Acute toxicity of carbonyl iron and sodium iron EDTA compared with ferrous sulfate in young rats.
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.
Whittaker
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Center for Food Safety and Applied Nutrition, Food and Drug Administration, College Park, Maryland 20740-3835, USA. paul.whittaker@cfsan.fda.gov
Ali
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Imam
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Dunkel
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D000276:Adjuvants, Immunologic / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D019587:Dietary Supplements / Q000506:poisoning; D004492:Edetic Acid / Q000493:pharmacokinetics / Q000633:toxicity*; D005290:Ferric Compounds / Q000493:pharmacokinetics / Q000633:toxicity*; D005296:Ferrous Compounds / Q000493:pharmacokinetics / Q000633:toxicity*; D006801:Humans; D054354:Iron Carbonyl Compounds; D007502:Iron Chelating Agents / Q000493:pharmacokinetics / Q000633:toxicity*; D007928:Lethal Dose 50; D008297:Male; D009942:Organometallic Compounds / Q000493:pharmacokinetics / Q000633:toxicity*; D011041:Poisoning / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species
D000276:Adjuvants, Immunologic; D003692:Delayed-Action Preparations; D005290:Ferric Compounds; D005296:Ferrous Compounds; D007502:Iron Chelating Agents; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D054354:Iron Carbonyl Compounds; C020748:ferrous sulfate; D004492:Edetic Acid; C019179:Fe(III)-EDTA