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.
Abstract:
According to the American Association of Poison Control Centers, exposures to excessive doses of iron supplements still occur in children less than 6 years of age. Since 1998, there has been one death among U.S. children in this age group. Exposures, including adverse events, to iron supplements and iron-containing vitamins for the years 1999 and 2000 were 23,215 and 24,249, respectively. To reduce the potential seriousness of such exposures, carbonyl iron (Fe(0)) has been suggested as a possible replacement for ferrous sulfate (FeSO(4)). Carbonyl Fe is a unique form of elemental iron because of its small particle size. It is highly bioavailable when used to correct iron deficiency anemia. There is also current interest in using sodium iron(III) ethylenediaminetetraacetate (NaFeEDTA) for food fortification. In this study both NaFeEDTA and carbonyl Fe were compared with FeSO(4), the most common form of iron for dietary supplements, to obtain information relevant to the acute toxicological profile in young rats. With FeSO(4) and NaFeEDTA, total liver nonheme iron increased with increasing dose, but the response was approximately 50% lower with NaFeEDTA compared with FeSO(4). Serum iron peaked at approximately 0.5 to 1 h for both FeSO(4) and carbonyl Fe, while NaFeEDTA was elevated up to 4 h. FeSO(4) had an LD(50) of 1.1 g Fe/kg and was approximately 45 times more toxic than carbonyl Fe, which had an LD(50) greater then 50 g Fe/kg. NaFeEDTA had an LD(50) of 1.3 g Fe/kg and, when compared with FeSO(4), had approximately the same level of toxicity.
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