section 8.2.2.). Except for the developmental toxlclty study,
an uncertainty factor of 10 was applied to estimate a chronic effect level
from a subchronlc effect level.
Effects attributed to subchrontc exposure to thallium Include mortality
after 5 months of exposure In an Inhalation study (U.S. EPA, 1979), de-
creased rate of body weight gain (Downs et al., 1960). alopecia, lacrlma-
tlon, exophthalmos and biochemical changes (U.S. EPA, 1986b; MRI, 1986),
Increased fetal loss (Roll and Matthlaschk, 1981) and hlstopathologlcal
alteration of the testes (Form1gl1 et al., 1986). Downs et al. (1960) also
reported mortality In their dietary studies, but Interpretation of the data
and Identification of the MED was precluded by high mortality 1n the control
or low dose groups. Mortality also appeared to be high In the drinking
water study by Manzo et al. (1983b), but control data were not reported.
CSs for these effects are calculated 1n Table 9-2.
0083d -66- 03/11/88
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TABLE 9-1
Systenlc Toxic I ty Suouary for Thai HUM Salts
§
CD
g
Route Thalllua Salt
Inhalation thalllua (III)
oxide
Oral thalllua (1)
acetate
Oral thalllua (III)
oxide
e» Oral thalllua (I)
•J-* sulfate
Oral thalllua (I)
sulfate
Oral thalllua (I)
acetate
Species/
Strain
rat/Ulstar
rat/Ulstar
rat/Ulstar
rat/Sprague-
Oawley
rat/Sprague-
Dawley
rat/Ulstar
Average
Nuaber at Body
Start/Sex Uelght
(kg)
90/F 0.35
S/F 0.15*
5/N 0.20*
20/F 0.22b
80/F 0.350J
NR/F 0.3501
;
Vehicle or
Physical
State/Purity
dust/<15 ppa
lapurltles
dlet/>90X
d1et/>90X
water/>99X
drinking
water/NR •
NR/NR
Exposure
1 ag/a» for 5
weeks. 2 ag/a*
for 13 weeks
(TWU1.7 ag/a»)
7 hours/day,
5 days/week
0.0015X diet
(IS ppa) for
15 weeks
0.002X diet
(20 ppa) for
15 weeks
0.01 og Tl2$04/
kg/day for 90
days
10 ag Tl/l
(10 ppa Tl) for
up to 36 weeks
3 ag/kg/day by
gavage on days
6-15 of gestatlo
Trans foraed
Anlaal Dose
(ag Tl/kg/day)
0.020c«d
0.058d.'.fl
0.089d«M
0.0008d-'
0.087d>k
2.39
n
Equivalent
Hunan Dosea Response
(ag Tl/kg/day)
0.003 Mortality
0.007 Alopecia ele-
vated kidney
weight
0.013 Decreased rate
of body weight
gain
0.0001 Alopecia.
exophthalaos.
lacrlaatlon.
at Id blocheal-
cal changes
0.015 Neurophyslo-
logtcal and
neuropatho-
loglcal changes
0.39 Increased
fetal loss
Reference
U.S. EPA.
1979
Downs et al..
1960
Downs et al..
1960
U.S. EPA.
1986b;
NR1. 1986
Hanzo et al..
19835
Roll and
Natthlaschk.
.1981
00
oo
-------
TABLE 9-1 (cont.)
Average Vehicle or Transformed
Route Thai ltu« Salt Species/ Nwber at Body Physical Exposure Animal Dose
Strain Start/Sex Weight State/Purity (ng T1/kg/day)
(kg) :
Oral thai Hum (I) rat/ 10/N 0.365^ drinking 10 ppm Tl for 0.074d»k
sulfate Ulstar water/NR up to 60 days
"•
Equivalent
Human Dosea Response
(mg Tl/kg/day)
0.013 Hlstopatho-
loglcal
alteration of
testes
Reference
Formlgll
et al.. 1986
.
'Calculated by multiplying the transformed animal dose by the cube root of the ratio of the animal body weight to the human reference body weight (70 kg).
^Estimated from tabular data provided by Investigators. •
Calculated by multiplying 1.7 mg/m* by 7 hours/24 hours and 5 days/7 days to expand to continuous exposure, and by 0.223 m*/day respiratory rate for
0.35 kg rats (U.S. EPA. 19856). and by 1/0.35 kg and by O.B949. the fraction of Tl In T1203. to express the result In terms of mg Tl/kg/day.
dAn uncertainty factor of 10 was applied to estimate a chronic effect level from a subchrontc effect level.
'Estimated from graphic data provided by Investigators.
