Iron Poisoning (Acute Iron Toxicity) — Comprehensive Research Report

1. Disease Information

Overview. Iron poisoning (acute iron toxicity) is a potentially lethal toxidrome resulting from ingestion of excessive elemental iron, most commonly from iron-containing dietary supplements, prenatal vitamins, or ferrous salt medications (ferrous sulfate, ferrous gluconate, ferrous fumarate). It is distinct from chronic iron overload disorders (hereditary hemochromatosis, transfusional hemosiderosis) — iron poisoning is an acute, dose-dependent, environmentally/behaviorally mediated toxic exposure rather than a genetic disorder of iron regulation, although both converge on overlapping downstream cellular iron-toxicity mechanisms (oxidative stress, ferroptosis). It remains "one of the leading causes of fatal poisoning in children under 6 years of age" historically, and continues to be an important cause of both unintentional pediatric poisoning and intentional (self-harm) poisoning in adolescents/adults (StatPearls: Iron Toxicity; Wikipedia: Iron poisoning).

Key identifiers: - ICD-10-CM: T45.4X1A (Poisoning by iron and its compounds, accidental, initial encounter); related codes T45.4X2A (intentional self-harm), T45.4X3A (assault), T45.4X4A (undetermined intent) (icd10data.com) - ICD-10 (WHO): T45.4 — Poisoning by iron and its compounds - MeSH: Overlaps with "Iron Overload" (D019190) and "Poisoning" (D011041); no dedicated acute-toxicity MeSH heading distinct from the general iron/poisoning headings - MONDO: No MONDO term dedicated specifically to "acute iron poisoning" was identified in this search (MONDO's iron-related terms center on hereditary iron-overload disorders, e.g., hemochromatosis, FTH1-related iron overload — Orphanet: FTH1-related iron overload); acute iron poisoning is more naturally represented as a toxic/environmental exposure entity than a MONDO disease class - UMLS/SNOMED CT: "Iron poisoning" / "Iron toxicity" concepts exist in clinical toxicology terminologies (WikEM, Medscape "Iron Toxicity" and "Pediatric Iron Toxicity")

Synonyms: Acute iron toxicity, acute iron overdose, ferrous sulfate poisoning, iron ingestion (toxic), iron salt poisoning.

Data provenance: Knowledge derives predominantly from aggregated poison-control-center surveillance (American Association of Poison Control Centers, AAPCC National Poison Data System), case reports/series (often intentional adult overdoses), retrospective cohort studies, and animal (mouse/rat) toxicology data — rather than large prospective clinical trials, given the acute/emergent nature and rarity of severe cases.

Sources: PubMed: Acute iron poisoning (PMID:8187690) · StatPearls: Iron Overload and Toxicity · Merck Manual: Iron Poisoning · Medscape: Iron Toxicity

2. Etiology

Disease causal factor: Ingestion of a supratherapeutic dose of elemental iron, overwhelming normal intestinal mucosal regulation of iron absorption and saturating plasma iron-binding capacity (transferrin), producing free/non-transferrin-bound iron that is directly cytotoxic. This is a purely environmental/exposure-mediated disease process — there is no genetic causal variant required, though genetic background (e.g., HFE hemochromatosis carrier status) may theoretically modulate baseline iron handling (not well studied for acute poisoning specifically).

Toxic dose thresholds (elemental iron, oral): - <20 mg/kg: generally non-toxic/asymptomatic - 20–40(–60) mg/kg: mild-to-moderate toxicity — self-limited GI symptoms (vomiting, abdominal pain, diarrhea) - >40–60 mg/kg: potentially serious/severe systemic toxicity - >60 mg/kg: potentially lethal - Animal-model acute lethal dose: ~150–200 mg/kg elemental iron - Lowest reported lethal dose in a human: a 21-month-old child who ingested 325–650 mg elemental iron as ferrous sulfate

A standard 325 mg ferrous sulfate tablet contains ~65 mg elemental iron (ferrous sulfate is ~20% elemental iron by weight); prenatal vitamins and adult-strength ferrous sulfate tablets are the highest-risk products because of their high elemental-iron density relative to pediatric multivitamins.

