Metal toxicity

Last updated: March 13, 2023

Summary

Exposure to heavy metals such as mercury, lead, iron, and arsenic is harmful to the human body and can potentially cause both acute symptoms (e.g., local irritation, gastroenteritis, and pneumonia) and longterm effects (e.g., abnormal physical development, cancer, damage to the central nervous system, and kidney). Toxic metals have many industrial purposes and therefore represent occupational hazards for a number of professions. Industrial pollution with heavy metals can affect the wider population through the contamination of food (e.g., mercury in fish) and water (e.g., lead, arsenic).

For chronic diseases resulting from the inhalation of metal dust, see “Pneumoconiosis.”

General considerations

Overview of metal toxicities ^[1]^[2]^[3]^[4]
Metal	Features of intoxication	Pathomechanism	Diagnostics	Treatment
Arsenic	Acute Nausea and vomiting Abdominal pain QT prolongation Chronic Hyperkeratosis Mees lines: white bands across the nails Neuropathy Severe intoxication may cause garlic‑like odor of the breath	Induces oxidative stress on endothelial cells and disrupts ATP production	Detectable in urine	Dimercaprol Succimer (dimercaptosuccinic acid): more commonly used in children
Lead	Intestinal colic (lead colic) Purple-blue line on the gums (lead line or Burton line) Paralysis of the radial or peroneal nerve (wrist/foot drop) Symptoms of anemia Nephropathy Encephalopathy, cognitive impairment Basophilic stippling of erythrocytes (disorder of heme synthesis)	Inhibition of aminolevulinate dehydratase → disruption of heme synthesis	Detectable in blood	Succimer Dimercaprol Calcium disodium edetate (CaNa₂EDTA)
Iron	Hemorrhagic gastroenteritis, shock symptoms Neurotoxicity and nephrotoxicity, respiratory depression	Free radical formation and lipid peroxidation → disruption of oxidative phosphorylation and mitochondrial function → cellular death	Clinical	Deferoxamine
Mercury	Purple-blue discoloration along the margins of the gums Neuropsychiatric symptoms including anxiety, abnormal irritability, ataxia, and tremor Gingival and/or buccal inflammation Severe poisoning leads to Minamata disease	Irreversibly inhibits selenoenzymes (restore antioxidant molecules) → ↑ oxidative damage ^[5]	Inorganic mercury in urine Organic mercury in blood	Dimercaprol Succimer (dimercaptosuccinic acid, DMSA) 2,3 dimercaptopropane-1-sulfonate
Chromium	Contact dermatitis Allergic asthma Hemorrhagic gastroenteritis Ulcerations of the nasal septum Welder's lung Lung cancer	Hexavalent chromium compounds → crossing into the cell membrane → reduction to trivalent chromium compounds → intracellular accumulation	Detectable in blood and urine	Stop exposure Cleaning contaminated skin with running water
Gold	Hypersensitivity reaction Pruritus Dermatitis Metallic taste Nephrotoxicity	Gold nanoparticles form reactive oxygen species → oxidative damage ^[6]	Clinical	Discontinuation of gold therapy
Copper	Gastrointestinal symptoms Abdominal pain Diarrhea Vomiting Altered level of consciousness Headache Coma Complications Liver failure Renal failure Intravascular hemolysis Death ^[7]	Catalyzes formation of reactive oxygen species → oxidative damage (via redox reactions) ^[8]	Detectable in blood and urine ^[7]	D-penicillamine ^[7]

