Iron toxicity

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  • Iron is the 4th most abundant atomic element in the earth's crust
  • Biologically a component of hemoglobin, myoglobin, catalase, xanthine oxidase, etc
  • Uptake highly regulated
  • Amount of elemental iron ingested determines the risk, not the amount of iron salt[1]

Elemental Iron Percentages

Iron Preparation % of Elemental Iron
Ferrous Fumarate 33%
Ferrous Sulfate 20%
Ferrous Gluconate 12%
Ferric pyrophosphate 30%
Ferroglycine sulfate 16%
Ferrous carbonate (anhydrous) 38%


Toxicity determined by mg/kg of elemental iron ingested[2]

Severity Elemental Iron Dose (mg/kg)^
Mild 10-20
Moderate 20-60
Severe >60

^Total amount of elemental iron ingested calculated by multiplying estimated number of tablets by the percentages of iron in the tablet preparation (see above)


  • Direct caustic injury to gastric mucosa[3]
  • Occurs early, usually within several hours
    • Causing vomiting, diarrhea, abdominal pain, and GI bleeding
    • Usually affects, the stomach, duodenum, colon rarely affected
    • Can lead to formation of gastric strictures 2-8 weeks post-ingestion
  • Impaired cellular metabolism
    • Inhibiting the electron transport chain causes lactic acidosis
    • Direct hepatic, CNS, and cardiac toxicity (decreased CO and myocardial contractility)
    • Cell membrane injury from lipid peroxidation[4]
  • Increased capillary permeability
    • Hypotension
    • Venodilation
    • Hypovolemic shock
  • Portal vein iron delivery to liver
    • Overwhelm storage capacity of Ferritin
    • Hepatotoxicity (cloudy swelling, periportal hepatic necrosis, elevated transaminases)
    • Destroys hepatic mitochondria, disrupts oxidative phosphorylation → worsening metabolic acidosis
  • Thrombin formation inhibition
    • Coagulopathy - direct effect on vitamin K clotting factors

Clinical Features

  • Absence of GI symptoms within 6hr of ingestion excludes significant iron ingestion (exception: enteric coated tablets)
  • Significant iron toxicity can result in a severe lactic acidosis from hypoperfusion due to volume loss, vasodilation and negative inotropin effects.
Iron Toxicity Stages
Staging Clinical Effect Time Frame
Stage 1 GI irritation: Nausea, vomiting, diarrhea, abdominal pain, hematemesis, hematochezia 30 mins-6 hours
Stage 2: Latent GI symptoms may improve or resolve 6-24 hours
Stage 3: Shock and metabolic acidosis Metabolic acidosis, lactic acidosis, dehydration 6-72 hours
Stage 4: Hepatotoxicity/Hepatic necrosis Hepatic failure with jaundice 12-96 hours
Stage 5: Bowel obstruction GI mucosa healing leads to scarring 2-8 weeks
  • Stage I: GI toxicity: nausea, vomiting, diarrhea, GI bleeding from local corrosive effects of iron on the gastric and intestinal mucosa
  • Stage II: Quiescent phase with resolution of GI symptoms and apparent clinical improvement
    • controversy between toxicologists whether this stage exists in significant poisonings
  • Stage III: Systemic toxicity: shock and hypoperfusion
    • Primarily hypovolemic shock and acidosis, myocardial dysfunction also contributes
    • GI fluid losses, increase capillary permeability, decreased venous tone
    • Severe anion gap acidosis
    • Free radical damage to mitochondria disrupt oxidative phosphorylation which leads to lactic acidosis
    • Hepatotoxicity from iron delivery via portal blood flow
  • Stage IV: Clinical recovery, resolution of shock and acidosis usually by days 3-4
  • Stage V: Late onset of gastric and pyloric strictures (2-8 week later) [5]

Differential Diagnosis

Heavy metal toxicity





Urine changes from rusty colored vin rose to clear.
  • Two large-bore peripheral IVs
  • CBC
  • Chemistry - notice that this can appear like DKA
    • Anion gap metabolic acidosis
    • Hyperglycemia
  • Coags
  • LFTs
  • Iron levels
  • Urinalysis
    • Used to follow efficacy of Fe chelation
    • Urine changes from rusty colored vin rose to clear
  • Urine pregnancy test
  • Type and Screen
  • XR KUB
    • In ambiguous cases consider abdominal xray as most Fe tabletss are radioopaque[6]
    • However, a normal XR KUB does not rule out significant ingestion, particularly if liquid iron or chewable vitamins with iron were ingested [7]
  • EKG
  • A serum glucose > 150mg/dL and leukocyte count above 15,000 is 100% Sp and 50% Sn in predicting Fe levels > 300mcg/mL, but the absence cannot exclude iron toxicity [8]


Serum iron concentration can guide treatment, but is not absolute in predicting or excluding toxicity.

