TOXICOLOGICAL PROFILE FOR 


THALLIUM 


Agency for Toxic Substances and Disease Registry 


U.S. Public Health Service 

July 1992 
ii 

DISCLAIMER 

The use of company or product name(s) is for identification only and

does not imply endorsement by the Agency for Toxic Substances and Disease

Registry. 










1 

1. PUBLIC HEALTH STATEMENT 

This Statement was prepared to give you information about thallium and

to emphasize the human health effects that may result from exposure to it.

The Environmental Protection Agency (EPA) has identified 1,177 sites on its

National Priorities List (NPL). Thallium has been found in at least 18 of

these sites. However, we do not know how many of the 1,177 NPL sites have

been evaluated for thallium. As EPA evaluates more sites, the number of sites

at which thallium is found may change. This information is important for you

to know because thallium may cause harmful health effects and because these 

sites are potential or actual sources of human exposure to thallium. 

When a chemical is released from a large area, such as an industrial

plant, or from a container, such as a drum or bottle, it enters the

environment as a chemical emission. This emission, which is also called a

release, does not always lead to exposure. You can be exposed to a chemical

only when you come into contact with the chemical. You may be exposed to it

in the environment by breathing, eating, or drinking substances containing the

chemical or from skin contact with it. 

If you are exposed to a hazardous chemical such as thallium, several

factors will determine whether harmful health effects will occur and what the 

type and severity of those health effects will be. These factors include the

dose (how much), the duration (how long), the route or pathway by which you

are exposed (breathing, eating, drinking, or skin contact), the other chemicals

to which you are exposed, and your individual characteristics such as

age, sex, nutritional status, family traits, life style, and state of health. 

1.1 WHAT IS THALLIUM? 

Pure thallium is a soft, bluish-white metal that is widely distributed

in trace amounts in the earth's crust. In its pure form, it is odorless and

tasteless. It can be found in pure form or mixed with other metals in the

form of alloys. It can also be found combined with other substances such as

bromine, chlorine, fluorine, and iodine to form salts. These combinations may

appear colorless to white or yellow. Thallium remains in the environment

since it is a metal and cannot be broken down to simpler substances. 

Thallium exists in two chemical states (thallous and thallic). The

thallous state is the more common and stable form. Thallous compounds are the

most likely form to which you would be exposed in the environment. Thallium

is present in air, water, and soil. We do not know how much time it takes for

thallium to move from one medium to another. 

Thallium is used mostly in the manufacture of electronic devices, 

switches, and closures. It also has limited use in the manufacture of special

glasses and for medical procedures that evaluate heart disease. Up until 1972

thallium was used as a rat poison, but was then banned because of its

potential harm to man. Thallium is no longer produced in the United States. 
2 

1. PUBLIC HEALTH STATEMENT 

All the thallium used in the United States since 1984 has been obtained from 

imports and thallium reserves. 

More information on the properties and uses of thallium and how it

behaves in the environment may be found in Chapters 3, 4, and 5. 

1.2 HOW MIGHT I BE EXPOSED TO THALLIUM? 

You can be exposed to thallium in air, water, and food. However, the

levels of thallium in air and water are very low. The greatest exposure 

occurs when you eat food, mostly home-grown fruits and green vegetables

contaminated by thallium. Small amounts of thallium are released into the air

from coal-burning power plants, cement factories, and smelting operations.

This thallium falls out of the air onto nearby fruit and vegetable gardens.

Thallium enters food because it is easily taken up by plants through the 

roots. Very little is known on how much thallium is in specific foods grown

or eaten. Cigarette smoking is also a source of thallium. People who smoke

have twice as much thallium in their bodies as do nonsmokers. Although fish

take up thallium from water, we do not know whether eating fish can increase

thallium levels in your body. It has been estimated that the average person

eats, on a daily basis, 2 parts thallium per billion parts (ppb) of food.

Even though rat poison containing thallium was banned in 1972, accidental

poisonings from old rat poison still occur, especially in children. 

Thallium is produced or used in power plants, cement factories, and

smelters. People who work in these places can breathe in the chemical or it 

may come in contact with their skin. Information on the amount of thallium in

workplace air in the United States could not be found. Hazardous waste sites

are also possible sources of exposure to thallium. An average of 23 ppb of

thallium in surface water and 11 ppb in groundwater have been found at

hazardous waste sites. Since thallium compounds mix easily in water, you can 

be exposed if you live near a chemical waste site where thallium emissions

have contaminated the water. An average of 1.7 parts of thallium per million

parts (ppm) of soil was found at hazardous waste sites. Since thallium sticks

to soil, you can be exposed at hazardous waste sites if you swallow or touch

contaminated soil. Thallium-contaminated dust in the air can also be 

swallowed after it is cleared from the lungs. Thallium is naturally found in

soil at levels from 0.3 to 0.7 ppm. 

More information on how you might be exposed to thallium is given in

Chapter 5. 

1.3 HOW CAN THALLIUM ENTER AND LEAVE MY BODY? 

Thallium can enter your body when you eat food or drink water

contaminated with thallium, breathe thallium in the air, and when your skin

comes in contact with it. When thallium is swallowed most of it is absorbed 

and rapidly goes to various parts of your body, especially the kidney and 
3 

1. PUBLIC HEALTH STATEMENT 

liver. Thallium leaves your body slowly. Most of the thallium leaves your

body in urine and to a lesser extent in feces. It can be found in urine

within 1 hour after exposure. After 24 hours, increasing amounts are found in

feces. It can be found in urine as long as 2 months after exposure. About

half the thallium that enters various parts of your body leaves them within

3 days. 

The significant, likely routes of exposure near hazardous waste sites

are through swallowing thallium-contaminated soil or dust, drinking

contaminated water, and skin contact with contaminated soil.

More information on how thallium enters and leaves the body is given in

Chapter 2. 

1.4 HOW CAN THALLIUM AFFECT MY HEALTH? 

Thallium can affect your nervous system, lung, heart, liver, and kidney

if large amounts are eaten or drunk for short periods of time. Temporary hair

loss, vomiting, and diarrhea can also occur and death may result after

exposure to large amounts of thallium for short periods. Thallium can be

fatal from a dose as low as 1 gram. No information was found on health

effects in humans after exposure to smaller amounts of thallium for longer

periods. Birth defects observed in children of mothers exposed to small

amounts of thallium did not occur more often than would be expected in the

general population. The length of time and the amount of thallium eaten by

the mothers are not known exactly. As in humans, animal studies indicate that

exposure to large amounts of thallium for brief periods of time can damage the

nervous system and heart and can cause death. Animal reproductive organs,

especially the testes, are damaged after drinking small amounts of thalliumcontaminated water for 2 months. These effects have not been seen in humans. 

No information was found on effects in animals after exposure to small amounts

of thallium for longer periods of time. No studies were found on whether

thallium can cause cancer in humans or animals. 

More information on the health effects of thallium in humans and animals 

can be found in Chapter 2. 

1.5 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN 

EXPOSED TO THALLIUM? 

Reliable and accurate ways to measure thallium in the body are

available. The presence of thallium in the urine and hair can indicate

exposure to thallium. Tests of your urine can detect thallium up to 2 months.

The normal amount of thallium in human urine amounts to less than 1 ppm and

5-10 ppb in human hair. Although thallium can be measured in blood, this

tissue is not a good indicator of exposure since thallium stays there too

short a time. We do not know yet whether thallium levels measured in the body

can be used to predict possible health effects. 
4

1. PUBLIC HEALTH STATEMENT 

More information on how thallium can be measured in exposed humans is

presented in Chapters 2 and 6. 

1.6 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

PROTECT HUMAN HEALTH? 

The federal government has set standards and guidelines to protect

individuals from the possible effects of excessive thallium exposure. The EPA

has determined a water quality criteria level of 13 ppb in surrounding waters

to protect humans from the harmful effects of drinking water and eating food

containing thallium. 

The Occupational Safety and Health Administration (OSHA) has established

an occupational limit of 0.1 mg of soluble thallium compounds per cubic meter

of workplace air (mg thallium/m3

/skin) for an 8-hour workday over a 40-hour

workweek. "Skin" indicates that measures must be taken to prevent skin

exposure to thallium. 

Additional information on governmental regulations regarding thallium

can be found in Chapter 7. 

1.7 WHERE CAN I GET MORE INFORMATION? 

If you have any more questions or concerns not covered here, please

contact your state health or environmental department or: 

Agency for Toxic Substances and Disease Registry

Division of Toxicology

1600 Clifton Road, E-29

Atlanta, Georgia 30333 

This agency can also provide you with information on the location of the

nearest occupational and environmental health clinic. Such clinics specialize

in recognizing, evaluating, and treating illnesses that result from exposure

to hazardous substances. 
5 

2. HEALTH EFFECTS 

2.1 INTRODUCTION 

The primary purpose of this chapter is to provide public health

officials, physicians, toxicologists, and other interested individuals and

groups with an overall perspective of the toxicology of thallium and a

depiction of significant exposure levels associated with various adverse

health effects. It contains descriptions and evaluations of studies and

presents levels of significant exposure for thallium based on toxicological

studies and epidemiological investigations. 

Pure thallium exists in nature but is usually found combined with other

elements in inorganic compounds. Thallium forms compounds in both the

monovalent and trivalent states; however, the monovalent state is the more

stable. This document includes nine of the commonly used thallium compounds.

Toxicity data were found for five of these compounds (thallium sulfate,

thallium oxide, thallium nitrate, thallium acetate, and thallium carbonate). 

2.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE 

To help public health professionals address the needs of persons living

or working near hazardous waste sites, the information in this section is

organized first by route of exposure--inhalation, oral, and dermal--and then

by health effect--death, systemic, immunological, neurological, developmental,

reproductive, genotoxic, and carcinogenic effects. These data are discussed

in terms of three exposure periods--acute (less than 15 days), intermediate

(15-364 days), and chronic (365 days or more). 

Levels of significant exposure for each route and duration are presented

in tables and illustrated in figures. The points in the figures showing

noobserved-adverse-effect levels (NOAELS) or lowest-observed-adverse-effect

levels (LOAELs) reflect the actual doses (levels of exposure) used in the

studies. LOAELs have been classified into "less serious" or "serious" 

effects. These distinctions are intended to help the users of the document

identify the levels of exposure at which adverse health effects start to

appear. They should also help to determine whether or not the effects vary

with dose and/or duration, and place into perspective the possible

significance of these effects to human health. 

The significance of the exposure levels shown in the tables and figures

may differ depending on the user's perspective. For example, physicians

concerned with the interpretation of clinical findings in exposed persons may

be interested in levels of exposure associated with "serious" effects. Public

health officials and project managers concerned with appropriate actions to

take at hazardous waste sites may want information on levels of exposure

associated with more subtle effects in humans or animals (LOAEL) or exposure

levels below which no adverse effects (NOAEL) have been observed. Estimates

of levels posing minimal risk to humans (Minimal Risk Levels, MRLs) may be of

interest to health professionals and citizens alike. 
6 

2. HEALTH EFFECTS 

Estimates of exposure levels posing minimal risk to humans (MRLs) have

been made, where data were believed reliable, for the most sensitive noncancer

effect for each exposure duration. MRLs include adjustments to reflect human

variability from laboratory animal data to humans. 

Although methods have been established to derive these levels (Barnes

et al. 1988; EPA 1989c), uncertainties are associated with these techniques.

Furthermore, ATSDR acknowledges additional uncertainties inherent in the

application of the procedures to derive less than lifetime MRLs. As an

example, acute inhalation MRLs may not be protective for health effects that

are delayed in development or are acquired following repeated acute insults,

such as hypersensitivity reactions, asthma, or chronic bronchitis. As these

kinds of health effects data become available and methods to assess levels of 

significant human exposure improve, these MRLs will be revised. 

2.2.1 Inhalation Exposure 

2.2.1.1 Death 

No studies were located regarding lethality in humans or animals after

inhalation exposure to thallium. 

2.2.1.2 Systemic Effects 

No studies were located in humans or animals regarding the effects on 

the respiratory, hematological, musculoskeletal, hepatic, renal, and

dermal/ocular systems after inhalation exposure to thallium. Limited

occupational data show the cardiovascular and gastrointestinal systems were

not susceptible to thallium. 

Cardiovascular Effects. There are few data in humans on the 

cardiovascular effects of thallium following inhalation. Data are limited to

a study evaluating the health of workers employed in a magnesium sea water

battery plant in England (Marcus 1985). There were no statistically

significant differences in cardiovascular effects in a cohort of 86 exposed

workers compared with 79 unexposed controls in the same factory. However, the

authors did not clearly define the cardiovascular parameters measured.

Workplace air levels were 0.014 and 0.022 mg/m3

 in machining and alloying

operation areas. Occupational exposure is expected to involve multiple

compound exposures. However, the authors did not provide data on other

chemicals to which workers have been exposed concomitantly. 

No studies were located regarding cardiovascular effects in animals

after inhalation exposure to thallium. 

Gastrointestinal Effects. Based on available medical records, there

were no differences in gastrointestinal effects in a cohort of 86 exposed 

workers in a magnesium sea water battery plant in England compared with 79 
7 

2. HEALTH EFFECTS 

unexposed controls (Marcus 1985). Maximum thallium levels in workplace air

were 0.014 and 0.022 mg/m3

 during machining and alloying operations,

respectively. 

No studies were located regarding gastrointestinal effects in animals

after inhalation exposure to thallium. 

2.2.1.3 Immunological Effects 

No studies were located regarding immunological effects in humans or

animals after inhalation exposure to thallium. 

2.2.1.4 Neurological Effects 

Human occupational studies indicate that thallium may affect the nervous

system following inhalation. Thirty-six workers involved in cement production

for 5-44 years (mean of 22.9) exhibited paresthesia, numbness of toes and

fingers, the "burning feet" phenomenon, and muscle cramps (Ludolph et al.

1986). Peripheral conduction was impaired and there were changes in

somatosensory action potential. Electroencephalographic recordings revealed

no abnormalities. This study did not evaluate an unexposed control group. It

should be further noted that 50% of the patients suffered concurrent disease

including diabetes, obesity, malabsorption syndrome, (alcoholic) liver

disease, disorders of joints and connective tissues, and hypertensive vascular

disease. These may have contributed to the neurological effects observed. 

No studies were located regarding neurological effects in animals after

inhalation exposure to thallium. 

No studies were located regarding the following effects in humans or

animals after inhalation exposure to thallium: 

2.2.1.5 Developmental Effects 

2.2.1.6 Reproductive Effects 

2.2.1.7 Genotoxic Effects 

Genotoxicity studies are discussed in Section 2.4. 

2.2.1.8 Cancer 

No studies were located regarding carcinogenic effects in humans or

animals after inhalation exposure to thallium. 
8 

2. HEALTH EFFECTS 

2.2.2 Oral Exposure 

2.2.2.1 Death 

There are numerous case reports of human lethality following acute oral

exposure to thallium. Death occurred in one individual 9 days following

intentional ingestion of a single estimated dose of 54-110 mg thallium/kg (as

thallium nitrate) (Davis et al. 1981). Cranial and peripheral nerves showed

axonal degeneration with preservation of most of the overlying myelin,

suggesting that thallium damaged axons. Two of three subjects who ingested

thallium (thallous acetate) also died; however death occurred 1 month after

onset of symptoms (Cavanagh et al. 1974). Dose could not be determined since

exposure occurred in three divided doses for unspecified durations. Distal

peripheral axon degeneration with preserved proximal fibers was reported in

one case (Cavanagh et al. 1974). Other studies (de Groot et al. 1985; Heath

et al. 1983; Roby et al. 1984) have reported that thallium (as thallium

sulfate, dose not specified) is lethal following ingestion, and there was

evidence for central-peripheral distal axonopathy (Roby et al. 1984). While

the finding of neurological effects was consistent among case reports, death

was attributable to cardiac or respiratory failure. No studies were located

concerning intermediate or chronic exposures. 