'Reference food factor for rats of 0.05 (U.S. EPA. 1985b).
{(Factor of 0.1759 (the fraction of Tl In T^H^) was applied to express, the dosage as mg Tl/kg/day.
"Factor of 0.8949 (the fraction of Tl In TlpOa) was applied to express the dosage as mg Tl/kg/day.
'Factor of 0.8097 (the fraction of Tl In T12504) was applied to express the dosage as mg Tl/kg/day.
^Reference rat body weight (U.S. EPA. 1985b)
kSee estimation of dosage In Section 6.1.2.1.
'Body weight estimate provided by Investigators.
-------
TASli 9-2
Compos lie Scores for Thai1 tun Using the Rata
Chronic
Route Animal Dose Human NED' RVd ' Effect RVe
(mg Tl/kg/day) (mg Tl/kg)
Inhalation 0.020 0.21 6.5 Mortality 10
Oral O.OS8 0.49 6.0 .Alopecia, elevated 4
kidney weight
Oral 0.089 0.91 5.6 Decreased rate of body 4
weight gain
Oral 0.0008 0.007 8.7 Alopecia, exophthalmos. 3
lacrlmat ton.' minor bio-
chemical zchanges
i
* Oral 0.087 1.05 5.5 tfeurophystologlcal and 7
neuropathologlcal change
Oral 2.3 27.3 3.3 Increased fetal loss 8
Oral 0.074 0.91 5.6 Hlstopathologlcal alter- 7
atton of testls
CSC RQ Reference
65 10 U.S. EPA. 1979
24 100 Downs et al..
1960
22.4 100 Downs et al..
1960
26.1 100 U.S. EPA. 1986b;
HRI. 1986
38.5 100 Nanzo et al..
19835
26.4 100 Roll and
Hatthlaschk. 1981
39.2 100 formtgll et al..
1986
'Individual salts of thallium are not listed because It Is assumed that toxlclty Is due to the thallium moiety
Calculated by multiplying the equivalent human dose (ag Tl/kg/day) by 70 kg to express the MED In term of ag/day for a 70 kg human
'Calculated as the product of RVd and RVe
-------
CSs for all effects ranged from 22.4-39.2, which correspond to an RQ of
100, with the exception of a CS of 65 and an RQ of 10 for mortality 1n sub-
chronic Inhalation exposure (U.S. EPA, 1979). The larger CS and smaller RQ
associated with Inhalation exposure may reflect greater toxlclty of thallium
by this route. The CS of 65 and the RQ of 10 are selected as most appro-
priately representing the toxlclty of thallium In thallium salts and are
presented In Table 9-3.
CSs for several salts of thallium can be calculated from the data In
Table 9-3 by correcting for molecular weight differences (I.e., by dividing
the MED by the decimal fraction of thallium In each of the salts, recalcu-
lating the RV. and multiplying the new RV. by the RV of 10 to calcu-
late a new CS). These data are presented 1n Tables 9-4 through 9-9.
In a series of earlier analyses the Agency derived RQs for several salts
of thallium. An RQ of 100 was derived for thallium (III) oxide based on the
dietary study by Downs et al. (1960) with that compound (U.S. EPA, 1983a).
An RQ of 100 was derived for thallium and compounds (U.S. EPA. 1983b) and
for 'thallium '(I) acetate (U.S. EPA, 1983c) based on the Downs et al. (1960)
study with thallium (I) acetate. An RQ of 100 was also derived for thallium
(I) carbonate (U.S. EPA, 1983d), thallium (I) chloride (U.S. EPA, 1983e),
thallium (I) nitrate (U.S. EPA, 1983f) and thallium (I) sulfate (U.S. EPA.
1983g) by analogy to thallium (I) acetate. The only toxlclty data available
1n these earlier analyses were the dietary studies by Downs et al. (I960).
The present analysis 1s larger 1n scope and Includes data that suggest
greater toxic potency by Inhalation compared with oral exposure. Therefore,
an RQ of 10 Is currently recommended for thallium and for the Individual
salts of thallium Included 1n Tables 9-4 through 9-9.
