A STUDY OF THALLIUM POISONING

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1VM^3 VJeies, Louis. A study of thallium poisoning... i'ew York, 1941. Gp.1.,90 typewritten leaves, tables, aia^rs. 29cm. Thesis (Ph.D.) - Yew York university. Graduate school, 1942. L i b 1i o p r a p h y : p .G 7 -90. .'.70277

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THIS DISSERTATION HAS BEEN M ICROFILM ED EXACTLY AS RECEIVED.

I-IBn.lRY OP N j'.VP j\,'kK LI.’TVERSITT ■ S I V S H G l r r HE I G H T S

A Study of Thallium Poisoning by

Louis Weiss, B.S., M.S*

Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at New York University November 1941 r i

f «

Dedication To my mother and father, whose great sacrifices made my education possible,

and

To my wife, Irma Tuck Weiss, whose encouragement and Inspiration aided in the completion of this work*

n

Acknowledgement I wlah to take this opportunity to express my sincerest appreciation to Professor Alexander 0* Gettler, who suggested the problem and whose counsel and guidance made possible the successful completion of this work*

Table of Contents Page I.

I n t r o d u c t i o n --------

1

a.

H i s t o r i c a l -------------

1

b.

Occurrence of Thallium Poisoning

------------

2

c • purpose of the I n v e s t i g a t i o n ---------------II.

The

Detection of Thallium

A. Precipitation

B.

--

6

Tests (Inorganic) - —

1. Thallous

bromide

2. Thallous

iodide

3. Thallous

chrornate

4. Thallous

sulphide ------

5. Thallic hydroxide

5

-------

6

----

6

— --

6

----------------------

7 7

----------------------

7

6 * Thallous

cobalti-nitrite --------

8

7. Thallous

chloroplatinate

8

--------------

Oxidation-Reduction Reactions (Inorganic)— 1. Potassium Permanganate —

---

8

2. Potassium Iodide-Starch C • Organic Reagents

--------

------

1. Oxidation-Reduction Reactions

8

9

— ---- -

g

----------

9

a. Dimethylparaphenylene diamine hydrochloride — -— b. Benzidene

---

9 --------

2. Replacement of Acidic Hydrogen — -------a. Thionalid

---------------------------

lo 11 11

b . Dithlzone ---------------------- — --- 12

D*

Special Tests

----------------------

1* Flame Test - - - - - - - - — 2. Spectrographic Test

12

-------

12 13

III. The Quantitative Determination of Thallium ----- 14 A*

Gravimetric Methods — 1. Thallous Bromide

—

---

14

---------------------

14

Table I. Determination of Thallium by Weighing as TIBr 2* Thallous Iodide Table II*

-------------------------------

18 19

Precipitation of Thallium as

Til using an Improved procedure to decrease the time between precipitation ---------------------- 21

and filtration

Table III. Thallous Iodide is precipitated from a dilute solution ofsulphuric acid-- 22 3* Thallic Oxide —

---------------------------- 23

4. Thallous Chroraate ------------------------ 24 B.

Volumetric Methods — ------------------------

25

1. Potassium Permanganate

25

2* Cerium Sulphate 3* Iodimetry —

---

---

------

26 26

Table IV. Standardization of Na 8 S a0 3 against TlaS O a in water s o l u t i o n -------Table V*

30

Iodimetric Determination of

Thallium in sulphuric acid solutions -— -- 31

Table VI*

Iodlmetric Determination of

Thallium in the presence of large amounts of sodium sulphate 4* Dithizone

---

33

----------

34

IV* Isolation, Detection and Identification of Thallium in Human Tissues

--------------------

--- -— -- 36

A* Destruction of Organic Matter 1* Ashing

36

---------

36

2. KC10 s - H C l -------------------------------- 37 3* HNOa - H bS0 4 ------------------------------- 38 4* HNOa - HflS0 4 - H C 1 0 * ---------------------- 40 Table VII.

Loss of Thallium in HNOa -

H bS0 4 - HC10 4 digestion ofhuman tissues B* Isolation of the Thallium

— - 44

------— - 45

C* Confirmatory T e s t s ------------------------ 47 1* Thallous bromide -----------

47

2. Thallous iodide ---------------— 3* Flame Test

-------------

4. Thallous chrornate 5* Thallic hydroxide —

47

—

48

------------------------------

6 * Thallous cobaltI-nitrite

V*

--

48 48

---------------- 48

Quantitative Determination of Thallium in Human Tissue

----------------

—

A* Review of the Methods — — -- ---

49

49

1*

The Shaw M e t h o d ----------------

49

2*

The Fridli Method

51

---

3*

The Schee Method

4*

The PIchler Method -------------------a* B r o m i d e

---

53

-------------------------

b* Iodide --— - - - - - - - — -------------— -

54 54 58

B* A Method for the Quantitative Determination of Thallium in Various Organs -------------Table VIII.

60

Quantitative Determination of

Thallium in Human Tissues b y the devised method

---

63

a. Normal Tissues ----—

---

66

b* Interfering Elements

---

67

VI. Determining the Thallium Distribution in the Various Organs in Fatal Thallium Poisonings Table IX*

--

69

Thallium content of tissues in

Thallium Poisonings

----

— ------

71

VII* The Minimum Lethal Absorbed Dose of Thallium— -

73

VIII. The Thallium Content of Urines of non-fatal Thallium Poisonings IX. X. XI.

(Human)----------------

Symptoms of Thallium P o i s o n i n g ----------------Pathological Findings in Huraas Cases Mechanism of Thallium Poisoning

XII. Treatment of Thallium Poisoning -—

--------

75 76 79 81

----

83

Summary - - - - - - - - — ---

86

Bibliography — -----

87

I. Introduction

a. Historical Thallium was first discovered by Sir William Crookes

i

In 1861, when he observed a bright green line in the spectrum of a specimen of flue dust obtained from a sulphuric acid plant*

The only minerals rich in thallium are crookeslte

(TlAgCu)aSe and lorandite (TlAsSa ), but thallium is present in small quantities In pyrites of copper and Iron, and in many 3 other minerals • In its brief history, thallium has become a widely used element in spite of its rather rare occurrence and high price.

Thallous chloride Is used to prolong the life of 4

filaments in Tungsten lamps •

Metallic thallium is added to

glass to give a high refractive index needed for optical work 3 and In the manufacture of Imitation gems * A thallium-silver e alloy has been found to be 'stainless* and an amalgam of thallium can be used in thermometers for temperatures as low 4

as -60°C •

3

There are many more uses

of minor consideration,

but the greatest quantity of the salts of this element is used In exterminating Insects and rodents.

Thallous sulphate was

first Introduced as a rodent poison in Europe in the form of 7

•Zelio paste*

in 1920 and Its use in this country was promoted e by James C. Munch, who stressed the dangers of handling by the layman because of the highly toxic nature of the salt. Thallium salts have been used in medicine in the past but

2

have been discarded because of their great toxicity* 9 Combemale reported the use of thallous acetate Internally in the treatment of night sweats in tubercular patients* This same salt has been used by many physicians to produce alopecia in children in order to treat ringworm of the scalp*

An

internal dose of eight milligrams per kilo body weight will produce complete alopecia in twenty-one days with a complete regrowth of hair in approximately three months*

This period 10

is sufficient for the treatment of the ringworm*

Cicero

treated several hundred Mexican children in this way when X-ray equipment was not available during the first World War. When this medical use of thallium acetate became widely known, several ointments containing this salt were sold in Europe ii and the United States for the removal of superfluous hair • b*

Occurrence of Thallium Poisonings* The toxicity of thallium salts was first reported in the 19

literature by Lamy

who was one of the first investigators 69

studying thallium chemistry.

Paulet

soon showed that

thallium was more toxic than lead by feeding sulphates of these metals to dogs* Although thallium salts have relatively wide industrial usage considering the high price, few industrial poisonings have

—3 — 13

occurred in chemical plants* and others 1 6 *16

Buschke and Langer

14

, Meyer

,

have compiled statistics on the health of

employees working in chemical plants manufacturing or purifying thallium salts*

In every case reported by these investigators

symptoms of poisoning were relieved and finally disappeared after exposure was terminated*

No report of fatal thallium

poisoning has ever been reported as being due to industrial contact although there is always the possibility that thallotoxlcosls was not recognized as such* By far the greatest number of thallium poisonings has been caused by the internal use of thallium acetate as a 7

depilatory for the treatment of ringworm in children*

Munch

showed that poisonings occurred in approximately five percent of the children treated in this manner and that only one tenth of one percent of the patients were fatally poisoned*

Ingram 17

insists that thallium acetate if used properly as an internally administered depilatory is not a dangerous chemical* xe In 1912, Saboraud prepared a depilatory to be applied externally by incorporating thallous acetate in a base*

He

specified that this cream was to be used only under constant supervision of a physician so as to limit the time, quantity and frequency of these applications*

Although dermatologists 1 9 '*0

have stressed the dangers of these treatments from time to time, xx Kora M* Lubin in 1931 manufactured and sold a thallium acetate cream depilatory under the trade name 'Koremlu'*

This prepara­

tion contained approximately seven percent of thallous acetate

*•4

and the consumer was instructed to apply freely over large surfaces of the body*

Many cases of poisoning were reported

>1 ai

*

from the use of this cream and its sale was discontinued shortly thereafter*

Thallium poisonings have also resulted

from the use of thallium depilatory creams

as

other than

T

iKoremlu**

Munch

tells us that there were fifty-nine poison­

ings resulting from the external application of these creams and that no fatalities occurred*

Here again we must think of

the possibility that deaths may not have been recognized as having been caused by the use of this medication and therefore were not reported* As early as 1920 thallous sulphate had been used commer­ cially in exterminating rodents and pests*

*Zelio»paste,

containing 2 % thallous sulphate was widely used in Europe for this purpose*

Many cases of human poisoning from this source

have been reported 8 * »8 6 »88 in the literature*

Recognizing

the fact that thallous sulphate preparations are highly toxic and will exterminate highly resistant species of rats and ants. Munch 87 does not recommend its use by the public since there is little or no taste, or smell*

In the United States, prepara­

tions are used in the form of pastes or mixtures with wheat, and some cases 8 8 **9 of thallotoxicosis have also been cited in the literature as occurring in this country*

In 1932,

Munch, Ginsburg and Nixon 80 reported seven deaths and thirteen more non-fatal poisonings occurring when a Mexican in California illegally procurred a sack of thallium coated barley and used

—5**

this to make tortillas* Since thallous acetate la not used as a depilatory any more, we may expect that practically all future cases of thallium poisoning will result from the use of thallous sulphate*