In rats, estimates of LD50 for thallium compounds were 32 and 39 mg

thallium/kg (as thallium acetate and thallic oxide, respectively) (Downs

et al. 1960). The lowest oral doses of thallium compounds showing lethality

ranged from 12 (guinea pig) to 29 (rat) mg thallium/kg (as thallium acetate)

and 5 (guinea pig) to 30 (dog and rabbit) mg thallium/kg (as thallic oxide)

(Downs et al. 1960). Rats exposed for 15 weeks to diets containing thallium

showed increased mortality at a dose of 4.5 mg thallium/kg/day (as thallic

oxide) and 2.3 mg thallium/kg/day (as thallium acetate) (Downs et al. 1960).

Continuous administration via drinking water of approximately 1.4 mg

thallium/kg/day to rats (as thallium sulfate) resulted in 15%-21% mortality

after 40 and 240 days of treatment, respectively (Manzo et al. 1983). When

rats were administered up to 0.20 mg thallium/kg/day (as thallium sulfate) by

gavage for 90 days, no deaths were reported (Stoltz et al. 1986). 

A NOAEL value and all reliable LOAEL values for death in each species

and duration category are recorded in Table 2-l and plotted in Figure 2-l. 

2.2.2.2 Systemic Effects 

No studies were located regarding hematological effects in humans or

animals following oral exposure to thallium. Case studies in humans who

ingested various thallium compounds show the respiratory and cardiovascular

systems as well as the liver, kidney, and muscles are susceptible. Hair loss

may also occur. These effects are discussed below. The highest NOAEL values

and all reliable LOAEL values for these systemic effects for each species and

duration category are recorded in Table 2-l and plotted in Figure 2-l. 



12 

2. HEALTH EFFECTS 

Respiratory Effects. Limited data in humans show that thallium can 

cause respiratory damage. Lungs showed diffuse alveolar damage with hyaline

membrane and focal organization in one case following acute ingestion of an

estimated 54-110 mg thallium/kg (as thallium nitrate). Bronchopneumonia was

also reported in this study (Davis et al. 1981). Similar findings were

reported after ingestion of thallium acetate; however, the doses that produced

these effects were not clearly defined (Cavanagh et al. 1974; de Groot et al.

1985; Roby et al. 1984). 

One study was located in animals. No adverse effects were observed on

the respiratory system of rats administered 0.20 mg thallium/kg/day (as

thallium sulfate) by gavage for 90 days (Stoltz et al. 1986). 

Cardiovascular Effects. Cardiovascular damage was reported in humans

after ingestion of a single estimated lethal dose of 54-110 mg thallium/kg (as

thallium nitrate) (Davis et al. 1981). There was extensive damage of the 

myocardium with myofiber thinning, accumulation of lipid droplets, myocardial

necrosis, and inflammatory reaction (Davis et al. 1981). Sinus bradycardia,

ventricular arrhythmias, and T-wave anomalies were reported in two additional

case reports; however, the authors did not provide data on dose and duration

(Roby et al. 1984). 

Limited studies were located regarding cardiovascular effects in animals

after oral exposure to thallium. Electrocardiographic changes were observed

in rabbits administered 56 mg thallium/kg/day (as thallous sulfate), which was

also lethal (Grunfeld et al. 1963). Abnormalities reported included T-wave

fluttering, prolonged Q-T intervals, heart block, atria1 and ventricular

ectopic rhythms, and ST-segment depression or elevation (Grunfeld et al.

1963). While thallium was detected in heart tissue (16-45 μg/g tissue),

histological examination did not reveal damage to the myocardium. When rats

were administered up to 0.20 mg thallium/kg/day (as thallium sulfate) by

gavage for 90 days, no cardiovascular effects were observed (Stoltz et al.

1986). 

Gastrointestinal Effects. In humans, acute ingestion of thallium

sulfate caused gastroenteritis, diarrhea or constipation, vomiting, and

abdominal pain (Davis et al. 1981; de Groot et al. 1985; Grunfeld and

Hinostroza 1964). Gastrointestinal disturbances were also reported in 189

cases of thallium poisoning which occurred in China from 1960 to 1977

(Dai-xing and Ding-nan 1985). High levels of thallium were detected in urine

and hair samples. The authors attributed exposure to ingestion of cabbage

from contaminated gardens. 

Data in animals are sparse. When rats were administered up to 0.20 mg

thallium/kg/day (as thallium sulfate) by gavage for 90 days, no adverse

effects were observed on the gastrointestinal system (Stoltz et al. 1986). 
13 

2. HEALTH EFFECTS 

Musculoskeletal Effects. Data are sparse regarding the muscular effects

in humans. Histopathological examination of muscle biopsies from two cases

revealed myopathic changes associated with thallium poisoning (Limos et al.

1982). Fiber necrosis, central nucleation, and fiber splitting were reported.

No data were provided on exposure levels. 

Hepatic Effects. Case reports in humans demonstrate that the liver is

susceptible to thallium toxicity. Centrilobular necrosis with fatty changes

has been reported (Cavanagh et al. 1974; Davis et al. 1981). It was not clear

whether the effects observed were a result of a direct effect on the liver or 

secondary to other effects. Serum glutamic oxaloacetic transaminase, serum

pyruvic oxaloacetic transaminase, and alkaline phosphatase levels were

elevated. 

Data in animals are sparse. No adverse effects were observed on the

liver when rats were administered 0.20 mg thallium/kg/day (as thallium

sulfate) by gavage for 90 days (Stoltz et al. 1986). 

Renal Effects. Human case studies report that thallium can affect the

kidneys (Cavanagh et al. 1974; Gastel 1978). Histological examination of the

kidneys in one case revealed extensive recent necrosis of the cortex (Cavanagh

et al. 1974). The authors reported that the effects were probably the result

of infarction. Renal function is also impaired following thallium exposure.

Diminished creatinine clearance, a raised blood urea, and proteinuria are

common (Cavanagh et al. 1974). 

In animals, there were no adverse renal effects in rats administered

0.20 mg thallium/kg/day (as thallium sulfate) by gavage for 90 days (Stoltz

et al. 1986). 

Dermal/Ocular Effects. Ingestion of thallium has been associated with

hair loss in humans. Loss can occur as early as 8 days after exposure

(Grunfeld and Hinostroza 1964). Several cases have reported loss of body

hair, full beard, and scalp hair (Grunfeld and Hinostroza 1964). In other

instances, body and pubic hair have been spared (Gastel 1978; Grunfeld and

Hinostroza 1964). Hair loss is temporary, and no local skin changes have been

reported. 

In animals, hair loss was observed in rats exposed to ≥ 1.2 mg

thallium/kg/day (as thallium acetate or thallium oxide) for 15 weeks (Downs

et al. 1960). Histological examination revealed that 1.8 mg thallium/kg/day

(as thallium oxide) caused atrophy of the hair follicles and there was a

decrease in size of sebaceous glands. 

No studies were located regarding the direct effects of thallium on the

eyes of humans. However, thallium caused damage to certain cranial nerves

which lead to eye disturbances. Decreased visual acuity due to bilateral

central scotomas and progressive optic atrophy have been associated with optic. 
14 

2. HEALTH EFFECTS 

nerve damage (Moeschlin 1980). Also, there are degenerative changes in

cranial nerves which innervate the extraocular muscles. Ptosis and 

disconjugate eye movements are common manifestations of eye disturbances

(Cavanagh et al. 1974; Davis et al. 1981). 

2.2.2.3 Immunological Effects 

No studies were located regarding immunological effects in humans or

animals after oral exposure to thallium. 

2.2.2.4 Neurological Effects 

Human case studies revealed that the nervous system is susceptible to 

thallium toxicity after acute oral exposure at high doses. Severe cranial and

peripheral neuropathy were reported following ingestion of a single estimated

dose of 54-110 mg thallium/kg (as thallium nitrate), which was also lethal

(Davis et al. 1981). Examination of nerves obtained on days 7 and 9

demonstrated axonal degeneration with secondary myelin loss. Axons were

swollen and contained distended mitochondria and vacuoles (Davis et al. 1981).

Distal peripheral axonal degeneration with preserved proximal fibers was

observed in another case in which death occurred; however, reliable exposure

data (dose and duration) were not reported (Cavanagh et al. 1974; Roby et al.

1984). 

No studies were located regarding neurological effects in humans after

intermediate oral exposure to thallium. Peripheral neuropathy was reported in

189 cases of thallium poisoning in China from 1960 to 1977 (Dai-xing and

Ding-nan 1985). Thallium was detected in urine samples of the exposed group

at higher levels (0.6-2.25 mg/L, P>0.0l) than in the unexposed individuals

(0.14-0.31 mg/L). Similarly, levels in the hair were 21.8-31.5 mg/kg (P>0.0l)

compared to 5.80-11.3 mg/kg in the unexposed group. The authors attributed

exposure to ingestion of cabbage grown in thallium-contaminated gardens. No

other details were provided. 

In animals, structural and functional changes were observed in

peripheral nerves in rats at 240 days, following treatment with 1.4 mg

thallium/kg/day (as thallium sulfate), but effects were not found at 40 days

(Manzo et al. 1983). There was a 44% decrease in the amplitude of motor

action potential (MAP), a 30% decrease in the amplitude of the sensory action

potential, and a 25% increase in MAP latency. Wallerian degeneration of

scattered fibers and vacuolization and delamination of the myelin sheath of

10% of the fibers were reported in 50% of the test animals (Manzo et al.

1983). Ultrastructural examination of fibers with Wallerian degeneration

showed complete destruction of the axon, with mitochondrial degeneration,

neurofilamentous clustering, and evidence of extensive lysosomal activity 
15 

2. HEALTH EFFECTS 

(Manzo et al. 1983). However, when rats were administered up to 0.20 mg

thallium/kg (as thallium sulfate) by gavage for 90 days, light microscopic

examination did not reveal neurological effects (Stoltz et al. 1986). No

electron microscopic evaluations were performed in this study. 

The highest NOAEL values and all reliable LOAEL values for neurological

effects in each species and duration category are recorded in Table 2-1 and

plotted in Figure 2-1. 

2.2.2.5 Developmental Effects 

Thallium can cross the human placenta; however, data are limited

regarding the developmental effects. A retrospective study was conducted to

assess the teratogenic potential of thallium in 297 children born to mothers

living in the vicinity of a cement plant in Germany that discharged thallium

into the atmosphere (Dolgner et al. 1983). Maternal intake was presumed to

have been due to consumption of home-grown vegetables and fruits contaminated

with thallium. Levels of thallium in 24-hour urine samples were determined to

assess the degree of past thallium exposure, s!nce there were no relaible data

on exposure during pregnancy. Maternal urinary levels were 0.6-2.2 μg/L

compared to less than 1 μg/L for the general population. In the absence of

reliable exposure data, no firm conclusions can be made about the

developmental toxicity of thallium in humans. The incidence of congenital

malformations and anomalies in the exposed group did not exceed the number of

expected birth defects in the general population. 

Data in animals are sparse. Rats were administered 0, 0.08, 0.4 or

1.6 mg thallium/kg/day as thallium sulfate on days 6-9 of gestation to

determine the effect of prenatal exposure on learning ability. The study

involved a conditioning program in which lever pressing was rewarded with a

food pellet (Bornhausen and Hagen 1984). Rats showed impairment of learning

after prenatal exposure at doses of 0.08 mg thallium/kg/day or greater but no

dose-response relationship was observed. The LOAEL of 0.08 mg thallium/kg/day

is recorded in Table 2-l and plotted in Figure 2-1. While performance

deficits suggest impairment of brain function, no structural alterations were

reported at any dose tested. 

2.2.2.6 Reproductive Effects 

No studies were located regarding reproductive effects in humans after

oral exposure to thallium. 

In animals, abnormalities in testicular morphology, function, or

biochemistry were evident in rats which received an average daily intake of

0.27 mg thallium/day (approximately 0.7 mg/thallium/kg/day, as thallium

sulfate) during a 60-day treatment period (Formigli et al. 1986). Males

exposed to thallium for 60 days exhibited epididymal sperm with increased

number of immature cells and significantly reduced motility. Histological 
16 

2. HEALTH EFFECTS 

examination revealed disarrangement of the tubular epithelium. In addition,

Sertoli cells showed cytoplasmic vacuolization and distension of the smooth

endoplasmic reticulum. Testicular ,β-glucuronidase activity was reduced

significantly (p<0.0l) in the thallium-treated males, but plasma testosterone

levels were unaffected. Abnormalities in testicular morphology, function, or

biochemistry were not observed in rats exposed for 30 days (Formigli et al.

1986); however, thallium levels were not measured in this dose group. The

LOAEL of 0.7 mg thallium/kg/day is recorded in Table 2-l and plotted in

Figure 2-l. 

2.2.2.7 Genotoxic Effects 

No studies were located regarding genotoxic effects in humans after oral

exposure to thallium. However, thallium caused dominant lethal mutations in

rats after oral exposure at a dose of 0.04 pg thallium/kg/day as thallium

carbonate (Zasukhina et al. 1983). Other genotoxicity studies are discussed

in Section 2.4. 

2.2.2.8 Cancer 

No studies were located regarding cancer effects in humans or animals

after oral exposure to thallium. 

2.2.3 Dermal Exposure 

2.2.3.1 Death 

No studies were located regarding death in humans or animals after

dermal exposure to thallium. 

2.2.3.2 Systemic Effects 

No studies were located regarding respiratory, cardiovascular,

gastrointestinal, hematological, musculoskeletal, hepatic, renal, and

dermal/ocular effects in humans or animals after dermal exposure to thallium. 

No studies were located regarding the following health effects in humans

or animals after dermal exposure to thallium: 

2.2.3.3 Immunological Effects 

2.2.3.4 Neurological Effects 

2.2.3.5 Developmental Effects 

2.2.3.6 Reproductive Effects 

2.2.3.7 Genotoxic Effects 

Genotoxicity studies are discussed in Section 2.4. 
17 

2. HEALTH EFFECTS 

2.2.3.8 Cancer 

No studies were located regarding carcinogenic effects in humans or

animals after dermal exposure to thallium. 

2.3 TOXICOKINETICS 

2.3.1 Absorption 

2.3.1.1 Inhalation Exposure 

No quantitative studies were located regarding absorption in humans or

animals after inhalation exposure to thallium. 

2.3.1.2 Oral Exposure 

Limited data show direct gastrointestinal tract absorption in humans.

Indirect oral exposure may also occur through breathing contaminated airborne

dust. The mucociliary clearance mechanism moves most particulates with a mass

median aerodynamic diameter (MMAD) of l-5 μm out of the lungs and into the

gastrointestinal tract. Larger particles (greater than 5 μm) impacting in the 

nasopharyngeal region would also be eventually ingested. 

Limited data were located regarding absorption in humans after oral

exposure to thallium. Following oral administration of a single tracer dose

of 500 microcuries (μCi) of thalliumz204 (as thallium nitrate) and 45 mg daily

for 5 days of thallium sulfate in a patient with terminal osteogenic sarcoma,

0.4% of the administered radioactivity was recovered in feces and 11% in urine

during a 72-hour collection period. In 5.5 days, the patient had excreted

15.3% of the administered dose in the urine. These data suggest that most of

the thallium was absorbed (Barclay et al. 1953). 

Animal studies suggest that thallium is completely absorbed when

ingested. Lie et al. (1960) administered a single trace dose of

thallium204 (as thallium nitrate) orally to rats at a dose of 0.767 mg

thallium/kg. The body burden of thallium204, as percent dose, decreased with

a single exponential function which extrapolated to 100% at zero time. The

authors, therefore, concluded that thallium is completely absorbed from the

gastrointestinal tract. 