Sources: California Poison Control: Iron Ingestion · Iron Ingestion: Evidence-Based Consensus Guideline · StatPearls (Archived): Iron Toxicity

Risk factors (environmental/behavioral, not genetic): - Age <5 years — accounts for the overwhelming majority of unintentional serious morbidity/mortality (young children accidentally ingesting adult-formulation iron tablets, mistaking them for candy due to bright coloring) - Household presence of prenatal vitamins or high-dose ferrous sulfate (highest elemental-iron-per-tablet products) - Adolescent/young adult female sex for intentional ingestion (self-harm/suicide attempts) — the dominant mechanism of severe iron poisoning in adults - Lack of child-resistant/unit-dose packaging (historically) - Careless storage — parents/caregivers may perceive iron/vitamin supplements as "safe," reducing vigilance

Protective factors: - Unit-dose (blister) packaging and child-resistant containers for products with ≥30 mg elemental iron/dosage unit (US FDA 1997 rule, effective July 1997) — associated with a marked reduction in pediatric iron-poisoning deaths - Label warning statements mandated by FDA guidance - Early recognition/early chelation therapy — greatly reduces mortality

Gene-environment interaction: Not a defined feature of this condition in the literature reviewed; acute iron poisoning is an environmentally/behaviorally driven exposure rather than a gene-environment interaction disease. (Contrast with hereditary hemochromatosis, where HFE variants confer chronically increased iron absorption — a distinct disease entity.)

Sources: FDA: Small Entity Compliance Guide, Iron-Containing Supplements Label Warning · Federal Register: Iron-Containing Supplements and Drugs · PubMed: Unit-dose packaging of iron supplements and reduction of iron poisoning in young children · AAP: Accidental Iron Poisoning in Children

3. Phenotypes

Iron toxicity classically progresses through five overlapping clinical stages (not all patients pass through every stage sequentially):

Additional/organ-specific phenotypes: - Cardiovascular: hypotension, cardiovascular collapse, cardiogenic and distributive shock - Hematologic: coagulopathy — iron (Fe³⁺/non-transferrin-bound iron) reversibly inhibits serine proteases of the coagulation cascade (thrombin, factor Xa, kallikrein), causing bleeding diathesis distinct from hepatic-synthetic coagulopathy - Renal: acute kidney injury from hypoperfusion/direct toxicity - CNS: lethargy progressing to coma in severe cases - Metabolic: anion-gap metabolic acidosis (from uncoupled oxidative phosphorylation, lactic acid accumulation, and hydrolysis of ferric iron to iron hydroxide releasing free H⁺)

Severity/frequency: Symptom severity is dose-dependent (see thresholds above); most pediatric exposures are asymptomatic or mild (small unintentional ingestions), while intentional adult overdoses (tens of tablets) are far more likely to reach severe/fatal stages.

Suggested HPO terms: HP:0002013 (Vomiting), HP:0002014 (Diarrhea), HP:0002027 (Abdominal pain), HP:0001649 (Tachycardia), HP:0001257 (Lethargy), HP:0011900 (Metabolic acidosis), HP:0001928 (Abnormal coagulation), HP:0006554 (Acute hepatic failure), HP:0100626 (Chronic hepatic failure — for late sequelae), HP:0002583 (Gastrointestinal obstruction), HP:0002014-adjacent for hematochezia/melena, HP:0001744-adjacent for shock.

Quality of life: Acute survivors of severe poisoning may face long-term morbidity from hepatic injury or GI stricture requiring reconstructive surgery; specific validated QoL instrument data for iron-poisoning survivors was not identified in this search.

Sources: WikEM: Iron toxicity · Medscape: Pediatric Iron Toxicity · Radiology: Fibrous Stricture of the Stomach Due to Iron (Feosol) Poisoning · PubMed: Gastrointestinal pathology in adult iron overdose (PMID:2231830) · PMC: Liver Transplantation for Acute Hepatic Failure Following Intentional Iron Overdose · Tennessee Poison Center: Delayed manifestations of iron poisoning

4. Genetic/Molecular Information

Iron poisoning is not a Mendelian genetic disease; it has no causal gene in the OMIM/ClinVar sense. There are no pathogenic variants, no inheritance pattern, and no chromosomal abnormalities associated with the exposure itself.