The latter, as it has been previously stated, is

an excellent rodenticide and Insecticide, and its use is common in the exterminating field*

In the laboratories of the Chief

Medical Examiner of New York City, three fatal and two nonfatal cases have been handled since 1935 and these will be discussed subsequently in this paper* c*

Purpose of the Investigation* It is the purpose of this research to: 1*

Review the literature which is very scanty and contradictory on the toxicology of Thallium*

2* Devise a simple, rapid and conclusive procedure for the isolation and identification of small amounts of thallium in biological specimens* 3* Develop a simple, rapid and accurate method for the quantitative determination of thallium in tissue* 4* Determine the distribution of thallium in the various organs in fatal cases of thallium poisoning* 5. Estimate the minimum lethal dose absorbed in thallium poisoning* 6 * Study the elimination of thallium in the urine from

cases where thallium poisoning has not resulted in death*

II*

The Detection of Thallium

When metallic thallium is dissolved in dilute sulphuric si acid, the moxnovalent thallous ion is formed • The thallous ion is the more stable and will not even be oxidised by ea

boiling with nitric acid

•

It may be converted to the

trivalent thallic form however, by addition of chlorine, bromine or aqua regia*

The analytical reactions of thallium

are governed by the particular ionic state in which the thallium exists and in some reactions upon the transfer of electrons when a change from one ionic state to the other is effected* A*

Precipitation Tests (Inorganic Reagents) 1*

Thallous bromide is precipitated by the addition

of HBr to a solution of a thallous salt*

Since the presence

of any free bromine would dissolve the salt by oxidising It to the soluble thallic bromide, sulphur dioxide Is bubbled into the reaction tube*

The thallous bromide is a coarse

precipitate ranging In color from a pale yellow to almost white*

The sensitivity of this reaction la quite low since

the limit concentration is approximately one part in 30,000* Cations of Group I interfere* 2*

Thallous iodide is precipitated by the addition of

dilute KI to a solution of a thallous ion In neutral or dilute mineral acid solution*

Oxidizing agents must be

avoided since they liberate iodine which converts thallous

-7 -

iodide to the soluble thallic iodide*

This may be avoided

by bubbling sulphur dioxide through the reaction mixture* If present, iodides of lead, silver, mercury and copper will also precipitate, but the copper may be dissolved by digesting the precipitate with dilute ammonia and the mercury dissolved by the addition of excess KI8 8 *

This is the most sensitive

qualitative precipitation reaction for the thallous ion, the limit concentration being one part in 80,0008**

The color

of thallous iodide may vary from a canary yellow to almost orange* 3*

Thallous chromate. a yellow insoluble salt, is

precipitated from a thallous solution when alkali chromates are added*

The chromate does not dissolve In cold dilute

nitric or sulphuric acids, but the test is most sensitive in ammonlacal solution*

Reducing agents interfere and an

excess of ammonium salts is inadvisable8 8 * 4*

Thallous sulphide is completely precipitated from

ammonlacal solutions upon the addition of HaS*

No precipita­

tion occurs when mineral acids are present and incomplete precipitation is effected in neutral solution*

The formation

of this black TlaS is a very sensitive reaction and may be used to separate thallium from other ions*

It will be discussed

later in this paper* 5«

Thallic hydroxide*

Bromine water is first added to

the solution in order to oxidize all the thallous ion present

-8 -

to the thallic state*

After three or four minutes, the addition

of sodium hydroxide will precipitate the highly insoluble brown ae hydroxide of thallium (thallic)* This is a highly sensitive reaction and is used to determine thallium gravimetrlcally; iron interferes* 6.

Thallous cobaltl-nltrlte*

The addition of sodium

cobalti-nitrite will precipitate red thallous cobalti-nitrite from neutral or slightly acid solution*

Potassium or ammonium,

if present, will give yellow precipitates*

It is important to

test the reagent against a known sample before use In an analysis*

The preparation of the reagent will be discussed

later* 7* Thallous chloroplatinate* yellow Tla (PtCla )* this reaction*

Ha (PtCla ) will precipitate

Potassium and ammonium also interfere in

It is a fairly sensitive test and the limit

concentration is approximately one part in 60,000* B.

Oxidation-Reduction Reactions (Inorganic Reagents) 1* KMnQ 4

(decolonization of)*

Thallous ion will be

oxidized to the thallic state in dilute sulphuric acid solution upon the addition of a dilute solution of potassium permanganate The test is carried out better when the solution is first heated to 60° or 70° before the addition of the permanganate*

This

accelerates the reaction and decolonization of the potassium permanganate when thallous ion is present*

Reducing agents

Interfere with this test which is extremely sensitive*

se

•

2*

KI-Starch* To a dilute mineral acid solution of a

thallous salt add bromine water dropwlse until a yellow color persists*

In three or four minutes the excess bromine is

removed by the addition of one cc* of a in water*

b%

solution of phenol

All of the thallium should now be in the thallic

37

state

and is capable of acting as a powerful oxidizing

agent*

Add one or two drops of normal KI and an equal amount

of a 1/6 starch suspension*

The presence of the thallium is

indicated by the familiar blue color of the starch-lodine complex* This reaction Is an extremely sensitive one but cannot be used in the presence of other oxidizing agents*

If ferric

ion Is present however, the test for thallium may be used without Interference from the iron by adding HaP0 4 and Na„HP0 4 to the original solution before the addition of the bromine* C*

Organic Reagents* 1* Oxidation-Reduction Reactions* a* Dimethyl-para-phenylene-dlamlne HC1

In a preliminary study of the reactions of thallium as in 1936, the author devised the following test for thallium* To approximately 20 cc. of the neutral solution of the thallous salt, bromine water is added dropwise until a yellow color persists*

After several minutes one cc* of

b% phenol

in water is added to remove the excess bromine and finally

10

one-half cc* of freshly prepared

1%

solution of dimethyl-

para-phenylene-diamine hydrochloride in water is added*

A

dark red color appears immediately if thallium is present and in a few minutes this changes to an intense blue*

When very

small amounts of thallium are present the red does not turn to blue even after thirty minutes have elapsed* The test can be carried out in NaOH, neutral or acetic acid solutions but not in the presence of appreciable amounts of mineral acid*

In neutral solution the sensitivity is very

great, the limit concentration being approximately one part in 500,000*

This sensitivity can be further Increased by

reducing the volumes accordingly and by doing the test in an alkaline solution* Oxidizing agents, including ferric and cupric ions, interfere with the test*

In an investigation made by the

author, the removal of iron was attempted by many different methods, but enough iron remained in solution to interfere with the thallium test*

It is worth noting that the test

was much more sensitive for iron than for thallium and its use had to be abandoned in toxlcologlcal work* b* Benz1dene

8«

Bromine water or aqua regia must first be added to oxidize all thallium present to the thallic state*

Sodium

hydroxide is then added and the solution boiled in order to precipitate and coagulate thallic hydroxide*

Filter, and

to the precipitate add one drop of benzidene acetate soluw tion*

The presence of thallium is indicated by the immediate

11-

appearance of an intense blue color which soon disappears if only small amounts of thallium are present. Felgl recommends the presence of traces of silicates or carbonates in the solution of NaOH used for the precipita­ tion of the thallium, its purpose being to absorb the colored compound formed.

Interfering ions are M n M ", Ce+ + , Ce++',‘ and

Co+ + . The reaction may also be done in acid or ethyl alcohol solution, in which case manganese, cerium and cobalt do not interfere.

This is a very sensitive test,

the limit concen­

tration being reported as one part in 166,000* 2* Replacement of Acidic Hydrogen (Organic Reagents) «o a. Thionalld (Beta-amino-naphthalide of thioglycollic acid)• If oxidizing agents or ferric lorn are present, these must first be destroyed or reduced with sulphur dioxide or hydroxylamlne in the presence of tartrate, cyanide and heat* The ferric ion is thus converted to the ferro-cyanide complex which does not interfere* To five cc. of the solution containing thallous ion, add sodium hydroxide until neutral*

Add one-half cc of 2n

NaOH in excess, one drop of cold saturated ammonium tartrate solution and one drop of 10$ KCN*

Heat to boiling and add

5 drops of 5$ thionalld in acetone*

If thallium is present,

a yellow crystalline precipitate is formed* This test is extremely sensitive, the limit concen­ tration being one part in 25,000,000.

Interfering ions are

12

mercury* lead and bismuth If present in larger amounts* 41

b.

Dlthlzone

(Diphenyl-thiocarbazone)

To 15 cc* of an ammonlacal solution of the thallous salt, add 1 cc. of 10$ KCN and 2 cc of dithlzone solution (1 mg. dissolved in 40 cc of chloroform).

A cherry red color

in the chloroform layer, due to a thallium-dithizone compound formed, indicates the presence of thallium. Although many investigations have been made, no method of distinguishing between thallium and lead has been found. Under the above conditions these two metallic elements behave in a similar manner and all analysts using this test for lead, disregard the possibility of the presence of thallium. Since the test is so extremely sensitive, small amounts of lead in the reagents, distilled water and glassware always produce some reaction.

This necessitates the use of a blank

at all times. D.

Special Tests 1.

Flame Test With a platinum wire, insert a speck of a thallous

halide into the outer cone of a non-luminous gas flame.

A

characteristic emerald green flame is emitted, lasting but a fraction of a second.

With a small spectroscope, it may

be observed that the thallium visible spectrum consists of a single green line at 535.0.

-1 3

4ft

2. Soectrographic Test Prepare a one-quarter Inch carbon electrode by drilling out a cavity about 1-16 inch in depth using a 3-16 inch drill. P l a n the sample in the cavity of the electrode with or without a small amount of ammonium sulphate.

Arc the sample ten

seconds using 220 volts D.C. with a current of approximately 3 amps*

Thallium emits very strong lines at 5350.5, 3575.7,

3519.2, 3229.8, 2918.3 and 2767.9.

Ill*

The Quantitative Determination of Thallium

Before attempting any analysis for thallium in human tissues, it was deemed advisable to search the literature for methods used in determination of small amounts of this element in water solution*

Furthermore, in some of these

methods, it became necessary to check these procedures and results experimentally and to devise some modifications in order to improve the accuracy and precision and to reduce the time necessary for the determination*

In this part of

the paper, methods from the literature will be summarized and any experiments in water solution carried out in this investigation will be stated and discussed* A*

Gravimetric Methods 48

1*

Thallous Bromide To every 15 cc. of the neutral or slightly acid

sample, add approximately 1 cc. of commercial HBr solution (34/£}«

A precipitate is formed immediately but begins to

redissolve due to the oxidation by the free bromine present. Sulphur dioxide is bubbled into the solution through a cap­ illary tube until the solution is saturated, and in this way any free bromine present has been changed to the bromide state*

A flocculent, white precipitate of thallous bromide

settles in a few minutes*

This may be centrifuged and washed

several times with dilute HBr solution previously saturated

15

with sulphur dioxide.

