Heavy metals are natural components of the earth's crust and as such are the oldest
toxins known to humans, having been used for thousands of years. Potential exposures
to heavy metals include natural sources (eg, groundwater, metal ores), industrial
processes, commercial products, folk remedies, and contaminated food and herbal products.
Virtually all heavy metals are toxic in sufficient quantities. Several, however, are
of particular interest because of their concentrations in the environment (lead, mercury,
and arsenic) or their use in criminal poisonings (arsenic and thallium). Entering
our bodies by way of food, drinking water, and air, metals produce toxicity by forming
complexes with cellular compounds containing sulfur, oxygen, or nitrogen. The complexes
inactivate enzyme systems or modify critical protein structures leading to cellular
dysfunction and death. The most commonly involved organ systems include central nervous,
gastrointestinal (GI), cardiovascular, hematopoietic, renal, and peripheral nervous
systems. The nature and severity of toxicity vary with the heavy metal involved, its
exposure level, chemical and valance states (inorganic versus organic), mode of exposure
(acute versus chronic), and the age of the individual. Children, with their developing
nervous systems, are particularly vulnerable to heavy metal intoxication (especially
lead) and deserve special consideration. This article presents an overview of the
aforementioned heavy metals with emphasis on clinical presentation and pathophysiology.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribers receive full online access to your subscription and archive of back issues up to and including 2002.
Content published before 2002 is available via pay-per-view purchase only.
Subscribe:
Subscribe to Clinics in Laboratory MedicineAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- A history of the use of arsenicals in man.J R Soc Med. 1993; 86: 287-289
- History of the development of arsenic derivatives in cancer therapy.Oncologist. 2001; 6: 3-10
- What killed Mozart?.Arch Intern Med. 2001; 161: 1381-1389
- Elemental contents in Napoleon's hair cut before and after his death: did Napoleon die of arsenic poisoning?.Anal Bioanal Chem. 2004; 379: 218-220
- Arsenic.in: Sullivan J.B. Krieger G.R. Clinical environmental health and toxic exposures. 2nd edition. Lippincott, William and Williams, Philadelphia2001: 858-866
- Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide.N Engl J Med. 1998; 339: 1341-1348
- Arsenic.in: Brent J. Wallace K.L. Burkhart K.K. Critical care toxicology. Mosby, Philadelphia2005: 799-815
- Chronic arsenic toxicity in Bangladesh and West Bengal, India: a review and commentary.Clin Toxicol. 2001; 39: 683-700
- Human exposures to arsenic from consumption of well water in West Bengal, India.Int J Occup Environ Health. 1998; 4: 217-230
- Arsenic poisoning.West J Med. 1988; 149: 308-315
- Arsenic speciation in human urine: are we all the same?.Toxicol Appl Pharmacol. 2004; 198: 297-306
- Speciation of key arsenic metabolic intermediates in human urine.Anal Chem. 2000; 72: 5172-5177
- Arsenic toxicology and industrial exposure.Annu Rev Pharmacol Toxicol. 1976; 16: 95-100
- Arsenate toxicity in human erythrocytes: characterization of morphologic changes and determination of the mechanism of damage.J Toxicol Environ Health A. 1998; 53: 345-355
- The metabolism of inorganic arsenic oxides, gallium arsenide, and arsine: a toxicochemical review.Toxicol Appl Pharmacol. 2003; 193: 309-334
