Acute toxicity of carbonyl iron and sodium iron EDTA compared with ferrous sulfate in young rats

P Whittaker1, S F Ali, S Z Imam

  • 1Center for Food Safety and Applied Nutrition, Food and Drug Administration, College Park, Maryland 20740-3835, USA. paul.whittaker@cfsan.fda.gov

Insights

Iron supplements like ferrous sulfate are toxic to young children. Carbonyl iron and sodium iron(III) ethylenediaminetetraacetate show lower toxicity, offering safer alternatives for iron supplementation and food fortification.

Area of Science:

  • Toxicology
  • Nutritional Science
  • Pediatric Health

Background:

  • Iron supplement overdose is a significant risk for children under 6.
  • Ferrous sulfate is the most common iron supplement but has high toxicity.
  • Safer iron forms like carbonyl iron and NaFeEDTA are being explored.

Purpose of the Study:

  • To compare the acute toxicity of carbonyl iron and NaFeEDTA with ferrous sulfate in young rats.
  • To evaluate the toxicological profiles of different iron formulations relevant to pediatric exposures.

Main Methods:

  • Acute toxicity testing in young rats.
  • Administration of ferrous sulfate, carbonyl iron, and NaFeEDTA at varying doses.
  • Measurement of liver nonheme iron and serum iron levels.
  • Determination of LD50 values for each iron compound.

Main Results:

  • Carbonyl iron demonstrated significantly lower toxicity (LD50 > 50 g Fe/kg) compared to ferrous sulfate (LD50 = 1.1 g Fe/kg).
  • NaFeEDTA showed similar toxicity to ferrous sulfate (LD50 = 1.3 g Fe/kg) but resulted in a 50% lower increase in liver nonheme iron.
  • Serum iron elevation was sustained longer with NaFeEDTA (up to 4 hours) compared to ferrous sulfate and carbonyl iron (0.5-1 hour).

Conclusions:

  • Carbonyl iron presents a substantially safer alternative to ferrous sulfate due to its markedly lower acute toxicity.
  • NaFeEDTA offers a potentially safer option for food fortification compared to ferrous sulfate, with reduced liver iron accumulation.
  • Further research into carbonyl iron and NaFeEDTA is warranted for developing safer iron supplements and fortified foods for children.

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