The prec5.pltate Is dried and weighed

as TlBrt4 . Of all the salts of thallium used in gravimetric work, the bromide is the most flocculent and easy to manipulate. It may be centrifuged or filtered in a few minutes as com­ pared with a waiting period of from twelve to thirty-six hours necessary for the other determinations*

This alone

prompted experimental investigation to determine the accuracy, precision and details of procedure necessary for duplication 4

of results* The use of the centrifuge

tube was immediately aban­

doned because it was too difficult to dry and too bulky for the pan of the balance.

In this and later gravimetric

work, use was made of the Pregl filter tube with an inverted syphon using a water suction pump (Fig. l).

This apparatus

is more commonly used in micro quantitative determinations «B of halogen in organic compounds . Five cc. portions of acetone and dilute HBr (saturated with S0a ) were held ready and when filtration was complete, these were used in smaller portions to wash the test tube, syphon and asbestos filter mat in the same way that the filtration was carried out.

The

washings are done alternately, the last one always being with acetone* The acetone used seemed to attack the one-hole rubber stopper connecting the filter tube with the syphon when the vapors of the acetone wash came in contact with the stopper*

Fig* 1*

Pregl Micro-Filtration Apparatus

-1 6

This was therefore replaced with a cork through which a hole was drilled large enough to accommodate the syphon tube snugly* When the precipitate was washed with the final portion of acetone, the suction hose was detached from the flask and the filter tube was removed.

After inserting a cotton filter in

the top of the filter tube, the lower end was attached to a thin rubber suction hose and the tube was placed in a regenerating block (Fig. 2) heated to 80° - 90° Centigrade

•

After

heating and passing filtered air through for ten minutes, the filter tube was wiped with a chamois cloth and allowed to cool for ten more minutes before being placed in the balance for weighing* The thallium used for this investigation was in the form of thallous sulphate (TlaS04 ) c.p. Elmer and Amend.

The white

crystalline salt was heated on a watch glass in the oven at 110°C. for five or six hours, and then desiccated in vacuo over night*

Using a very good macro balance (Gottingen)

sensitive to 0.05 milligram, 1*2349 grams of the salt were weighed out and dissolved in distilled water in a liter volumetric flask*

When this was diluted to the liter mark,

the solution then contained one milligram of thallous ion per cc. of solution.

This solution was used throughout the

entire study* A preliminary analysis was made in order to ascertain whether consistent results can be obtained in the bromide

Fig* 2.

Regenerating Block

-1 7

procedure*

Five cc. of the thallous sulphate solution

containing five milligrams of thallium were diluted to fifteen cc. and the thallium was precipitated as TlBr according to the procedure described above*

Using the macro balance, it

was found that in the two separate samples run In this same way, 6*4 milligrams of TlBr were obtained in each*

This

corresponds to 4.6 milligrams of thallium recovered* The consistency of these results was promising, but the apparent loss of 0*4 milligrams in each case made two alternatives possible*

First, there was the possibility

that the solution of thallous sulphate prepared did not contain 1*0 milligrams of thallium per cc., but rather 0*92 milligrams.

Another logical explanation was that 0*56 mgs*

of TlBr remained dissolved in the mother liquor when the bromide precipitation was carried out in 15 cc. of solution* This qusstion was solved by running a series of analyses using the same procedure but increasing the quantity of thallium added*

It was found to be more convenient in this

series to precipitate the thallous bromide from 30 cc. of solution.

The results are represented in Table I*

-1 8

Table I. Determination of Thallium by Weighing as T l B r < m g s . Tl added

m g s . TlBr recovered

m g s . Tl recovered

m g s . Tl lost

% recovered

5.0

5.8

4*2

0.8

84.0

10.0

13.0

9.4

0.5

94.0

10.0

12.7

9.1

0.9

91.0

lb.O

19.2

13.8

1.2

92.0

15.0

19.3

13.8

1.2

92.0

20.0

26.8

19.3

0.7

96.5

25.0

33.6

24.2

0.8

97.8

If the solution of thallous sulphate did not contain 1.0 mgs. of thallium per cc. as calculated and prepared, the apparent loss of thallium in this series would have multiplied as the amount of thallium added was increased* The constant loss of thallium proved that this mas due to the solubility of the thallous bromide*

This conclusion

is further corroborated by the fact that approximately 0*8 - 0*9 mgs. thallium was lost when precipitation was carried out in thirty cc. of solution and approximately 0*4 mg. was lost when precipitated from 15 cc* When the bromide precipitation is used, to the final result 0.4 mg. thallium may be added for every 15 cc. of the solution from which the bromide is precipitated.

If

this is done to the results in Table I, it is found that

-1 9

The percent recovery then becomes constant rather than Increasing as Indicated.

With the use of this factor the

procedure Is both accurate and precise, the percent recovery ranging from 96-105/6 regardless of the quantity of thallium added.

Because of these considerations and In view of the

fact that the flocculent TlBr is most easily manipulated in gravimetric work, this procedure was studied further in an attempt to use this in quantitative determinations of thallium in human tissues* 2. Thallous Iodide To approximately 15 cc. of a neutral or slightly acid solution add one cc. of water containing 0*15 gms. of KI*

It is extremely important that the KI added is not

more than one percent in excess, since further addition of 4T

KI tends to Increase the solubility of the thallous iodide

«

48

Mach and Lepper

further suggest that If there Is a possibility

that thalllc ion is present, sulphur dioxide should be added and any excess of it boiled out before the KI is added*

Let

stand for 12 - 18 hours, filter through an asbestos mat, and wash with

KI or a saturated solution of thallous iodide*

Finally wash with 80/6 acetone, dry at 120-130°C. and weigh as Til* Because the solubility of the thallous iodide is much lower than that of the bromide already studied,

it was decided

that experiments be performed in an attempt to eliminate

-2 0 -

some of the undesirable features of this gravimetric procedure. If one repeats the procedure as described, it is found that the thallous iodide formed is of very minute particle size and it is essential to wait the indicated time between the precipitation and filtration.

Furthermore, when the latter

operation is performed, a thin film of the yellow thallous iodide sticks to the glass and is extremely difficult to remove.

Many empirical experiments were performed each time

changing slightly some part of the original procedure, until the following improved procedure was adopted* The 15 cc. of the solution to be analysed were placed in an eight inch test tube mounted in a burette clamp. Through a piece of glass tubing drawn to a capillary,

sulphur

dioxide was bubbled in until the solution was almost saturated with the gas.

At this point, 5 or 6 drops of HI (used for

ethoxy determinations) are added while the sulphur dioxide continues to bubble through the solution until the latter becomes saturated with the gas.

Let stand for one hour and

filter through a Pregl filter tube as previously described. Wash alternately with dilute FI (saturated with sulphur dioxide) and alcohol being sure that the last wash is always with the alcohol.

Dry for ten minutes with filtered air while

the filter tube is being heated in the regenerating block between 80° - 90°C.

Wipe with a chamois cloth, cool for ten

minutes and weigh in a microchemical balance* A series of determinations was thus carried out using

-2 1 -

5*0 mgs* In each case but changing the time allowed between precipitation and filtration* Table II*

The results are shown in

It is apparent that the active bubbling of the

sulphur dioxide causes rapid coagulation of the thallous iodide and quantitative results are obtained in this way even after no more than one hour of waiting between the precipitation and filtration*

Furthermore, it was observed that no thin

film of thallous iodide clings to the glass as in the procedure originally described* Table II Precipitation of Tl as Til using an improved procedure to decrease the time between precipitation and filtration* Tl added mgs.

Til recov. mgs.

Tl recov. mgs.

Tl lost mgs •

recov

1

5.0

7.951

4.90

0.10

98.0

1

5.0

8.015

4.94

0.06

98.8

18

5*0

8.097

4.99

0.01

99.8

18

5.0

8.048

4.96

0.04

99.2

48

5.0

7.967

4.92

0.08

98*4

48

5.0

7 i993

4.93

0.07

98.6

72

5.0

8.005

4.94

0.06

98.8

72

5.0

8.032

4.96

0.04

99.2

96

5.0

7.999

4.93

0.07

98.6

Time hrs*

%

-2 2 -

Another series of analyses was

carried out in which

one cc. of concentrated sulphuric acid was added to the solution before the precipitatl.on of thallous iodide was attempted*

This was done in expectation that an acid digestion

would be used when experiments with human tissue would be tried later In such cases the solution from which thallium would have to be precipitated would be a dilute solution containing sulphuric acid*

At the same time, the thallium was varied

from 1*0 - 5*0 mgs*

The results of this investigation are

shown in Table III* Table III Precipitation of Tl as Til from dilute H aS04 solutions Tl added mgs*

Til Recov. mgs •

Tl recov. mgs.

Tl lost mgs.

recov

1.0 1.0 1.0

1.423 1*493 1.540

0.88 0.92 0.95

0.12 0.08 0.05

88.0 92.0 95.0

2.0 2.0 2.0

3.110 3.165 3.116

1.91 1.95 1.92

0*09 0.05 0.08

95.5 97.5 96.0

3.0 3.0 3.0

4.739 4.804 4.707

2*92 2.96 2.90

0.08 0.04 0.10

97.3 98.7 96.7

4.0 4.0 4.0

6.330 6.411 6.297

3.90 3.95 3.38

0.10 0.05 0.12

97.5 93.8 97.0

5.0 5.0 5.0

7.973 7.997 8.029

4.92 4*93 4.96

0.08 0.07 0.04

98.5 98.8 99*2

%

23—

Examination of the results shows that the precipitation of thallium as thallous iodide from water or dilute sulphuric acid is highly satisfactory, using the modified procedure devised during this study.

Further investigation of the

possible use of this method when thallium is present in human tissue was made and reported later In this paper* 3. Thallic Oxide sc

The original procedure of Browning and Palmer modified by Mach and Lepper

as follows:

has been

To 50-100 cc. of

a monovalent thallium solution ada 5$ KOH until neutral and then add 25 cc. of the KOH in excess.

Add 25 cc. of an

solution of potassium ferricyanide, the function of vjhich is to oxidize the thallium to the trivalent state.