- The metabolism of arsenic in humans acutely intoxicated by As2O3. Its significance for the duration of BAL therapy.Clin Toxicol. 1981; 18: 1067-1075
- Enzymatic reduction of arsenic compounds in mammalian systems: reduction of arsenate to arsenite by human liver arsenate reductase.Chem Res Toxicol. 2000; 13: 26-30
- Arsenic: health effects, mechanisms of actions, and research issues.Environ Health Perspect. 1999; 107: 593-597
- Arsenicals. Volume 3.Academic Press, New York1966
- Acute arsenical poisoning in Dunedin.N Z Med J. 1979; 89: 379-381
- Acute arsenic ingestion.Ann Emerg Med. 1987; 16: 702-704
- Massive arsenic poisoning effect of hemodialysis and dimercaprol on arsenic kinetics.Intensive Care Med. 1992; 18: 47-50
- Hematologic aspects of arsenic intoxication.N Engl J Med. 1965; 273: 18-23
- Electrocardiographic changes in acute arsenic poisoning.Ir J Med Sci. 1981; 150: 338-339
- Electrocardiographic findings with arsenic poisoning.Calif Med. 1968; 109: 158-162
- Subacute arsenic neuropathy: clinical and electrophysiological observations.J Neurol Neurosurg Psychiatry. 1981; 44: 896-900
- Electrophysiological profile in arsenic neuropathy.J Neurol Neurosurg Psychiatry. 1991; 54: 1103-1105
- Acute arsenic intoxication presenting as Guillain-Barre-like syndrome.Muscle Nerve. 1987; 10: 114-120
- Inorganic arsenic and the nervous system.Brain. 1966; 89: 479-498
- Chronic arsenic poisoning.Toxicol Lett. 2002; 128: 69-72
- Arsenic-induced skin toxicity.Hum Toxicol. 1989; 8: 99-104
- Cutaneous manifestations of arsenic poisoning due to certain Chinese herbal medicine.Australas J Dermatol. 1974; 15: 121-131
- Een verschijnsel bij polyneuritis arsenicosa.Ned Tijdschr Verloskd Gynaecol. 1919; 1: 391-396
- Blackfoot disease and arsenic: a never-ending story.J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2005; 23: 55-74
- Arsenic and cancer.Can Med Assoc J. 1975; 113: 396-401
- Acute maternal arsenic intoxication with neonatal death.Am J Dis Child. 1969; 117: 328-330
- Survival after a lethal dose of arsenic trioxide.Clin Toxicol. 2004; 42: 889-895
- Validity of hair mineral testing.Biol Trace Elem Res. 2002; 87: 1-28
- DMSA and DMPS—water soluble antidotes for heavy metal poisoning.Annu Rev Pharmacol Toxicol. 1983; 23: 193-215
- DMSA, DMPS, and DMPA—as arsenic antidotes.Fundam Appl Toxicol. 1984; 4: S58-S70
- Mobilization of heavy metals by newer, therapeutically useful chelating agents.Toxicology. 1995; 97: 23-38
- British Anti-Lewisite: 2, Dithiol compounds as antidotes for arsenic.Biochem J. 1946; 40: 535-548
- Hemodialysis clearance of arsenic.Clin Toxicol. 1980; 17: 451-456
- Arsine toxicity: chemical and mechanistic implications.J Toxicol Environ Health. 1995; 46: 399-409
- Acute arsine intoxication as a consequence of metal burnishing operations.Am J Ind Med. 1997; 32: 211-216
- Arsine poisoning.N Engl J Med. 1974; 291: 1171-1174
- The action of arsine on reduced glutathione.Med Lav. 1961; 52: 11-13
- In vitro tissue specificity for arsine and arsenite toxicity in the rat.Toxicol Sci. 1999; 52: 122-129
- Evidence for oxidative damage to red blood cells in mice induced by arsine gas.Toxicology. 1990; 63: 25-34
- Arsine poisoning, mode of action and treatment.J Pharmacol Exp Ther. 1946; 5: 99-108
- A study of the mechanism of acute hemolytic anemia from arsine.Med Lav. 1960; 51: 37-41