Relevant molecular target/pathway genes (not causal, but mechanistically involved in toxicity/handling): - TF (transferrin) — plasma iron-binding protein; saturation of TF binding capacity (normally 20–35% saturated) is the threshold event producing non-transferrin-bound iron (NTBI) toxicity - SLC40A1 (ferroportin) — cellular iron export - FTH1/FTL (ferritin heavy/light chain) — intracellular iron storage/sequestration; ferritin destruction is implicated as a source of catalytic free iron in iron-mediated hepatocyte injury (paralleling acetaminophen hepatotoxicity mechanisms) - HFE — theoretically could modulate baseline transferrin saturation/absorption but is not established as a modifier of acute poisoning severity in the literature surveyed

Epigenetics/somatic considerations: Not applicable — this is an acute exogenous toxic exposure, not a heritable or somatic-mutation disease.

Sources: PMC: Iron Load Toxicity in Medicine — Molecular and Cellular Aspects · PMC: Non-Transferrin-Bound Iron (NTBI), Labile Plasma Iron (LPI), and Iron Toxicity · ScienceDirect: Iron mediated toxicity and programmed cell death

5. Environmental Information

Primary environmental/exposure factors: - Iron-containing oral dietary supplements: ferrous sulfate, ferrous gluconate, ferrous fumarate, carbonyl iron, prenatal multivitamins - Product form and elemental-iron density (adult-strength tablets vs. pediatric chewables) — a major determinant of exposure severity - Household storage practices and accessibility to young children - Packaging regulation status (unit-dose blister packaging vs. bulk bottles)

Behavioral/lifestyle factors: - Deliberate self-poisoning (intentional overdose), disproportionately among adolescent and young adult females — the dominant severe-poisoning mechanism in the adult population - Caregiver perception of supplements as "safe," reducing protective vigilance

Infectious agents: Not applicable — iron poisoning is a chemical/toxicologic, not infectious, process.

Suggested exposure-ontology grounding (ECTO-style): "exposure to iron salts via ingestion" / "ferrous sulfate ingestion."

Sources: AAP: Accidental Iron Poisoning in Children · SAGE: Iron Packaging Regulations in the United States and Pediatric Morbidity

6. Mechanism / Pathophysiology

Causal chain (initial trigger → clinical manifestation):

1. Ingestion of excess elemental iron → normal intestinal mucosal regulatory mechanisms (which limit absorption under physiologic conditions) are overwhelmed by supratherapeutic dose.
2. Direct corrosive mucosal injury — iron salts act as a direct GI irritant/corrosive, producing hemorrhagic gastritis/enteritis, mucosal necrosis, and erosion (Stage I phenotype). "Iron promotes direct mucosa irritation and at the intracellular level favors free radical production, oxidative damage, hinders oxidative phosphorylation, and ultimately causes cell death" (ScienceDirect: Iron Poisoning overview).
3. Systemic absorption and saturation of plasma protein binding — once transferrin's iron-binding capacity is exceeded (pathologically detectable when transferrin saturation exceeds ~75%), non-transferrin-bound iron (NTBI) appears in plasma; its redox-active, chelatable fraction is termed labile plasma iron (LPI). NTBI/LPI enter cells via transporters outside normal transferrin-receptor-mediated regulation, bypassing cellular iron homeostasis controls.
4. Cellular/mitochondrial toxicity — free iron concentrates in mitochondria and catalyzes Fenton-type reactions, generating reactive oxygen species (ROS) that cause lipid peroxidation of mitochondrial membranes, uncoupling oxidative phosphorylation, and disrupting the electron transport chain. This is mechanistically convergent with ferroptosis — an iron-dependent regulated cell-death pathway involving glutathione/GPX4 depletion and lipid-peroxide accumulation, a mechanism well-characterized in iron-catalyzed acetaminophen hepatotoxicity and increasingly recognized as relevant to iron-overdose hepatocyte injury.
5. Metabolic acidosis — arises from two convergent mechanisms: (a) impaired oxidative phosphorylation → anaerobic metabolism → lactic acidosis; (b) when plasma protein-binding capacity is saturated, ferric iron hydrolyzes with water to form iron hydroxide and free H⁺ ions, directly compounding acidosis.
6. Coagulopathy — non-transferrin-bound Fe³⁺ (and its hydrolytic species) reversibly inhibits serine proteases of the coagulation cascade: thrombin's fibrinogen-clotting and fibrinopeptide-A-generating activity is markedly suppressed, as is factor Xa and kallikrein activity. This effect is reversible with iron chelation (EDTA in vitro), and is distinct from the coagulopathy of established hepatic synthetic failure — both mechanisms can coexist in severe poisoning.
7. Hepatotoxicity — the liver, as the first-pass site of portal-venous iron delivery and major iron-storage organ, sustains direct mitochondrial/oxidative injury, potentially progressing to fulminant hepatic failure (Stage IV) requiring transplantation in severe/intentional overdoses.
8. Cardiovascular collapse/shock — from combined hypovolemia (GI fluid/blood loss), direct iron-mediated myocardial and vascular endothelial toxicity, and acidosis-driven cardiac dysfunction; this is the dominant cause of death in Stage III.
9. Delayed structural sequelae — the initial corrosive mucosal injury heals by fibrotic scarring, which can mechanically obstruct the gastric outlet or proximal small bowel weeks later (Stage V).