Let stand

for 18 hours and filter the brown (Tl(0H)a through a Gooch crucible.

Dry for exactly one hour at 200°C. in an atmosphere

free of carbon dioxide. Browning

48

Cool and weigh as TlaOa *

modified the procedure once more by treating

the monovalent thallium solution with bromine water until a yellow color persisted.

In a few minutes,

in the presence

of this excess bromine, all the thallium is in the trivalent state.

Add ammonium hydroxide until the solution is strongly

ammoniacal and proceed with the Tl(0H)a formed as above* This determination cannot be carried out in the presence of phosphates, since calcium, iron and magnesium phosphates will be precipitated when the solution is made alkaline.

Goroncy and Berg60

separated

-2 4 -

the Iron and phosphates from thallium while thallium was In the monovalent state, using the basic acetate procedure# They found that some of the thallium was co-preclpitated and in order to make the separate.on complete, they had to repeat the basic acetic separation three times*

The co-precipltation

of thallous Ion with hydroxides and phosphates was confirmed by experiments in this investigation*

No further study of

this method was therefore made in this work, since it was deemed impractical to use in the presence of the large quantities of iron and phosphates present in human tissue* 4* Thallous Chromate ex

The procedure of Browning and Hutchins was modified by sa Moser and Brukl • Neutralize the solution with ammonium hydroxide and add an excess of 3 cc. for each 100 cc. of solution.

Heat to 70 - 80°C. and while stirring, add a 10#

solution of potassium chromate until the solution is respect to the chromate* 12 hours before filtering* followed by 50# alcohol*

2% with

Cool and let stand for at least Wash with

1%

potassium chromate

Dry for 1 hour between 120 - 130°C* S3

and weigh as TlBCr04 *

Hillebrand and Lundell

recommend

this as being the best gravimetric determination of thallium* The chromate procedure cannot be used in the presence of large amounts of ammonium salts, substances that will reduce chromate, phosphates, or metals (iron) that will precipitate in alkaline solution.

No further investigation

along these lines was made in this study since all these

-2 5

interferences are found in human tissues* B*

Volumetric Methods* 1.

Potassium Permanganate S3

Sir A. J. Berry

reviewed this method for the deter­

mination of thallium in dilute sulphuric acid solutions con64

eluding that it was not reliable*

Bodnar and Terenyi

used

additions of small amounts of hydrochloric acid and obtained fair results when analysing samples of 50-150 mgs. of thallium, standardizing the permanganate against measured amounts of es

thallium*

Proszt

studied the use of the method on samples

of 1-6 mgs. of thallium and found that only in a very limited range of acidity was there any reasonable degree of duplication of results* The following procedure was used during the present investigation of the method*

The solution to be titrated

(5 cc*) was diluted with 10 cc. of 20 % sulphuric acid and 1 cc. of 10 % hydrochloric acid was added*

The solution was

then heated to boiling and approximately 0*05 n KMn04 was added dropwise from a 10 cc* burette with constant shaking* The endpoint was recognized by the characteristic pink or violet color of permanganate*

When the permanganate was

first standardized against sodium oxalate, it was found that the recovery in this procedure using 5*0 mgs. of thallium ranged from 117-24>£*

If slightly larger or smaller amounts

of hydrochloric acid were present, the results were much more

-2 6 -

In error and in many cases, no end point could be discerned* This method cannot be recommended even in pure water solutions of thallium salts* 2. Cerium Sulphate B8

Willard and Young

studied the use of eerie sulphate

as a standard oxidizing agent in the volumetric determination of thallium*

Precise results were obtained when using this

in hot hydrochloric acid solutions, determining the end point electrometrically or visually if the solution is clear*

Swift

07

and Garner

attempted to use iodine monochloride as an indicator

but had little success* Reducing agents Including ferrous ion interfere with this determination.

The presence of large amounts of iron

in tissue would necessarily interfere with this reaction and so no further study of it was made* 3. Iodlmetry In a study in which thallium was determined quantita08

tively In organic compounds,Nametkin and Melnikoff use of the lodlmetric method*

made

The thallium is oxidized to

the thallic state upon addition of bromine water, excess of which is removed upon addition of a phenol-water solution* When potassium iodide is then added, the thallic ion oxidizes the iodide to free Iodine while it returns to the thallous state*

The liberated iodine is then titrated with standard

27

sodium thlosulphate using starch as an indicator#

The authors

report that the thallium is thus determined accurately to within 0*2 - 0.3/6# 87

Since Fridli

had already shown that thallium can be

determined in this manner in the presence of large amounts of ferric ion, experiments were done In this investigation to check on the results reported in the literature# Reagents; App* 0*01 n NaaSaO a Approximately 2.5 gms. of pure crystalline NaaS aOa • 5 Ha0 are dissolved in hot water which has been previously sterilized by boiling.

Add one cc. of 0.1 n NaOH and dilute

to one liter with the sterile water# The addition of the 69 indicated quantity of NaOH will adjust the pH of the solution to between 9.0 and 10.0, at which pH the bacteria that decompose thlosulphate remain inactive.

The solution

thus prepared was used in the following experiments for several years without changing in strength noticeably.

For

the duration of the investigation the flask was kept tightly stoppered and in a dark cabinet# 5# Phenol solution Approximately 10 grams of white phenol crystals (c.p.) were dissolved in water and diluted to two hundred cc#

28-

Bromlne water Into a brown colored glass bottle half filled with distilled water, liquid bromine was added until approximately a one-half inch layer of the halogen settled at the bottom# The water was decanted off and discarded#

The liquid bromine

was washed twice more and finally left in contact with water# Distilled water was added from time to time as the bromine water was used up in the several studies# Starch indicator One gram of soluble starch was mixed with a 3-5 cc# of distilled water until a paste was obtained#

This was

added dropwise with stirring to 100 cc. of boiling distilled water to which one gram of KI was added#

When the solution

had cooled to room temperature, 5 cc. of the

phenol

solution were added to prevent the formation of molds.

This

starch-KI-phenol Indicator was used for more than 2 years and still there was no apparent change#

-29Experlmental Procedure A series of determinations was made to standardize the sodium thlosulphate solution against the thallous sulphate previously used and checked gravimetrically as Til.

To 40 cc*

of distilled water, measured quantities of the TlaS04 solution added*

One drop of concentrated

sulphuric acid was added to each sample and bromine water added dropwise with stirring until a yellow color persisted* After 3-5 minutes, one cc. of the phenol solution was added to remove the excess bromine which had previously oxidized the thallium to the thallic state#

After another lapse of

3-5 minutes, approximately 0*5 gms. of solid KI was added# Shaking the 12b cc.

Erlenmeyer flask dissolved this quickly

and the flask and contents were covered with a watch glass and allowed to stand for ten minutes out of direct sunlight. When thallium was present, a blue color was obtained upon the addition of 1 cc. of the starch-KI-phenol indicator# Titration with the thlosulphate completed the determination using a 10 cc. burette marked in 0.05 cc. divisions# Several blanks were run, but in no case was there any detectable color produced when the indicator was added# Determinations on samples of

1.0-10.0 mgs. of thallium were

made and the results shown in Table IV*

A few trial titraw

tions will give the observer enough experience after which there is no difficulty In observing the end point*

-3 0 -*

Table IV Standardization of NaaSa0s against TlaS04 in water solution* mgs. T l j / cc. NaaSaOa

Mgs. Tl added

cc. NaaSa0a used

1.0 1.0 1.0 1.0 1.0 1.0

0*93 0.92 0.93 0.93 0.94 0.97

1.08 1.09 1.08 1.08 1.07 1.03

2.0 2.0 2.0 2.0 2.0 2.0

2.05 1.90 1.92 1.95 1.90 1.92

0.98 1.05 1.04 1.03 1.05 1.04

3.0 3.0 3.0 3.0 3.0 3.0

2.90 2.87 2.87 2.90 2.87 2.85

1.03 1.05 1.05 1.03 1.05 1.05

4.0 4.0 4.0 4.0 4.0 4.0

3.78 3.77 3.88 3.71 3.78 3.80

1.06 1.06 1.03 1.08 1.06 1.05

5.0 5.0 5.0 5.0 5.0 5.0

4.75 4.73 4.73 4.72 4.67 4.73

1.05 1.06 1.06 1.06 1.07 1.06

10.0 10.0 10.0 10.0 10.0 10.0

9.22 9.30 9.36 9.17 9.29 9.38

1.09 1.08 1.07 1.09 1.08 1.07

Av. 1.080

Av. 1.042

Av. 1.045

Av. 1.057

Av. 1.060

Av. 1.080

31

Since the detenninations proved the precision of the method was high for small samples of thallium in water solu­ tion, further experiments were done varying the acid and salt concentrations* Three (3.0) mg. samples of thallium were added to 40 cc* of distilled water and to each flask a measured quantity of concentrated sulphuric acid was added*

The same procedure

as used in the standardization was otherwise followed* Results are shown in Table V. Table V* Iodimetric Determination of 3.0 mgs. samples of Thallium in sulphuric acid solutions*

%

cc. Na^SgOg used

Mgs. Tl recov. (cc. Na8S803 x 1.06)

0.1 0.1 0*1

2.82 2.83 2.90

2*99 3.00 3.07

99.7 100.0 102.3

1.0 1.0 1.0

2.95 2.97 2.94

3.13 3.15 3.12

104.3 105.0 104.0

2.0 2.0 2.0

3.06 3.03 3.05

3.24 3.21 3.23

108.0 107.0 107.7

4.0 4*0 4*0

3.10 3.14 3.18

3.29 3.33 3.37

109.7 111.0 112.3

cone* added

recov.

In samples containing more than 1 cc. of concentrated sulphuric acid, the blue color of the starch-iodine complex

••32

returns in less than one minute after the endpoint has been recognized*

This, plus the fact that the titre keeps increasing

as the acid concentration increases, is indication that air oxidation occurs very rapidly in highly acidic solutions• It must therefore be concluded that in all future determin­ ations, the acid concentration must be kept to a minimum* In determining thallium iodimetrically in the presence 37

of iron, Pridli

adds large amounts of phosphates to the

solution before the addition of the bromine water*

Several

controls were run during this study to determine whether the addition of these phosphates will alter the results*

Three

mgs. samples of thallium were diluted to 40 cc. with distilled water and two (2) drops of concentrated sulphuric acid were added to each*

This was followed by the addition of 4 gms*

of NaaHP04 . 12 Ha0 and 6 cc. of 85# HoP0*, after which the previously described procedure (Brfl, phenol, K I , starch, thlosulphate) was carried out*

The titres obtained in the

presence of the phosphates corresponded exactly with those obtained during the standardizations in water solutions in both accuracy and precision.