- Hematological responses to arsine exposure: quantitation of exposure response in mice.Fundam Appl Toxicol. 1985; 5: 499-505
- The effects of sulfur, thiol, and thiol inhibitor compounds on arsine-induced toxicity in the human erythrocyte membrane.Toxicol Sci. 2000; 55: 468-477
- Sequence of toxic events in arsine-induced hemolysis in vitro: implications for the mechanism of toxicity in human erythrocytes.Fundam Appl Toxicol. 1997; 38: 123-128
- Acute intravascular haemolysis and renal failure due to arsine poisoning.Postgrad Med J. 1969; 45: 170-172
- LLC-PK1 cells as a model for renal toxicity caused by arsine exposure.J Toxicol Environ Health A. 2000; 60: 67-79
- Renal damage from industrial arisine poisoning.Br J Ind Med. 1970; 27: 372-377
- Arsine poisoning.Br J Ind Med. 1956; 13: 217-221
- Emergency; arsine poisoning.AMA Arch Ind Health. 1957; 16: 32-41
- Rapid drop in infant blood lead levels during the transition to unleaded gasoline use in Santiago, Chile.Arch Environ Health. 2004; 59: 182-187
- Arsine gas poisoning: the importance of exchange transfusions in severe cases.Br J Ind Med. 1986; 43: 353-355
- Arsine poisoning.Br J Ind Med. 1970; 27: 56-60
- Arsine poisoning. Report of five cases in the petroleum industry and a discussion of the indications for exchange transfusion and hemodialysis.Arch Environ Health. 1969; 19: 133-143
- Metabolism of arsenic after acute occupational arsine intoxication.J Toxicol Environ Health. 1997; 52: 331-342
- Thallium and arsenic poisoning in a small midwest town.Ann Emerg Med. 2002; 39: 307-311
- The toxicology of thallium.Lancet Dec. 1930; 20: 1340-1344
- Thallium Poisoning.Arch Neurol. 1972; 26: 456-464
- Thallotoxicosis.JAMA. 1963; 183: 516-522
- Thallium poisoning: an outbreak in Florida 1988.South Med J. 1992; 85: 1203-1206
- Thallium poisoning in cocaine abusers.Am J Emerg Med. 1986; 4: 545-548
- Treatment of severe thallium intoxication.Clin Toxicol. 1997; 35: 97-100
- Thallium poisoning from maliciously contaminated food.Clin Toxicol. 1994; 32: 723-730
- Thallium poisoning: diagnosis may be elusive but alopecia is the clue.BMJ. 1993; 306: 1527-1529
- Thallium-contaminated heroin.Ann Intern Med. 1996; 124: 616
- Acute thallium toxicosis in a dog.J Am Vet Med Assoc. 1992; 201: 883-885
- Distribution of thallium in the organism and its elimination.Acta Pharmacol Toxicol (Copenh). 1956; 12: 251-259
- Thallium in biochemistry.Int J Biochem. 1990; 22: 429-438
- The interrelationship between thallium and potassium in animals.J Pharmacol Exp Ther. 1967; 155: 187-201
- A review of thallium toxicity.Vet Hum Toxicol. 1993; 35: 445-453
- Uncoupling of mitochondrial oxidative phosphorylation by thallium.Biochem Biophys Res Commun. 1976; 69: 68-73
- The effects of thallium salts, with particular reference to the nervous system changes: a report of three cases.Q J Med. 1974; 170: 293-319
- Skin signs in the diagnosis of thallium poisoning.Br J Dermatol. 1998; 138: 321-325
- Thallium poisoning.Clin Toxicol. 1980; 17: 133-146
- Acute alopecia: clue to thallium toxicity.Pediatr Dermatol. 1993; 10: 29-31
- Thallium poisoning: a dermatological perspective.Br J Dermatol. 1989; 121: 787-791
- Neuropsychology of thallium poisoning.J Neurol Neurosurg Psychiatry. 1997; 63: 247-250
- Acute thallium poisoning: toxicological and morphological studies of the nervous system.Ann Neurol. 1980; 10: 38-44
- Alopecia secondary to thallium intoxication.Arch Dermatol. 1969; 99: 777
- [Structure of the hair in thallium poisoning].Z Rechtsmed. 1984; 91: 201-214