2.3.1.3 Dermal Exposure 

No reliable quantitative studies were located regarding absorption in

humans or animals after dermal exposure to thallium. 
18 

2. HEALTH EFFECTS 

2.3.2 Distribution 

2.3.2.1 Inhalation Exposure 

No studies were located regarding distribution in humans or animals

after inhalation exposure to thallium. 

2.3.2.2 Oral Exposure 

There is little information on distribution of thallium in humans. 

Analysis of human tissues indicate that thallium is distributed throughout the

body. A female cancer patient was administered a tracer dose of 1.8 mg

thallium204 (as thallium nitrate) orally and thereafter an oral dose of 36 mg

thallium/kg (as thallium sulfate) (Barclay et al. 1953). The thallium tissue

levels, reported as percent of average body distribution per gram, were

highest in scalp hair (420%), renal papilla (354%), renal cortex (268%), heart

(236%), bone tumor (233%) and spleen (200%). Lower levels were found in the

brain (45%-70%). 

In animals distribution of thallium from the blood stream is rapid and

widespread. Thallium was found to accumulate in the kidney (17 μg/g) followed

by the heart (7 μg/g), brain (6 μg/g), bone (8 μg/g), skin (3 μg/g), and blood

(0.67 μg/g) in rats administered approximately 1.4 mg thallium/kg (as thallium

sulfate) in drinking water (Manzo et al. 1983). In male rats administered

740 μg thallium/kg (as thallium sulfate) in drinking water, 6.3 μg thallium/g

tissue was found in the testes compared to less than 0.08 μg thallium/g tissue

in untreated controls (Formigli et al. 1986). In rats fed 2.3-3.0 mg

thallium/kg (as thallium acetate or thallic oxide), the largest amount of

thallium was detected in the kidney (24-31 μg/g wet tissue) with lower levels

in the liver (13-16 μg thallium/g) and bone (19 μg thallium/g). Smaller

amounts (5-9 μg/g) were found in the brain, lung, and spleen (Downs et al.

1960). 

Lie et al. (1960) studied the tissue distribution of thallium in rats

administered a single tracer dose of thallium204 (as thallium nitrate) orally

at a dose of 0.76 mg thallium/kg. Approximately 7 days post-treatment, the

highest level of thallium was detected in kidneys (4.7% of the body burden per

gram of tissue). Lesser amounts were detected in salivary glands (1.08%),

testes (0.88%), muscle (0.79%), bone (0.74%), gastrointestinal tract (0.62%),

spleen (0.56%), heart (0.54%), liver (0.52%), respiratory system (0.47%), hair

(0.37%), skin (0.37%), and brain (0.27%). The biological half-life for

thallium was 3.3 days. 

2.3.2.3 Dermal Exposure 

No studies were located regarding distribution in humans or animals

after dermal exposure to thallium. 
19 

2. HEALTH EFFECTS 

2.3.2.4 Other Exposure 

Parenteral studies also indicate extensive tissue distribution of 

thallium. Adult white mice dosed intraperitoneally with thallium204 at a dose 

of 4 mg thallium/kg as thallous sulfate showed high thallium concentrations in

bone tissue, kidney (particularly in the medulla), pancreas, and large

intestine approximately 1 hour after dosing (Andre et al. 1960). Thallium

levels in bone decreased after 10 days or more, but thallium was still

detectable 28 days posttreatment. Parenteral administration of thallium

resulted in peak concentrations in the brain, spinal cord, spleen, liver, and

kidney. 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). 

Thallium204 as thallous sulfate has been shown to cross the placenta and

locate in the fetus within 15 minutes following intraperitoneal injection

(50 μCi, specific activity not stated) (Olsen and Jonsen 1982) and 32 minutes

after intravenous administration (0.16-5.2 mg thallium/min/kg) (Rade et al.

1982). The concentration of thallium in the fetus was substantially lower

than that in maternal tissues by both routes of administration. 

2.3.3 Metabolism 

No studies were located regarding metabolism of thallium in humans or

animals. 

2.3.4 Excretion 

2.3.4.1 Inhalation Exposure 

In humans, thallium urinary levels ranging from ≤50 μg/L to 236 μg/L

were found in 39 workers exposed to thallium in a magnesium seawater battery

plant (Marcus 1985). Workers employed in a cement factory showed urinary

levels between 0.3-6.3 μg thallium/g creatinine (Schaller et al. 1980). 

No studies were located regarding excretion in animals after inhalation

exposure to thallium. 

2.3.4.2 Oral Exposure 

In humans, 15.3% of the administered radioactivity was detected in urine

5.5 days postdosing and 0.4% in feces in 3 days (Barclay et al. 1953). An

excretion half-life of 21.7 days was estimated (EPA 1980a). 

In rats administered 10 mg thallium/kg (as thallium sulfate) by gavage,

32% of the administered dose was eliminated in feces and 21% in urine (Lehman

and Favari 1985) by 8 days postdosing. 
20

2. HEALTH EFFECTS 

Lie et al. (1960) administered a single tracer dose of thallium204 (as

thallium nitrate) orally to rats at a dose of 767 μg thallium/kg. The ratio

of fecal to urinary excretion of thallium increased from about 2 to 5 between

days 2 and 16. 

2.3.4.3 Dermal Exposure 

No studies were located regarding excretion in humans or animals after

dermal exposure to thallium. 

2.4 RELEVANCE TO PUBLIC HEALTH 

As discussed in Section 2.2, estimates of levels of exposure to thallium

posing minimal risk to humans (MRLs) were to have been made, where data were

believed reliable, for the most sensitive noncancer effect for each route and

exposure duration. Because no data were located on effects of acute-duration

or intermediate-duration inhalation exposure to thallium in humans or animals,

and because available information concerning effects of chronic-duration

inhalation exposure in humans was not quantitative, no inhalation MRLs were

derived. Limited data on human and animal acute oral exposure to thallium

suggests that the nervous system may be the target organ, but reliable

doseresponse data were not available (Bornhausen and Hagen 1984; Cavanagh et al.

1974; Davis et al. 1981; Roby et al. 1984). Data on effects of

intermediateduration oral exposure in animals do not reliably identify the most

sensitive target organ or the threshold for adverse effects. No data on effects of

chronic-duration oral exposure to thallium were located. Therefore, acuteduration,

intermediate-duration, and chronic-duration oral MRLs were not

derived. Acute-duration, intermediate-duration, and chronic-duration dermal

MRLs were not derived for thallium due to the lack of an appropriate

methodology for the development of dermal MRLs. 

Inhalation and oral studies in humans and oral studies in animals 

demonstrate that thallium compounds such as thallium oxide and thallium

sulfate can be lethal at relatively low doses (about 1 gram). However, these

doses are high compared to exposure levels that would be expected from

thallium at NPL sites. Thallium compounds can affect the respiratory,

cardiovascular, and gastrointestinal systems, liver, kidneys, and the male

reproductive system. Temporary hair loss has also been associated with

ingestion of thallium in humans. Thallium compounds can also affect the

peripheral and central nervous systems. The rate of congenital malformations

among children of mothers exposed to thallium did not exceed the rate expected

for the general population. No studies have been located regarding thallium

exposure and development of cancer in humans or animals. 

Death. Thallium was lethal in humans following acute oral exposure at

doses of 54-110 mg thallium/kg of body weight as thallium sulfate (Davis

et al. 1981). The estimated lethal dose for the average adult for thallium is

1 g (approximately 14-15 mg/kg) (Gosselin et al. 1984). No studies were 
21 

2. HEALTH EFFECTS 

located concerning intermediate and chronic exposures in humans by oral,

inhalation, or dermal route. 

Death has been reported in animals exposed to low doses for brief

periods. The lowest doses showing lethality ranged from 5 to 30 mg

thallium/kg for several species (Downs et al. 1960). Exposure to low doses of

thallium (1.4 mg thallium/kg/day, as thallium sulfate) for longer durations

(40-240 days) can also cause death (Manzo et al. 1983). No studies were

located on chronic oral exposures or inhalation or dermal exposure for any

duration in animals. 

Mortality data of exposed humans and results of studies in several

animal species suggest that humans are at risk of death from exposure to high

concentrations of thallium. Neurological damage was a consistent feature

among humans who died following thallium exposure. However, death was

regularly attributed to cardiac or respiratory failure. Ingestion of lethal

doses readily resulted in cardiac and respiratory depression which generally

overshadowed the characteristic manifestation of neuropathy. 

Systemic Effects. 

Respiratory Effects. Human case studies reported respiratory effects

following acute oral exposure. Alveolar damage, hyaline membrane formation,

and pulmonary edema have been reported (Davis et al. 1981; Roby et al. 1984).

It has been suggested that thallium may have a direct effect on pulmonary

epithelial and endothelial cells. Alveolar damage suggests that respiratory

effects may be an area of concern following thallium exposure. 

Cardiovascular Effects. Studies in humans demonstrated cardiovascular 

effects following oral exposure to thallium. Myocardial damage and

electrocardiographic changes were observed (Davis et al. 1981; Roby et al.

1984). Following a single oral dose (56 mg thallium/kg as thallium sulfate),

rabbits showed electromyographic abnormalities without changes in the

myocardium (Grunfeld et al. 1963). The precise mechanism of thallium-induced

cardiovascular injury is not clear. However, parenteral injection of thallium

causes a direct effect on the cardiovascular system. Intravenously applied

thallium caused a significant dose-dependent decrease in mean arterial

pressure and heart rate, the maximum fall in blood pressure occurring within

3-5 minutes (Lameijer and van Zwieten 1976). The authors presumed a direct

influence of thallium on the sinus node. Based on human and animal data,

cardiovascular effects may be an area of concern following thallium exposure. 

Musculoskeletal Effects. Very little information was found on the

effects of thallium on muscles. Myopathic changes included fiber necrosis,

fiber splitting, and central nucleation (Limos et al. 1982). It should be

noted that these effects occurred in cases involving axon degeneration of the

nerve. It is, therefore, not clear if the effects observed were due to a 
22 

2. HEALTH EFFECTS 

direct toxic effect on muscle or were the result of rapid atrophy of the

paralyzed muscle secondary to severe axonal degeneration. 

Hepatic Effects. Oral studies in humans suggest that the liver is

susceptible to thallium toxicity. Necrosis, fatty changes, and altered serum

enzyme levels were reported. No studies were located demonstrating that

thallium causes liver toxicity in humans or animals by inhalation or dermal

exposure. Parenteral injection in animals has been observed to cause liver

effects. Single intraperitoneal doses of 33-132 mg thallium/kg/day (as

thallium chloride) were associated with ultrastructural.and biochemical

changes in the liver consistent with injury to the membranes of subcellular

organelles in the hepatocytes (Woods and Fowler 1986). In rats administered

subcutaneous injections of thallium (7.8-15.5 mg thallium/kg, as thallium

acetate), there were degenerative changes in mitochondria and increased

glycogen deposits (Herman and Bensch 1967). The precise mechanism for liver

toxicity is not known; however, thallium may combine with the sulfhydryl

groups of mitochondria, interfering with oxidative phosphorylation. Because

these effects occurred under conditions not likely to result in human

exposure, it is not clear whether similar effects on subcellular organelles

will occur in humans following relevant routes of exposure. 

Renal Effects. Very little information was found on the effects of

thallium on the kidney in humans. Tubular necrosis has been reported in some

cases following ingestion. However, these effects were reportedly due to

infarction rather than a direct affect on kidney tissue. Thallium did not

cause injury to the kidneys of rats following oral exposure. No studies were

located regarding renal effects in humans or animals after inhalation or

dermal exposure to thallium. Parenteral exposure studies in animals

demonstrate that thallium can affect the kidney following subcutaneous

administration. Accumulation of debris in the lumen of the convoluted tubules 

and progressive changes in the mitochondria of the tubule cell were observed

(Herman and Bensch 1967). By 12 weeks, many cup-shaped mitochondria were

present, and, in some mitochondria, partial loss of cristae was evident.

This route of exposure is not likely to result in significant human exposure.

Therefore, it is not clear if similar effects will occur in humans by relevant

exposure routes. 

Dermal/Ocular Effects. Hair loss has been reported in humans following

exposure to thallium. However, the effect is reversible. Animal studies

confirm human findings. However, these studies should be interpreted with

caution since rodent hair does not continue to grow as does cycling human head

hair. Animal studies suggest that thallium affects hair follicles directly or

that hair loss is the result of effects of thallium on the sympathetic nervous

system (Carson et al. 1986). No direct ocular effects of thallium have been

reported. However defects of the oculomotor nerve, ocular muscle, and ptosis

have been reported (Cavanagh et al. 1974; Davis et al. 1981). 
23 

2. HEALTH EFFECTS 

Immunological Effects. No studies were located regarding the

immunological effects in humans or animals after inhalation, oral, or dermal

exposure to thallium. In the absence of histopathologic evaluation and direct

tests of immune functions, the potential for thallium to affect the immune

system in humans cannot be determined. 

Neurological Effects. Human case reports demonstrated that thallium

caused disturbances of the peripheral and central nervous systems following

acute oral exposure. Ataxia, tremor, and multiple cranial palsies have been

reported following oral exposure to thallium as has numbness of toes and

fingers, "burning feet" phenomenon, and muscle cramps. Convulsions and death

can also occur. While thallium characteristically produces distal,

predominantly sensory neuropathy in humans, structural alterations underlying

the changes have not been firmly established. Histological evaluations have

shown axonal degeneration and myelin loss. 

The mechanism by which thallium exerts its effects is not clear.

However, parenteral studies in animals suggest that the effects observed may

be due in part to the depletion or inhibition of critical enzyme systems.

There was depletion of succinic dehydrogenase and guanine deaminase in the rat

cerebrum after intraperitoneal injection of 5 mg thallium/kg (as thallium

acetate) (Hasan et al. 1977a, 1977b) as well as depletion of monoamine

oxidase, acid phosphatase, and cathepsin activity (Hasan et al. 1977b).

Adenosine triphosphatase and adenosine deaminase activities were unaffected.

At the same dose, sequestrated axons were observed in the hypothalamus, and

there were increased Golgi zones and electron dense bodies in the hypothalamus

and hippocampus (Hasan et al. 1977a, 1978). Also, the protein content of the

corpus striatum was significantly increased (Hasan et al. 1977b).

Furthermore, there was a significant increase in the spontaneous discharge

rate of cerebellar Purkinje neurons of rats administered intraperitoneal

injections of 5 mg thallium/kg/day (as thallium acetate) (Marwaha et al.

1980). 

The effects in the hypothalamus, hippocampus, and corpus striatum are

consistent with a reported differential distribution of thallium in the brain.

In rats that received a single intraperitoneal injection of 13-39 mg

thallium/kg/day (as thallium sulfate), the highest thallium concentrations

were found in the hypothalamus and the lowest in the cortex (Rios et al.

1989). It was also noted that thallium accumulated more rapidly in the

hypothalamus than in other brain regions (Rios et al. 1989). Differential

distribution of thallium suggests that some areas of the brain may be affected

more severely than others. Brown et al. (1985) provided data suggesting a

dose-related selective toxicity between brain regions. Lipid peroxidation

rates and P-galactosidase activity were increased in the cerebellum and

brainstem following intraperitoneal injections of 3 mg thallium/kg/day (as

thallium acetate). However, when 6 mg thallium/kg/day (as thallium acetate)

were administered, lipid peroxidation rates were increased in the cerebellum, 
24 

2. HEALTH EFFECTS 

brainstem, striatum, and cortex. β-Galactosidase activity was also increased

in the cerebellum, cortex, hippocampus, and brainstem. 

Developmental Effects. A retrospective study was conducted to compare

the incidence of congenital abnormalities in children born to mothers who had

been exposed to thallium during pregnancy (Dolgner et al. 1983). The number

of anomalies in the exposed group did not exceed the number of expected birth

defects for the general population. 