Blanks however yielded a titre

of 0.06 cc* It was obvious from the above study that the phosphates did not account for the relatively low precision of Frldli*s results*

As will be described later in greater detail,

Frldll ashes the tissue with large amounts of NaOH, later neutralizing this with sulphuric acid which is added in

-3 3

slight excess*

Thus, before the addition of the phosphates,

the solution is already heavily laden with large amounts of sodium sulphate*

A series of blanks and controls to

determine whether this salt interferes with the iodimetry was run in the following manner:

to measured amounts of thallium

in solution, 5 cc. of concentrated sulphuric acid were added and diluted to 20 cc*

The acid was neutralized with

20/o

NaOH and reacidified with 1 or 2 drops of concentrated sulphuric acid*

The phosphates were then added and the rest

of the procedure followed as previously described.

Results

are shown in Table VI* Table VI m g s . Tl added

cc• Na^S^O^ used

minus av. blank (0.54 cc. NaftS s0a )

m g s • Tl recov. (cc.NARSg03 x 1.06 )

% recov.

none ti tt ti ti

0.39 0.71 0.46 0.73 0.41

2.0 2.0 2*0 2*0 2.0

2.28 2.25 2 .33 2.45 2.20

1.74 1.71 1.81 1.91 1.66

1.84 1.81 1.92 2.02 1.76

92.0 90.5 96.0 101.0 88.0

3*0 3.0 3.0 3.0

3.12 3.05 3.23 3.50

2.58 2.51 2.69 2.96

2.73 2.66 2.85 3.14

91.0 88.7 95.0 104.7

-3 4

It may be concluded from these studies that the volu­ metric iodimetric determination of thallium in water solu­ tion is very precise and accurate for quantities of thallium varying from 1-10 mgs*

Controls and blanks under varied

conditions illustrated the fact that large amounts of sulphuric acid and sodium sulphate must be avoided and that phosphates do not interfere at all*

Later in this paper

there will be described experiments on the application of this procedure in the determination of small quantities of thallium in human tissues* 60 4* Pithizone Concentrated ammonia is added to the solution until any phosphates present precipitate*

The phosphates

are then redissolved with 10# citric acid solution which also 'serves’ to keep any iron present in solution*

Approx­

imately 4 drops of phenol red (yellow color) are added and concentrated ammonia is added once more until the color of the solution is orange or pink*

One-half cc. of 10#

KCN is then added to prevent interference from many other metals*

Titration with the dithizone standard solution

(App* 10 mgs. dithizone dissolved in 400 c c . chloroform) is then carried out using a separatory funnel*

Small amounts of

the dithizone solution are added at a time and the red chloro­ form layer containing the thallium-dithizone compound is drawn off before more dithizone is added*

This is repeated

35

until the green color of the dithizone remains after shaking with the aqueous layer#

The burette is read, and the number

of cc. of dithizone used is multiplied by a factor determined in standardizing the dithizone solution against known amounts of thallium using the same procedure#

A blank on the reagents

and glassware must always be run and subtracted from the titre* Under these conditions, the only interfering element is lead which acts exactly as thallium does in its relation 61 to dithizone# Haddock has determined 0#005 - 0*2 mgs# of thallium with a high degree of precision, but the use for thallium must be disregarded in toxicology, since lead is found to be present even in normal tissues#

Although

many investigators have tried to distinguish between these two elements by varying the conditions of dithizone extraction, no one has as yet been successful#

Whenever dithizone is

used to determine lead in tissue, the possibility of the presence of thallium is disregarded because of its relatively rare occurrence#

-3 6

IV#

Isolation, Detection and Identification of Thallium in Human Tissues A*

Destruction of Organic Matter 1.

Ashing 37

Pridli

, being familiar with the volatility of

thallium salts, added 10 grams of solid NaOH to every 50-100 grams of tissue used in analysis*

The mixture was warmed to

a homogeneous mass and heated over a free flame until no more fumes were being evolved*

While this was taking place the

mass was occasionally stirred*

After the ash was cooled,

it was finally pulverized and reheated to a red heat, being careful not to subject the ash to very high temperatures# The cooled ash was then neutralized with 10 % sulphuric acid and 20 cc* of the acid was then added in excess#

The solution

was then heated on a water bath for thirty minutes and filtered* The clear colorless filtrate contained any thallium present in the form of thallous sulphate# A few samples of tissue were digested in this manner and the deficiencies of the method were readily apparent# The hygroscopic nature of the NaOH yielded a gummy, slow bubbling mass, from which the emission of fumes is a very slow process even over a free flame*

Because of the volatility

of the thallium even in the alkaline medium, only a dull red heat can be used at any time and in many samples the ashing turns out to be incomplete#

Finally,

the resulting solution

-3 7

containing the thallous sulphate is heavily laden with the sodium sulphate formed when the sulphuric acid is used to neutralize the large amounts of sodium hydroxide originally added*

This salt interferes with the gravimetric determin­

ations as well as the precision of the iodimetric volumetric method (Table VI)* 2*

KClOa - HC1 The method of Fresenius and Babo

63

makes use of the

oxidizing property of freshly prepared chlorine*

The finely

ground tissue is mixed with enough water to make a fluid mass, after which 10-15 cc. of concentrated HC1 and 1-2 grams of KC10a are added*

The flask containing this mixture is

set on the steam bath and shaken frequently to bring the chlorine in active contact with the suspended organic material* When the contents are hot, 0*3 - 0*5 gms. of KC10a are added to the flask every few minutes with constant shaking*

This

procedure is continued until all the organic material is dissolved and the solution is yellow in color*

When this has

cooled, the undigested fat may be filtered off through glass wool*

Thallium, if present, will be in solution as thallic

chloride, TlCla * With the required addition of KC10a every few minutes and the constant shaking, this method necessitates the individual attention of the analyst*

This prolongs the time

required for any determination since no other work can be accomplished in the laboratory while digestions are being

-3 9

done*

Furthermore, even though this method takes a long

time, the digestion Is by no means complete even after all the organic material has gone into solution* Here again, the resulting solution is heavily laden with salt*

Usually, so much potassium chlorate must be

added in the digestion, that the final solution is generally saturated with the potassium chloride formed*

It must be

remembered too that much chlorine Is present at the end and that this must be boiled off before further work can be done. 3.

HNOa - HaS04 In the laboratories of the Chief Medical Examiner

of New York City, the following procedure was used success­ fully for many years in preparation of the sample for the Marsh Test for arsenic.

The method is also suitable for

samples containing thallium and was used exclusively In the early part of this research.

It will be referred to often

in Part V of this paper* The finely ground tissue (up to 500 grams) is trans­ ferred to a 1 or 2 liter Erlenmeyer flask and covered with concentrated nitric acid.

The flask is set in a warm place

(behind a steam bath) for several hours or over night, and finally directly on the bath until all the tissue Is dissolved* When cooled, the solidified fat is filtered off through glass woo), and the solution caught in a 500 cc.

Kjeldahl

flask*

39

Several glass beads and 18 cc. of concentrated sulphuric acid are added and the solution heated until all nitric acid fumes are evolved.

When the hot sulphuric acid begins to

char the mass, the flame is extinguished and the mixture allowed to cool*

Ten cc. of concentrated nitric acid are

added and heating continued until charring results again# Small portions of nitric acid are thus continually added and heating continued until no more charring occurs in the hot concentrated sulphuric acid*

After the solution is

cooled to room temperature, 10-20 cc. of distilled water are added and then boiled off until sulphur trioxide fumes appear*

Boiling with water helps to eliminate the last

traces of fumes of oxides of nitrogen and so this process is repeated once.

The final solution is diluted with distilled

water, the resulting color being a straw yellow# Prom the time the heating is begun in the KJeldahl flask until digestion is complete a period of approximately five hours elapses*

This may be shortened by adding the

concentrated nitric acid dropwise to the hot, charred mass without loss of time during cooling and reheating*

The

process requires the undivided attention of the analyst during this stage since a sudden evolution of gas often tends to force the liquid out of the flask# Although this digestion is much more complete than the sodium hydroxide fusion or the chlorate-hydrochloride method, it does not digest as much organic matter as in the perchloric

-4 0 -

acid method.

This will be discussed in greater detail in

the following pages* 4.

HNOa - H aS04 ~ HC104 The use of hot perchloric acid as a powerful oxidizing 64

agent has been advocated by G. Fredrick Smith

who has made

extensive application of this chemical in analytical chemistry* 66

Kahane

has added much to its adoption in destruction of

organic matter in improving the nitric-sulphuric acid digestion. Although Smith and Kahane have insisted that there is no danger involved in the use of perchloric acid, it is well to remember that accidents have been reported from time to time in the News Edition of the American Chemical Society.

In

preliminary studies made during this investigation, violent ignitions in the KJeldahl flask occurred several times, leaving a white ash and a cracked flask.

Since the perchloric

acid was always used in an open system, no injuries were ever sustained. After attempting many of the methods reported, two precautions were adopted as being necessary for safety when large amounts of tissue were used.

First, it Is essential

that the fat undigested by the nitric acid be removed as previously described, before any perchloric acid is added. Secondly, no perchloric acid should be added in bulk, but rather dropwlse only as rapidly as it is consumed in the

41

oxidation*

Since the action is exothermic, if large amounts

of undigested material and perchloric acid are permitted to accumulate,

the digestion gets out of control and accidents

are likely to occur*

After the following procedure was

Adopted* not a single ignition took p).ace, although several hundred samples of 50 gms. of tissue or more were digested# In a 500 cc* Erlenmeyer flask, 100 cc. of concentrated nitric acid are added to 50 grams of finely ground tissue* After standing in a warm place for approximately one-half hour, the flask is placed directly on the steam bath and allowed to remain until all the tissue is dissolved*

This

does not take more than one and one-half to two hours, after which the contents are permitted to cool to room temperature* The undigested,

solidified fat Is filtered off through glass

wool and discarded, and the filtrate caught in a 300 cc# Kjeldahl flask*

The Erlenmeyer is rinsed twice with 10 cc*

portions of concentrated nitric acid which are then combined with the filtrate*

Several glass beads and 6 cc. of concen­

trated sulphuric acid are added and the entire contents boiled over a free flame# When all the nitric acid has been boiled off, charring begins and Is generally accompanied by frothing*

It is well

to lower the flame at this point and then to increase it when the black liquid has ceased frothing*

When the charring

has continued for several minutes, to the jet black liquid a mixture of 2 volumes of perchloric acid (66^) and 1 volume of concentrated nitric acid is added dropwise*

While strong

-42 heating is continued, the mixture is added as rapidly as it is being consumed in the digestion, the color going from black to red to yellow and sometimes to colorless.