- The ‘dying back’ process. A common denominator in many naturally occurring and toxic neuropathies.Arch Pathol Lab Med. 1979; 103: 659-664
- What have we learnt from Graham Frederick Young? Reflections on the mechanism of thallium neurotoxicity.Neuropathol Appl Neurobiol. 1991; 17: 3-9
- Soluble or insoluble Prussian blue for radiocesium and thallium poisoning?.Ann Pharmacother. 2004; 38: 1509-1514
- Thallium toxicity and the role of Prussian blue in therapy.Toxicol Rev. 2003; 22: 29-40
- Combined D-penicillamine and Prussian blue as antidotal treatment against thallotoxicosis in rats: evaluation of cerebellar lesions.Toxicology. 1994; 89: 15-24
- Ferric-cyanoferrate (II):An effective antidote in thallium poisoning.Eur J Pharmacol. 1969; 6: 340-344
- Prussian blue in therapy of thallotoxicosis: an experimental and clinical investigation.Acta Med Scand. 1971; 189: 321-324
- Elimination of thallium in rats as influenced by Prussian blue and sodium chloride.Acta Pharmacol Toxicol (Copenh). 1976; 39: 256-261
- Effects of Prussian blue and N-acetylcysteine on thallium toxicity in mice.Clin Toxicol. 1997; 35: 163-166
- Thallium pharmacokinetics and its modification by Prussian blue.Naunyn Schmiedebergs Arch Pharmacol. 1974; 284: 295-306
- D-penicillamine and Prussian blue as antidotes against thallium intoxication in rats.Toxicology. 1992; 74: 69-76
- Dimercaptosuccinic acid and Prussian blue in the treatment of acute thallium poisoning in rats.Clin Toxicol. 2003; 41: 137-142
- Studies of any toxicological effects of Prussian blue compounds in mammals–a review.Food Chem Toxicol. 1994; 32: 577-582
- The effect various substances on the excretion and the toxicity of thallium in the rat.Acta Pharmacol Toxicol (Copenh). 1956; 12: 260-268
- The effect of Prussian blue and sodium-ethylenediaminetetraacetic acid on the faecal and urinary elimination of thallium by the dog.Res Vet Sci. 1978; 25: 337-342
- Comparative efficacy of thallium adsorption by activated charcoal, Prussian blue, and sodium polystyrene sulfonate.Clin Toxicol. 1999; 37: 833-837
- Parameters for the adsorption of thallium ions by activated charcoal and Prussian blue.Clin Toxicol. 1984; 22: 331-339
- Hat industry.in: Goldwater L.J. Mercury: a history of quicksilver. York Press, Baltimore (MD)1955
- Heavy metal toxicity, Part I: arsenic and mercury.J Emerg Med. 1998; 16: 45-56
- ATSDR. Toxicological profile for MERCURY.in: US Department of Health and Human Services. Agency for Toxic Substances and Disease Registry, Atlanta (GA)1999: 3-676
- “Two minutes with Venus, two years with mercury”: mercury as an antisyphilitic chemotherapeutic agent.J R Soc Med. 1990; 83: 392-395
- Lide Dr., CRC handbook of chemistry and physics. 86th edition. CRC Press, Boca Raton (FL)2005
- Mercury exposure: evaluation and intervention in the inappropriate use of chelation agents in the diagnosis and treatment of putative mercury poisoning.Neurotoxicology. 2005; 26: 691-699
- Mercury exposure and cutaneous disease.J Am Acad Dermatol. 2000; 43: 81-90
- Elemental mercury embolism to the lung.N Engl J Med. 2000; 342: 1791
- Systemic mercury intoxication following rupture of a Miller-Abbott tube.Am J Gastroenterol. 1978; 69: 478-480
- Elemental mercury in the appendix: an unusual complication of a Mexican-American folk remedy.Clin Toxicol. 1999; 37: 103-107
- Conservative management of elemental mercury sequestration in the appendix.Clin Toxicol. 2003; 41: A52