Arsenic toxicity

Sources of exposure: metal smelting; , pesticides, herbicides, contaminated water (esp. in developing countries) ^[9]
Pathophysiology
- Has direct toxic effects on endothelial cells
- Induces oxidative stress, and disrupts ATP production
Clinical features ^[2]^[3]
- Acute toxicity
  - Nausea and vomiting
  - Abdominal pain, diarrhea
  - Tachycardia, QT prolongation
  - Garlic-like odor on the breath
  - CNS (coma, seizures)
- Chronic toxicity
  - Carcinogenic
    - Lung cancer
    - Skin cancer (squamous cell carcinoma)
    - Hepatic angiosarcomas
  - Arsenical keratosis: hyperkeratosis (especially on the soles and palms) → risk of developing squamous cell carcinoma)
  - White bands across the nails (Mees lines)
  - Peripheral polyneuropathy
Diagnostics: urinalysis
Treatment ^[1]
- Consider gastric lavage, activated carbon in acute toxicity
- Dimercaprol, succimer (in children)

Arsenical keratosis after long-term exposure to arsenic Squamous cell carcinoma in situ due to chronic arsenic exposure

Lead toxicity

Sources of exposure ^[10]^[11]^[12]
- Battery manufacturing, metallurgy, corrosion inhibition
- Gun ranges (lead ammunition) ^[13]
- Tableware containing lead (e.g., ceramic crockery)
- Drinking water (contaminated by lead plumbing) or contaminated sources
- Lead-containing paint (common source of exposure in children) from:
  - Antique or imported toys
  - Walls of older homes (houses built before 1978 may still have lead-based paint) ^[14]
- Consumption of illicitly distilled alcohol (moonshine)
Pathophysiology: : inhibition of aminolevulinate dehydratase and ferrochelatase → heme synthesis disruption → ↑ protoporphyrin and ↑ aminolevulinic acid in RBCs
Clinical features
- Nervous system ^[15]^[16]
  - Polyneuropathy, encephalopathy, headache, fatigue, muscle weakness, paresthesias, delirium, seizures
  - Demyelination of peripheral nerves→ peripheral neuropathy → paralysis of muscles supplied by the radial or peroneal nerve (wrist/foot drop)
  - Cognitive impairment, memory loss
  - Acute encephalopathy: persistent vomiting, ataxia, seizures, coma
- Kidneys: nephropathy, renal cell carcinoma
- Red blood cells: symptoms of anemia
- Other:
  - Purple-blue line on the gums (lead line or Burton line)
  - Severe abdominal pain (lead colic)
  - Constipation
  - Hypertension
  - Miscarriages, infertility
- Children are especially susceptible to the neurologic effects of lead poisoning
  - Many children are asymptomatic and should be assessed for blood lead levels if they have risk factors
  - “See screening in high-risk pediatric populations” below
Diagnostics
- Blood lead level (BLL) measurement
- Basophilic stippling of erythrocytes on peripheral blood smear (lead inhibits RNA degeneration)
- Microcytic, hypochromic anemia (lead inhibits heme synthesis) ^[17]
- Ring sideroblasts in bone marrow
- Imaging (not routinely indicated)
  - Lead flecks on abdominal x-ray
  - Lead lines on long-bone x-rays
- Inspection of the patient's environment for lead sources to prevent further exposure
Screening in high-risk pediatric populations ^[18]^[19]
- Living in older housing with peeling paint
- Sibling or playmate with lead poisoning
- Recent immigrant, refugee, or foreign adoptee
- History of pica
Treatment of lead toxicity ^[20]
- Decrease exposure: professional lead paint abatement, dust reduction, minimization of contact with bare soil
- Nutrition: calcium, iron, zinc, vitamin C, and vitamin D-rich diet ^[21]
- Chelation therapy indications: ^[22]
  - Oral succimer with/without intravenous or intramuscular CaNa₂EDTA (calcium disodium ethylenediamine tetraacetic acid) ^[23]
    - Children with BLL ≥ 45 μg/dl ^[24]
    - Asymptomatic adults with BLL ≥ 80 μg/dl
    - Symptomatic adults with BLL ≥ 50 μg/dl
  - IM dimercaprol (British antilewisite, BAL) with/without CaNa₂EDTA
    - Patients with lead encephalopathy
    - BLL ≥ 70 μg/dl

ABCDEFGH: Anemia, Basophilic stippling, Constipation, Demyelination, Encephalopathy, Foot drop, Gum deposition/Growth retardation/Gout, Hyperuricemia/Hypertension

“It sucks to be a child with lead poisoning!” - succimer is used to treat lead poisoning in children.