When

further addition of the nitric-perchloric mixture causes no change, no more is added, but the strong heating is continued in order to expel

any excess of the nitric or

perchloric acid. When the flask has cooled to room temperature, 10 cc. of distilled water are added and then boiled out until sulphur trioxide fumes appear.

This is repeated again to

be sure that all traces of nitric have been expelled. cool, dilute with 5 cc. of distilled water.

When

This final

solution should be colorless, except in cases where large amounts of blood have been digested, the resulting pale yellow color being due to large amounts of iron present. Approximately 7 cc. of the nitric-perchloric mixture are consumed

when a 50 gram sample is being digested.

Once

the charring has taken place, no more than 10 minutes are generally required for this addition until the digestion is complete;

a great improvement over the nitric-sulphuric

procedure previously discussed* It is well to note that the sulphuric acid used has been kept to a minimum quantity.

This is necessary in order to

obtain good results in both the qualitative and quantitative procedures to be used later on the sample.

It might be well

to refer back to Table V in which the effects of increasing sulphuric acid concentration on the iodimetric determination

-4 3

of thallium was studied#

If during the charring the sample

appears to become solid, the heat should be removed and the flask permitted to cool#

Two or three cc. of concentrated

sulphuric acid should be added and the digestion carried on in the usual manner# Aside from the great saving of time, this nitricsulphur Ic-perchloric digestion as described is far superior to the nitric-sulphuric digestion#

In more than

90%

of the

tissues digested the final solution obtained was completely colorless#

In contrast with these results we have those

of the nitric-sulphuric digestion where all samples yielded a yellow solution#

Before the procedure was adopted using

the mixture of nitric and perchloric acids on the charring sample, a dozen 50 gram samples of tissue were digested using perchloric acid along for this purpose*

Fifty percent

of these tissues yielded solutions that were yellow, the remaining ones being colorless# Because of the volatility of thallium salts reported in the literature and the high temperatures produced during the nitric-perchloric oxidation of the charred tissue, some analyses were tried to determine whether any thallium Is lost during this digestion#

To some tissues, the thallium

was added before digestion, to others after the digestion was complete#

The results are tabulated in Table VII#

The

lodimetric determination of thallium in human tissues was

44 -

used, the procedure for which may he found in Part V of this paper*

After the titre (NasSaO s ) was obtained, the blank

for tissue and reagents ( o . H figure multiplied by 1*06*

cc.) was subtracted end the

The latter figure represents

the fact that 1 cc of thiosulphate used in titration corresponds to 1.06 mgs. of thallium as determined previously and tab­ ulated in Table IV# Table VII Loss of Thallium in Nitric-Sulphuric-Perchloric Digestions of Human Tissue*____________________ I* Tl Added mgs* 1.0 2.0 3.0

cc. thio* used 0.91 1.75 2.65

II. 1.0 2.0 3.0

Thallium added before digestion minus blank 0.80 1.64 2.54

Tl recov. mgs*

% recov*

0.85 1.74 2.69

85.0 87.0 89.7

Thallium added after digestion 1.02 1.97 2.89

0.91 1*86 2.78

0.96 1.97 2.95

9G.0 98.5 98.3

Examination of Table VII Indicates clearly that approximately 10$ of the thallium is lost during the digestion with the nitric,

sulphuric and perchloric acids.

Since the

loss is fairly consistent as can be seen from further results in Part V of this paper, it will be shown that good results can be obtained by correcting for this loss due to volatility.

-46 B*

Isolation of the Thai H i m

The Kjeldahl flask containing approximately 7 cc* of the colorless solution Is allowed to stand with occasional shaking for several hours, preferably over night.

The solu­

tion is then filtered from any Insoluble material into an 6 Inch test tube and enough distilled water used In two portions to wash the flask, to make the combined filtrates no more than 15 cc*

The solution is then diluted to 30 cc*

with distilled water and sulphur dioxide bubbled in until the solution is saturated with the gas*

While the sulphur

dioxide treatment is continued, one-half cc. of hydriodic acid is added dropwlae allowing the active bubbling to do the stirring*

The bubbling is continued for 6 minutes*

If no yellow turbidity Is observed within 5 minutes, the analysis should be discontinued and the case reported as a negative one*

If a yellow turbidity or precipitate

is formed, the sample should be allowed to stand for an hour, no more, and then centrifuged 10 cc* at a tine in a 15

r.c*

centrifuge cone*

In this way, the precipitate is

concentrated* Some observers have made the error of considering the formation of a yellow Iodide precipitate as a final positive test for thallium*

This cannot be done because other Ions,

notably Hg, Cu and Ag will do the same*

In this method, an

attempt is made to isolate or separate the thallium, if present, from most of the other substances found in tissue*

-4 6 -

Onoe having done this, the object Is to convert the Til to a soluble thallium salt on which further tests can be carried out* The yellow Iodide precipitate Is then washed with 2 cc. of dilute hydrlodlc acid {saturated with sulphur dioxide) and then with 2 cc* of ammonia*

If any mercury

Is present It Is redisaolved In the excess Iodide which Is present, whereas the ammonia wash dissolves any copper which colors the ammonia blue*

Two cc. of dilute nitric acid (1:3)

are added to the Iodide precipitate which usually dissolves completely*

The liquid is transferred to a micro watch

glass (approximately 1 Inch in diameter) which Is kept on a steam bath*

When all the nitric acid has been volatilised,

a few drops of water are added and evaporated off, to remove any traces of the nitric acid*

The thallium Is now In the

form of white thalloua nitrate (TlNOa ) which is soluble In water* A few drops of distilled water are added to the TlNOa on the watch glass and stirred occasionally with a sealed fine capillary*

After a half hour, the solution Is transferred

to a micro centrifuge tube, using a micro capillary pipette* In a hand centrifuge, any solid matter Is sent to the bottom of the tube, leaving a colorless solution above for the thallium testa*

47

C•

Confirmatory Tests

Examination of the qualitative tests for thallium previously described in this paper will show that every test for Tl is also given by several other ions.

There is no

single specific test for thallium* If we study the thallium tests we find that this element is a very unique one.

Comparing it with the Five Group

Classification of the cations in analytics]

chemistry, we

find that it may be classed with the elements of Groups I, III and V, and in many ways resembles lead as well*

To

confirm the presence of thallium, therefore, it is recommended that at least one test from each of these groups be done* A positive must be obtained in each case.

The following

tests were used during this studyi 1*

Thallous bromide* With a capillary tube, a small portion of the

solution is transferred to a small centrifuge cone* While sulphur dioxide is bubbled through the solution a small droplet of hydrobromlc acid is added and the sulphur dioxide bubbled in for a few more seconds* The precipitate of TIBr is centrifuged in order to see its white color* 2*

Thallous iodide* This test is done in an identical manner as the

bromide test above except that hydriodlc acid is used

-4 8 -

in place of the hydrobromic acid* 3*

The iodide is yellow*

Flame test* If the halides precipitated above are separated

from the solutions by siphoning off the liquids with a capillary, they may be taken up on a platinum wire* If the latter is then introduced into the outer cone of a non-luminous gas flame, a characteristic green color of short duration may be observed*

A hand spectro­

scope will show that the spectrum consists of a single green line* 4*

Thallous chromate* A small portion of the solution is made ammoniacal

in a small centrifuge cone.

To this a droplet of

dilute potassium chromate is added and the yellow TlfcCr04 is precipitated* 5*

Thallic hydroxide. Bromine water is added to a small portion of the

solution until a yellow color persists.

After 5 minutes,

enough ammonia is added so that the solution is alkaline. Brown thallic hydroxide will precipitate* 6.

Thallous cobaltl-nitrite To a small portion of the solution add a tiny

drop of sodium cobaltl-nitrite reagent*

If necessary,

warm to 5 o * C . and allow to cool slowly*

A scarlet

red crystalline precipitate la formed*

49

The reagent should be prepared as follows: Dissolve 20*7 gms. of c*p. NaNO, and 29.1 gms. of Co{NOa )s • 6 Ha0 In 50 cc* of distilled water and add 1 cc* of 6N acetic acid* 24 hours*

Let the mixture stand for

Filter and dilute to IOC cc*

This reagent

will last for several weeks but should be tested before use* Using the entire procedure as described, as little as 0*05 mgs* of thallium mixed with 50 grams of tissue were isolated and identified*

This sensitivity is more than

enough for cases of thallium poisoning*

All the above tests

should be obtained in toxlcological work*

V*

Quantitative Determination of Thallium in Human Tissue A*

heview of the Methods 1*

The Shaw Method*® Using the HC1-KC10# digestion, 10-20 grams of tissue

containing thallium are thus treated*

When cool,

the fat Is

filtered off and the filtrate evaporated until the solution becomes slightly dark*

Chlorine water Is then added until

the solution clears and in the presence of an excess of chlorine,

the solution is extracted twice with ether which

dissolves the TlCl* end FeCl»*

The solvent Is evaporated

and to the residue Is added some water, a few drops of

-5 0

concentrated hydrochloric acid and a few cc. of concentrated sulphuric acid*

This is evaporated until fumes of sulphur

trioxide appear and while hot, concentrated nitric acid is added to complete the oxidation.

Cool, add ammonium chloride

and evaporate to dryness to remove any nitrites that may have been formed* Bromine water is then added to oxidize the thallium to the higher valence state*

The reagent also contains some

HCl and NaBHP0*, the latter being used to minimize the ionization of the ferric salts*

The solution is then boiled

for 3 minutes to remove any excess of bromine.

When cool,

the volume is adjusted by adding distilled water and KI is added tc react with the thallic ion.

Iodine is liberated

according to the following equation: TlCla + 2 KI --- ^ TlCl «■ 2 KC1 + Ia The iodine is then extracted with carbon disulphide and the color compared with standards prepared as follows: A known quantity of thallium is oxidized with bromine rater containing HCl and NaaK ? 0 a . The solution Is boiled, cooled and treated with KI* extracted with carbon disulphide*

The iodine is

Chromates interfere

with the method, which the author claims is accurate to within

Shaw also claims that the entire

procedure can be accomplished in 2-3 hours* The method Incorporates several practices long discarded In toxicology*

The digestion using HCl and KCIO, Is a very

51

slow process yielding in the end a solution with much undigested be

organic material.

