July 2008 (Vol 29, No 7)

Toxicology Brief — Iron Toxicosis

  • by
  • Erin Freed , CVT

Iron, A Heavy Metal, is the most abundant trace mineral in the body.1-4 Although iron is essential for the transport of oxygen, the presence of excess iron in the blood can lead to iron toxicosis. The most common cause of iron overdose is accidental ingestion of iron-containing compounds; however, iat­rogenic overdose via injection of agents to treat iron deficiency (e.g., iron dextran complex) is possible. Iron-containing agents that animals may accidentally ingest include multivitamins, birth control pills, fertilizers, and chemical hand and foot warmers.2,5


Iron can exist in two different ionic states — ferrous (Fe2+) and ferric (Fe3+) — within the body. Although ferrous iron is more readily absorbed by the body, both forms can be absorbed if they are ionized.3,4,6 Metallic iron and iron oxide (i.e., rust) do not readily ionize; therefore, these forms are typically not problematic if ingested.1-4

After iron is ionized, most of it is absorbed by mucosal cells in the duodenum and upper jejunum. However, in cases of overdose, the entire intestinal tract may absorb iron.3,4,6,7 Absorption is also increased in the presence of vitamin C or a high-sugar diet.3,4,6,8 The iron is then transported across cell membranes to the blood, where it binds to transferrin,9 which is the primary iron transport protein.5 Transferrin is produced in the liver and is normally 25% to 30% saturated with iron.9 Most iron is transported by transferrin to the bone marrow for the production of hemoglobin. The body absorbs 2% to 15% of ingested iron, but only 0.01% is eliminated daily10; the remainder is stored in the liver, spleen, and bone marrow.1,2 When iron toxicosis occurs, transferrin becomes saturated so that the total serum iron (SI) concentration exceeds the transferrin iron-binding capacity; therefore, the amount of free circulating iron in the blood increases. This free iron enters cells of the liver, heart, and brain, where it causes hepatic and myocardial damage by binding to cell membranes and stimulates lipid peroxidation — in which free radicals remove electrons from the lipid in cell membranes, resulting in cell damage.1,2,5,11,12

The occurrence of toxicosis also depends on the amount of iron already in the body.1,2 Animals that have a large amount of stored iron may develop signs of toxicosis even when the level of iron ingested causes no problems in other animals.1,2

Toxicity and Clinical Signs

Toxicity is not expected in healthy dogs and cats that ingest less than 20 mg/kg of elemental iron.1,2 Ingestion of 20 to 60 mg/kg of elemental iron may cause toxicosis with mild gastrointestinal (GI) signs.2 Ingestion of more than 60 mg/kg of elemental iron is considered potentially serious and may result in GI hemorrhage as well as metabolic acidosis and elevated liver enzyme values.2,4 Death may result if an animal ingests 100 to 200 mg/kg of elemental iron and does not receive treatment.1,2,4,8


Toxicosis can be characterized as peracute, subacute, or chronic. In peracute toxicosis, such as that occurring after an iron injection, clinical signs develop within minutes to a few hours after exposure. Signs are similar to those of an anaphylactic reaction and may include hypovolemic shock followed by sudden death as a result of vascular collapse.13 At the injection site, the skin may be discolored and edema may occur.8

Subacute toxicosis, such as that occurring after oral ingestion, can be grouped into four phases. During the first phase, signs develop up to 6 hours after exposure2 and include bloody vomiting and diarrhea caused by GI hemorrhage.4,6-8 In the second phase, which occurs within 6 to 24 hours of exposure, the patient's condition appears to improve.2 During the third phase, which occurs about 12 to 96 hours after exposure,2 GI signs recur, along with shock, central nervous system depression, metabolic acidosis, liver failure, pulmonary edema, hemorrhage, or even death.4,6,7 Acute renal failure secondary to shock may also develop. Animals that survive this phase may enter a fourth phase 2 to 6 weeks after exposure.4,6 In this phase, gastric obstruction may develop secondary to gastric or pyloric stenosis.1,2,13

Chronic toxicosis occurs when iron is repeatedly ingested at low levels that individually do not have adverse effects. Long-term iron exposure may lead to the development of iron deposits in the liver, heart, pancreas, and adrenal and parathyroid glands. Death generally results from myocardial damage.12


If a patient has ingested an iron salt-containing substance in amounts sufficient to cause toxicity, the veterinary staff should observe the patient's clinical signs and measure the SI level and total iron-binding capacity (TIBC). Testing an animal's SI concentration is the best method of confirming a tentative diagnosis of iron toxicosis.2 The SI test measures bound and free SI content, whereas the TIBC test assesses the total amount of iron that the transferrin can bind. SI testing should be conducted within a few hours of ingestion to obtain a baseline level. Testing should be repeated 4 to 6 hours after the first assays because SI levels may vary widely within the first few hours following ingestion.1 Normal ranges for SI and TIBC vary depending on the type of laboratory test used. The technician should check the range of the specific test to determine whether results are abnormal. Toxicosis can be confirmed if the SI value is greater than the TIBC value.