Heme synthesis and corresponding diseases Burton line Basophilic stippling of erythrocytes Lead poisoning

Iron toxicity

Definition: chemical element often used as a supplement in pediatrics and prenatal care and in the management of anemia
Pathophysiology
- Iron-mediated toxicity and cell death is caused by:
  - Free radical formation
  - Lipid peroxidation
  - Disruption of oxidative phosphorylation and mitochondrial function
Types

Acute vs. chronic iron poisoning
Characteristics	Acute iron poisoning	Chronic iron poisoning
Epidemiology	Toxicity is common in pediatric care (ingestion of red iron tablets mistaken for candy).	Most commonly occurs in patients with primary (hereditary) or secondary (e.g., blood transfusion in sickle cell disease/thalassemia) hemochromatosis
Clinical features	Initially hemorrhagic gastroenteritis, possibly symptoms of shock Abdominal pain, vomiting (most common symptoms in children) Causes dark-colored stools Possibly Renal and liver failure, unconsciousness, and respiratory depression GI scarring and stricture formation → intestinal obstruction	Hepatomegaly, cirrhosis Diabetes mellitus Skin hyperpigmentation (bronze skin) Hypogonadism, erectile dysfunction Arthralgia Cardiomyopathy, arrhythmia, CHF
Diagnostics	Anion gap metabolic acidosis Abdominal x-ray: Radiopaque iron tablets may be visible.	↑ Liver enzymes (AST, ALT) Further diagnostics depend on the suspected underlying disease.
Management	Chelation with deferoxamine OR deferasirox Gastric lavage or whole bowel irrigation	Phlebotomy in patients without anemia Chelation with deferoxamine OR deferasirox

Mercury toxicity

Sources of exposure
- Organometallic methylmercury in fish ^[25]
- Inorganic, metallic mercury in thermometers, amalgam (dental fillings), pyrotechnics, and metalworking
Clinical features
- Acute toxicity
  - Gastroenteritis (bloody diarrhea)
  - Kidney failure
  - Inflammation of the airways (from inhalation exposure)
- Chronic toxicity (Minamata disease) ^[26]
  - Glomerulonephritis (albuminuria)
  - CNS disorders: ataxia; , erethism mercuralis (abnormal irritability; ), and tremor
  - Polyneuropathy
  - Gingival and/or buccal inflammation with bluish‑violet discoloration of the margins of the gums ^[27]
  - Teratogenicity
Diagnostics ^[28]
- Inorganic mercury in urine
- Organic mercury in blood
Treatment ^[28]^[29]
- Dimercaprol (BAL)
- Succimer (dimercaptosuccinic acid; DMSA)
- 2,3 dimercaptopropane-1-sulfonate (DMPS)
- D‑penicillamine

Cadmium toxicity

Sources of exposure: food, batteries, metallurgy, plastics and paint manufacturing, cigarette smoke
Clinical features ^[30]^[31]
- Acute toxicity: irritation of the airways (pulmonary edema, interstitial pneumonia)
- Chronic toxicity
  - Kidney damage (tubulointerstitial nephritis), renal cell carcinoma
  - Lung disease (emphysema, carcinoma)
  - Anosmia
  - Osteoporosis/osteomalacia
  - Itai‑itai disease: chronic cadmium toxicity with kidney failure and osteomalacia (with aching joints and bones)
Diagnostics
- Acute toxicity: increased blood cadmium
- Chronic toxicity
  - Increased urine cadmium
  - β2 microglobulin in urine
Treatment: not known ^[32]