Existing evidence suggests that thallium causes alterations in the

functional competence of the nervous system. There was impairment of learning

in rats prenatally exposed to 0.08 mg thallium/kg/day or greater during

gestation but no dose-response relationship was found (Bornhausen and Hagen

1984). No structural alterations in the brain were reported in this study.

It should be noted that these effects were reported to occur at dose levels

below those at which other neurological effects (e.g. structural and

functional alterations of peripheral nerves) have been observed. While

existing data suggest, in part, that thallium may be a potential developmental

neurotoxicant, additional testing batteries are needed. These studies would

be useful in determining the full spectrum of behavioral alterations and for

assessing the relative importance of this finding and human health risk. 

In animals, cultured rat embryos exposed to thallium at concentrations

of 10, 30, or 100 μg/mL showed dose-related growth retardation at all levels,

suggesting embryotoxic effects (Anschutz et al. 1981). Complete growth

inhibition was reported at 100 μg/mL. At 3 μg/mL (lowest dose tested), the

treated and control embryos did not differ significantly. Administration by

intraperitoneal injection to pregnant rats at a dose of 2.0 mg thallium/kg/day

(as thallium sulfate) during gestation days 8-10 resulted in reduced fetal

body weights, hydronephrosis, and the absence of vertebral bodies (Gibson and

Becker 1970). While these data suggest that thallium is a developmental

toxicant, the evidence is limited and does not allow a conclusive decision

about the human health implications. 

Reproductive Effects. No studies were located regarding reproductive

effects in humans after inhalation, oral, or dermal exposure to thallium. 

In rats, thallium administered in the drinking water at 0.74 mg/kg/day

(as thallium sulfate) for 60 days caused decreased sperm motility, inhibition

of β-glucuronidase activity and histopathological alterations of the testes

(Formigli et al. 1986). Mutagenicity studies employing dominant lethal assays

in mice provide some evidence of the potential reproductive effects of

thallium (see Genotoxic Effects). There was increased embryolethality

following oral exposure. While there are no human data regarding the

reproductive effects of thallium, animal data suggest that the male

reproductive system may be susceptible to the toxic action of thallium. 
25 

2. HEALTH EFFECTS 

Genotoxic Effects. No studies were located regarding the genotoxic

effects of thallium in humans. Results of animal and bacterial assays suggest

thallium is genotoxic. Thallium induced dominant lethals in male rats

in vivo. The overall embryonic mortality increased at doses of 0.04 μg

thallium/kg/day or greater as thallium carbonate (Zasukhina et al. 1983). In

vitro DNA damage tests employing rat embryo cells were positive (Table 2-2).

Thallium enhanced viral-induced transformations in Syrian hamster embryo cells

(Table 2-2). The significance of this response in the overall assessment of

the mutagenic potential of thallium is reduced since this end point is not

well understood. In vitro tests employing bacterial assays were positive

(Table 2-2). Existing data suggest that genotoxicity may be an area of

concern for thallium exposure in humans. 

Cancer. No studies were located regarding carcinogenicity in humans or

animals after inhalation, oral, or dermal exposure to thallium. In the

absence of epidemiological studies or long-term animal bioassays, the

potential for thallium to cause cancer in humans cannot be determined. 

2.5 BIOMARKERS OF EXPOSURE AND EFFECT 

Biomarkers are broadly defined as indicators signaling events in

biologic systems or samples. They have been classified as markers of

exposure, markers of effect, and markers of susceptibility (NAS/NRC 1989). 

A biomarker of exposure is a xenobiotic substance or its metabolite(s)

or the product of an interaction between a xenobiotic agent and some target

molecule(s) or cell(s) that is measured within a compartment of an organism

(NAS/NRC 1989). The preferred biomarkers of exposure are generally the

substance itself or substance-specific metabolites 'in readily obtainable body

fluid(s) or excreta. However, several factors can confound the use and

interpretation of biomarkers of exposure. The body burden of a substance may

be the result of exposures from more than one source. The substance being

measured may be a metabolite of another xenobiotic substance (e.g., high

urinary levels of phenol can result from exposure to several different

aromatic compounds). Depending on the properties of the substance (e.g.,

biologic half-life) and environmental conditions (e.g., duration and route of

exposure), the substance and all of its metabolites may have left the body by

the time biologic samples can be taken. It may be difficult to identify

individuals exposed to hazardous substances that are commonly found in body

tissues and fluids (e.g., essential mineral nutrients such as copper, zinc,

and selenium). Biomarkers of exposure to thallium are discussed in

Section 2.5.1. 

Biomarkers of effect are defined as any measurable biochemical,

physiologic, or other alteration within an organism that, depending on

magnitude, can be recognized as an established or potential health impairment

or disease (NAS/NRC 1989). This definition encompasses biochemical or 

27 

2. HEALTH EFFECTS 

cellular signals of tissue dysfunction (e.g., increased liver enzyme activity

or pathologic changes in female genital epithelial cells), as well physiologic

signs of dysfunction such as increased blood pressure or decreased lung

capacity. Note that these markers are often not substance specific. They

also may not be directly adverse, but can indicate potential health impairment

(e.g., DNA adducts). Biomarkers of effects caused by thallium are discussed

in Section 2.5.2. 

A biomarker of susceptibility is an indicator of an inherent or acquired

limitation of an organism's ability to respond to the challenge of exposure to

a specific xenobiotic substance. It can be an intrinsic genetic or other

characteristic or a preexisting disease that results in an increase in

absorbed dose, biologically effective dose,. or target tissue response. If

biomarkers of susceptibility exist, they are discussed in Section 2.7,

"POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE." 

2.5.1 Biomarkers Used to Identify and/or Quantify Exposure to

Thallium 

Thallium levels in urine, blood, and hair have been used as indications

of exposure to thallium. The determination of thallium in urine has been the

most widely used of biological indicators of thallium exposure. Typical

thallium levels in unexposed individuals are below 1 μg/g creatinine (Schaller

et al. 1980). Because of the quantitative renal excretion of creatinine and

its rather consistent rate of production, creatinine constitutes an endogenous

substance suitable for clearance testing. Higher values have been detected in

areas where thallium is used or emitted. Urinary levels in cement workers

ranged between <0.3 and 6.3 μg thallium/g creatinine (Schaller et al. 1980).

A mean urinary thallium level of 76 μg/L was reported in a population living

in the vicinity of a cement production plant (Brockhaus et al. 1981).

Apostoli et al. (1988) reported mean urinary thallium levels of 0.38 and

0.33 μg/L in two groups of workers employed in two cement production plants

and two cast iron foundries. Unexposed subjects showed lower mean levels

CO.22 μg/L). Urinary levels in toxic cases may be 3,100 μg/L (Gastel 1978)

and ≥ 5,000 μg/L in fatal cases (Roby et al. 1984). 

While thallium can be detected in blood, it is cleared from the blood

very rapidly. In one case in which a patient with osteogenic sarcoma was

administered oral doses of 1.8 mg thallium204 (as thallium nitrate)

(approximately 4 ng thallium/kg), 3% of the administered dose was detected in

blood within 2 hours post-treatment while 1.6% was detected within 24 hours

(Barclay et al. 1953). Since measurements of blood thallium reflect only

recent exposures, it is not generally considered to be a reliable means of

monitoring human populations for exposure to thallium.

Thallium is excreted in hair and measurement of hair levels may be an

indicator of thallium exposure. The normal concentration range of thallium in

human hair is approximately 5-10 ng/g. Seven percent of the administered 
28 

2. HEALTH EFFECTS 

radioactivity was detected in scalp hair of a cancer patient who had been

administered 1.8 mg thallium204 (as thallium nitrate) (Barclay et al. 1953).

It should be noted that thallium may adsorb to hair and become incorporated

into the hair matrix, making it difficult to distinguish between thallium

incorporated into the hair from the body burden and external deposition of

thallium. 

2.5.2 Biomarkers Used to Characterize Effects Caused by Thallium 

Neurological damage is the primary toxic effect associated with exposure

to thallium. Various effects on the nervous system of people exposed to

thallium can be detected by monitoring the incidence of signs and symptoms

such as ataxia, lethargy, painful extremities and numbness of toes and

fingers. Electromyographic measurements of nerve conduction velocity and

amplitude can be monitored to detect early signs of neurotoxicity. However,

since neurological damage occurs with other compounds, these tests are not

specific for thallium exposure. Also, thallium accumulates in hair. Dark

pigmentation of the hair roots and hair loss are common diagnostic features

(Gastel 1978). Depletion and inhibition of several enzymes in the brain have

been associated with thallium exposure. Hasan et al. (1977a, 1977b) reported

depletion of succinic dehydrogenase and guanine deaminase in the rat cerebrum

after parenteral administration of 5 mg thallium/kg (as thallium acetate) as

well as depletion of monoamine oxidase, acid phosphatase, and cathepsin

activity (Hasan et al. 1977b). However, the usefulness of the data is reduced

since the procedure is highly invasive. 

2.6 INTERACTIONS WITH OTHER CHEMICALS 

Studies have shown that trace metals can influence the toxicity of

thallium. Potassium has been shown to increase renal excretion of thallium 

(Gehring and Hammond 1967; Lund 1956a), decrease the degenerative effects of

thallium on epiphysial cartilage in mouse limb bud cultures, decrease

placental transport of thallium (Sabbioni et al. 1980), and increase the

lethality of thallium in animals (Gehring and Hammond 1967). Other interactions

can influence thallium toxicity through accelerated elimination.

Potent diuretics such as furosemide enhanced the urinary excretion of thallium

in rats (Lameijer and van Zwieten 1977a, 1978; Lehman and Favari 1985). Oral

administration of activated charcoal and Prussian blue accelerated the 

elimination of orally administered thallium in rats (Lehman and Favari 1985;

Lund 1956b). These agents adsorb thallium in the gastrointestinal tract, and

are themselves unabsorbed, thus reducing gastrointestinal absorption of

thallium. 

2.7 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 

Limited toxicity data suggest there are certain subgroups of the general

population which may be more susceptible to thallium exposure than other 
29 

2. HEALTH EFFECTS 

groups. People with preexisting neurological disease, kidney, and liver

damage may be at risk. 

Neurological injury is a major effect associated with exposure to

thallium in humans (Cavanagh et al. 1974; Davis et al. 1981; Ludolph et al.

1986; Roby et al. 1984). In people with neurological damage of other

etiology, thallium may add to or magnify the effect on the nervous system. 

Other subgroups that are potentially more sensitive to thallium exposure

are individuals with liver and kidney disease. In humans, necrosis of the

liver with fatty changes and elevated serum enzymes have been observed

(Cavanagh et al. 1974; Davis et al. 1981). Individuals with preexisting liver

disease may sustain additional liver damage at lower than usual dose levels

producing liver injury. Renal damage has also been associated with thallium

exposure. Tubular necrosis and renal failure may occur (Cavanagh et al. 1974;

Gastel 1978). In people with renal disease, there may be decreased capacity

to excrete thallium. Also, individuals with potassium deficiency may be at

risk since potassium has been shown to increase renal excretion of thallium

(Gehring and Hammond 1967; Lund 1956a). 

2.8 MITIGATION OF EFFECTS 

This section will describe clinical practice and research concerning

methods for reducing toxic effects of exposure to thallium. This section is

intended to inform the public of existing clinical practice and the status of

research concerning such methods. However, because some of the treatments

discussed may be experimental and unproven, this section should not be used as

a guide for treatment of exposures to thallium. When specific exposures have

occurred, poison control centers and medical toxicologists should be consulted

for medical advice. 

Exposure to thallium may occur by inhalation, ingestion, or dermal

absorption, but ingestion appears to be the predominant route of exposure for

humans (see Chapter 5). Thallium ingestion causes acute gastrointestinal

symptoms and multiple systemic effects, including respiratory, neurological,

cardiovascular, hepatic, and renal damage and alopecia (see Section 2.2). 

Procedures that have been suggested following acute, high-level exposure

to thallium consist of measures to reduce or eliminate further absorption.

Following inhalation exposure, these measures are removal of the victim and

administration of high-flow, humidified oxygen (Bronstein and Currance 1988;

Stutz and Janusz 1988). Following dermal exposure, contaminated clothing is

removed and skin thoroughly washed. Following ocular exposure, the eyes are.

flushed (Bronstein and Currance 1988; Stutz and Janusz 1988). Treatment for

acute, high-level oral exposure to thallium is designed to remove thallium

from the gastrointestinal tract as quickly as possible, to prevent absorption

of any remaining thallium and to increase excretion of thallium (Proctor et

al. 1988). However, some of the methods recommended to accomplish these aims 
30 

2. HEALTH EFFECTS 

are controversial. Emptying the stomach by gastric lavage or administration

of syrup of ipecac has been suggested within the first few hours following

exposure, if the victim is alert and has an intact gag reflex. Following

gastric emptying, it has been suggested that serial doses of activated

charcoal be administered to adsorb residual and rescreted thallium, and a mild

cathartic also used to accelerate fecal excretion (Ellenhorn and Barceloux

1988; Stutz and Janusz 1988). 

Prussian blue (potassium ferric ferrocyanide) binds with thallium in the

intestine and neither the Prussian blue nor its complex with thallium is

absorbed systemically. The oral or duodenal administration of this compound

effectively prevents absorption and increases fecal excretion (Ellenhorn and

Barceloux 1988; Haddad and Winchester 1990; Proctor et al. 1988). However,

this use of Prussian blue has not been approved by the U.S. Food and Drug

Administration (FDA), but is approved for use in Europe (Ellenhorn and

Barceloux 1988; Haddad and Winchester 1990). 

Oral administration of potassium chloride in large doses has been

recommended in victims with intact renal function to enhance thallium 

clearance from tissue storage sites and increase renal excretion. However,

there may be a transient worsening of symptoms following this treatment due to

the redistribution of thallium from tissue stores into the serum, and there is

some controversy concerning the efficacy of potassium chloride administration

(Ellenhorn and Barceloux 1988; Proctor et al. 1988). 

Hemodialysis or hemoperfusion may be beneficial in cases of severe

poisoning. Hemodialysis has been found to be quite effective in reducing

thallium concentrations in the blood in some cases and only minimally

effective in others. Hemoperfusion may give better results than hemodialysis.

These procedures may be used in cases where renal failure and paralytic bowel

render other treatments ineffective (Ellenhorn and Barceloux 1988; Haddad and

Winchester 1990; Proctor et al. 1988). 

It is unlikely that populations surrounding hazardous waste sites would

be exposed to thallium at levels that would result in symptoms requiring any

of these measures. Supportive follow-up medical care is likely to be the only

treatment for long-term neurological effects of thallium exposure. Additional

details regarding the treatment of acute, high-level thallium poisoning may be

obtained from the cited references. 

2.9 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of

ATSDR (in consultation with the Administrator of EPA and agencies and programs

of the Public Health Service) to assess whether adequate information on the

health effects of thallium is available. Where adequate information is not

available, ATSDR, in conjunction with the National Toxicology Program (NTP), 
31 

2. HEALTH EFFECTS 

is required to assure the initiation of a program of research designed to

determine the health effects (and techniques for developing methods to

determine such health effects) of thallium. 

The following categories of possible data needs have been identified by

a joint team of scientists from ATSDR, NTP, and EPA. They are defined as

substance-specific informational needs that, if met, would reduce or eliminate

the uncertainties of human health assessment. In the future, the identified

data needs will be evaluated and prioritized, and a substance-specific

research agenda will be proposed. 

2.9.1 Existing Information on Health Effects of Thallium 

The existing data on health effects of inhalation, oral, and dermal

exposure of humans and animals to thallium are summarized in Figure 2-2. The

purpose of this figure is to illustrate the existing information concerning

the health effects of thallium. Each dot in the figure indicates that one or

more studies provide information associated with that particular effect. The

dot does not imply anything about the quality of the study or studies. Gaps

in this figure should not be interpreted as "data needs" information (i.e.,

data gaps that must necessarily be filled). 