- Mercury neurotoxicity: effects and mechanisms.in: Chang L.W. Dyer R.S. Handbook of neurotoxicology. Marcel Dekker, New York1995: 31-59
- Respiratory failure and death following acute inhalation of mercury vapor: a clinical and histologic perspective.Chest. 1991; 99: 185-190
- Acute mercury vapour intoxication: report of six cases.Nephrol Dial Transplant. 1989; 4: 133-136
- The toxicology of mercury: current exposures and clinical manifestations.N Engl J Med. 2003; 349: 1731-1737
- The rise and fall of pink disease.Soc Hist Med. 1997; 10: 291-304
- Mercury poisoning and acrodynia.Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998; 85: 349
- Adult pink disease.BMJ. 1970; 1: 298
- Can tremor be used to measure the effect of chronic mercury exposure in human subjects?.Neurotoxicology. 1996; 17: 213-227
- Acute mercury intoxication examined with coordination ability and tremor.Neurotoxicol Teratol. 1996; 18: 505-509
- Acute mercury poisoning (acrodynia) mimicking pheochromocytoma in an adolescent.J Pediatr. 1993; 122: 252-253
- Mercury intoxication and arterial hypertension: report of two patients and review of the literature.Pediatrics. 2000; 105: E34
- Mercury intoxication presenting with hypertension and tachycardia.Arch Dis Child. 1999; 80: 556-557
- Dimercaptosuccinic acid loading test for assessing mercury burden in healthy individuals.Ann Clin Biochem. 2004; 41: 233-236
- Unanswered questions in metal chelation.Clin Toxicol. 1992; 30: 529-547
- The first known use of vermillion.Experientia. 1995; 51: 759-761
- Yellow mercuric oxide ointment and mercury intoxication.Eur J Pediatr. 1986; 145: 217-218
- Case report: severe mercuric sulphate poisoning treated with 2,3-dimercaptopropane-1-sulphonate and haemodiafiltration.Crit Care. 2003; 7: R1-R6
- Gastrointestinal absorption of inorganic mercuric compounds in vivo and in situ.Toxicol Appl Pharmacol. 1984; 74: 223-229
- Gingivo-mucosal and cutaneous reactions to amalgam fillings.J Clin Periodontol. 2005; 32: 430-433
- Oral lichen planus and allergy to dental amalgam restorations.Arch Dermatol. 2004; 140: 1434-1438
- Acute mercury intoxication with lichenoid drug eruption followed by mercury contact allergy and development of antinuclear antibodies.Acta Derm Venereol. 1992; 72: 294-296
- Homocysteine and the renal epithelial transport and toxicity of inorganic mercury: role of basolateral transporter organic anion transporter 1.J Am Soc Nephrol. 2004; 15: 2023-2031
- Plasma mercury during prolonged acute renal failure after mercuric chloride ingestion.Hum Toxicol. 1983; 2: 535-537
- Membranous nephropathy from exposure to mercury in the fluorescent-tube-recycling industry.Nephrol Dial Transplant. 2001; 16: 2253-2255
- Minamata disease: methylmercury poisoning in Japan caused by environmental pollution.Crit Rev Toxicol. 1995; 25: 1-24
- The discovery of the causal agent of Minamata disease.Am J Ind Med. 1992; 21: 275-280
- Congenital Minamata disease: warnings from Japan's experience.J Child Neurol. 2000; 15: 458-464
- The Minamata disease.Am J Forensic Med Pathol. 1982; 3: 335-338
- Minamata disease.Neuropathology. 2000; 20: S14-S19
- Methylmercury poisoning in Iraq.Science. 1973; 181: 230-241
- Metabolism of methyl mercury (203Hg) compounds in man.Arch Environ Health. 1969; 19: 478-484
- Dose-dependence of methylmercury metabolism. A study of distribution: biotransformation and excretion in the squirrel monkey.Arch Environ Health. 1975; 30: 307-313