Chromium toxicity

Sources of exposure: galvanization (chrome plating), paint and glass manufacturing, tanning leather, building materials (potassium dichromate in cement → “cement eczema” is an occupational hazard among construction workers)
Pathophysiology: hexavalent chromium compounds → crossing into the cell membrane → reduction to trivalent chromium compounds → intracellular accumulation
Clinical features ^[33]
- Acute toxicity
  - Contact dermatitis
  - Allergic asthma
  - Hemorrhagic gastroenteritis
- Chronic toxicity
  - Ulceration of the nasal septum from contact with contaminated fingers → risk of perforation
  - Lung cancer
  - Welder's lung
Diagnostics: urine or blood
Treatment ^[33]
- Stop exposure.
- Cleaning contaminated skin with running water

Thallium toxicity

Sources of exposure
- Glass industry
- Rat poison
Clinical features
- Hair loss
- Polyneuropathy
- Memory disorders ^[34]
- White bands across the nails (Mees lines)
Diagnostics: present in blood and/or urine

Vanadium (vanadium pentoxide)

Sources of exposure: metallurgy, alloys
Clinical features
- Acute
  - Mucous membrane irritation
  - Bronchitis
  - Bronchopneumonia
- Chronic
  - Welder's lung
  - Pulmonary fibrosis
  - Black‑green discoloration of the tongue
Diagnostics: present in blood and/or urine

Manganese toxicity

Sources of exposure: metallurgy, welding
Clinical features ^[35]
- Manganese pneumonia: a form of fibrinous pneumonia
- Manganism: a form of parkinsonism (see “Secondary parkinsonism”)
- Decreased fertility
- Fetal toxicity
Treatment ^[35]
- Chelation therapy with EDTA
- Levodopa for manganism

Nickel toxicity

Sources of exposure: alloys (e.g., in coins, jewelry)
Clinical features
- Acute toxicity: contact dermatitis
- Chronic toxicity
  - Squamous‑cell carcinoma of the nose or paranasal sinuses
  - Lung cancer

Platinum toxicity

Sources of exposure
- Jewelry
- Catalytic converters
Clinical features
- Obstructive lung diseases (immediate reaction allergy)
- Nephrotoxicity

Gold toxicity

Source of exposure ^[36]^[37]^[38]
- Chrysotherapy
- Gold nanoparticles for diagnosis (e.g., antibody sensing) and therapy (e.g., cancer treatment)
Clinical features
- Typical
  - Pruritus
  - Dermatitis
  - Stomatitis
  - Metallic taste
- Severe cases
  - Vasomotor reaction: nausea, flushing, hypotension including syncope, sweating, and weakness
  - Renal: proteinuria
  - Hematological: thrombocytopenia, neutropenia, and aplastic anemia
  - Gastrointestinal: diarrhea and enterocolitis
Diagnostics: laboratory studies
- CBC: decreased WBCs, decreased platelet count
- LFTs: decreased transaminases
- Renal function tests: increased creatinine, increased urea, increased uric acid
- Urinalysis: proteinuria, hematuria
Treatment: discontinuation of gold therapy
Complications
- Renal: membranous glomerulonephritis
- Cardiovascular: myocardial infarction, stroke

Copper toxicity

Source of exposure ^[7]
- Genetic: Wilson disease
- External
  - Uncoated copper cookware heated with acidic food
  - Contaminated water
  - Copper-containing creams for burn healing
  - Suicide attempts (via i.v. copper sulfate injection)
Clinical features
- Gastrointestinal: abdominal pain, diarrhea, or vomiting (early symptoms)
- Hepatic: jaundice
- Altered mental status: encephalopathy, coma
Diagnostics ^[39]
- Laboratory studies: increased serum copper, ceruloplasmin
- Urinalysis: increased copper excretion
Treatment ^[7]
- Early stage: zinc
- Chelating agents: penicillamine, trientine
Complications
- Liver failure
- Heart failure
- Kidney failure
- Intravascular hemolysis
- Death

