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Thallium toxicity: A growing concern

optical lenses. It is also useful in the A. Saha Abstract manufacture of imitation jewellery, National Institute of This review article deals with the growing concern of the pigments, and fireworks (green color). Occupational Health, toxicity of thallium. This article describes the Meghani Nagar, Ahmedabad, India characteristics of thallium, its potential sources of Potential sources of exposure exposure, kinetics, and toxicity on human being and Exposure occurs by oral, dermal, and For correspondence: diagnosis of thallium poisoning. This article also describes inhalation routes. Water-soluble salts Dr. A. Saha, some episodes of thallium poisoning arising from both are more toxic than the less water- Senior Research occupational and nonoccupational exposure. soluble salts (e.g., thallium sulfate is Officer (Medical), Key words: Acute poisoning, Chronic toxicity, Thallium more toxic than sulfide). Dermal National Institute of exposure may even occur through Occupational Health, rubber gloves.[8] Meghani Nagar, Ahmedabad – 380 016, INTRODUCTION India. E-mail: Industrial exposure [email protected] In most of the cases, thallium is Thallium is a toxic heavy metal, which was accidentally emitted in the atmosphere as dust. discovered by Sir William Crookes in 1861 by burning the Among the dusts of thallium dust from a sulfuric acid industrial plant.[1] Since long back, compounds, thallium sulfate is the thallium has been used extensively, and human exposure to majority. This dust emitted from thallium compounds has occurred naturally. Apart from industrial outlets is either inhaled or thallium exposure in industrial set ups, poisoning of settled down to contaminate surface community people from thallium compounds has also taken water or soil. Thallium exposure place from time to time. Many cases of industrial and occurs mainly from the following nonindustrial thallium poisoning have already been reported industrial emissions. from different countries at regular intervals.[2]–[7] Some · Coal fired power plants. incidents of such poisoning have resulted in fatalities. Cases · Smelting operations (mainly lead of thallium poisoning from compounds already banned have and zinc). also been reported. In India also, cases of thallium poisoning · Cement industries. have been observed even in the recent past. In such a · Rodenticide manufacturing scenario, day-by-day, thallium poisoning is drawing more and plants. more attention from the point of view of occupational health, · Refinery (as a byproduct of as well as public health. cadmium production).

Thallium, a bluish white heavy elemental metal exists in two Nonindustrial exposure oxidative states, +3 (thallic), and the more common and stable · Consumption of fruits and +1 (thallous). It has an atomic weight of 203 and a melting vegetables grown in contaminated point of 303.5°C. Thallium is present in the environment as a soil and the use of tobacco result of natural process and from man-made sources. It is products. ubiquitous in nature and occurs especially in sulfide ores of · Acute and chronic poisoning cases various heavy metals, but normally in low concentrations. where exposure has occurred Only a few areas contain a naturally very high-thallium directly from a thallium compound concentration. either self inflicted or induced (e.g., poisoning from rodenticides). Use of thallium has been extensive and it has ranged from Other exposure (rare atypical rodenticide to photoelectric cells, lamps, electronics, low- exposure) temperature thermometers, and semiconductors. Thallium · Thallium poisoning has occurred has also been used in imaging procedures (Th-201 is widely following nasal insufflations of a used in myocardial imaging), scintillation counters, and substance that was believed to be

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cocaine.[9] In severe cases, where people die within 8–10 h, increasing · Poisoning from thallium has also occurred after ingestion tachycardia, progressive hypotension, early hyporeflexia, and of herbal medication/nutritional supplement. peripheral cyanosis is observed.