Cell types/tissues implicated: gastrointestinal mucosal epithelial cells (enterocytes, gastric mucosa), hepatocytes, cardiomyocytes/vascular endothelium, and — at the molecular level — mitochondria across affected cell types.

Suggested GO terms: GO:0006879 (cellular iron ion homeostasis), GO:0055072 (iron ion homeostasis), GO:0034614 (cellular response to reactive oxygen species), GO:0006749 (glutathione metabolic process), GO:0034599 (cellular response to oxidative stress), GO:0006119 (oxidative phosphorylation), GO:0097267 (omega-hydroxylase P450 pathway — n/a), GO:1990448 (ferroptosis-related term where available, e.g., GO:0097707 "ferroptosis").

Suggested CHEBI terms: CHEBI:18248 (iron atom/ion), CHEBI:29033 (Fe(II) ion), CHEBI:29034 (Fe(III) ion), CHEBI:75771 (ferrous sulfate), CHEBI:75832 (ferrous gluconate).

Sources: PMID:8187690 — Acute iron poisoning · PMC: Iron Load Toxicity in Medicine · PMC: Role of Mitochondrial Iron Uptake in Acetaminophen Hepatotoxicity · PubMed: Ferroptosis and Intrinsic Drug-induced Liver Injury (PMID:39649034) · PubMed: Blood coagulation and acute iron toxicity — reversible iron-induced inactivation of serine proteases (PMID:6421970) · PMC: Oxidation Inhibits Iron-Induced Blood Coagulation · PMC: Non-Transferrin-Bound Iron, Labile Plasma Iron, and Iron Toxicity

7. Anatomical Structures Affected

Organ level: - Primary: stomach and small intestine (direct corrosive injury); liver (systemic iron trapping and hepatotoxicity) - Secondary/complication-related: cardiovascular system (shock), kidneys (acute kidney injury secondary to hypoperfusion), coagulation system (functional coagulopathy) - Body systems: digestive, hepatobiliary, cardiovascular, hematologic

Tissue/cell level: - Gastric and intestinal mucosal epithelium (erosion, hemorrhagic necrosis) - Hepatocytes (oxidative/mitochondrial injury, necrosis, fulminant failure) - Vascular endothelium (increased permeability contributing to shock) - Cardiomyocytes (direct toxic and hypoperfusion-related injury)

Subcellular level: mitochondria (site of iron concentration, ROS generation, oxidative-phosphorylation uncoupling); cell membranes (lipid peroxidation target)

Suggested UBERON terms: UBERON:0000945 (stomach), UBERON:0002108 (small intestine), UBERON:0002107 (liver), UBERON:0000948 (heart), UBERON:0002113 (kidney), UBERON:0001969 (blood plasma).

Suggested GO Cellular Component terms: GO:0005739 (mitochondrion), GO:0016020 (membrane).

Sources: PubMed: Gastrointestinal pathology in adult iron overdose (PMID:2231830) · Radiology: Fibrous Stricture of the Stomach Due to Iron Poisoning

8. Temporal Development

Onset: Acute — symptoms typically begin within 30 minutes to 6 hours of ingestion (Stage I); onset pattern is acute/toxic rather than insidious, dose-dependent in latency and severity.

Progression (staged, as above): - Stage I (0–6 h): corrosive GI phase - Stage II (6–24 h): latent/deceptive improvement - Stage III (24–48+ h): shock/metabolic decompensation — responsible for the majority of deaths - Stage IV (2–5 days): hepatotoxicity/hepatic failure - Stage V (2–8 weeks): GI stricture/obstruction

Not all patients progress through every stage; a patient with a small ingestion may resolve after Stage I, while patients with massive ingestion can rapidly develop multi-organ failure and death within the first 24–48 hours without ever exhibiting a clear "latent" phase.