0083d -70- 03/11/88
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TABLE 9-3
Thallium (and Salts)
Minimum Effective Dose (MED) and Reportable Quantity (RQ)
Route: Inhalation
Dose*:"^ 0.21 mg Tl/day
Effect: mortality
Reference: U.S. EPA, 1979
RVd: 6.5
RVe: 10
Composite Score: 65
RQ: 10
'Equivalent human dose
0083d -71- 03/11/88
-------
TABLE 9-4
Thallium (III) oxide
Minimum Effective Dose (MED) and Reportable Quantity (RQ)
Route: Inhalation
Dose*: 0.23 rug/day
Effect: mortality
Reference: U.S. EPA, 1979
RVd: 6.5
RVe: 10
Composite Score: 65
RQ: 10
^Equivalent human dose
0083d -72- 03/11/88
-------
TABLE 9-5
Thallium (I) acetate
Minimum Effective Dose (MED) and Reportable Quantity (RQ)
Route: Inhalation
Dose3: 0.27 mg/dayb
Effect: mortality
Reference: U.S. EPA, 1979
RV(j: . 6.4
RVe: 10
Composite Score: 64
RQ: 10
Equivalent human dose
bBy analogy to thallium (III) oxide with which the experiment was performed.
0083d -73- 03/11/88
-------
TABLE 9-6
Thallium (I) carbonate
Minimum Effective Dose (MED) and Reportable Quantity (RQ)
Route: Inhalation
Dose3: 0.24 mg/dayb
Effect: mortality
Reference: U.S. EPA, 1979
RVd: 6.4
RVe: 10
Composite Score: 64
RQ: 10
Equivalent human dose
bBy analogy to thallium (III) oxide with which the experiment was performed.
0083d -74- 03/11/88
-------
TABLE 9-7
Thallium (I) chloride
Minimum Effective Dose (MED) and Reportable Quantity (RQ)
Route: Inhalation
Dosea: 0.25 mg/dayb
Effect: mortality
Reference: U.S. EPA, 1979
RVd: 6.4
RVe: 10
Composite Score: 64
RQ: 10
Equivalent human dose
bBy analogy to thallium (III) oxide with which the experiment was performed.
0083d -75- 03/11/88
-------
TABLE 9-8
Thallium (I) nitrate
Minimum Effective Dose (MED) and Reportable Quantity (RQ)
Route: Inhalation
Dosea: 0.27 mg/dayb
Effect: mortality
Reference: U.S. EPA, 1979
RVd: • 6.4
RVe: 10
Composite Score: 64
RQ: 10
Equivalent human dose
bBy analogy to thallium (III) oxide with which the experiment was performed.
0083d -76- 03/11/88
-------
TABLE 9-9
Thallium (I) sulfate
Minimum Effective Dose (MED) and Reportable Quantity (RQ)
Route: Inhalation
Dosea: 0.26 mg/dayb
Effect: mortality
Reference: U.S. EPA. 1979
RVd: 6.4
RVe: .10
Composite Score: 64
RQ: 10
Equivalent human dose
bBy analogy to thallium (III) oxide with which the experiment was performed.
0083d -77- 03/11/88
-------
U.S. EPA (1983h) did not derive an RQ for thallium (I) selenlde by
analogy, because both the thallium and selenium moieties are toxic and
because deriving an RQ by analogy does not account for the additive or
potentiating effects of toxic substltuents. In agreement with this analy-
sis, data are considered Insufficient for derivation of an RQ for thallium
(I) selenlde (Table 9-10).
9.2. BASED ON CARCINOGENICITY
As discussed 1n Section 6.2., cardnogenlclty data for thallium consist
of an unfinished Inhalation study and a few human health effects studies
that are Inadequate for Identifying a carcinogenic response to thallium.
NTP (1987) has not scheduled any thallium compounds for cardnogenlclty
testing. Because of the lack of animal or human data, thallium and Us
salts are classified In EPA Group D and hazard ranking based on cardno-
genlclty Is not possible.
0083d -78- 03/11/88
-------
TABLE 9-10
Thallium (I) selenlde (Tl2Se)
Minimum Effective Dose (MED) and Reportable Quantity (RQ)
Route:
Dose:
Effect:
Reference:
RVd:
RVe:
Composite Score:
RQ: Data are not sufficient for deriving an RQ
0083d -79- 03/11/88
-------
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.* ' •*.*"*
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0083d -91- 03/11/88
-------
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0083d -92- 03/11/88
-------
MulUns, D.J. and R.O. Moore. 1960. The movement of thallium Ions In
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0083d -93- 03/11/88
-------
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0083d -94- 03/11/88
-------
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0083d -95- 03/11/88
-------
Sax. N.I., Ed. 1984. Dangerous Properties of Industrial Materials, 6th ed.
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', • *...*.», t ^ « . ,
Singh, I. 1983. Induction of reverse mutation and mltotlc gene conversion
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149-152.
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0083d -96- 03/11/88
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Snider, E.H. and F.S. Manning. 1982. A survey of pollutant emission levels
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Stephenson, T. and J.N. Lester. 1987a. Heavy metal behaviour during the
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ScJ. Total Environ. 63: 199-214.