Kinetics The ingestion of lower lethal doses causes gastrointestinal Exposure to thallium is possible through oral, inhalation, hemorrhage, gastroenteritis, metallic taste, salivation, dermal, eye, parenteral, and other routes. Water-soluble salts nausea, and vomiting. Afterwards, neurological disorders, (sulfate, carbonate) are easily absorbed from the gut than the hallucination, lethargy, delirium, convulsions, tingling pain less water-soluble (sulfide, iodide) forms. Excretion occurs in extremities, and muscular weaknesses are followed by through urine, faeces, and salivary secretion. In an affected coma. The cause of death is respiratory failure or cardiac subject, considerable levels of thallium may be found in blood arrest. and hair also. Chronic toxicity The toxicokinetics of thallium in human beings is explained The symptoms of chronic toxicity show strong variation and by a three-compartment model. are in general milder than in cases of acute poisoning. A · Central compartment consisting of blood, as well as well- relatively long-latent period of even several weeks may be perfused peripheral organs and tissues, is the fast followed by just a few symptoms. exchange compartment. · Peripheral sensorial disturbances, mental aberrations, · Brain, the target organ for neurotoxicity constitutes the loss of weight, and sleeplessness have been the most slow exchange compartment. common features. · Intestine as well as the intestinal contents, where the · Disturbances of vision, pain without marked polyneuritis, absorption of thallium takes place. loss of hair are reported. Later severe polyneuritis may develop. In the first phase, lasting about 4 h, thallium is distributed · Cardiac disorders include hypertension, irregular pulse, through the entire central compartment. In the second phase and angina-like pain. (4 – 48 h), distribution occurs in the brain. Afterwards, · Other symptoms include gastric antacidity, lack of thallium is distributed throughout the body tissues. appetite, loss of weight, albuminurea, haematuria, endocrine disorders, psychoses, and encephalitis. Effects of thallium poisoning Initially, thallium was used as medicine, mainly as a depilatory Diagnosis agent. This use has resulted in many cases of intoxication. Because thallium is tasteless, odorless, colorless and highly Diagnosis is based on a characteristic clinical presentation toxic it was frequently used for suicide, homicide, and illegal and on laboratory confirmation of thallium in biological fluids. abortion. Accidental exposure to thallium has also occurred · The triad of gastroenteritis, polyneuropathy and alopecia after ingestion of contaminated food.[10] is regarded as the classic syndrome of thallium poisoning. · Typical alopecia and Mee’s lines in the nails appear after Depending upon the mode and dose of exposure, thallium 2 weeks [Figure 1]. toxicity represents either as acute manifestation or as chronic manifestation.

Acute poisoning Acute intoxication by thallium salts in humans, causing severe symptoms have been reported after ingestion of single or multiple oral doses of the order of 100 mg or more for adults. The main features of acute thallium toxicity in order of appearance are as follows (where intoxication is less severe): · Anorexia, constipation, vomiting, retrosternal, and abdominal pain. · Polyneuritis (sensory and motor), insomnia and darkening of hair roots. · Alopecia, Mee’s lines (whitish lines in nails), alteration Figure 1: Mee’s line and erosion of nails in a case of thallium in blood pressure and ST, T changes in ECG. poisoning