If a patient has ingested radiopaque iron-containing tablets, it may be useful to obtain abdominal radiographs.4,6 Radiography should be conducted within a few hours of ingestion and then repeated after GI decontamination (discussed below).1,2,9,11


If an animal has ingested less than 20 mg/kg of elemental iron, the veterinary staff should observe the patient and provide treatment based on clinical signs. If an animal has ingested more than 20 mg/kg of elemental iron, GI decontamination through induced vomiting or gastric lavage should be considered up to 1 to 2 hours after ingestion, unless the animal is already vomiting. Magnesium hydroxide may decrease the absorption of iron by transforming elemental iron into ferric oxide, which is not readily absorbed. Activated charcoal does not bind well to iron and is therefore not likely to be helpful in treating iron overdoses.11 GI protectants (such as misoprostol or sucralfate), along with an H2 blocker (such as famotidine, cimetidine, or ranitidine), may be administered. A proton pump inhibitor, such as omeprazole, can also be added, and intravenous fluid support — which helps manage shock and hypotension — can be offered. Electrolyte level and acid-base status should also be monitored in patients exhibiting clinical signs. Supportive care should be provided as needed.1,2,11


When the SI value is greater than the TIBC value or is above 300 µg/dl, excess iron must be removed from the blood. The drug of choice for this purpose is deferoxamine mes­ylate, an iron chelator. This agent is best given within the first 24 hours of exposure, at a rate of 40 mg/kg IM q4-8h or 15 mg/kg/hr IV.5 This hypotensive drug is excreted primarily by the kidneys. It should be infused slowly, and care must be taken when administering it to animals that are in shock or have renal insufficiency.8,13 Administering ascorbic acid after the gut has been cleared of iron increases the effectiveness of the drug.11 Use of deferoxamine mesylate will cause the urine color to become vin rose (i.e., deep red) if SI is elevated. Treatment is usually continued until the urine is no longer discolored, until clinical signs start to resolve, or until the SI value is less than 300 µg/dl.9,11 Patients should be monitored for at least 4 to 6 weeks after exposure for evidence of GI obstruction caused by scarring of the tract.1,2,4


The patient's outcome depends on the amount of iron ingested and how quickly the owner seeks medical attention for the pet. If signs do not develop within 6 hours of exposure, or if the patient receives early decontam­ination, the prognosis is good.5 The prognosis is guarded after signs have developed,1,2 but the prognosis is poor when the SI value is greater than 500 µg/dl and a chelator is not available.1,2

Role of the Technician

Technicians should educate owners about the signs of iron toxicosis and instruct them to keep iron-containing products away from pets. However, if a product containing iron is ingested, the owner should immediately contact the hospital or an animal poison control center.

When a client contacts the hospital to report that his or her pet has ingested a product containing iron, the technician should determine what type of product was ingested (e.g., multivitamins), how much the pet ingested (e.g., 10 tablets), and how much time has elapsed since the exposure. To help the veterinary staff calculate the amount of elemental iron ingested and administer the appropriate treatment, the client should bring the packaging that contained the ingested product (e.g., multivitamins, birth control pills, fertilizer).

Although iron toxicosis occurs infrequently, the veterinary staff should be know­l­edgeable about how to manage affected patients.

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1. Albretsen JC: Iron, in Plumlee KH (ed): Clinical Vet­eri­nary Toxicology. St. Louis, Mosby, 2004, pp 202-204.

2. Albretsen JC: The toxicity of iron, an essential element. Vet Med 101:82-90, 2006.

3. Goyer RA: Toxic effects of metals, in Klaassen CD (ed): Casarett & Doull's Toxicology: The Basic Science of Poisons, ed 5. New York, McGraw-Hill, 1996, pp 715-716.

4. Greentree WF, Hall JO: Iron toxicosis, in Bonagura JD (ed): Kirk's Current Therapy XII: Small Animal Practice. Philadelphia, WB Saunders, 1995, pp 240-242.

5. Hall JO: Iron, in Peterson ME, Talcott PA (eds): Small Animal Toxicology, ed 2. St. Louis, Elsevier, 2007, pp 433-437.

6. Hillman RS: Hematopoietic agents: Growth factors, minerals, and vitamins, in Hardman JG, Limbird LE, Molinoff PB, et al (eds): Goodman & Gilman's The Pharmacological Basis of Therapeutics, ed 9. New York, McGraw-Hill, 1995, pp 1311-1340.

7. Liebelt EL: Iron, in Haddad LM, Shannon MW, Winchester JF (eds): Clinical Management of Poisoning and Drug Overdose, ed 3. Philadelphia, WB Saunders, 1998, pp 757-766.

8. Osweiler GD, Carson TL, Buck WB, Van Gelder GA: Clinical and Diagnostic Veterinary Toxicology, ed 3. Dubuque, IA, Kendall/Hunt Publishing, 1985, pp 104-106.

9. Beasley VA: A Systems Affected Approach to Veterinary Toxicology. Urbana, IL, University of Illinois, 1999, pp 464-467.

10. Klaassen CD (ed): Casarett & Doull's Toxicology: The Basic Science of Poisons, ed 6. New York, McGraw-Hill, 2001, pp 842-843.

11 Osweiler GD: Toxicology. Philadelphia, Williams & Wilkins, 1996, pp 188-191.

12. Hooser SB: Iron, in Ramesh CG (ed): Veterinary Toxicology: Basic and Clinical Principles. New York, Elsevier/Academic Press, 2007, pp 433-437.

13. Howland MA: Risks of parenteral deferoxamine for acute iron poisoning. J Toxicol Clin Toxicol 34:491-497, 1996.

Tags: Toxicology Veterinary Technician Journal Canine Feline