Most of the information concerning the health effects of thallium in

humans is found in case reports of accidental or intentional acute ingestion

of thallium. No information was found on effects after intermediate and 

chronic exposures. Reports of chronic inhalation exposure in the workplace

exist; however, these are limited to sites outside the United States. No

information was found on effects of thallium after acute and intermediate 

inhalation exposure or on effects after acute, intermediate, or chronic dermal

exposures. 

In animals, information exists on acute and intermediate oral exposures

to thallium in several species. However, no studies were located regarding

chronic oral exposures and on effects following acute, intermediate, and

chronic inhalation or dermal exposures. 

2.9.2 Data Needs 

Acute-Duration Exposure. No studies were found on the adverse effects 

of acute-duration inhalation exposure in humans or animals. Inhalation is not

likely to lead to significant exposure of the general population near

hazardous waste sites. Thallium and compounds are not volatile and are

subject to precipitation washout. The available information on effects of

acute-duration exposure to thallium and compounds in humans is limited to case

reports that indicate neurological, gastrointestinal, lung, liver, kidney, and

heart effects following oral exposure (Cavanagh et al. 1976; Davis et al.

1982; deGroot et al. 1985; Roby et al. 1984). Some studies did not report 

33 

2. HEALTH EFFECTS 

reliable exposure data. Estimated dose levels were provided in other

cases,but these doses far exceeded those expected to occur in the environment.

Human exposure data were not sufficient to derive an acute oral MEL since

reliable NOAEL and LOAEL values could not be determined. Since thallium binds 

tightly to soil particles, dermal contact may be significant, particularly in

children who may ingest thallium-contaminated soil. Additional dermal studies

would be useful to determine if soil-bound thallium is bioavailable. Acute 

oral data in animals demonstrated lethal (Downs et al. 1960) and developmental

neurological effects (Bornhausen and Hagen 1984) of thallium, but data were

not sufficient to derive an acute oral MEL. Additional studies in other 

species would be useful to identify the most sensitive effect and a doseresponse

relationship following acute oral exposure to thallium. Information

was not available to derive acute inhalation and dermal MRLs. 

Intermediate-Duration Exposure. No studies are available on adverse 

health effects of intermediate-duration inhalation exposure in humans to

thallium and compounds. Since thallium is not volatile, this route may not be

a major concern to humans exposed near hazardous waste sites. No information

is available on the effects of intermediate-duration inhalation exposure in

animals. Limited oral studies in animals demonstrated neurological and

reproductive effects (Formigli et al. 1986; Manzo et al. 1983). Data from

these studies were not sufficient to derive an intermediate MEL. These 

studies employed one dose level, precluding dose-response evaluations.

Additional oral studies employing other animal species and additional dose

levels would be useful in identifying susceptible organs and intermediateduration threshold for effects. There are no data on intermediate-duration 

exposure in humans or animals and toxicokinetics data are lacking. Additional

studies would be useful in determining potential target organs and critical

effects levels. 

Chronic-Duration Exposure and Cancer. A few studies are available 

evaluating the effects on humans chronically exposed to thallium in workplace

air (Ludolph et al. 1986; Marcus 1985). One study demonstrated that the

nervous system is adversely affected by inhalation exposure (Ludolph et al.

1986); however, no exposure data are provided. In the absence of quantitative

exposure data, available studies are not sufficient to derive a chronicduration MRL. Because thallium is not volatile and is subject to

precipitation washout from the atmosphere, exposure by this route may not be a

major concern at hazardous waste sites. No studies are available on the

effects of chronic oral or dermal exposure in humans or in animals by any

route of exposure. Because long-term environmental exposure to thallium can

occur in humans at hazardous waste sites, oral chronic animal studies of

various species at several dose levels would be useful in identifying

susceptible target organs and defining chronic thresholds. 

No studies are available on the carcinogenic effects of inhalation,

oral, or dermal exposure in humans or animals to thallium and compounds.

Considering the positive results of the genotoxicity assays (Casto et al. 
34 

2. HEALTH EFFECTS 

1979; Kanematsu et al. 1980; Zasukhina et al. 1981, 1983), studies to assess

the carcinogenic potential would be useful. There are some populations in the

vicinity of hazardous waste sites that might be exposed to low doses of

thallium for long periods of time. 

Genotoxicity. No information was available on the genotoxic effects of

thallium and compounds in humans. Microbial and in vitro and in vivo 

mammalian assays evaluating DNA damage and repair were positive (Kanematsu

et al. 1980). Additional in vivo studies evaluating structural and numerical

chromosomal aberrations would be useful to confirm the genotoxic potential of

thallium in humans. 

Reproductive Toxicity. No epidemiological studies have been conducted

in humans to establish a relationship between thallium exposure and adverse

effects on reproduction. Subchronic oral studies in rats suggest that the

testes may be susceptible (Formigli et al. 1986). These studies evaluated

only one dose level precluding dose-response evaluations. Results of dominant

lethal assays (Zasukhina et al. 1983) suggest thallium may act through a

genotoxic mechanism resulting in adverse reproductive effects. Subchronic

oral studies in other animal species evaluating various dose levels would be

helpful in confirming potential reproductive effects and identifying a

threshold for this effect. 

Developmental Toxicity. No studies were found in humans on the 

developmental toxicity of thallium and compounds following inhalation

exposure. As stated previously, inhalation exposure is not expected to be an

important source of exposure in the general population living near hazardous

waste sites. There is one human study involving the ingestion of contaminated

homegrown vegetables (Dolgner et al. 1983). It failed to clearly establish

any relationship between thallium exposure and occurrence of developmental

effects. Animal studies show that thallium can cross the placenta by the

parenteral route (Olsen and Jonsen 1982; Rade et al. 1982) and suggest that it

is a developmental, neurological toxicant by the oral route (Bornhausen and

Hagen 1984). While data are limited on thallium-induced alterations on the

functional competence of the nervous system, it should be noted that these

effects were reported to occur at dose levels below those at which other

neurological effects occurred. Additional animal studies involving other

species and employing various dose levels by oral exposure during critical

developmental periods would be helpful in confirming this effect and

determining a threshold level for this effect. Since dermal exposure through

soil contact may be a significant source of exposure in children living near

hazardous waste sites, studies are needed to determine if soil-bound thallium

is bioavailable. 

Immunotoxicity. No studies were located regarding immunotoxicity in

humans or animals following inhalation, oral or dermal exposures. Since

subchronic studies do not suggest the immune system is a target, additional

studies are not essential at this time. 
35 

2. HEALTH EFFECTS 

Neurotoxicity. Clinical neurological signs as well as histological

lesions in cranial and peripheral nerves have been demonstrated in humans

following inhalation (Ludolph et al. 1986) or oral (Cavanagh et al. 1974;

Davis et al. 1981; Dai-xing and Ding-nan 1985; Roby et al. 1984) exposure.

Exposure levels were not provided or if available, levels far exceeded those

expected to occur in the environment. No studies are available on effects

following dermal exposure. Structural and functional changes in peripheral

nerves in animals following oral exposure (Manzo et al. 1983) confirm findings

in humans. Since studies evaluated only one dose level and one additional 

study using multiple doses did not demonstrate neurological effects (Stoltz

et al. 1986), data gaps exist relative to dose-response relationships for this

target tissue. Additional oral studies would be useful in identifying a

threshold for this effect. Further, parenteral studies in animals demonstrated

biochemical changes in various parts of the brain suggesting a doserelated

selective toxicity between brain regions (Brown et al. 1985; Hasan

et al. 1977a,b, 1978; Rios et al. 1989). Additional animal studies to

evaluate preferential deposition of thallium in certain brain regions would be

useful in confirming the extent of neurological damage induced by thallium. 

Epidemiological and Human Dosimetry Studies. Epidemiological studies

evaluating the potential health effects of thallium are limited. One study

reported peripheral neuropathy in a group of cement workers exposed to

thallium (Ludolph et al. 1986). The relative usefulness of this study is

limited since an unexposed control group was not evaluated, exposure

concentrations were not reported, and the study population was small. Since

thallium is nonvolatiie, inhalation exposure may not be a major concern near

hazardous waste sites. However, there is potential for oral exposure. Longterm epidemiological studies by the oral route evaluating low-dose exposure

would be useful in characterizing the nature of organ changes produced by

thallium. Since neurological effects are well characterized, these studies

should consider reproductive effects based on animal data suggesting that the

male organs are susceptible to thallium toxicity (Formigli et al. 1986). 

Biomarkers of Exposure and Effect. The presence of thallium in urine is

the most reliable biomarker of exposure. The metal can be detected in urine

more than several days after exposure (Brockhaus et al. 1981; Schaller et al.

1980). 

Alopecia and changes in the nervous system are characteristic of

thallium exposure (Dai-zing and Ding-nan 1985; Gastel 1978; Grunfeld and

Hinostroza 1964; Ludolph et al. 1986). Electromyographic measurements of

nerve conduction velocity and amplitude can be monitored to detect early signs

of neurotoxicity in people exposed to thallium. While such tests are not 

specific for thallium-induced toxicity, they do identify potential health

impairment. Studies to develop more specific biomarkers of thallium-induced

effects would be useful in assessing the potential health risk of thallium

exposure near hazardous waste sites. 
36 

2. HEALTH EFFECTS 

Absorption, Distribution, Metabolism, and Excretion. No quantitative

information is available on absorption of thallium in humans or animals by

inhalation or dermal exposure. However, animal studies following

intratracheal administration suggested that uptake through respiratory

epithelium was rapid and complete (Lie et al. 1960). Data regarding

absorption in humans are limited. In one study in which a patient with

terminal osteogenic sarcoma was given a single oral dose of thalliumzo4,

complete absorption was suggested based on an increased urinary radioactivity

over a 72-hour period (Barclay et al. 1953). Additional oral studies that

provide data on rate and extent of absorption would be useful since this

appears to be the primary exposure route. In one study in which rats were

administered radiolabel thallium nitrate by oral exposure, body burden of

radioactivity was expressed as a percent of administered dose over time,

suggesting virtually complete and rapid uptake by this route (Lie et al.

1960). 

No information was found on the distribution of thallium following

inhalation or dermal exposure. There are a few studies by oral exposure,

which indicate that thallium is found in many tissues of the body (Barclay

et al. 1953). Data in humans reported tissue levels are highest in the scalp

hair, kidney, heart, bone, and spleen. Lower levels were found in the brain

(Barclay et al. 1953). Animal studies confirmed that thallium is widely

distributed (Downs et al. 1960; Grunfeld et al. 1963; Lie et al. 1960).

However, in animals, thallium is chiefly distributed to the kidneys and liver.

Additional studies are needed as a basis for understanding species differences

in distribution of thallium. Data exist suggesting that thallium can cross

the placental barrier by parenteral administration (Olsen and Jonsen 1982;

Rade et al. 1982). However, in human studies evaluating developmental

toxicity, the increase of congenital malformation and anomalies in the exposed

group did not exceed the number of expected defects in the general population

(Dolgner et al. 1983). Additional animal studies by the oral route would be

useful in confirming that thallium can locate in the fetus and providing a

basis for assessing if there is potential human health risk. 

No information is available on the metabolism of thallium. Additional 

studies are needed to determine if thallium is transformed in the body and

would provide a basis for understanding target organ toxicity. 

No data are available on excretion of thallium in humans or animals by

inhalation or dermal exposure. There are data on excretion in humans and

animals by oral exposure. In one study in which a patient was administered

radiolabel thallium nitrate, one half of the radioactivity was detected in the

urine 21.7 days after exposure, suggesting that thallium is slowly excreted

from the body (Barclay et al. 1953). In animals, excretion is more rapid

(e.g., half in 3.3 days) and occurs primarily via feces (Lehman and Favan

1985; Lie et al. 1960). Additional studies of other animal species by all

routes of exposure would be useful in clarifying differences in excretion

patterns. 
37 

2. HEALTH EFFECTS 

Comparative Toxicokinetics. Since human and animal toxicokinetics data 

are limited, very little data exist on comparative kinetics across species.

Human data are limited to one study (Barclay et al. 1953) and animal data are

primarily in rats (Downs et al. 1960; Lehman and Favan 1985; Lie et al. 1960).

These data suggest some kinetics differences, particularly in distribution and

excretion patterns. Additional studies using other animal species would be

useful in clarifying species differences. 

Mitigation of Effects. Recommended methods for the mitigation of the

acute effects of thallium poisoning involve prevention of thallium absorption

from the gastrointestinal tract by administration of emetics, cathartics,

and/or binding agents and removal of absorbed thallium from the serum by

hemodialysis or hemoperfusion or by administration of potassium chloride

(Ellenhorn and Barceloux 1988; Haddad and Winchester 1990; Proctor et al.

1988). No information was located concerning mitigation of effects of lowerlevel or longer-term exposure to thallium. Further information on techniques

to mitigate such effects would be useful in determining the safety and

effectiveness of possible methods for treating thallium-exposed populations

surrounding hazardous waste sites. 

2.9.3 On-going Studies 

A number of research projects are in progress investigating the toxicity

of thallium. These projects are summarized in Table 2-3. 







45 

4. PRODUCTION, IMPORT, USE, AND DISPOSAL 

4.1 PRODUCTION 

The domestic production of thallium ceased in 1981. Prior to this,

thallium had been recovered as a byproduct from the flue dust and residuals

that resulted from the smelting of zinc, copper, and lead ores through

treatment by electrolysis, precipitation, or reduction (HSDB 1989; Sax and

Lewis 1987; U.S. Bureau of Mines 1983, 1988). Based upon the estimated

thallium content of zinc ores, United States mine production of thallium was

0.45 metric tons in 1986 and 1987 and 14.06 metric tons in the rest of the 

world (U.S. Bureau of Mines 1983, 1988). No data were located regarding the

production of thallium acetate, thallium nitrate, thallium chloride, thallium

sulfate or thallium oxide. 

There are six facilities in the United States that either import

thallium, use thallium and its compounds in manufacturing processes, or

produce them as byproducts. These facilities are listed in Table 4-l. 

4.2 IMPORT/EXPORT 

Currently all thallium used in the United States is obtained from

thallium reserves or is imported. The combined import of thallium and

thallium compounds ranged from 1.27 metric tons in 1983 to 2.04 metric tons in

1987. Between 1983-1986 the countries from which thallium and thallium 

compounds were imported were Belgium (54%), the Netherlands (16%), the FederalRepublic of Germany (14%), the United Kingdom (6%), and other sources (10%)

(U.S. Bureau of Mines 1988). 

No information was located regarding the export of thallium or thallium

compounds. 

4.3 USE 

Today's primary user of thallium is the semiconductor industry which in

1987 used 60%-70% of total U.S. thallium imports in its production of switches

and closures. The remainder of thallium used was in the pharmaceutical

industry to produce thallium for cardiac imaging, and to manufacture highly

refractive optical glass (HSDB 1989; U.S. Bureau of Mines 1988; Windholz

1983). 

Thallium compounds have a variety of uses. Thallium sulfate is used in

the semiconductor industry and in low range thermometers, optical systems, and

photoelectric cells, and as a chemical intermediate for other thallium

compounds and thallium metals (HSDB 1989). Thallium acetate is used to

prepare solutions of high specific gravity for use in separating ore

constituents by flotation (HSDB 1989). Thallium chloride is used as a

catalyst in chlorination (Windholz 1983). Thallium nitrate is used with other 

47 

4. PRODUCTION, IMPORT, USE, AND DISPOSAL 

compounds and resins for use as signals at sea. It is also used in the

production of low melting glass, photocells, fireworks and as an oxidizing

agent in organic syntheses (HSDB 1989; Weast 1985). Thallium oxide is used in

the manufacture of highly refractive glass and for the production of

artificial gems (Windholz 1983). Thallium and compounds were once used as a

pesticide for control of rodents and insects, but the use of thallium as a

pesticide was banned in 1972 (EPA 1985b). 