Stephenson., T. and J.N. Lester.. .1.987b, Heavy .metal behaviour during the
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Stoklnger. H.E. 1981. The metals: 32 thallium, TI. 14: Patty's Industrial
Hygiene and Toxicology, Vol. 2A, 3rd ed., G.C. Clayton and F.E. Clayton, Ed.
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Talas, A. and H.H. Wellhoener. 1983. Dose-dependency of thalHum(U)
kinetics as studied 1n rabbits. Arch. Toxlcol. 53(1): 9-16.
0083d -97- 03/11/88
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Talas, A., O.P. Pretschner and H.H. Wellhoner. 1983. Pharmacok1net1c
parameters for thallium (I)-1ons 1n man. Arch. Toxlcol. 53(1): 1-7.
Tlkhova, T.S. 1964. Industrial hygiene 1n the manufacture of metallic
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Tlkhova, T.S. 1967. Thallium and Us compounds. Iri: Novye Dannye po
Toks1kolog11 Redkldh Hetallov 1 Ikh Soed1nen11, Z. Izrael'son, Ed.
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USDI (U.S. Department of the Interior). 1986. Mineral Industry Surveys.
Prepared ,1n the Division .of Nonf.errous Metals, Apr.1l 7, 1986. Bureau of
Mines, USDI, Washington, DC. p. 3, 52-53.
U.S. EPA. 1978. In-depth Studies on Health and Environmental Impacts of
Selected Water Pollutants. Prepared by E.G. and G. Bionomics. Contract No.
68-01-6464.
U.S. EPA. 1979. Study of Carc1nogen1c1ty and Tox1c1ty of Inhaled Antimony
Trloxlde, Antimony Ore Concentration and Thalllc Oxide In Rats. MRI Project
No. 4466-B. Contract No. 210-77-0156. OTS F1che No. 0511065.
0083d -98- 03/11/88
-------
U.S. EPA. 1980a. Guidelines and Methodology Used In the Preparation of
Health Effect Assessment Chapters of the Consent Decree Hater Criteria
Documents. Federal Register. 45:(231): 49347-49357.
U.S. EPA. 1980b. Ambient Water Quality Criteria Document for Thallium.
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 440/5-80-074. NTIS PB81-117848.
U.S. EPA. 1983a. Reportable Quantity Document for Thalllc Oxide [Thallium
(III) Oxide]. 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. 1983b. Reportable Quantity Document for Thallium (and Compounds).
Prepared, by the Office of Health.and,Environmental Assessment, Environmental
t ' * # •** *
Criteria and Assessment Office, Cincinnati, OH for the Office of Emergency
and Remedial Response, Washington, DC.
U.S. EPA. 1983c. Reportable Quantity Document for Acetic Acid, Thallium
(I) Salt [Thallium (I) Acetate]. Prepared by the Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office,
Cincinnati, OH for the Office of Emergency and Remedial Response, Wash-
ington, DC.
0083d -99- 03/11/88
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U.S. EPA. 1983d. Reportable Quantity Document for Carbonic Acid, 01 thal-
lium (I) Salt [Thallium (I) Carbonate]. Prepared by the Office of Health
and Environmental Assessment, Environmental Criteria and Assessment Office,
Cincinnati, OH for the Office of Emergency and Remedial Response, Wash-
ington, DC.
U.S. EPA. 1983e. Reportable Quantity Document for Thallium (I) Chloride.
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. 1983f. Reportable Quantity Document for Thallium (I) Nitrate.
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. 1983g. Reportable Quantity Document for Sulfurlc Acid, Thallium
(I) Salt (Thallium Sulfate). Prepared by the Office of Health and Environ-
mental Assessment, Environmental Criteria and Assessment Office, Cincinnati,
OH for the Office of Emergency and Remedial Response, Washington, DC.
U.S. EPA. 1983h. Reportable Quantity Document for Thallium (I) Selenlde.
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.
0083d -100- 03/11/88
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U.S. EPA. 1984. Methodology and Guidelines for Reportable Quantity
Determinations 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. 1985a. Integrated Risk Information System (IRIS): Reference Dose
(RfD) for Oral Exposure for Thallium (I) Selenlte. Online. (Revised;
Verification date 08/05/85.) Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, Cincinnati, OH.
U.S. EPA. 1985b. Reference Values for Risk Assessment. Prepared by the
Office of Health and Environmental Assessment, Environmental Criteria and
Assessment Office, Cincinnati, OH for the Office of Solid Waste, Washington,
DC.' (Table 2).