Disease course pattern: Self-limited (in mild ingestions) to rapidly progressive/fulminant (in severe ingestions), with a distinct delayed structural complication window (weeks) that is atypical among acute poisonings and requires specific counseling/follow-up.

Critical period for intervention: Early recognition and chelation (ideally initiated in Stage I–II, before shock/organ failure) is the key modifiable window — "[Deferoxamine] greatly reduces mortality in children, provided it is given at an early stage" (ScienceDirect: Deferoxamine overview).

Sources: Medscape: Pediatric Iron Toxicity · EM Board Bombs: A Rusty Diagnosis — Acute Iron Poisoning · Tennessee Poison Center: Delayed manifestations of iron poisoning

9. Inheritance and Population

Epidemiology (US, AAPCC data): - 2022: 5,311 single exposures to iron/iron salts reported to US poison control centers — 2,154 in children <6 years, 209 in children 6–12 years, 762 in adolescents 13–19 years; 2 deaths reported. An additional 7,565 single exposures to iron-containing multivitamins were reported, 81% in children <6 years. - Historical incidence: ~11,000 iron exposures per year in US children <6 years old (2015 AAPCC data) - Mortality trend: From 1983–2000, at least 43 US children died from iron supplement ingestion; from 1983–1991, iron accounted for >30% of deaths from unintentional pediatric drug-product ingestion. Fatal pediatric iron ingestions have declined markedly since the 1990s, coincident with unit-dose packaging/labeling regulation (1997 FDA rule) — one pediatric iron-poisoning death reported 1998–2002 following the regulation.

Inheritance pattern: Not applicable — iron poisoning is an acquired toxic exposure, not an inherited disease. No penetrance, expressivity, anticipation, mosaicism, founder-effect, or carrier-frequency concepts apply.

Population demographics: - Unintentional poisoning: overwhelmingly children <5 years old ingesting adult-formulation iron products - Intentional/severe poisoning: predominantly adolescent and young adult females attempting self-harm — the dominant mechanism behind severe/fatal adult cases described in case series (e.g., five fatal cases of suicidal ingestion of 20–60 iron/iron-folic tablets in adolescent females, with autopsy findings of multi-organ petechial hemorrhage, GI mucosal necrosis/erosion) - Sex ratio: skewed toward young children of either sex for unintentional exposures; skewed toward females for intentional adult/adolescent poisoning - Geographic distribution: Reported globally; incidence and severity strongly modulated by product-packaging regulation, healthcare access, and cultural availability of iron supplements (notably relevant in regions with widespread maternal iron-supplementation programs)

Sources: UpToDate: Acute iron poisoning · Medscape: Pediatric Iron Toxicity · PubMed: Unit-dose packaging of iron supplements (PMID:15939855) · Journal of Population Therapeutics and Clinical Pharmacology: Suicidal Acute Iron Poisoning in Adolescent Females — A Case Series · PMC: Fatal Iron Toxicity in an Adult — Clinical Profile and Review

10. Diagnostics

Clinical/laboratory tests: - Serum iron level (peak, typically drawn 2–6 h post-ingestion): correlates with severity — - <300 µg/dL: mild/unlikely severe toxicity - 300–500 µg/dL: mild toxicological effects - 500–1000 µg/dL: moderate-to-severe toxicity (500 µg/dL is a classic threshold indication for deferoxamine) - >1000 µg/dL: death is common - Total iron-binding capacity (TIBC) — historically used but now considered unreliable in acute overdose (assay interference) - Serum glucose and WBC count — elevated values (glucose >150 mg/dL, WBC >15,000/µL) have been proposed as early surrogate markers correlating with significant ingestion, though sensitivity/specificity are limited - Arterial/venous blood gas — assesses metabolic (anion-gap) acidosis, a marker of systemic toxicity severity - Coagulation studies (PT/INR, PTT, fibrinogen) — assess iron-induced serine-protease inhibition and/or hepatic synthetic coagulopathy - Liver function tests — for Stage IV hepatotoxicity surveillance - Abdominal X-ray (KUB) — iron tablets are radiopaque; a positive film supports the diagnosis and guides need for whole bowel irrigation (WBI), though a negative film does not exclude significant ingestion (chewable/liquid formulations may not be radiopaque, and tablets may already have dissolved)

Diagnostic/clinical criteria: No formal DSM/ICD diagnostic-criteria instrument; diagnosis is clinical (history of ingestion + staged symptom pattern) supported by serum iron level and imaging.