References

Lansdown ABG. GOLD: human exposure and update on toxic risks. Crit Rev Toxicol. 2018; 48 (7): p.596-614.doi: 10.1080/10408444.2018.1513991 . | Open in Read by QxMD
Arthur AB, Klinkhoff A, Teufel A. Nitritoid reactions: case reports, review, and recommendations for management.. J Rheumatol. 2001; 28 (10): p.2209-12.
Dreaden EC, Alkilany AM, Huang X, Murphy CJ, El-Sayed MA. The golden age: gold nanoparticles for biomedicine.. Chem Soc Rev. 2012; 41 (7): p.2740-79.doi: 10.1039/c1cs15237h . | Open in Read by QxMD
Arsenic Toxicity - How Should Patients Overexposed to Arsenic Be Treated and Managed?. https://www.atsdr.cdc.gov/csem/csem.asp?csem=1&po=13. Updated: January 15, 2010. Accessed: January 9, 2018.
Arsenic Toxicity - Clinical Assessment. https://www.atsdr.cdc.gov/csem/csem.asp?csem=1&po=12. Updated: January 15, 2010. Accessed: January 9, 2018.
Ratnaike RN. Acute and chronic arsenic toxicity.. Postgrad Med J. 2003; 79 (933): p.391-6.
Pearce JMS. Burton’s line in lead poisoning. Eur Neurol. 2006; 57 (2): p.118-119.doi: 10.1159/000098100 . | Open in Read by QxMD
Ralston NV, Raymond LJ.. Dietary selenium's protective effects against methylmercury toxicity.. Toxicology. 2010.
Umair M, Javed I, Rehman M, Madni A, Javeed A, Ghafoor A, Ashraf M.. Nanotoxicity of Inert Materials: The Case of Gold, Silver and Iron.. Journal of Pharmacy and Pharmaceutical Sciences. 2016.
Royer A, Sharman T. Copper Toxicity. StatPearls. 2020.
Lisa M. Gaetke, Hannah S. Chow-Johnson, and Ching K. Chow. Copper: Toxicological relevance and mechanisms. Archives of Toxicology. 2015.
Arsenic Fact Sheet. http://www.who.int/mediacentre/factsheets/fs372/en/. Updated: November 1, 2017. Accessed: January 9, 2018.
Eating Fish: What Pregnant Women and Parents Should Know. https://www.fda.gov/Food/ResourcesForYou/Consumers/ucm393070.htm. Updated: November 29, 2017. Accessed: January 13, 2018.
Minamata Disease. http://www.bu.edu/sustainability/minamata-disease/. . Accessed: May 10, 2017.
Khosrojerdi H, Sarabadani J. Bluish discoloration of periodontal tissue. APJMT. 2012; 1 (1).doi: 10.22038/apjmt.2012.45 . | Open in Read by QxMD
Ye B-J, Kim B-G, Jeon M-J, et al. Evaluation of mercury exposure level, clinical diagnosis and treatment for mercury intoxication. Ann Occup Environ Med. 2016; 28 (1): p.5.doi: 10.1186/s40557-015-0086-8 . | Open in Read by QxMD
Bernhoft RA. Mercury toxicity and treatment: A review of the literature. J Environ Public Health. 2012; 2012: p.1-10.doi: 10.1155/2012/460508 . | Open in Read by QxMD
Lead Poisoning and Health Fact Sheet. http://www.who.int/mediacentre/factsheets/fs379/en/. Updated: August 1, 2017. Accessed: January 9, 2018.
Wani AL, Ara A, Usmani JA. Lead toxicity: a review. Interdiscip Toxicol. 2015; 8 (2).doi: 10.1515/intox-2015-0009 . | Open in Read by QxMD
Flora G, Gupta D, Tiwari A. Toxicity of lead: a review with recent updates. Interdiscip Toxicol. 2012; 5 (2).doi: 10.2478/v10102-012-0009-2 . | Open in Read by QxMD
Laidlaw MAS, Filippelli G, Mielke H, Gulson B, Ball AS. Lead exposure at firing ranges—a review. Environmental Health. 2017; 16 (1).doi: 10.1186/s12940-017-0246-0 . | Open in Read by QxMD