• ',.•..:... .-.'•,...< * .'.. ••.,.-'... ., ...-• •-.. • ..... - • . . •
U.S. EPA. 1985c. Integrated Risk Information System (IRIS): Reference Dose
(RfD) for Oral Exposure for Thalllc Oxide. Online. (Revised; Verification
date 08/05/85.) Office of Health and Environmental Assessment, Environ-
mental Criteria and Assessment Office, Cincinnati, OH.
U.S. EPA. 1985d. Integrated Risk Information System (IRIS): Reference Dose
(RfD) for Oral Exposure for Thallium (I) Acetate. Online. (Revised;
Verification date 08/05/85.) Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office. Cincinnati, OH.
0083d -101- 03/11/88
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U.S. EPA. 1985e. Integrated Risk Information System (IRIS): Reference Dose
(RfO) for Oral Exposure for Thallium (I) Carbonate. Online. (Revised;
Verification date 08/05/85.) Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, Cincinnati, OH.
U.S. EPA. 1985f. Integrated Risk Information System (IRIS): Reference Dose
(RfD) for Oral Exposure for Thallium (I) Chloride. Online. (Revised;
Verification date 08/05/85.) Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, Cincinnati, OH.
U.S. EPA. 1985g. Integrated Risk Information System (IRIS): Reference Dose
(RfD) for Oral Exposure for Thallium (I) Nitrate. Online. (Revised;
Verification date 08/05/85.) Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, Cincinnati, OH.
U.S. EPA. . 1985h. Integrated Risk Information System (IRIS): Reference Dose
(RfD) for Oral Exposure for Thallium (I) Sulfate. Online. (Revised;
Verification date 08/05/85.) Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, Cincinnati, OH.
U.S. EPA. 1986a. Methodology for Evaluating Potential Carclnogenlclty In
Support of Reportable Quantity Adjustments Pursuant to CERCLA Section 102.
Prepared by the Office of Health and Environmental Assessment, Carcinogen
Assessment Group, for the Office of Solid Haste and Emergency Response,
Washington, DC.
0083d -102- 03/11/88
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U.S. EPA. 1986b. Subchronlc (90-day) Toxlclty of Thallium (I) Sulfate (CAS
No. 7446-18-6) In Spr ague-Daw "ley Rats. Final Report. Prepared for the
Office of SOlId Waste, U.S. EPA, Washington, DC. Project No. 8702-L (18).
U.S. EPA. 1986c. Guidelines for Carcinogen Risk Assessment. Federal
Register. 51(185): 33992-34003.
U.S. EPA. 1987a. Quality Criteria Water - 1986. Office of Water Regula-
tions and Standards, Washington, DC. EPA 440/5-86-001.
U.S. EPA. 1987b. Integrated Risk Information System (IRIS): Reference Dose
(RfD) for Oral Exposure for Thallium (I) Sulfate. Online: Input pending.
(Revised; Verification date 06/17/87.) Office of Health and Environmental
Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH.
U.S;, EPA.. ;.1987c. 40 CF.R . 14-1. Drinking Water;,. Proposed Substitution . of
Contaminants and Proposed List of Additional Substances Which Hay Require
Regulation Under the Safe Drinking Water Act. Federal Register. 52(130):
25734.
Venugopal, B. and T.D. Luckey. 1978. Chapter 3. Toxlclty of group III
metals. In.: Metal Toxlclty In Mammals. 2. Chemical Toxlclty of Metals and
Metalloids. Plenum Press, New York. p. 122-127, 353-402.
Wallwork-Barber, M.K., K. Lyall and R.W. Ferenbaugh. 1985. Thallium
movement 1n a simple aquatic ecosystem. J. Environ. Sd. Health, Part A.
20: 689-700.
0083d -103- 03/11/88
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Ueast. R.C., Ed. 1985. CRC Handbook of Chemistry and Physics, 66th ed.
CRC Press, Boca Raton, FL. p. B150-B151, 0195, D215.
Wlndholz, M., Ed. 1983. The Merck Index. An Encyclopedia of Chemicals,
Drugs, and Blologlcals, 10th ed. Merck and Co., Inc., Rahway, NJ.
p. 1324-1325.
Woods, J.S. and B.A. Fowler. 1986. Alteration of hepatocellular structure
and function by thallium chloride: Ultrastructural, morphometrlc, and
biochemical studies. Toxlcol. Appl. Pharmacol. 83(2): 218-229.
Zasukhlna, G.D., I.M. Vasllyeva, N.I. Sdlrkova, et al. 1983. Mutagenlc
effect of thallium and mercury salts on rodent cells with different repair
activities. Mutat. Res. 124(2): 163-173.