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· Thallium levels are usually examined in urine, blood and Other studies[14–16] have reported that thallium (as thallium hair samples. sulfate, dose not specified) is lethal following ingestion, and there was evidence for central–peripheral distal Episodes of thallium poisoning axonopathy.[16] Although the finding of neurological effects was Chronic occupational thallium poisoning has been reported consistent among case reports, death was attributable to from Japan in a male worker who handled thallium containing cardiac or respiratory failure. raw materials for glass manufacturing over a period of four years and complained of alopecia, abdominal pain, diarrhea, Laboratory methods to determine thallium in body and tingling in extremities. Mild glove stocking type fluids and tissue samples polyneuropathy was found in this patient. Thallium content Thallium concentration in environmental samples being very of hair as determined by ICP-MS method was found to be low, determination directly from the sample or from the 20 ng/g.[5] digestion solution usually lacks sufficient accuracy. In such circumstances, preconcentration procedures are necessary. Acute thallium poisoning of eight people due to unknown Sampling and sample preparation also needs special care cause has been reported from Poland where some cases have because these can result in thallium loss or contamination. fatal outcome also.[3] Thallium is almost always determined as total metal, rather 1. Thallium poisoning from maliciously contaminated food than as specific thallium compounds. Among the analytical has been reported from New York, where thallium intake techniques that can be used are spectrophotometry, mass occurred through candy and the victims suffered from spectrophotometry (MS), atomic absorption spectrometry variable gastro intestinal symptoms and painful (AAS), voltametry, neutron activation analysis (NAA), X-ray paraesthesia of hands and feet.[2] fluorimetry, and inductively coupled plasma (ICP) techniques. 2. A case of thallium poisoning is known from New York, Selection of analytical methods should be done carefully on where poisoning began during first trimester of pregnancy the basis of character of sample in which thallium is to be and resulted in fetal demise. This case documents that estimated. To determine presence of thallium in water thallium passes through both placenta and breast milk.[11] samples amperometric titration or ICP-MS can be useful. 3. Thallium poisoning has been reported from Israel in the Inductively coupled plasma – atomic emission spectrometry year 2000 after a gap of 30 years when an old man (ICP–AES) is of use in analyzing biological materials as well developed both acute and chronic symptoms as air particulates. Other useful methods for biological concomitantly after ingestion of thallium compounds samples are ICP–MS and DPASV (differential pulse anodic through alcoholic beverages.[4] stripping voltametry). The ICP–MS can be used for analysis 4. Not only is thallium poisoning occurring from occupational of rocks also and spectrometry may be used for environmental and nonoccupational sources, it is also taking place with samples. Routine methods in use are GFAAS (graphite furnace suicidal and homicidal intentions. In some places, it is atomic emission spectrometry), DPASV, ICP–MS, and showing resurgence after a silence of even decades. photometry. As most of the techniques require a careful Naturally, it is becoming a growing concern and a matter sample pretreatment/preconcentration step, it is strongly of toxicological interest. In such circumstances, the recommended that all analyses should be accompanied by a clinicians should keep the diagnostic features of thallium quality assurance program. poisoning in their mind in view of the fact that early suspicion of this poisoning and thereby early institution ACKNOWLEDGMENTS of specific therapy can save the life of the victims. I acknowledge the help of Dr. H. G. Sadhu, Assistant Director, Mortality in thallium poisoning National Institute of Occupational Health towards this article who There are numerous case reports of human lethality following has taken great care to obtain the photographs. acute oral exposure to thallium. Death occurred in one individual 9 days following intentional ingestion of a single REFERENCES estimated dose of 54–110 mg thallium/kg (as thallium nitrate). Cranial and peripheral nerves showed axonal degeneration 1. Galvan-Arzate S, Santamaria A. Thallium toxicity. Toxicol Lett 1998;99:1-13. with preservation of most of the overlying myelin, suggesting 2. Meggs WJ, Hoffman RS, Shih RD, Weisman RS, Goldfrank LR. Thal- [12] that thallium damaged axons. Two of three subjects who lium poisoning from maliciously contaminated food. J Toxicol Clin ingested thallium (thallous acetate) also died; however death Toxicol 1994;32:723-30. occurred 1 month after onset of symptoms. Dose could not 3. Sadlik JK. Thallium Poisoning. Poster Presentation. XXXV TIAFT be determined since exposure occurred in three divided doses Annual Meeting. 4. Atsmon J, Talianski E, Landau M, Neufeld MY. Thallium poisoning in for unspecified durations. Distal peripheral axon degeneration Israel. 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case of chronic occupational thallium poisoning in a glass factory. In- 12. Davis LE, Standefer JC, Kornfeld M, Abercrombie DM, Butler C. Acute dustrial Health 1998;36:300-3. thallium poisoning and morphological studies of the nervous system. 6. Feldman J, Levisohn DR. Acute alopecia: clue to thallium toxicity. Ann Neurol 1981;10:38-44. Pediatr Dermatol 1993;10:29-31. 13. Cavanagh JB, Fuller NH, Johnson HR, Rudge P. The effects of thal- 7. Moore D, House I, Dixon A. Thallium poisoning. Diagnosis may be lium with particular reference to the nervous system changes: A report elusive but alopecia is the clue. BMJ 1993;307:324. of three cases. Q J Med 1974;43:293-319. 8. Reed D, Crawley J, Faro S, Pieper S, Kurland L. Thallotoxicosis, acute 14. De Groot G, van Leusen R, van Heijst AN. Thallium concentrations in manifestations and sequele. J Am Med Assoc 1963;183;516-22. fluids and tissues in a fatal case of thallium poisoning. Vet Hum Toxicol 9. Insley BM, Grufferman S. Ayliffe. Thallium poisoning in cocaine abus- 1985;27:115-9. ers. Am J Emerg Med 1986;4:545-8. 15. Heath A, Ahlmen J, Branegard B, Lindstedt S, Wickstrom I, Andersen 10. Saha A, Sadhu HG, Karnik AB, Patel TS, Sinha SN, Saiyed HN. Ero- O. Thallium poisoning—toxin and therapy in three cases. J Toxicol sion of Nails Following Thallium Poisoning: A Case Report. Occup Clin Toxicol 1983;20:451-63. Environ Med 2004. (In Press). 16. Roby DS, Fein AM, Bennett RH, Morgan LS, Zatuchni J, Lippmann 11. Hoffman RS. Thallium poisoning during pregnancy: a case report and ML. Cardiopulmonary effects of acute poisoning. Chest 1984;85:236- comprehensive literature review. J Toxicol Clin Toxicol 2000;38:767-75. 40.

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