4.4 DISPOSAL 

Thallium is listed as a hazardous substance, therefore, disposal of

waste thallium is controlled by a number of federal regulations, including

land disposal restrictions (see Chapter 7). Industries producing or using

thallium reported off-site waste transfers of about 40,000 pounds of thallium

in 1987 (TRI 1989). Land disposal restrictions were implemented by EPA in

1987. Prior to this time disposal of pesticides had been to municipal and

industrial landfills. Since thallium is relatively stable in the environment,

we can assume that landfills, as well as other superfund sites, contain

thallium or thallium-containing products. 

49 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.1 OVERVIEW 

Thallium is a heavy metallic element that exists in the environment

mainly combined with other elements (primarily oxygen, sulfur, and the

halogens) in inorganic compounds. Thallium is quite stable in the

environment, since it is neither transformed nor biodegraded. 

Compounds of thallium are generally soluble in water and the element is

found primarily as the monovalent ion (Tl+

). Thallium tends to be sorbed to

soils and sediments (Frantz and Carlson 1987; Mathis and Kevern 1975;

Wallwork-Barber et al. 1985) and to bioconcentrate in aquatic plants,

invertebrates, and fish (Barrows et al. 1978; Zitko and Carson 1975).

Terrestrial plants can also absorb thallium from soil (Ewers 1988; Sharma

et al. 1986). 

Major releases of thallium to the environment are from processes such as

coal-burning and smelting, in which thallium is a trace contaminant of the raw

materials, rather than from facilities producing or using thallium compounds.

Humans may be exposed to thallium by ingestion, inhalation, or dermal

absorption. However, the general population is exposed most frequently by

ingestion of thallium-containing foods, especially home-grown fruits and green

vegetables. Inhalation of contaminated air near emission sources or in the

workplace may also contribute to thallium exposure of some individuals. 

The EPA has identified 1,177 NPL sites. Thallium has been found at 18

of the sites evaluated for this chemical. However, we do not know how many of

the 1,177 sites have been evaluated for this chemical. As more sites are

evaluated, these numbers may change (View 1989). The frequency of these sites

within the United States can be seen in Figure 5-l. Seventeen sites are

located in the United States and 1 site is located in the commonwealth of 

Puerto Rico (not shown). 

5.2 RELEASES TO THE ENVIRONMENT 

Manufacturers, processors, and users of thallium and thallium compounds

are required to report quantities of releases of these substances to

environmental media annually (EPA 1988c). According to the SARA Section 313

Toxics Release Inventory (TRI), an estimated total of 56,511 pounds of

thallium were released to the environment from manufacturing and processing

facilities in the United States in 1987 (Table 5-l) (TRI 1989). The TRI data

should be used with caution since the 1987 data represent first-time reporting

by these facilities. Only certain types of facilities were required to

report. This is not an exhaustive list. However, the major sources of 


52 

5. POTENTIAL FOR HUMAN EXPOSURE 

thallium releases to the environment are not from facilities that produce or

use thallium and its compounds, but from processes such as coal-burning or

smelting in which thallium is a trace element of the raw materials (Schoer

1984). Data on thallium emissions from these sources are not included in the

TRI. 

5.2.1 Air 

Thallium is released to the atmosphere mainly from coal-burning power

plants, cement factories, and ferrous and nonferrous smelting operations (EPA

1988a; Ewers 1988; Sharma et al. 1986). Thallium emissions in the United

States were estimated at 140 tons/year each from coal-burning power plants and

from iron and steel production (Ewers 1988; Schoer 1984; Smith and Carson

1977). Total air releases reported from industrial sources were about 27 tons

in 1987 (TRI 1989). 

Davison et al. (1974) reported concentrations of thallium on airborne

fly ash emitted from a coal-burning power plant ranging from 29 to 76 μg/g,

the thallium concentration increasing with decreasing particle size. The

highest concentrations (greater than 60 μg/g) were on particles less than

7.3 μm in diameter. The authors reported that these concentrations were

representative of eight other United States power plants burning various types

of coal. The highest thallium concentrations were also found on the smaller

diameter (0.2 – 0.8 μm) particles of fly dust emitted from a West German cement

plant (Ewers 1988). 

No quantitative estimates of thallium emissions from other domestic

sources were located. However, additional sources of airborne thallium may

include manufacturers of alloys, artificial gems, electronics equipment,

optical glass, and domestic heating plants (EPA 1987a; Sharma et al. 1986;

Valerio et al. 1988). 

5.2.2 Water 

The major sources of thallium releases to water include nonferrous

metals, iron and steel manufacturers and various mining, inorganic chemicals,

refining, and ore-processing industries (EPA 1980a, 1983c; Ewers 1988).

Thallium concentrations in raw or treated waste waters from these industries 

ranged up to 2 g/L (EPA 1983c). Thallium has been detected in urban waste

waters, apparently from commercial and industrial sources (Callahan et al.

1979a; Levins et al. 1979). Total water releases reported from industrial

sources were 1,850 pounds in 1987 (TRI 1989). Thallium has been detected in

both surface and groundwater samples at hazardous waste sites. Data from the

Contract Laboratory Program (CLP) Statistical Database indicate that thallium

occurred in surface water at 1% of sites at a geometric mean concentration of

23 ppb in positive samples and in groundwater at 7% of sites at a mean

concentration of 11 ppb in positive samples (CLPSD 1989). Note that the

Contract Laboratory Program (CLP) Statistical Database includes data from both 
53 

5. POTENTIAL FOR HUMAN EXPOSURE 

NPL and non-NPL sites. No other quantitative estimates of total thallium

releases to water were located. 

5.2.3 Soil 

Thallium releases to soil are mainly solid wastes from coal combustion

and smelting operations (Ewers 1988). Thallium was detected at a geometric

mean concentration of 1.7 ppm in positive soil samples from 3.5% of an

unspecified number of hazardous waste sites (CLPSD 1989). Although direct

soil releases are likely to be small, since thallium-containing wastes are

subject to EPA land disposal restrictions, atmospheric thallium pollution may

contribute to soil contamination in the vicinity of thallium emission sources

(Brockhaus et al. 1981). It should be noted that land disposal restrictions

were implemented by EPA in 1987. Prior to this time disposal of pesticides

had been to municipal and industrial landfills. Since thallium is relatively

stable in the environment, we can assume that landfills, as well other

Superfund sites, contain thallium or thallium-containing products. 

5.3 ENVIRONMENTAL FATE 

5.3.1 Transport and Partitioning 

Thallium is a nonvolatile heavy metal, and if released to the atmosphere

by anthropogenic sources, may exist as an oxide (thallium oxide), hydroxide

(TlOH), sulfate (thallium sulfate), or as the sulfide Tl2S (EPA 1988a). These

thallium compounds are not volatile (EPA 1983c; Weast 1970). It has been

speculated that thallium sulfate and TlOH will partition into water vapor

(such as clouds and rain drops) because they are soluble in water and thus,

precipitation may remove these forms of thallium from the atmosphere (EPA

1988a). Thallium oxides are less soluble in water, and may be subject to only

atmospheric dispersion, and gravitational settling. No corroborative

information was located. The atmospheric half-life of suspended thallium

particles is unknown. 

Thallium exists in water primarily as a monovalent ion (thallium+

);

thallium may be trivalent (T13+) in very oxidizing water (Callahan et al.

1979b). Tl+

 forms complexes in solution with halogens, oxygen, and sulfur

(Lee 1971). Thallium may precipitate from water as solid mineral phases.

However, thallium chloride, sulfate, carbonate, bromide, and hydroxide are

very soluble in water. For example, the solubility of thallium sulfate at 0°C

is about 27 g/L (EPA 1980a). In extremely reducing water, thallium may

precipitate as a sulfide (Tl2S), and in oxidizing water, T13+ may be removed

from solution by the formation of Tl (OH)3 (Lee 1971). Stephenson and Lester

(1987a, 1987b) argued that the partial removal of thallium from water was the

result of precipitation of unknown solids during the treatment of sewage

sludge. 
54 

5. POTENTIAL FOR HUMAN EXPOSURE 

Thallium may partition from water to soils and sediments. Mathis and

Kevern (1975) presented indirect evidence that thallium was adsorbed by lake

sediments. Furthermore, thallium may be adsorbed by micaceous clays in

solution (Frantz and Carlson 1987). 

Partition coefficients such as adsorption constants describe the

tendency of a chemical to partition to solid phases from water. Adsorption

constants for inorganic ions such as Tl+ cannot be predicted a priori, but

must be measured for each adsorbent. Thallium adsorption data in Magorian

et al. (1974) for a hectorite clay (a rare montmorillonite clay mineral) at pH

8.1 suggest that an adsorption constant for this specific system may be

approximately 19 L/g. No other information on the adsorption of thallium by

earth materials was located. 

Thallium may be bioconcentrated by organisms from water. A

bioconcentration factor (BCF) relates the concentration of a chemical in the

tissues of aquatic animals or plants to the concentration of the chemical in 

the water in which they live. Experimentally-measured BCF values have been

reported: 18.2 for clams and 11.7 for mussels (Zitko and Carson 1975).

Bioconcentration factors for the muscle tissue of juvenile Atlantic salmon

have ranged from 27 to 1,430 (Zitko et al. 1975). The maximum BCF for

bluegill sunfish was 34 in the study of Barrows et al. (1978). Thallium is

absorbed by plants from soil and thereby enters the terrestrial food chain

(Ewers 1988; Sharma et al. 1986). Cataldo and Wildung (1983) demonstrated

that thallium could be absorbed by the roots of higher plants from the

rhizophere. 

5.3.2 Transformation and Degradation 

5.3.2.1 Air 

Metallic thallium oxidizes slowly in air (Lee 1971), and thallous

chloride is photosensitive (Cotton and Wilkinson 1980). However, there was no

evidence that thallium is transformed significantly by photochemical reactions

in the atmosphere (Callahan et al. 1979b). 

5.3.2.2 Water 

Little is known about thallium transformation in water by either abiotic

or biotic processes (EPA 1988a). Pertinent data regarding the photolysis or

hydrolysis of common thallium compounds were not located. 

5.3.2.3 Soil 

Callahan et al. (1979b) concluded that there was no evidence that

thallium is biotransformed in the environment. No other information was 

located. 
55 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 

5.4.1 Air 

Data on thallium levels in ambient air are sparse. In six United States

cities, the thallium concentrations ranged from 0.02 to 0.1 ng/m3

, with a

typical concentration of 0.04 ng/m3

 (EPA 1980a, 1988a). Concentrations of

thallium in Chadron, Nebraska reportedly ranged from 0.04 to 0.48 ng/m3

 (EPA

1980a, 1988a), and geometric mean concentrations measured during 1985-1986 in

Genoa, Italy were about 0.015 μg/m3

 (Valerio et al. 1988). The estimated

thallium concentration near a coal-burning power plant was 0.7 μg/m3

 (EPA

1988a). 

Thallium levels have also been measured in workplace air. Marcus (1985)

reported maximum thallium levels in workplace air at 0.014 and 0.022 mg/m3 

during machining and alloying operations, respectively, of a magnesium alloy

used in batteries at a plant in England. Air samples in two cement plants and

two foundries in Italy had thallium concentrations of less than 1 μg /m3 

(Apostoli et al. 1988). 

5.4.2 Water 

Since thallium is a naturally-occurring element, it may be present in

ambient waters in trace amounts. However, monitoring data indicate elevated

thallium concentrations near industrial and commercial sources and hazardous 

waste sites. 

A survey of tap water from 3,834 homes in the United States detected

thallium in 0.68% of samples at an average thallium concentration of 0.89 μg/L

(EPA 1980a, 1988a). Thallium was detected in 10% of urban stormwater runoff

samples at concentrations ranging from 1 to 14 μg/L (Cole et al. 1984).

Thallium has been measured in seawater at 0.01-14.00 μg/L (Sharma et al. 

1986). 

Water concentrations of thallium in rivers in the United States and 

Canada that receive mining operations effluents ranged from 0.7 to 88.3 μg/L

(EPA 1980a, 1988a; Zitko et al. 1975). 

5.4.3 Soil 

Estimates of thallium concentration in the earth's crust range from 0.3

to 0.7 ppm (EPA 1988a), so thallium is likely to be present in soils in trace

amounts. The limited data available indicate that soil thallium levels may be

increased near thallium-emitting industrial sources and at hazardous waste

sites. Measured thallium concentrations in lake sediments ranged from 0.13 to

0.27 μg/g in four remote Rocky Mountain lakes (Heit et al. 1984) to

2.1-23.1 mg/kg ( mean value 13.1 mg/kg) in a Michigan lake reportedly polluted

by airborne particulate matter (EPA 1988a). Up to 5 mg/kg thallium was 
56 

5. POTENTIAL FOR HUMAN EXPOSURE 

reported in stream sediments near metal industry runoff areas (Wallwork-Barber

et al. 1985). 

5.4.4 Other Environmental Media 

Trace amounts of thallium are found in most foods (Ewers 1988), but few 

foods, except vegetables grown in thallium-polluted soil, are likely to have

significant thallium concentrations (Ewers 1988; Sharma et al. 1986). 

Data on thallium content of specific foods grown and consumed in the

United States were not located. However, a recent study of the thallium

content of food in the United Kingdom reports levels of thallium in meat,

fish, fats, and green vegetables (Sherlock and Smart 1986). 

5.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 

Human exposure to thallium may occur by inhalation, ingestion, or dermal

absorption. The general population is exposed most frequently by ingestion of

thallium-containing foods (EPA 1980a, 1988a; Ewers 1988). From the very

limited data available, EPA estimated daily intakes for the general adult

population from drinking water, air, and food (EPA 1980a). More recent data

on thallium concentrations in food and dietary intake of the general

population (Sherlock and Smart 1986) confirm that food (green vegetables in

particular) is probably the major source of thallium exposure. Although these

data are from the United Kingdom, it is not likely that the thallium content

of the food supply of the United States would be significantly different.

Limited data on thallium concentrations in cigars and cigarettes suggest

smoking may be a source of thallium. The extent of exposure from this source

is not clear since thallium levels in cigarette smoke are not known.

Table 5-2 summarizes the estimated typical daily intakes from water, food, and

air. 

Occupational exposure to thallium may be significant for workers in

smelters, power plants, cement factories, and other industries that produce or

use thallium compounds or alloys. Exposure may occur by dermal absorption

from handling thallium-containing compounds, ores, limestone, or cement or by

inhalation of workplace air (Ewers 1988; Marcus 1985; Schaller et al. 1980). 

Urinary thallium levels are considered the most reliable indicator of

thallium exposure. Although data on exposure levels in workplace air are rare

(see Section 5.4.1), studies associating workplace exposure and elevated

urinary thallium confirm the occurrence of industrial exposures in Europe

(Apostoli et al. 1988; Marcus 1985; Schaller et al. 1980). Similar data were

not located for U.S. workplaces. However, NIOSH estimated that more than 

58 

5. POTENTIAL FOR HUMAN EXPOSURE 

1,600 people are occupationally exposed to thallium in the United States (NOES

1989). The NOES database does not contain information on the frequency,

concentration, or duration of exposure of workers to any of the chemicals

listed therein. This survey provides only estimates of the number of workers

potentially exposed to chemicals in the workplace. 

5.6 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 

Populations with potentially high exposures are those living near coalBurning power plants, metal smelters, or cement plants (Sharma et al. 1986).

The airborne particulate emissions from these plants may have high thallium

levels, especially on the small-diameter, respirable particles (Davison et al.