Zlskpveru, R.,. C. Achenbach, H.R« . Schulten and R. Roll. 1983. Thallium
determinations In fetal tissues and maternal brain and kidney. Toxlcol.
Lett. 19: 225-231.
ZHko, V. and W.V. Carson. 1975. Accumulation of thallium In clams and
mussels. Bull. Environ. Contam. Toxlcol. 14(5): 530-533.
ZHko, V., W.V. Carson and W.G. Carson. 1975. Thallium: Occurrence In the
environment and toxldty to fish. Bull. Environ. Contam. Toxlcol. 13:
23-30.
0083d -104- 03/11/88
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APPENDIX A
LITERATURE SEARCHED
This HEED 1s based on data Identified by computerized literature
searches of the following:
CHEMLINE
TSCATS
CASR online (U.S. EPA Chemical Activities Status Report)
TOXLINE
TOXLIT
TOXLIT 65
RTECS
OHM TADS
STORET
SRC Environmental Fate Data Bases
SANSS
AQUIRE
TSCAPP
NTIS
Federal Register
CAS ONLINE (Chemistry and Aquatic)
HSDB
These searches were conducted In October 1987. and the following secondary
sources were reviewed: - ' '
ACGIH (American Conference of Governmental Industrial Hyglenlsts).
1986. Documentation of the Threshold Limit Values and Biological
Exposure Indices, 5th ed. Cincinnati, OH.
ACGIH (American Conference of Governmental Industrial Hyglenlsts).
1987. TLVs: Threshold Limit Values for Chemical Substances In the
Work Environment adopted by ACGIH with Intended Changes for
1987-1988. Cincinnati. OH. 114 p.
Clayton, G.D. and F.E. Clayton, Ed. 1981. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed., Vol. 2A. John Wiley and
Sons. NY. 2878 p.
Clayton, G.D. and F.E. Clayton. Ed. 1981. Patty's Industrial
Hygiene and Toxicology. 3rd rev. ed., Vol. 2B. John Wiley and
Sons. NY. p. 2879-3816.
Clayton, G.D. and F.E. Clayton, Ed. 1982. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed., Vol. 2C. John Wiley and
Sons, NY. p. 3817-5112.
0083d -105- 03/11/88
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Grayson, H. and D. Eckroth. Ed. 1978-1984. Klrk-Othmer Encyclo-
pedia of Chemical Technology, 3rd ed. John Wiley and Sons, NY. 23
Volumes.
Hamilton, A. and H.L. Hardy. 1974. Industrial Toxicology, 3rd ed.
Publishing Sciences Group, Inc., Littleton, MA. 575 p.
IARC (International Agency for Research on Cancer). IARC Mono-
graphs on the Evaluation of Carcinogenic Risk of Chemicals to
Humans. IARC, MHO, Lyons, France.
Jaber, H.M., H.R. Mabey, A.T. Lieu, T.M. Chou and H.L. Johnson.
1984. Data acquisition for environmental transport and fate
screening for compounds of Interest to the Office of Solid Waste.
EPA 600/6-84-010. NTIS PB84-243906. SRI International. Henlo
Park, CA.
NTP (National Toxicology Program). 1987. Toxicology Research and
Testing Program. Chemicals on Standard Protocol. Management
Status.
Ouellette, R.P. and J.A. King. 1977. Chemical Week Pesticide
Register. McGraw-Hill Book Co., NY.
Sax, I.N. 1984. Dangerous Properties of Industrial Materials, 6th
ed. Van Nostrand Relnhold Co., NY.
SRI (Stanford Research Institute). 1987. Directory of Chemical
Producers. Menlo Park, CA.
U.S. EPA. 1986. Report on Status Report In the Special Review
'' 'Program, Registration Standards' Program and the Data Call In
Programs. Registration Standards and the Data Call 1n Programs.
Office of Pesticide Programs, Washington, DC.
USITC (U.S. International Trade Commission). 1986. Synthetic
Organic Chemicals. U.S. Production and Sales, 1985, USITC Publ.
1892, Washington, DC.
Verschueren, K. 1983. Handbook of Environmental Data on Organic
Chemicals, 2nd ed. Van Nostrand Relnhold Co., NY.
Worthing, C.R. and S.B. Walker, Ed. 1983. The Pesticide Manual.
British Crop Protection Council. 695 p.
Wlndholz. M., Ed. 1983. The Merck Index, 10th ed. Merck and Co..
Inc., Rahway, NJ.
0083d -106- 03/11/88
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In addition, approximately 30 compendia of aquatic toxlclty data were
reviewed. Including the following:
Battelle's Columbus Laboratories. 1971. Water Quality Criteria
Data Book. Volume 3. Effects of Chemicals on Aquatic Life.