- An autopsy case of Minamata disease (methylmercury poisoning): pathological viewpoints of peripheral nerves.Toxicol Pathol. 2002; 30: 714-722
- Congenital Minamata disease: intrauterine methylmercury poisoning.Teratology. 1978; 18: 285-288
- Clinical and epidemiological aspects of methylmercury poisoning.Postgrad Med J. 1980; 56: 1-10
- Association between thimerosal-containing vaccine and autism.JAMA. 2003; 290: 1763-1766
- Disposition of toxic drugs and chemicals in man.6th edition. Biomedical Publications, Foster City (CA)2002
- Delayed cerebellar disease and death after accidental exposure to dimethylmercury.N Engl J Med. 1998; 338: 1672-1676
- Tests of efficacy of antidotes for removal of methylmercury in human poisoning during the Iraq outbreak.J Pharmacol Exp Ther. 1981; 218: 74-83
- Treatment of methyl mercury poisoning in mice with 2,3-dimercaptosuccinic acid and other complexing thiols.Acta Pharmacol Toxicol (Copenh). 1978; 42: 248-252
- The efficacy of 2,3-dimercaptopropanol and D-penicillamine on methyl mercury induced neurological signs and weight loss.Life Sci. 1978; 23: 1025-1034
- Lead poisoning in a historical perspective.Am J Ind Med. 2000; 38: 244-254
- Lead Poisoning and the fall of Rome.J Gnathol. 1965; 85: 53-60
- Perspectives on lead toxicity.Clin Biochem. 1993; 26: 371-381
- Occupational lead poisoning.Am Fam Physician. 1998; 57 (731–2): 719-726
- Management of lead poisoning from ingested fishing sinkers.Arch Pediatr Adolesc Med. 1998; 152: 485-488
- Seasonality and trend in blood lead levels of New York state children.BMC Pediatr. 2004; 4: 8
- Intellectual impairment in children with blood lead concentrations below 10 microg per deciliter.N Engl J Med. 2003; 348: 1517-1526
- Lead neurotoxicity in children: basic mechanisms and clinical correlates.Brain. 2003; 126: 5-19
- Neurologic concepts of lead poisoning in children.Pediatr Ann. 1992; 21: 384-388
- Selective vulnerability of the developing brain to lead.Curr Opin Neurol. 1998; 11: 689-693
- Lead-induced changes in human erythrocytes and lymphocytes.J Appl Toxicol. 2005; 25: 109-114
- Comparison of dimercaptosuccinic acid and calcium disodium ethylenediaminetetraacetic acid versus dimercaptopropanol and ethylenediaminetetraacetic acid in children with lead poisoning.J Pediatr. 1997; 130: 966-971
- American Academy of Pediatrics issues treatment guidelines for lead exposure in children.Am Fam Physician. 1995; 52: 1022-1023
- Effect of chelation therapy on the neuropsychological and behavioral development of lead-exposed children after school entry.Pediatrics. 2004; 114: 19-26
- The effect of chelation therapy with succimer on neuropsychological development in children exposed to lead.N Engl J Med. 2001; 344: 1421-1426
- The relationship of bone and blood lead to hypertension. The normative aging study.JAMA. 1996; 275: 1171-1176
- Pica-associated cerebral edema in an adult.J Neurol Sci. 2004; 225: 149-151
- Severe lead-induced peripheral neuropathy in a dialysis patient.Am J Kidney Dis. 2000; 35: 963-968
- Toxicokinetics of bone lead.Environ Health Perspect. 1991; 91: 33-37
- Lead poisoning from retained lead projectiles: a critical review of case reports.Hum Exp Toxicol. 1994; 13: 735-742
- Effect of repeated occupational exposure to lead, cessation of exposure, and chelation on levels of lead in bone.Am J Ind Med. 1991; 20: 723-735
Article info
Identification
Copyright
© 2006 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