1974; Ewers 1988). Human populations living in the vicinity of these plants

may be exposed by inhalation or by ingestion of fruits and vegetables homegrown

in contaminated soils (Brockhaus et al. 1980, 1981; EPA 1988a; Sharma

et al. 1986). 

Workers in industries producing or using thallium-containing materials

also have potentially high exposures as noted above (Section 5.5). 

Limited data suggest that smokers may have potentially high exposure to

thallium. Although recent authoritative evaluations of cigarette smoke 

constituents do not include thallium, thallium was detected at 

0.057-0.170 μg/g in cigar stubs and 0.024 μg/g in cigarette tobacco (EPA

1980a; Smith and Carson 1977). One study indicates that the urinary excretion

of thallium in smokers is about twice that of nonsmokers (EPA 1980a; Smith and

Carson 1977). 

5.7 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of

ATSDR (in consultation with the Administrator of EPA and agencies and programs

of the Public Health Service) to assess whether adequate information on the

health effects of thallium is available. Where adequate information is not

available, ATSDR, in conjunction with the NTP, is required to assure the

initiation of a program of research designed to determine the health effects

(and techniques for developing methods to determine such health effects) of

thallium. 

The following categories of possible data needs have been identified by

a joint team of scientists from ATSDR, NTP, and EPA. They are defined as

substance-specific informational needs that, if met, would reduce or eliminate

the uncertainties of human health assessment. In the future, the identified

data needs will be evaluated and prioritized, and a substance-specific

research agenda will be proposed. 
59 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.7.1 Data Needs 

Physical and Chemical Properties. Additional measurements of the 

aqueous solubility of environmentally relevant thallium compounds would

provide a more accurate basis for applying mineral equilibria to predict the

fate of thallium in water (EPA 1988a). 

Production, Import/Export, Use, and Disposal. According to the

Emergency Planning and Community Right-to-Know Act of 1986, 42 U.S.C. Section

11023, industries are required to submit chemical release and off-site

transfer information to the EPA. The Toxics Release Inventory (TRI), which

contains this information for 1987, became available in May of 1989. This

database will be updated yearly and should provide a list of industrial

production facilities and emissions. 

Data on production, use, and disposal (HSDB 1989; TRI 1989; U.S. Bureau

of Mines 1988) are adequate. Additional information is unlikely to

significantly affect estimates of human exposure. 

Environmental Fate. Little information is available on partitioning of

thallium in the atmosphere (EPA 1988a). This lack of data is not important

since thallium is nonvolatile. The reaction mechanisms controlling the fate

of thallium in water are not well known. Adsorption-desorption reactions with

soils and sediments (Frantz and Carlson 1987; Magorian et al. 1974; Mathis and

Kevern 1975) suggest that movement of thallium can be reduced. Additional

research would provide a more accurate basis for predicting the fate of

thallium in water. Very little is known about potential transformation

mechanisms for thallium in air, water, or soil (Callahan et al. 1979b; EPA

1988a), but this lack of detailed data may not be a major limitation because

many transition metals are not susceptible to transformation or degradationtype processes. 

Bioavailability From Environmental Media. Thallium can be absorbed 

following inhalation of contaminated workplace air, ingestion of contaminated

food, or dermal contact (Dai-xing and Ding-nan 1985; Dolgner et al. 1983;

Marcus 1985). The most significant routes of exposure near hazardous waste

sites are likely to be through drinking thallium-contaminated water and skin

contact with or ingestion of thallium that is attached to soil particles.

Information on the percent of thallium taken into the body from environmental

media that is actually absorbed or bioavailable would be useful in clarifying

the toxic potential of thallium in humans. The relative absorption of

different species/forms of thallium from inorganic and biological matrices

would also be useful. 

Food Chain Bioaccumulation. There are no specific data on the

bioaccumulation of thallium or its potential to be transferred from lower

trophic levels to higher organisms. Because thallium can be bioconcentrated,

it may be that it can also be accumulated in living tissues. We know that 
60 

5. POTENTIAL FOR HUMAN EXPOSURE 

thallium may be bioconcentrated by aquatic plants, invertebrates, and fish

(Barrows et al. 1978; Zitko and Carson 1975; Zitko et al. 1975). Information

on biotransformation in aquatic biota would provide further insight into the

extent of chemical speciation and forms of thallium to which humans could be

exposed near hazardous waste sites. Terrestrial plants absorb thallium from

soil (Cataldo and Wildung 1983). Additional measurements of the

bioconcentration of thallium by plants and animals and information on soil

types and conditions which enhance thallium uptake by plants would be helpful

to better define the tendency of thallium to partition to living tissues.

Detectable levels of thallium have been found in many foods (Ewers 1988;

Sharma et al. 1986; Sherlock and Smart 1986). However, no data were located

on biomagnification of thallium in the food chain. Information on food chain

bioaccumulation would be useful in assessing the potential for human exposure

to thallium from food. 

Exposure Levels in Environmental Media. Data on thallium levels in all 

environmental media are sparse (EPA 1988a). More research using sensitive

analytical methods for all media, especially in the vicinity of potential

thallium pollution sources and waste sites, and specific data on the thallium

content of the American diet would increase the accuracy of human exposure

estimates. 

Exposure Levels in Humans. Thallium has been detected in human urine 

and urinary thallium excretion is used as a measure of thallium absorption

(Dai-xing and Ding-nan 1985; Dolgher et al. 1983; Marcus 1985). Reliable data

on urinary thallium in unexposed individuals and correlating urinary thallium

levels with environmental exposures at hazardous waste sites would help to

identify populations at risk in the vicinity of these sites from thallium

exposure. 

Exposure Registries. No exposure registries for thallium were located.

This compound is not currently one of the compounds for which a subregistry

has been established in the National Exposure Registry. The compound will be

considered in the future when chemical selection is made for subregistries to

be established. The information that is amassed in the National Exposure

Registry facilitates the epidemiological research needed to assess adverse

health outcomes that may be related to the exposure to this compound. 

5.7.2 On-going Studies 

Remedial investigations and feasibility studies conducted at the 18 NPL

sites known to be contaminated with thallium will add to the available 

database on exposure levels in environmental media, exposure levels in humans,

and exposure registries. 

No other information was located on any on-going studies on the fate,

transport, or potential for human exposure for thallium. 
61 

6. ANALYTICAL METHODS 

The purpose of this chapter is to describe the analytical methods that

are available for detecting and/or measuring and monitoring thallium in

environmental media and in biological samples. The intent is not to provide

an exhaustive list of analytical methods that could be used to detect and

quantify thallium. Rather, the intention is to identify well-established

methods that are used as the standard methods of analysis. Many of the

analytical methods used to detect thallium in environmental samples are the

methods approved by federal agencies such as EPA and the National Institute

for Occupational Safety and Health (NIOSH). Other methods presented in this

chapter are those that are approved by groups such as the Association of

Official Analytical Chemists (AOAC) and the American Public Health Association

(APHA). Additionally, analytical methods are included that refine previously

used methods to obtain lower detection limits, and/or to improve accuracy and

precision. 

Thallium is almost always determined as total metal, rather than

specific thallium compounds. Among the wide range of techniques that can be

used to measure thallium are spectrophotometry, mass spectrometry,

voltammetry, neutron activation analysis, and x-ray fluorimetry (Sharma et al.

1986). However, direct aspiration atomic absorption analysis is the most

widely used and straightforward method for determining thallium; furnace

atomic absorption analysis is used for very low analyte levels and inductively

coupled plasma atomic emission analysis for multianalyte analyses that include

thallium. 

6.1 BIOLOGICAL MATERIALS 

Methods for detection of thallium in biological materials are summarized

in Table 6-1. Normally, for determination in biological samples, the sample

is digested in an oxidizing acid mixture, such as 3:l:l (v/v/v)

nitric:perchloric:sulfuric acid mixture (Kneip and Crable 1988), followed by

atomic spectrometric determination. Alternatively, thallium can be extracted

from biological samples such as blood or urine by chelating agents such as

diethylthiocarbamate in methylisobutylketone and measured by atomic absorption

analysis. 

6.2 ENVIRONMENTAL SAMPLES 

Methods for the determination of thallium in environmental samples are

summarized in Table 6-2. Thallium is readily measured in multielement

analyses of air, water, and solid waste samples by inductively coupled plasma

atomic emission spectroscopy. For individual analyses of thallium, direct

aspiration atomic absorption spectroscopy is a very convenient method of

analysis; if lower detection limits are needed, furnace atomic absorption

analysis can be employed. Other sensitive means of measuring thallium include

anodic stripping voltammetry and laser-excited atomic fluorescence

spectroscopy, which have been used for biological samples (see Table 6-2). 


64 

6. ANALYTICAL METHODS 

6.3 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of

ATSDR (in consultation with the Administrator of EPA and agencies and programs

of the Public Health Service) to assess whether adequate information on the

health effects of thallium is available. Where adequate information is not

available, ATSDR, in conjunction with the NTP, is required to assure the

initiation of a program of research designed to determine the health effects

(and techniques for developing methods to determine such health effects) of

thallium. 

The following categories of possible data needs have been identified by

a joint team of scientists from ATSDR, NTP, and EPA. They are defined as

substance-specific informational needs that, if met, would reduce or eliminate

the uncertainties of human health assessment. In the future, the identified

data needs will be evaluated and prioritized, and a substance-specific

research agenda will be proposed. 

6.3.1 Data Needs 

Methods for Biomarkers of Exposure and Effect. The only means available

to indicate exposure to thallium is detection of thallium in tissue and

biological fluids. Sensitive, specific, readily used atomic spectrometric

techniques are available for the detection and quantitative measurement of

thallium after the sample matrix in which it is contained has been digested

with oxidant acids or after thallium has been extracted with 

methylisobutylketone (Baselt 1988). The determination of specific compounds

that contain thallium are relatively unimportant because of the uncomplicated

chemistry of this element and there is no evidence in the literature for the

production of metabolites. If such metabolites do in fact exist, methods for

their determination would be useful in monitoring exposure to thallium.

Studies are needed to determine whether solid tissues provide a "matrix

effect" biasing the accuracy of determinations from tissues. Thallium exists

in both stable univalent (I) and trivalent (III) states. Additional studies

would be useful in clarifying if relative concentration of thallium in various

tissues would be affected by the valence or if there is a biochemical

conversion of Tl+

 and T13+ into a single species. 

Biomarkers for effects of thallium intoxication are alopecia,

neurological effects, and albuminuria (Baselt 1988), which are indicative of

exposure to many other toxicants as well. Therefore, methods are needed for

more specific biomarkers for effects of thallium exposure. 

Methods for Determining Parent Compounds and Degradation Products in

Environmental Media. Methods for determining the parent compound, thallium,

in water, air, and waste samples with excellent selectivity and sensitivity

are well developed (EPA 1983a,b, 1985a, 1986a, b,c; NIOSH 1984b), so the

database in this area is good and undergoing constant improvement. 
65 

6. ANALYTICAL METHODS 

Sampling methodologies for very low-level elemental pollutants such as

thallium continue to pose problems such as nonrepresentative samples,

insufficient sample volumes, contamination, and labor-intensive, tedious

extraction and purification procedures (Green and LePape 1987). 

6.3.2 On-going Studies 

Examination of the literature suggests that studies are underway to

improve means for determining thallium and other heavy metals in biological

samples and environmental media. Improvements continue to be made in

detection limits and ease and speed of analysis. 




70 

7. REGULATIONS AND ADVISORIES 

Because of its potential to cause adverse health effects in exposed

people, a number of regulations and guidelines have been established for

thallium by various national and state agencies. These values are summarized

in Table 7-l. 
______________________ 

71 

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9. GLOSSARY 

Acute Exposure - Exposure to a chemical for a duration of 14 days or less, as

specified in the Toxicological Profiles. 

Adsorption Coefficient (KOC) - The ratio of the amount of a chemical adsorbed per

unit weight of organic carbon in the soil or sediment to the concentration of the

chemical in solution at equilibrium. 

Adsorption Ratio (Kd) - The amount of a chemical adsorbed by a sediment or soil

(i.e., the solid phase) divided by the amount of chemical in the solution phase,

which is in equilibrium with the solid phase, at a fixed solid/solution ratio. It

is generally expressed in micrograms of chemical sorbed per gram of soil or

sediment. 

Bioconcentration Factor (BCF) - The quotient of the concentration of a chemical in

aquatic organisms at a specific time or during a discrete time period of exposure

divided by the concentration in the surrounding water at the same time or during

the same period. 

Cancer Effect Level (CEL) - The lowest dose of chemical in a study, or group of

studies, that produces significant increases in the incidence of cancer (or

tumors) between the exposed population and its appropriate control. 

Carcinogen - A chemical capable of inducing cancer. 

Ceiling Value - A concentration of a substance that should not be exceeded, even

instantaneously. 

Chronic Exposure - Exposure to a chemical for 365 days or more, as specified in

the Toxicological Profiles. 

Developmental Toxicity - The occurrence of adverse effects on the developing

organism that may result from exposure to a chemical prior to conception (either

parent), during prenatal development, or postnatally to the time of sexual

maturation. Adverse developmental effects may be detected at any point in the life

span of the organism. 

Embryotoxicity and Fetotoxicity - Any toxic effect on the conceptus as a result of

prenatal exposure to a chemical; the distinguishing feature between the two terms

is the stage of development during which the insult occurred. The terms, as used

here, include malformations and variations, altered growth, and in utero death. 

EPA Health Advisory - An estimate of acceptable drinking water levels for a

chemical substance based on health effects information. A health advisory is not a

legally enforceable federal standard, but serves as technical guidance to assist

federal, state, and local officials. 
88 

9. GLOSSARY 

Immediately Dangerous to Life or Health (IDLH) - The maximum environmental 

concentration of a contaminant from which one could escape within 30 min without

any escape-impairing symptoms or irreversible health effects. 

Intermediate Exposure - Exposure to a chemical for a duration of 15-364 days, as

specified in the Toxicological Profiles. 

Immunologic Toxicity - The occurrence of adverse effects on the immune system that

may result from exposure to environmental agents such as chemicals. 

In Vitro - Isolated from the living organism and artificially maintained, as in a

test tube. 

In Vivo - Occurring within the living organism. 

Lethal Concentration (LO) (LCLO) - The lowest concentration of a chemical in air 

which has been reported to have caused death in humans or animals. 

Lethal Concentration (50) (LC50) - A calculated concentration of a chemical in air 

to which exposure for a specific length of time is expected to cause death in 50%

of a defined experimental animal population. 

Lethal Dose (LO) (LDLO) - The lowest dose of a chemical introduced by a route other

than inhalation that is expected to have caused death in humans or animals. 

Lethal Dose (50) (LD50) - The dose of a chemical which has been calculated to cause 

death in 50% of a defined experimental animal population. 

Lethal Time (50) (LT50) - A calculated period of time within which a specific

concentration of a chemical is expected to cause death in 50% of a defined

experimental animal population. 

Lowest-Observed-Adverse-Effect Level (LOAEL) - The lowest dose of chemical in a 

study, or group of studies, that produces statistically or biologically

significant increases in frequency or severity of adverse effects between the

exposed population and its appropriate control. 

Malformations - Permanent structural changes that may adversely affect

survival, development, or function. 

Minimal Risk Level - An estimate of daily human exposure to a dose of a chemical

that is likely to be without an appreciable risk of adverse noncancerous effects

over a specified duration of exposure. 

Mutagen - A substance that causes mutations. A mutation is a change in the genetic

material in a body cell. Mutations can lead to birth defects, miscarriages, or

cancer. 
89 

9. GLOSSARY 

Neurotoxicity - The occurrence of adverse effects on the nervous system following

exposure to chemical. 

No-Observed-Adverse-Effect Level (NOAEL) - The dose of chemical at which there 

were no statistically or biologically significant increases in frequency or

severity of adverse effects seen between the exposed population and its

appropriate control. Effects may be produced at this dose, but they are not

considered to be adverse. 