Selected Data from the Literature through 1968. Prepared for the
U.S. EPA under Contract No. 68-01-0007. Washington, DC.
Johnson, W.W. and H.T. Flnley. 1980. Handbook of Acute Toxlclty
of Chemicals to F1sh and Aquatic Invertebrates. Summaries of
Toxlclty Tests Conducted at Columbia National Fisheries Research
Laboratory. 1965-1978. U.S. Dept. Interior, F1sh and Wildlife
Serv. Res. Publ. 137, Washington, DC.
McKee, J.E. and H.W. Wolf. 1963. Water Quality Criteria, 2nd ed.
Prepared for the Resources Agency of California, State Water
Quality Control Board! Publ. No. 3-A.
Plmental, 0. 1971. Ecological Effects of Pesticides on Non-Target
Species. Prepared for the U.S. EPA, Washington, DC. PB-269605.
Schneider, B.A. 1979. Toxicology Handbook. Mammalian and Aquatic
Data. Book 1: Toxicology Data. Office of Pesticide Programs, U.S.
EPA, Washington, DC. EPA 540/9-79-003. NTIS PB 80-196876.
0083d -107- 03/11/88
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APPENDIX B-l
Summary Table for Thallium and Salts
Inhalation Exposure
Subchronlc
Chronic
Carclnogenlclty
Oral Exposure
Subchronlc
Chronic
Carclnogenlclty
REPORTABLE QUANTITIES
Based on chronic toxlclty:
Based on Carclnogenlclty:
Species
ID
ID
ID
rat
rat
ID
10
ID
Exposure Effect RfD or qj* Reference
ID ID ID ID
ID ID ID ID
ID ID ID ID
0.25 mg thallium (I) NOAEL 0.002 rag/kg/day U.S. EPA, 1986b;
sul fate/kg/day for or 0.1 rag /day HRI, 1986
90 days
0.25 mg thallium (I) NOAEL 0.2 yg/kg/day U.S. EPA. 1986b;
sul fate/kg/day for or 0.01 mg/day HRI, 1986
90 days
ID ID ID ID
U.S. EPA. 1979
ID = Insufficient data
-------
APPENDIX B-2
g
GO
C3
a.
i
Inhalation Exposure
Subchronlc
Chronic
Carcinogenic Ity
Oral Exposure
g Subchronlc
Chronic
CarctnogenlcUy
REPORTABLE QUANTITIES
Based on chronic toxlclty:
o
S£ Based on cancer:
Species
ID
ID
ID
rat
rat
ID
10
ID
Summary Table for Thallium (III) oxide
Exposure Effect RfD or q-\* Reference
•
ID ID ID ID
ID ID ID ID
ID • ID HI 10
...
0.25 mg thallium (I) NOAEL 0.002 mg/kg/day U.S. EPA. 1986b;
sul fate/kg/day for or 0.2 rug/day NRI, 1986
90 days
0.25 mg thallium (I) NOAEL 0.2 pg/kg/day U.S H'A. I'lOOh;
sulfate/kg/day for or 0.02 mg/day NRI, 1986
90 days
ID ID ID ID
•
U.S. EPA. 1979
CO
00
ID = Insufficient data
-------
APPENDIX B-3
1
o
o
CO
Inhalation Exposure
Subchronlc
Chronic
Carclnogentclty
Species
ID
ID
ID
Summary
ID
ID
ID
Table for Thallium (I) acetate
Exposure Effect RfD or q-\* Reference
• •
ID ID ID
ID ID ID
ID ID ID
Oral Exposure
i
=J Subchrontc
Chronic
Carclnogenlclty
rat 0.25 mg thallium (I) NOAEL
sulfate/kg/day for
90 days
rat 0.25 mg thallium (I) NOAEL
sulfate/kg/day for
90 days
ID ID ID
0.003 mg/kg/day
or 0.2 rag/day
0.3 ng/kg/day
or 0.02 mg/day
ID
U.S. EPA. 1986b;
HRI. 1986
U.S. EPA. 1986b;
NRI. 1986
ID
REPORTABLE QUANTITIES
Based on chronic toxlclty: 10
Based on cancer:
ID
U.S. EPA. 1979
ID = Insufficient data
-------
as
APPENDIX B-4
Summary Table for Thallium (I) carbonate
1
o
§
Inhalation Exposure
Subchronlc
Chronic
Carclnogenlclty
Oral Exposure
Subchronlc
Chronic