Differential diagnosis: Other causes of anion-gap metabolic acidosis and toxic ingestion (salicylates, ethylene glycol, methanol), other causes of hematemesis/corrosive GI injury (caustic ingestion, NSAID gastropathy), sepsis/septic shock (can mimic Stage III), other causes of fulminant hepatic failure (acetaminophen, viral hepatitis).

Genetic testing: Not applicable/not indicated (no causal genetic variant).

Screening: No population screening program exists (this is an acute poisoning, not a chronic/heritable condition); the relevant "screening" analog is regulatory/product-based prevention (packaging, labeling) rather than clinical genetic or biochemical screening.

Suggested NCIT/LOINC anchors: serum iron (LOINC 2498-4), TIBC (LOINC 2500-7), abdominal X-ray (a radiologic procedure, NCIT-codable).

Sources: Medscape: Iron Toxicity — Workup · California Poison Control: Iron Ingestion · Iron Ingestion: Evidence-Based Consensus Guideline for Out-of-Hospital Management

11. Outcome / Prognosis

Mortality: With prompt recognition and treatment, outcomes for mild-to-moderate unintentional pediatric ingestions are generally good, and fatal pediatric ingestions have declined substantially since packaging/labeling regulation. However, severe (typically intentional, high-dose) ingestions carry substantial mortality: "A majority of acute iron toxicity cases [reaching severe multi-organ involvement] are fatal given the rapid progression to multi-organ failure" in reported case series, and reported US poison-control mortality remained at 2 deaths in 2022 among >5,300 reported iron exposures.

Morbidity: - Acute survivors of Stage III/IV disease may have prolonged ICU courses, need for liver transplantation in fulminant hepatic failure, and dialysis for acute kidney injury. - Delayed morbidity: gastric outlet obstruction/intestinal stricture (Stage V) can require reconstructive GI surgery (pyloroplasty, gastrojejunostomy, gastric resection) weeks to months after the acute event.

Prognostic factors: Elemental iron dose ingested, peak serum iron level, time-to-treatment (chelation), presence/severity of metabolic acidosis and shock at presentation, and development of hepatic failure.

Recovery potential: Generally favorable with early deferoxamine chelation in symptomatic-but-not-yet-shocked patients; poor once fulminant hepatic failure or refractory shock/coagulopathy develop.

Sources: PMC: Fatal Iron Toxicity in an Adult — Clinical Profile and Review · PMC: Liver Transplantation for Acute Hepatic Failure Following Intentional Iron Overdose · PubMed: Suicidal iron overdose — case report and review of literature

12. Treatment

Initial/supportive management: - Aggressive IV fluid resuscitation for hypovolemia/shock - Correction of metabolic acidosis and electrolyte abnormalities - Whole bowel irrigation (WBI) with polyethylene glycol solution (adults: 1–2 L/h; children: 25–40 mL/kg/h) when radiopaque tablets are visible on abdominal X-ray, continued until the film clears — though "existing data are still insufficient to support or exclude its efficacy" rigorously, it remains standard practice for radiographically confirmed significant ingestions. - Activated charcoal is NOT effective — it does not adsorb iron and should be given only if co-ingestants are suspected; concurrent WBI may further reduce charcoal's efficacy for those co-ingestants. - Endoscopic removal or, rarely, gastrotomy for large iron tablet bezoars/masses not clearable by WBI

Pharmacotherapy — chelation: - Deferoxamine (desferrioxamine) — the mainstay/first-line chelator for acute iron poisoning. Mechanism: high affinity for ferric (Fe³⁺) iron, forming the stable octahedral complex ferrioxamine, 1:1 molar binding, which is renally excreted (producing the classic "vin rosé"/rusty-red urine). Indications for IV infusion: significant clinical toxicity signs, metabolic acidosis, shock, serum iron >500 µg/dL, and/or radiographically visible tablet burden. Dosing: IV infusion starting at 15 mg/kg/h (not exceeding 1 g/h), typically over 6 hours with reassessment; hypotension is the main dose-limiting adverse effect, mitigated by ensuring adequate hydration first. - Oral chelators (deferiprone, deferasirox) — primarily used for chronic transfusional iron-overload states (e.g., thalassemia), not first-line for acute poisoning, though deferiprone has shown efficacy in animal models of acute iron overdose (decreased morbidity/mortality in rats) and limited human case reports (efficacy of oral deferiprone in acute iron poisoning) — these remain investigational/adjunctive for acute toxicology, with deferoxamine as standard of care given cost/access limitations of parenteral therapy being the main barrier globally.