Secondly, J. Proszt

boiling off excess bromine,

showed that when

some of the thallic ion will

revert to the thallous state, and recommended the addition of phenol without boiling for the removal of bromine. Furthermore the process is much too lengthy and requires too many steps for good duplication.

In this method we have two

digestions, two evaporations to dryness and three or four extractions. No mention was made in the original paper of any danger being involved.

During this investigation, it was decided

that the method should be checked.

When the solution con­

taining the excess chlorine was being shaken with ether, an explosion occurred in the separatory funnel, breaking the glass and sending the burning ether to the desk and floor. Fortunately, no injuries were sustained but it 5s felt that this should be reported in this paper. 2.

The Fridli Method*7 Finely ground tissue (50 - 100 gramB) were mixed

with 10 grams of solid sodium hydroxide and warmed to an homogeneous mass.

With occasional stirring, the mixture

was heated over a free flame until no more fumes were being evolved.

The ash was allowed to cool, and then was pulverized

and reheated to a red heat.

When cool again, 10 % sulphuric

acid was added until slightly acid and then 20 cc. of this

—5 2 -

acid were added in excess.

The solution was heated on a

steam bath for 30 minutes with stirring and then filtered# Enough wash water was used so that the combined filtrates had a volume of 200 cc« To 20 cc. of the filtrate were added 1 drop of bromine water, 1 cc. of

5% phenol,

b cc of 50# HaP04 * added*

2 grams of NaaHP04 . 12 H a0 and

After 10 minutes, 0.5 gm. of KI

was

If a yellow color (iodine) appeared, the quantitative

procedure was carried out as follows: To the remaining 180 cc. of the filtrate, 10 grams of NaaHP04 . 12 Ha0 and 20 cc. of 50^ HaP04 were added to minimize the ionization of the ferric salts*

Bromine water Is then added dropwise until

a yellow color persists, oxidizing the thallium to the thallic state*

After e few minutes the excess bromine

was removed by adding 2 cc of

phenol*

After several

minutes, 0*5 gm. of KI was added and after 5 minutes the liberated iodine was titrated with approximately 0.01 N thiosulphate*

No mention was made of using

an indicator or of the method by which the thiosulphate was standardized# It is often difficult to determine when the digestion is complete since the temperature must be kept down to a red heat*

In some of the samples digested in this manner,

the resulting solution was blue or green, this color hindering

-53 the work thereafter*

Several samples were colorless and the

completed determinations gave results less accurate and precise than Fridll claims.

For instance when 2.0 mgs. of

thallium were added to tissues, 2.27;

1.75;

the titres obtained were

2.15 cc of thiosulphate used.

When these

figures were multiplied by the factor obtained in the standard­ ization of thiosulphate against thallium in dilute sulphuric acid solution, the recoveries of thallium were 2.38;

1.84;

2.26 mgs* This low precision was in part at least, due to the large concentration of salt in solution, formed when the 10 grams of sodium hydroxide were neutralized.

Experiments

carried out to prove this are shown in Table VI of this paper* •T

3*

The Schee Method The organs were digested with potassium chlorate

and hydrochloric acid as previously described in Part IV A of this paper, and the resulting solution was neutralized and made alkaline by the addition of ammonia.

Ammonium

sulphide was then added and the sulphide precipitate was filtered off.

The latter was washed with ammonium sulphide

water and then permitted to dry on the filter paper.

The

paper containing the sulphide precipitate was transferred to a porcelain crucible which was then heated over a free flame until no more fumes were evolved.

The resulting ash was

extracted with hot water which dissolved the newly formed

54 TlaS04 leaving the insoluble FeaOa behind when filtration was next carried out*

se The clear filtrate is then treated by the Browning-Palmer Method for the determination of thallium*

The following

equations describe this volumetric procedure using potassium permanganate: 1.

Tl.SO*

♦ 4 K aFe(CN)e ♦ 6 K O H

^

4 K4Fe(CN)e + K aS04 + 2 Tl(OH}a The insoluble thallic hydroxide was filtered off and the second step in the procedure followed: 5 K4Fe(CN)e ♦ KMn04 ♦ 4 HaS04 ____ ^

2.

b

K aFe(CN)e ♦ 3 K 8S04 ♦ Mn304 + 4 H„0.

It

is interesting to note that since thepublication

of this

paper in 1928, no author has mentioned its use in

thallium studies*

In this Investigation, many attempts to

repeat the work of Schee resulted in a total loss of the thallium during the ignition of the sulphide precipitate* Furthermore, the use of the Browning-Palmer volumetric method for the final determination of the thallium is illogical, since the lodlmetrlc method has long been shown to be more precise* 4*

The Plchler Method44

a. Bromide The finely ground tissue was digested using potassium chlorate and hydrochloric acid as previously described in

-5 5 -

Part IV A of this paper and the insoluble fat filtered off and discarded*

The filtrate was then concentrated on a water

bath and ammonia added until the phosphates precipitated* Without filtering, hydrogen sulphide was passed through the liquid and the resulting black precipitate filtered off* The latter was then dissolved in dilute sulphuric acid (1:6) and the solution concentrated over a water bath*

The solution

was finally heated over a free flame until one-half cc. of concentrated sulphuric acid remained.

When cool, 10 cc. of

water were added and the solution allowed to stand overnight, then filtered* The clear colorless solution was then treated according to Part III A of this paper which describes the procedure for the gravimetric determination of thallium as thallous bromide*

Using the TlBr precipitate, Pichler examined the

green flame produced in the spectroscope to determine the presence of the thallium* The first thing that was altered in this procedure was the method of digestion*

The improved methods (HN0a-HaS04

and HN0a -HCl04-HaS04 ) reduced the time of analysis to a great extent and the results obtained were the same*

Secondly,

the solution containing the suspended sulphides was permitted to stand stoppered up over night, slnco the precipitate seemed to be of small particle alee and did not settle easily* The Pichler method was lengthy in another part of the procedure*

The sulphide precipitate was dissolved in dilute

56 sulphuric acid which was subsequently boiled down to one-half cc*

Experience shows that the boiling off of large amounts

of sulphuric acid (conc.) is a very slow process.

In addition,

there Is a great tendency to spatter, In which case there Is danger of injury to the analyst, as well as great probability of mechanical loss of the thallium.

After the first few trial

runs in this study, the solution of the sulphides was accomplished with approximately 50 cc. of boiling dilute nitric acid (1:4).

The filtrate was caught In a 100 cc.

beaker and approximately 2 cc. of concentrated sulphuric acid were added.

After stirring, the beaker was placed over

a gas multieburner hot plate and a few glass beads were added.

Over a small flame, the nitric acid and the water

evaporated in approximately fumes appeared. occurred.

2

hours and sulphur trioxide

Using this procedure, spattering very rarely

It must be added that the final sulphuric acid

solution was boiled out twice with a few cc. of water to make sure that no nitric, acid remained. An examination of Part III Al of this paper will show that the determination of thallium as the bromide is very good for this metallic ion when present in water solution. If the correction for the solubility of thallous bromide la made as suggested, small amounts of thallium Q.-5 mgs.) can be determined with an accuracy of 96-105^.

In order to test

the Pichler procedure which finally uses the bromide deter­ mination, many controls were run using varying amounts of

57

thallium

autopsies

similar who

and

were

was

amounts

thallium*

the

come

evident

Thus

it m a y

from

the

the

be

if

look

Since

as

and

was

work,

the

I*

that

dogs

of

the

Jerome

dogs

Silverman,

no unnatural

organs

latter,

true

patient

paralysis for

except

in

the

a hemorrhagic

which

received

in dogs

I and

large

II

and

not

living

and

free

with

is

is

has

clues

the

loss

obtained,

must

pathologist*

suffered

from

severe

of appe t i t e , alopecia,

the if is

of T h a l l i u m

a heavy metal

we m a y

protein

acid

than

and possibly

Mechanism

evident

The

any

pains

tremors,

the

toxicologist

thallium*

copper,

is

that

followed by

thallium

reacts

action

the

rather

expeot

a protein precipitant*

salt

of

concluded

the

XI*

lead

any

in those

physician

extremities

convulsions, should

this

reported

In

This

examinations

others*

Specifically, in

in

tract*

appearance

in

In

advised,

found

gastro-lntestinal

of

pathological

conclusions*

aided

appearances

and

Thus

protein large

of

we the

amounts

converted

produced*

that

The

Poisoning*

chemically it w i l l

find

that

stomach of

act

the

similar in

when

the a

lining a

poison

are

to body

thallous corrosive ingested*

to a dea d m e t a l - a l b u m l n a t e albuminate

will

dissolve

82

slowly,

become

liberated The body, on

thallium action

but

this*

of

the

from

the

small

The

nervous

suggest

that

than most

it

the

produces Much at

true

of

the

body

as

it

of

is

between

being

also

the m e t a l The

and

thallium

be

are

that

are

readily

column IX

eliminated

leads

one

this

length

action

shows

the

this

tissue

where

usually

is

particularly over

the

that

entire The

larger

amounts

organ*

of even

is

is

thallium

to b e l i e v e

poison

alopecia

IX

expected

of

through perspiration*

affeoted • Table in

be

amounts

patient*

produces

balance,

affected by

contradict

This

of

thallium poisonings

small

Irritating

the

present*

felt

excretion.

involving

than may

in muscle

the

the

prevalent

the h o r m o n e

havoc

relatively

an

the

of

evidence

concentrate

and deatn

the

are m o r e

in m ost

of T a b l e

which

considerable

the b e l i e f

is m o r e

by

of

tissues

symptoms

that

produced

of

of

action

all

endocrines

spinal

to

found

ingestion

the

in m o r e

However,

places

in

effects

possible

tissue

effect

toxic

protein precipitant

weakness

the

the

kidneys may

of

tends

the

of

obvious

is

Examination

poison

occurs the

the

the

body*

Instance,

symptoms

in b r a i n

the

that

result

amount

nerve

supposition. that

It

will

others.

found

are

For

Furthermore, disturbed,

spread

thallium

thallium on

once

metal

the

organs.