Carclnogenlclty
REPORTABLE QUANTITIES
Based on chronic toxlclty:
Based on cancer:
Species
ID
ID
ID
rat
rat
ID
10
ID
Exposure Effect RfD or q^* Reference
ID ID ID ID
ID ID ID ID
ID ID ID ID
• •
0.25 rag thallium (I) NOAEL 0.002 mg/kg/day U.S. EPA. 1986b;
sul fate/kg/day for or 0.2 mg/day HRI. 1986
90 days
0.25 mg thallium (I) NOAEL 0.2 yg/kg/day U.S. EPA. 1986b;
sulfate/kg/day for or 0.02 mg/day HRI. 1986
90 days
ID ID ID ID
•
U.S. EPA. 1979
00
00
ID = Insufficient data
-------
APPENDIX B-5
f *
Summary Table for Thallium (I) chloride
ro
O
«s,
s^
Species
Inhalation Exposure
Subchronlc ID
Chronic ID
Carclnogenlclty ID
Oral Exposure
Subchronlc rat
Chronic rat
Carclnogenlclty ID
REPORTABLE QUANTITIES
Based on chronic toxlclty: 10
Based on cancer: ID
Exposure Effect RfD or qj* Reference
-
ID ID ID ID
ID ID ID ID
ID ID ID ID
«
0.25 rag thallium (I) NOAEL 0.002 rog/kg/day U.S. EPA, 19865;
sul fate/kg/day for or 0.2 rag /day NRI. 1986
90 days
0.25 rag thallium (I) NOAEL 0.2 yg/kg/day U.S. EPA. 19865;
sul fate/kg/day for or 0.02 mg/day NRI. 1986
90 days
ID ID ID ID
U.S. EPA. 1979
00
00
ID = Insufficient data
-------
g
APPENDIX B-6
Summary Table for Thallium (I) nitrate
Species
Inhalation Exposure
Subchronlc ID
Chronic ID
Carclnogenlclty ID
Oral Exposure
i
£ Subchronlc rat
i
Chronic rat
Carclnogenlclty ID
REPORTABLE QUANTITIES
Based on chronic toxlctty: 10
o
££ Based on cancer: ID
i
Exposure Effect RfD or qj* Reference
••
ID ID ID ID
ID ID ID ID
ID ' . ID ID ID
0.25 nig thallium (I) NOAEL 0.003 rag/kg/day U.S. EPA. 1986b;
sul fate/kg/day for or 0.2 nig/day HRI. 1986
90 days
0.25 mg thallium (I) NOAEL 0.3 yg/kg/day U.S. EPA. 1986b;
sul fate/kg/day for or 0.02 nig /day HRI. 1986
90 days
ID ID ID ID
U.S. EPA. 1979
ID = Insufficient data
-------
00
CO
APPENDIX B-7
Summary Table for Thallium selenlde (TISe)
Inhalation Exposure
Subchrontc
Chronic
Carctnogenlclty
Oral Exposure
Subchronlc
Chronic
Carclnogenlclty
RE PORT ABLE QUANTITIES
Based on chronic toxIcHy:
Based on cancer:
Species
10
ID
ID
rat
rat
ID
ID
ID
Exposure Effect RfD or qj* Reference
;.•
ID ... • ID ID ID
ID ; ID ID ID
ID ID ID ID
0.25 mg thallium (I) NOAEL 0.003 mg/kg/day U.S. EPA. 1986b;
sul fate/kg/day for or 0.2 rag /day NRI, 1986
90 days
0.2S mg thallium (I) NOAEL 0.3 ng/kg/day U.S. EPA. 1986b;
sul fate/kg/day for or 0.02 rag/day HRI. 1986
90 days
ID ID ID ID
•
ID - Insufficient data
-------
APPENDIX B-8
Summary Table for Thallium (I)sulfate
Inhalation Exposure
Subchronlc
Chronic
Carclnoyenlclty
Oral Exposure
i
£ Subchronlc
Species
ID
ID
ID
rat
Exposure. Effect RfD or qi* Reference
'•:
ID . ID ID ID
ID . ID ID ID
ID ID ID ID
:- •
0.25 rag thallium (I) NOAEL 0.002 rag/kg/day U.S. EPA. 1986b;
r..1ftl*. /I,*. /A**, £.» «... A 1 mr./A*t. UD1 1OOC.
Chronic
Carclnogenlclty
90 days
rat 0.25 mg thallium (I) NOAEL
sulfate/kg/day for
90 days
ID ID ID
0.3 yg/kg/day
or 0.02 mg/day
ID
U.S. EPA. 1986b;
HRI. 1986
ID
REPORTABLE QUANTITIES
Based on chronic toxlctty: 10
Based on cancer: ID
U.S. EPA. 1979
ID = Insufficient data
------- |