Protect Your Family from Sources of Lead. https://www.epa.gov/lead/protect-your-family-sources-lead. Updated: May 26, 2022. Accessed: June 17, 2022.
Rao JVI, Vengamma B, Naveen T, Naveen V. Lead encephalopathy in adults. J Neurosci Rural Pract. 2014; 5 (2): p.161-163.doi: 10.4103/0976-3147.131665 . | Open in Read by QxMD
Mason LH, Harp JP, Han DY. Pb neurotoxicity: Neuropsychological effects of lead toxicity. BioMed Res Int. 2014; 2014: p.1-8.doi: 10.1155/2014/840547 . | Open in Read by QxMD
Aly MH, Kim HC, Renner SW, Boyarsky A, Kosmin M, Paglia DE. Hemolytic anemia associated with lead poisoning from shotgun pellets and the response to succimer treatment. Am J Hematol. 1993; 44 (4): p.280-283.doi: 10.1002/ajh.2830440412 . | Open in Read by QxMD
Warniment C, Tsang VK, Galazka VS. Lead poisoning in children. Am Fam Physician. 2010; 81 (6): p.751-757.
$A Targeted Approach to Blood Lead Screening in Children, Washington State - 2015 Expert Panel Recommendations.
$Managing elevated blood lead levels among young children: Recommendations from the Advisory Committee on Childhood Lead Poisoning Prevention.
Fact sheet: Nutrients that reduce lead poisoning. https://www.lead.org.au/fs/Fact_sheet-Nutrients_that_reduce_lead_poisoning_June_2010.pdf. Updated: June 1, 2010. Accessed: May 10, 2017.
$Oral chelation therapy for patients with lead poisoning.
$Review of Succimer for treatment of lead poisoning .
Peterson KE, Salganik M, Campbell C et al. Effect of succimer on growth of preschool children with moderate blood lead levels. Environ Health Perspect. 2004; 112 (2): p.233-237.
Godt J, Scheidig F, Grosse-Siestrup C, et al. The toxicity of cadmium and resulting hazards for human health. J Occup Med Toxicol. 2006; 1: p.22.doi: 10.1186/1745-6673-1-22 . | Open in Read by QxMD
Cadmium Toxicity - What Diseases Are Associated with Chronic Exposure to Cadmium?. https://www.atsdr.cdc.gov/csem/csem.asp?csem=6&po=12. Updated: December 10, 2013. Accessed: January 13, 2018.
Rafati-Rahimzadeh M, Rafati-Rahimzadeh M, Kazemi S, Moghadamnia A. Cadmium toxicity and treatment: An update. Caspian J Intern Med. 2017; 8 (3): p.135-145.doi: 10.22088/cjim.8.3.135 . | Open in Read by QxMD
Baruthio F. Toxic effects of chromium and its compounds. Biol Trace Elem Res. 1992; 32 (1-3): p.145-153.doi: 10.1007/bf02784599 . | Open in Read by QxMD
Crossgrove J, Zheng W. Manganese toxicity upon overexposure. NMR Biomed. 2004; 17 (8): p.544-553.doi: 10.1002/nbm.931 . | Open in Read by QxMD
Kemnic TR, Coleman M. Thallium Toxicity. StatPearls. 2020.
Buchwald A. Serum copper elevation from estrogen effect, masquerading as fungicide toxicity.. Journal of medical toxicology : official journal of the American College of Medical Toxicology. 2008; 4 (1): p.30-2.doi: 10.1007/BF03160948 . | Open in Read by QxMD
Mercury Levels In Fish. http://americanpregnancy.org/pregnancy-health/mercury-levels-in-fish/. Updated: February 21, 2017. Accessed: May 10, 2017.

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