of

and

throughout

indications

certain

effects

absorbed,

time

that

in acute

fairly

well

generally cases,

elapses

corroborates

distributed

-8 3 -

throughout

the body*

No mechanism has

as

yet been

thoroughly

confirmed*

XII*

As

of T h a l l i u m poisoning*

in other poisonings,

soon after

the

as p o s s i b l e induction pumping

of

thallium has

from

of

repeated

of

large

the

washed,

should

be

been

can be m o s t

ingested*

is h i g h l y

further

takes

When

the

This

U

through

the *

or should

administration

stomach has

of

as m u c h

place,

emetics

each with

cleansing

accomplished

of

effectlve

remove

recommended*

following

of w a t e r *

To

absorption

administration

times,

quantities

thoroughly

the

stomach

several

treatment

system before

vomiting,

the

be

tract

Treatment

been

gastro-intestlnal

of enemas

use

and

cathartics* The

ingestion

since most

of

removed from Fluids etc*

such

will

the

of

thallium

the b o d y as m i l k ,

the

volumes

of

should be

where raw

accomplish

i n j u r e d mucomf>f

large

it

or

this,

can

soft and

fluids

eliminated

do

its

boiled

at

must

the

same

gastro-intestlnal

and

damage

eggs,

be

continued,

thus

alowly«

mineral

time

be

oil,

soothe

the

tract*

sc Munch soon

as p o s s i b l e *

sodium

iodide

thallium dally hour

suggests

in

during

that

This

a

starts

intravenously

the

tissues*

this

speolmen be

He

treatment flamed,

chemical

treatment

with dally

in order

the

observing

that

residue the

begun

injections

to p r e c i p i t a t e

recommends and

be

green

urines of

the

color

aa

of the be

taken

twenty-four supposedly

due

to

thallium*

The

conditions

and Munch

until

a pale

only

little

thallium

Munch

purpose

of

minimum

and

the

this

this

is

must

too much

It

istration

at

the

any

disturbance

increase

of of

Although Munch during he

the

admits

it

1932 having

favorable on

a

teat

iodide be

these

administered

Indicating

Intravenous thallous

injections

iodide

that

thallium down

as

rapidly

as

time*

it

is

pointed out in order

to

recommends

hydrochloride

to

stimulate

the

diet

having

in o r d e r

tried

this

of Thallotoxlcosis only

However,

on a

sould be m ade whether

similar

ingestion

of

large

admin­ secretion,

occur*

treatment

with

can be

numbers

results

large

that

in C a l i f o r n i a ,

Judgment

on

a

to o v e r c o m e

few patients

before

to

release

he

In

The

by Munch

not

sodium

formed by

Further,

reports

it

of

slowly*

calcium metabolism which may

continued

under

soluble

calcium

to d e t e r m i n e

obtained by

the

obtained,

controlled

tried

study

is

further

outbreak

results*

further

In order

is

of p i l o c a r p i n e

and

that

poor

the

this

carefully

thallium

with

to k e e p

to e x c r e t e

be

a very

excreted*

dissolves

thiosulphate*

this

color

is b e i n g

which

la

recommends

green

follows

thiosulphate

latter

can

volumes

apparently

passed of

animals

not be of

liquids

alone* While of

the

in

order

attests

are

being made

thallium from the to

combat

the p a t i e n t m u s t

be

the

body,

effects

treated for

to

encourage

therapy must of

the

be

poison*

the u s u a l

elimination given In

simultaneously

this

connection,

gastro-intestlnal

-8 5

disorders,

nervous

stimulants

or

It m u s t thallium dose

is

sedatives

not

very

the

effects

reached

good

the

long

time

than

six m o n t h s

liquids

analysis present* chances is

If are

wholesome

earlier tissues,

t h a l l i u m are

complete

the

urine

death good and

recovery

or a year*

should be

of

that

if h o s p i t a l i z a t i o n

of

and

the

does

that the

not

the

and

stages the

so

that

of

the

a lethal

chances

for

life

early*

However,

apparent

for

is

attained

in less

seldom this for

time,

patient are

within will

large

several

detectable

occur

symptoms

arises

generally

administered no

it

if e l i m i n a t i o n

occurs

During

shows

if

necessary*

stated

in the in

dermatitis

whenever

therefore be

is e f f e c t e d

are

of

conditions,

the

of

first

recover

treated

volumes

months

amount

if

a

until thallium

week, the

promptly*

diet

—8 6

Summary

1.

A study of the qualitative reactions of the thallium ions has been made resulting in a conclusive method for the detection of small amounts of thallium in human tissues*

This Includes at least three teats characteristic

of different groupsi 2*

iodide, hydroxide and cobaltl-nitrite*

The quantitative methods for the determination of thallium have been studied and a simple and reliable procedure has been developed for the accurate determination of thallium present in small amounts In biological specimens* The latter consists of a digestion with nitric, perchloric and sulphuric acids, followed by an iodlmetrlc deter­ mination*

6* In normal tissues, it has been shown that the amount cf thallium present, if any, is below the sensitivity of the method (0*05

mgs*)

4* The distribution of thallium in tissues of humans and dogs poisoned by this metal has been determined* 5* The amount of thallium in several samples of urine in two non-fatal thallium poisonings (human) was determined* 6* It has been shown by this study that in fatal poisonings, oocurrlng when the amounts of the poison are very small and are approaching the medicinal dose, approximately 5 - 1 2 sigs* of thallium are present per kilo body weight* 7* Most acute fatal cases end in death within a few days* Alopecia, the only specific symptom or pathological finding, never occurs in less than two weeks*

The diagnosis of

the usual thallium poisoning (fatal) rests with the toxiooloalst*

87

1*

Crookes, Wta., Chem. Neva 3, 193*4 (1861)

2.

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3*

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4*

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6*

Rosenhaln, W., Glass Manufacture* (1908)

6*

Johnson, J. Y., British Patent No. 297,665, Sept. 27, 1928

7*

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8*

Munch, J.C., Soap 1&, (1937)

9*

Combemale, Bui. Acad. Med. (Paris)

Van Nostrand, 183-8

(3) 3£

572 (1898)

10*

Cicero, R*, Arch. Dermatol* u. Syph. 160

438 (1919)

11*

Kallett and Schllnk, 100.000,000 Guinea Pigs. Vanguard Press, 80 (1933/

12*

Lamy, A*, Sur Les Effects Toxiques Du Thallium* Rend. Acad. Scl. 57, 442-6 (1863)

13*

Buschke, A* and Langer, B«, Die forenslsehe and gewerbllchhygienlsche Bedentung des Thalliums, Munchen. med. ■ochnschr. 7j|, 1494-7 (1927)

14.

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15.

Teleky,

16*

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17*

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18*

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The Compt.

Wien. med. Wochnschr* 7g, 506-8 (1928) 733 (1927)

8-10 (1932)

-8 8

19

Pacini, A., Oior. ltal. dl dermat. e. sif. 67, 287-91 (1926)

20

Prieto, J. C., Zentralbl. f. Haut u. Geechlechtskr. 30. 637 (1929)

21

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22

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23

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24

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25

Kaps, L., Wien. Klin. Wchnachr. 4^, 967-70 (1927)

26

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•7

Munch, J.C. and Silver, J., U.S. Dept. Agriculture* Tech. Bull. No. 238 (April, 1931)

28

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29

Jordan, E.P., J.A.M.A. 104. 1319-21 (1935)

30

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31

Partington, J.P., Textbook ol* Inorganic Chemistry# MacMillan, p. 887 (1930)

32

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33

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34

Feigl, F«, ?ual. Analyse nit Hilfe von Tupfelreaktlonen* Leipzig (1936)

36

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36

Wlllm, J.M., Bull. soo. ohla. de Paris (2) 6, 152 (1863)

37

Pridll, H., Deut. z. Oes. Oerioht. Med.

Lancet

1340-1344 (1930)

1372—3 (1932)

4

27.

47t*-88 (1930)

-8 9 -

38*

Weiss, L., Master*s Thesis, New York University (1936)

39*

Felgl, F., Chem. Ztg. 44, 689-90 (1920)

40.

Berg, R. end Roehllng, W., Zeit. f. Angew. Chem. 48. 430-2 (1936)

41*

Winter, 0.3*, Robinson, H.M., Lamb, F.W. and Miller, E.J. Ind. and Eng. Chem., Anal. Ed., Vol. 7, No. 4, p. 265 (1935)

42*

B r o d e , W a l l a c e R., Chemical Spectroscopy, page John Wiley (1939)

43*

Noyes and Bray. Qualitative Analysis for the Rare Elements. MacMillan, p. 370 (1927)

44*

Pichler, A*A« Benedetti, Unpublished Communication to A* 0. Oettler (1931)

46*

Pregl, F., Quantitative Organic Mlcro-Analysls. Blakiston (1930)

46*

Takeno, Ryoji, J. Chem. Soc., Japan 54. 741-2 (1933)

47.

Soule, S., Chemist Analyst 17. No* 3-4 (1928)

48*

Mach, F. and Lepper, W., Zeit. Anal. Chem. 68. 41 (1926)

49*

Browning, Philip E«, Ind. and Eng. Chem., Anal. Ed. 4, 417 (1932)

60*

Qoronoy and Berg, R«, Deut. Z. f.d.ges. ger. Med. 20. 222 (1932-3).

51.

Browning, P.B. and Hutchins, 460 (1899)

62.

Moser, L* and Brukl, A., Monatahefte

53.

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Q.P.,

Am. J. Scl.

4

, 8,

f. Chemle 47. 709 (1926)

64.

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69. 33 (1926)

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(1928)

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401

422,

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59*

W i l l a r d , H. a n d F u r m a n , N*» V a n N o s t r a n d , p. 2 1 1 ( 1 9 3 9 ;

60.

Kaye,

Sidney,

61 .

Haddock,

62*

Paulet,

Master*a

L.A., The

Thesis,

Analyst

Compt. Rend.

Elem.

394

Sci.

(1935)

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l ’A c i d P e r c h l o r i q u e s u r l e a et Cie, 6 Rue de la Sorbo n n e .

66*

S h a w , P a u l A*, (March 1933)

Chem.,

68*

Schee,

Jos.,

Detection

a n d Eng*

Med.

Anal.

7^

A.,

70.

C l a r a v i n o , E>, 6 7 4 - 5 (1936)

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72.

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73.

Schwab,

R.,

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Ber.

W.E.,

L.,

Arch,

ges.

Med.

Physiol,

pharm.

Opthalmol.

Buschke,

75.

Mamoli,

76*

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77*

Merkel, Hermann. 237-49 (1929)

A. ,

di biol.

Deut.

Z»

.

..

-

-

I

■

93,

des (1909)

95 .

(1928)

1197-1200

547-61

(1927)

(1934)

Monatsbl.

Accad.

'*

•*

20.

ges.

p.

pharmak.

43-9

229-250

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(1928)

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d.r.

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of

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and Warren, Blakiston*

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de

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dl

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