Peak Serum Iron Level (mcg/dL)^ Category
<300 Nontoxic or mild
300-500 Significant GI symptoms and potential for systemic toxicity
>500 Moderate to severe systemic toxicity
>1000 Severe systemic toxicity and increased morbidity

^usually around 4hrs post ingestion although very high doses may lead to delayed peak



  • Patients with asymptomatic ingestion of < 20mg/kg of elemental iron may only require observation for 6 hours
  • Volume resuscitation

Orogastric Lavage

  • Unclear benefit. Risk of aspiration, perforation, laryngospasm
  • Intubate prior to procedure if patient not protecting airway
  • Indication: Normal saline via large orogastric tube for moderate to severe iron poisoning if there are still many iron tablets (20-30) in abdominal radiograph may be beneficial

Whole bowel irrigation

  • Indicated for large ingestion
  • Administer polyethylene glycol solution at 2 L/hr in adults and 250-500 mL/hr in children
  • Do not base only on radioopaque evidence of iron pills as not all formulations are readily visible on XR
  • Orogastric lavage only is not likely to be successful after iron tablets have moved past the pylorus
  • Supported by case reports and uncontrolled case series, but rationale behind it makes it largely supported by toxicologists[9]
  • Promotes increased gastric emptying and avoids large bezoar formation[10]


  • Indications
    • Pregnancy
    • Systemic toxicity and iron level > 350 mcg/dL
    • Iron level >500mcg/dL
    • Metabolic acidosis
    • Altered Mental Status
    • Progressive symptoms, including shock, coma, seizures, refractory GI symptoms
    • Large number of pills on KUB
    • Estimated dose > 60mg/kg Fe2+
  • Administered IV due to poor oral absorption
    • One mole of Deferoxamine (100mg) binds one mole of iron (9mg) to form ferrioxamine
    • Results in vin-rose urine (ferrioxamine is a reddish compound)
  • Dose
    • 5-15 mg/kg/hr, max of 35 mg/kg/hr or 6g total per day
    • Start slower at 5-8 mg/kg/hr if hypotensive and uptitrate as tolerated
    • Titrate up for worsening metabolic acidosis, progressive organ failure, persistent vin rosé urine (ongoing choleation)
    • Can give 90 mg/kg IM if unable to obtain IV, but must establish IV ASAP given patient will need fluid resuscitation
  • Adverse reactions
    • Hypotension
    • May cause flushing (anaphylactoid reaction)
    • Rarely causes ARDS - associated with prolonged use
    • Safe in pregnancy (give if obvious signs of shock/toxicity)


  • Not effective in removing iron due to large volumes of distribution
  • Dialysis can removes deferoxamine-iron complex in renal failure patients

Exchange transfusion

  • Minimal evidence but has been described in larger overdoses[11]

Not Indicated

Activated charcoal

  • Does not absorb significant amounts if iron and is not recommended

Poison Control

  • 1-800-222-1222 (United States)


  • Discharge after 6hr observation for asymptomatic (or only vomited 1-2x) AND ingestion <20mg/kg
  • Admit to ICU if deferoxamine required
  • Psychiatric evaluation if intentional ingestion

See Also

External Links


  1. The Royal Children's Hospital Melbourne Clinical Practice Guidelines. 2020.
  2. Robotham JL, Lietman PS: Acute iron poisoning. A review. Am J Dis Child 1980; 134:875-879.
  3. Robotham JL, Lietman PS. Acute iron poisoning. A review. Am J Dis Child 1980; 134:875-879.
  4. Aisen P et al. Iron toxicosis. Int Rev Exp Pathol 1990. 31:1-46.
  5. Fine, J. Iron Poisoning. Curr Probl Pediatr, Vol 30, Iss 3, p 71-90, March 2000
  6. The Royal Children's Hospital Melbourne Clinical Practice Guidelines. 2020.
  7. Everson GW, Oudjhane K, Young LW, Krenzelok EP. Effectiveness of abdominal radiographs in visualizing chewable iron supplements following overdose. Am J Emerg Med. 1989 Sep;7(5):459-63. doi: 10.1016/0735-6757(89)90245-3. PMID: 2757710.
  8. Lacouture PG et al. Emergency assessment of severity in iron overdose by clinical and laboratory methods. J Pediatr 1981; 99:89-91.
  9. Hoffman RS et al. Goldfrank's Toxicologic Emergencies. 10th Ed. Pg 618-219. McGraw Hill, 2015.
  10. Position paper: Whole bowel irrigation. J Toxicol Clin Toxicol 2004; 42:843-854.
  11. Movassaghi N. et al. Comparison of exchange transfusion and deferoxamine in the treatment of acute iron poisoning. J Pediatr 1969; 75:604-608.