Octanol-Water Partition Coefficient (KOW) - The equilibrium ratio of the

concentrations of a chemical in n-octanol and water, in dilute solution. 

Permissible Exposure Limit (PEL) - An allowable exposure level in workplace air

averaged over an 8-hour shift. 

q1* - The upper-bound estimate of the low-dose slope of the dose-response curve as

determined by the multistage procedure. The q1* can be used to calculate an 

estimate of carcinogenic potency, the incremental excess cancer risk per unit of

exposure (usually μg/L for water, mg/kg/day for food, and μg/m3

 for air). 

Reference Dose (RfD) - An estimate (with uncertainty spanning perhaps an order of

magnitude) of the daily exposure of the human population to a potential hazard

that is likely to be without risk of deleterious effects during a lifetime. The

RfD is operationally derived from the NOAEL (from animal

and human studies) by a consistent application of uncertainty factors that reflect

various types of data used to estimate RfDs and an additional modifying factor,

which is based on a professional judgment of the entire database on the chemical.

The RfDs are not applicable to nonthreshold effects such as

cancer. 

Reportable Quantity (RQ) - The quantity of a hazardous substance that is

considered reportable under CERCLA. Reportable quantities are (1) 1 pound or

greater or (2) for selected substances, an amount established by regulation either

under CERCLA or under Sect. 311 of the Clean Water Act. 

Quantities are measured over a 24-hour period. 

Reproductive Toxicity - The occurrence of adverse effects on the reproductive

system that may result from exposure to a chemical. The toxicity may be directed

to the reproductive organs and/or the related endocrine system. The manifestation

of such toxicity may be noted as alterations in sexual

behavior, fertility, pregnancy outcomes, or modifications in other functions that

are dependent on the integrity of this system. 

Short-Term Exposure Limit (STEL) - The maximum concentration to which workers can 

be exposed for up to 15 min continually. No more than four excursions are allowed

per day, and there must be at least 60 min between exposure periods. The daily

TLV-TWA may not be exceeded. 
90 

9. GLOSSARY 

Target Organ Toxicity - This term covers a broad range of adverse effects on

target organs or physiological systems (e.g., renal, cardiovascular) extending

from those arising through a single limited exposure to those assumed over a

lifetime of exposure to a chemical. 

Teratogen - A chemical that causes structural defects that affect the development

of an organism. 

Threshold Limit Value (TLV) - A concentration of a substance to which most workers 

can be exposed without adverse effect. The TLV may be expressed as a TWA, as a

STEL, or as a CL. 

Time-Weighted Average (TWA) - An allowable exposure concentration averaged over a

normal 8-hour workday or 40-hour workweek. 

Toxic Dose (TD50) - A calculated dose of a chemical, introduced by a route other

than inhalation, which is expected to cause a specific toxic effect in 50% of a

defined experimental animal population. 

Uncertainty Factor (UF) - A factor used in operationally deriving the RfD from

experimental data. UFs are intended to account for (1) the variation in

sensitivity among the members of the human population, (2) the uncertainty in

extrapolating animal data to the case of human, (3) the uncertainty in

extrapolating from data obtained in a study that is of less than lifetime

exposure, and (4) the uncertainty in using LOAEL data rather than NOAEL data.

Usually each of these factors is set equal to 10. 
A-1 

APPENDIX A 

USER’S GUIDE 

Chapter 1 

Public Health Statement 

This chapter of the profile is a health effects summary written in nontechnical

language. Its intended audience is the general public especially people ,living in

the vicinity of a hazardous waste site or substance release. If the Public Health

Statement were removed from the rest of the document, it would still communicate

to the lay public essential information about the substance. 

The major headings in the Public Health Statement are useful to find specific

topics of concern. The topics are written in a question and answer format. The

answer to each question includes a sentence that will direct the reader to

chapters in the profile that will provide more information on the given topic. 

Chapter 2 

Tables and Figures for Levels of Significant Exposure (LSE) 

Tables (2-1, 2-2, and 2-3) and figures (2-1 and 2-2) are used to summarize health

effects by duration of exposure and end point and to illustrate graphically levels

of exposure associated with those effects. All entries in these tables and figures

represent studies that provide reliable, quantitative estimates of No-ObservedAdverse-Effect Levels (NOAELs), Lowest-Observed-Adverse-Effect Levels (LOAELs) for

Less Serious and Serious health effects, or Cancer Effect Levels (CELs). In

addition, these tables and figures illustrate differences in response by species,

Minima1 Risk Levels (MRLs) to humans for noncancer end points, and EPA’s estimated

range associated with an upper-bound individual lifetime cancer risk of 1 in

10,000 to 1 in 10,000,000. The LSE tables and figures can be used for a quick

review of the health effects and to locate data for a specific exposure scenario.

The LSE tables and figures should always be used in conjunction with the text. 

The legends presented- below demonstrate the application of these tables and

figures. A representative example of LSE Table 2-l and Figure 2-1 are shown. The

numbers in the left columrn of the legends correspond to the numbers in the

example table and figure. 

LEGEND 

See LSE Table 2-1 

1) Route of Exposure One of the first considerations when reviewing the toxicity

of a substance using these tables and figures should be the relevant and

appropriate mute of exposure. When sufficient data exist, 
A-2 

APPENDIX A 

three LSE tables and two LSE figures are presented in the document. The

three LSE tables present data on the three principal routes of exposure, i.e.,

inhalation, oral, and dermal (LSE Table 2-1, 2-2, and 2-3, respectively). LSE

figures are limited to the inhalation (LSE Figure 2-1) and oral (LSE Figure 2­

2) routes. 

2) Exposure Duration Three exposure periods: acute (14 days or less); intermediate

(15 to 364 days); and chronic (365 days or more) are presented within each

route of exposure. In this example, an inhalation study of intermediate

duration exposure is reported. 

3) Health Effect The major categories of health effects included in LSE tables and

figures are death, systemic, immunological, neurological, developmental,

reproductive, and cancer. NOAELs and LOAELs can be reported in the tables and

figures for all effects but cancer. Systemic effects are further defined in the

“System” column of the LSE table. 

4) Key to Figure Each key number in the LSE table links study information to one

or more data points using the same key number in the corresponding LSE figure.

In this example, the study represented by key number 18 has been used to define

a NOAEL and a Less Serious LOAEL (also see the two “18r” data points in Figure

2-l). 

5) Species The test species, whether animal or human, are identified in this

column. 

6) Exposure Frequency/Duration The duration of the study and the weekly and daily

exposure regimen are provided in this column. This permits comparison of NOAELs

and LOAELs from different studies. In this case (key number 18), rats were

exposed to [substance XI via inhalation for 13 weeks, 5 days per week, for 6

hours per day. 

7) System This column further defines the systemic effects. These systems include:

respiratory9 cardiovascular, gastrointestinal, hematological, musculoskeletal,

hepatic, renal, and dermal/ocular. “Other” refers to any systemic effect (e.g.,

a decrease in body weight) not covered in these systems. In the example of key

nmber 18, one systemic effect (respiratory)was investigated in this study. 

8) NOAEL A No-Observed-Adverse-Effect Level (NOAEL) is the highest exposure level

at which no harmful effects were seen in the organ system studied. Key number

18 reports a NOAEL of 3 ppm for the respiratory system which was used to derive

an intermediate exposure, inhalation MRL of 0.005 ppm (see footnote “b”). 

9) LOAEL A Lowest-Observed-Adverse-Effect Level (LOAEL) is the lowest exposure

level used in the study that caused a harmful health effect. LOAELs have been

classified into “Less Serious” and “Serious” effects, These distinctions help

readers identify the levels of exposure at which adverse health effects first

appear and the gradation of effects with increasing dose. A brief description

of the specific end point used to 
A-3 

APPENDIX A 

quantify the adverse effect accompanies the LOAEL. The “Less Serious”

respiratory effect reported in key number 18 (hyperplasia) occurred at a LOAEL

of 10 ppm. 

10) Reference The complete reference citation is given in Chapter 8 of the

profile. 

11) CEL A Cancer Effect Level (CEL) is the lowest exposure level associated with

the onset of carcinogenesis in experimental or epidemiological studies. CELs

are always considered serious effects. The LSE tables and figures do not

contain NOAELs for cancer9 but the text may report doses which did not cause a

measurable increase in cancer. 

12) Footnotes Explanations of abbreviations or reference notes for data in the

LSE tables ate found in the footnotes. Footnote “b” indicates the NOAEL of 3 

ppm in key number 18 was used to derive an MRL of 0.005 ppm. 

LEGEND 

See LSE Figure 2-1 

LSE figures graphically illustrate the data presented in the corresponding LSE

tables. Figures help the reader quickly compare health effects according to

exposure levels for particular exposure duration. 

13) Exposure Duration The same exposure periods appear as in the LSE table. In

this example, health effects observed within the intermediate and chronic

exposure periods are illustrated. 

14) Health Effect These are the categories of health effects for which reliable

quantitative data exist. The same health effects appear in the LSE table. 

15) Levels of Exposure Exposure levels for each health effect in the LSE tables

are graphically displayed in the LSE figures. Exposure levels are reported on

the log scale “y” axis. Inhalation exposure is reported in mg/m3

 or ppm and oral

exposure is reported in mg/kg/day. 

16) NOAEL In this example, 1% NOAEL is the critical end point for which an

intermediate inhalation exposure MRL is based. As you can see from the LSE

figure key, the open-circle symbol indicates a NOAEL for the test species

(rat). The key numbr 18 corresponds to the entry in the LSE table. The dashed

descending arrow indicates the extrapolation from the exposure level of 3 ppm

(see entry 18 in the Table) to the MRI, of 0.005 ppm (see footnote “b” in the

LSE table). 

17) CEL Key number 38r is one of three studies for which Cancer Effect Levels

(CELs) were derived. The diamond symbol refers to a CEL for the test species

(rat). The number 38 corresponds to the entry in the LSE table. 
A-4 

APPENDIX 

18) Estimated Upper-Bound Human Cancer Risk Levels This is the range associated

with the upper-bound for lifetime cancer risk of 1 in 10,000 to 1 in

10,000,000. These risk levels are derived from EPA’s Human Health Assessment

Group’s upper-bound estimates of the slope of the cancer dose response curve at

low dose levels (q1*). 

19) Key to LSE Figure The Key explains the abbreviations and symbols used in the

figure. 


A-7 

APPENDIX A 

Chapter 2 (Section 2.4) 

Relevance to Public Health 

The Relevance to Public Health section provides a health effects summary based

on evaluations of existing toxicological, epidemiological and toxicokinetic

information. This summary is designed to present interpretive,

weight-of-evidence discussions for human health end points by addressing the

following questions. 

1. What effects are known to occur in humans? 

2. What effects observed in animals are likely to be of concern to

humans? 

3. What exposure conditions are likely to be of concern to humans,

especially around

hazardous waste sites? 

The section discusses health effects by end point. Human data are presented

first, then animal data. Both are organized by route of exposure (inhalation,

oral, and dermal) and by duration (acute, intermediate, and chronic). In vitro 

data and data from parenteral routes (intramuscular, intravenous, subcutaneous,

etc.) are also considered in this section. If data are located in the

scientific literature, a table of genotoxicity information is included. 

The carcinogenic potential of the profiled substance is qualitatively evaluated,

when appropriate, using existing toxicokinetic, genotoxic, and carcinogenic data.

ATSDR does not currently assess cancer potiency or perform cancer risk

assessments. MRLs for noncancer end points if derived, and the end points from

which they were derived are indicated and discussed in the appropriate

section(s). 

Limitations to existing scientific literature that prevent a satisfactory

evaluation of the relevance to public health are identified in the Identification

of Data Needs section. 

Interpretation of Minimal Risk Levels 

Where sufficient toxicologic information was available, MRLs were derived. MRLs

are specific for route (inhalation or oral) and duration (acute, intermediate,

or chronic) of exposure. Ideally, MRLs can be derived from all six exposure

scenarios (e.g., Inhalation - acute, -intermediate, -chronic; Oral - acute -

intermediate, - chronic). These MRLs are not meant to support regulatory action,

but to aquaint health professionals with exposure levels at which adverse health

effects are not expected to occur in humans. They should help physicians and

public health officials determine the safety of a community living near a

substance emission, given the concentration of a contaminant in air or the

estimated daily dose received via food or water. MRLs are based largely on

toxicological studies in animals and on reports of human occupational exposure. 
A-8 

APPENDIX A 

MRL users should be familiar with the toxicological information on which the

number is based. Section 2.4, "Relevance to Public Health," contains basic

informationknown about the substance. Other sections such as 2.6, “Interactions

with Other Chemicals” and 2.7, "Populations that are Unusually Susceptible"

provide important supplemental information. 

MRL users should also understand the MRL derivation methodology. MRLs are

derived using a modified version of the risk assessment methodology used by the

Environmental Protection Agency (EPA) (Barnes and Dourson, 1988; EPA 1989a) to

derive reference doses (RfDs) for lifetime exposure. 

To derive an MRL, ATSDR generally selects the end point which, in its best

judgement, represents the most sensitive human health effect for a given exposure

route and duration. ATSDR cannot make this judgement or derive an MRL unless

information (quantitative or qualitative) is available for all potential effects

(e.g., systemic, neurological, and developmental). In order to compare NOAELs

and LOAELs for specific end points, all inhalation exposure levels are adjusted

for 24hr exposures and all intermittent exposures for inhalation and oral routes

of intermediate and chronic duration are adjusted for continous exposure (i.e.,

7 days/week). If the information and reliable quantitative data on the chosen

end point are available, ATSDR derives an MRL using the most sensitive species

(when information from multiple species is available) with the highest NOAEL that

does not exceed any adverse effect levels. The NOAEL is the most suitable end

point for deriving an MRL. When a NOAEL is not available, a Less Serious LOAEL

can be used to derive an MRL, and an uncertainty factor (UF) of 10 is employed.

MRLs are not derived from Serious LOAELs. Additional uncertainty factors of 10

each are used for human variability to protect sensitive subpopulations (people

who are most susceptible to the health effects caused by the substance) and for

interspecies variability (extrapolation from animals to humans). In deriving an

MEL, these individual uncertainty factors are multiplied together. The product

is then divided into the adjusted inhalation concentration or oral dosage

selected from the study. Uncertainty factors used in developing a

substance-specific MRL are provided in the footnotes of the LSE Tables. 



C-l 

APPENDIX C 

PEER REVIEW 

A peer review panel was assembled for thallium. The panel consisted of

the following members: Dr. Curtis Klaassen, Associate Director, Environmental

Health Science Division, Dept. of Pharmacology and Toxicology, University of

Kansas; Dr. David Brown, Director, Toxicology Programs, Northeastern

University; Dr. Kenneth Reuhl, Associate Professor, Department of Pharmacology

and Toxicology, Rutgers University College of Pharmacology. These experts

collectively have knowledge of thallium's physical and chemical properties,

toxicokinetics, key health end points, mechanisms of action, human and animal

exposure, and quantification of risk to humans. All reviewers were selected

in conformity with the conditions for peer review specified in Section

104(i)(13) of the Comprehensive Environmental Response, Compensation, and

Liability Act, as amended. 

Scientists from the Agency for Toxic Substances and Disease Registry

(ATSDR) have reviewed the peer reviewers' comments and determined which

comments will be included in the profile. A listing of the peer reviewers'

comments not incorporated in the profile, with a brief explanation of the

rationale for their exclusion, exists as part of the administrative record for

this compound. A list of databases reviewed and a list of unpublished

documents cited are also included in the administrative record. 

The citation of the peer review panel should not be understood to imply

its approval of the profile's final content. The responsibility for the

content of this profile lies with the ATSDR. 

U.S. Government Printing Office: 1992 - 636 281