Surgical/interventional: - Late complications (gastric outlet obstruction, pyloric/small-bowel stricture) may require surgical correction: Mikulicz (Heineke-Mikulicz) pyloroplasty, gastrojejunostomy, or gastric resection with Billroth I anastomosis. - Liver transplantation for fulminant hepatic failure refractory to medical management (reported in severe intentional overdoses).

Supportive/rehabilitative care: ICU-level monitoring, correction of coagulopathy (FFP/blood products as needed), dialysis for renal failure, nutritional support post-surgical GI reconstruction.

Experimental: Deferiprone as an oral alternative/adjunct for acute poisoning remains under investigation, particularly attractive in resource-limited settings lacking IV deferoxamine access.

Treatment outcomes/adverse events: Deferoxamine-induced hypotension (rate-related); rare deferoxamine-associated ARDS with prolonged high-dose infusion (a recognized but not detailed-in-this-search complication historically reported in the toxicology literature).

Suggested NCIT terms: NCIT:C15986 (Pharmacotherapy) with therapeutic_agent bound to CHEBI (deferoxamine — CHEBI:4058) or NCIT (deferoxamine, deferiprone, deferasirox); NCIT:C15329 (Surgical Procedure) for pyloroplasty/gastrojejunostomy/gastric resection; NCIT:C15289 (Organ Transplantation) for liver transplant; a WBI/decontamination procedure term (gastrointestinal decontamination) if a suitable NCIT concept exists.

Sources: ScienceDirect: Deferoxamine overview · Merck Manual: Iron Poisoning · Medscape: Pediatric Iron Toxicity Treatment & Management · PubMed: The efficacy of oral deferiprone in acute iron poisoning · PMC: Management of Acute Ferrous Sulfate Poisoning Using Activated Charcoal Monotherapy: A Case Report · PubMed: Gastrotomy and whole bowel irrigation in iron poisoning · PMC: A Review on Iron Chelators in Treatment of Iron Overload Syndromes

13. Prevention

Primary prevention: - Unit-dose (blister) packaging for iron-containing supplements/drugs with ≥30 mg elemental iron per dosage unit — mandated by 1997 FDA rule; associated with a marked drop in pediatric iron-poisoning deaths (reduced to essentially one reported US pediatric death 1998–2002). Note: the unit-dose packaging mandate was later withdrawn in 2003 following Nutritional Health Alliance v. FDA, which held the FDCA did not authorize FDA to regulate packaging specifically for poison prevention purposes — though label warning-statement requirements persisted. - Child-resistant containers (general Poison Prevention Packaging Act mechanisms) - Safe storage counseling for caregivers, particularly regarding prenatal vitamins and adult-strength ferrous sulfate

Secondary prevention: - Early recognition and prompt poison-control/ED evaluation after any known or suspected iron ingestion in a child, given the deceptive Stage II latent period - Abdominal radiography to assess ingestion burden and guide decontamination

Behavioral/public health interventions: - Poison control center public-awareness campaigns (e.g., 1-800 poison helpline) - Label warning statements on iron-containing products (bright-color tablet warnings, "keep out of reach of children") - For adolescent/adult intentional-ingestion risk: mental health screening and access-restriction counseling in at-risk populations (given the demographic skew toward young female self-harm)

Screening: No genetic/biochemical population screening applies; the closest analog is regulatory product-safety oversight rather than clinical screening.

Sources: FDA: Guidance for Industry — Iron-Containing Supplements and Drugs: Label Warning · Federal Register: Iron-Containing Supplements and Drugs; Removal of Unit-Dose Packaging Requirements · SAGE Journals: Iron Packaging Regulations in the United States and Pediatric Morbidity

14. Other Species / Natural Disease

Acute iron toxicity is well documented as an induced/experimental toxicology model rather than a naturally occurring veterinary disease entity in the OMIA sense. Relevant cross-species data:

• Rats: LD50 estimates for ferrous sulfate vary widely by study — approximately 780–1,100 mg iron/kg body weight in one estimate, and up to 2.8 g/kg in another; ferrous sulfate heptahydrate showed no acute toxicity up to 2,000 mg/kg in some OECD-guideline studies. Comparator salts: ferrous chloride oral LD50 300–2,000 mg/kg (132–881 mg Fe/kg); ferric sulfate oral LD50 500–2,000 mg/kg (females). Repeated-dose/reproductive-developmental toxicity of ferrous sulfate heptahydrate has been assessed at 30–1,000 mg/kg/day in OECD combined study designs.
• Mice: Used in classic iron-toxicity determination studies (e.g., "Determination of Iron Toxicity in Mice," ScienceDirect).
• Young rats: Comparative acute toxicity of carbonyl iron and sodium iron EDTA vs. ferrous sulfate has been specifically studied, relevant to formulating safer pediatric iron products (carbonyl iron shows a substantially better safety margin than ferrous sulfate in this context).
• Veterinary relevance: Accidental iron-supplement ingestion (e.g., companion animals ingesting human iron tablets/prenatal vitamins) is a recognized veterinary toxicology concern, paralleling the pediatric human scenario, though detailed OMIA/VetCompass-specific case data were not retrieved in this search.

Comparative biology: The core toxic mechanism — mucosal corrosion, NTBI-driven oxidative/mitochondrial injury, and coagulation-factor inhibition — is conserved across mammalian species, supporting rodent models as reasonably translatable for acute-toxicity dose-response and chelator-efficacy studies (e.g., deferiprone efficacy data derived from rat acute-overdose models).

Suggested NCBITaxon terms: NCBITaxon:9606 (Homo sapiens), NCBITaxon:10116 (Rattus norvegicus), NCBITaxon:10090 (Mus musculus).

Sources: OECD SIDS Initial Assessment Profile — Ferrous compounds · ResearchGate: Acute Toxicity of Carbonyl Iron and Sodium Iron EDTA Compared with Ferrous Sulfate in Young Rats · ScienceDirect: Determination of Iron Toxicity in Mice

15. Model Organisms

Rodent models (rat, mouse): The dominant experimental system for acute iron-toxicity research — used to establish LD50/dose-response relationships for various iron salts (ferrous sulfate, ferrous chloride, ferric sulfate, carbonyl iron, sodium iron EDTA), and to test chelator efficacy. Notably, oral deferiprone reduced morbidity and mortality in rat models of acute iron overdose, directly informing the human investigational use described above (§12).

Model characteristics: - Recapitulates key phenotypes: GI mucosal injury, systemic organ toxicity, mortality dose-dependence - Used to compare relative toxicity/safety margins of different iron formulations (informing safer pediatric supplement formulation design, e.g., carbonyl iron vs. ferrous sulfate) - Used for OECD-guideline repeated-dose and reproductive/developmental toxicity screening of iron salts

Limitations: Rodent GI anatomy/physiology and dosing-route pharmacokinetics differ from humans; LD50 estimates vary substantially between studies/rodent strains/iron salt forms, complicating direct extrapolation of a single "lethal dose" figure to humans (human thresholds are instead derived largely from case-series/poison-control data rather than allometric scaling from animal LD50s).

Applications: Dose-response characterization, chelator (deferoxamine, deferiprone) efficacy and pharmacokinetic testing, comparative formulation safety (carbonyl iron vs. ferrous salts) to inform pediatric product design and regulatory policy.

Resources: No dedicated genetically engineered (knockout/transgenic) mouse model is relevant here, since this is a toxic-exposure phenotype rather than a genetic disease — models are induced (dosing) rather than genetic.

Sources: PubMed: The efficacy of oral deferiprone in acute iron poisoning · ResearchGate: Acute Toxicity of Carbonyl Iron and Sodium Iron EDTA Compared with Ferrous Sulfate in Young Rats · OECD SIAM: Ferrous compounds SIDS assessment

Summary of Key Ontology Term Suggestions

Notes on evidence gaps

This report identified no MONDO/OMIM identifier specifically dedicated to acute iron poisoning as distinct from chronic iron-overload disorders — a curator populating a dismech-style entry should likely model this as an environmental/toxic-exposure disease entity (paralleling entries like Arsenic_Poisoning) rather than force-fitting it to a hereditary-iron-overload MONDO branch. Quantitative QoL data, detailed genetic-modifier studies, and single-cell/omics profiling specific to acute iron poisoning were not found and are likely genuinely sparse in the literature (this is predominantly a clinical-toxicology/emergency-medicine literature base rather than a molecular-genetics one).

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