Genotoxicity of iron compounds in Salmonella typhimurium and L5178Y mouse lymphoma cells.
The mutagenic activity of elemental and salt forms of iron (Fe), including compounds currently being used in dietary supplements and for food fortification, were evaluated for mutagenicity in Salmonella typhimurium and L5178Y mouse lymphoma cells. Except for the weak response obtained with ferrous fumarate, none of the compounds induced a mutagenic response in Salmonella. In the mouse lymphoma assay, responses were related to the Fe compound and/or reduction of ferric (Fe+3) to ferrous (Fe+2). Responses with the elemental forms of Fe were divergent. Electrolytic Fe with a relatively larger particle size and irregular shape was negative. The smaller-sized carbonyl Fe, which after 4 hr attached to and was taken up by the cells, induced mutagenic responses both with and without S9. With ferric chloride (FeCl3) and ferric phosphate (FePO4), there was an increase in mutant frequency only with S9. With the Fe+2 compounds, ferrous sulfate (FeSO4) and ferrous fumarate (FeC4H2O4), positive responses were observed without S9. The Fe chelate, sodium Fe(III)EDTA was positive in both the presence and absence of S9. The lowest effective doses (LED) for induction of mutagenicity were identified for these compounds and an LED ratio calculated. The LED ratio ranges from 1 for FeSO4 to 30 for carbonyl Fe, which are similar to oral LD50 values obtained in animal studies.
Center for Food Safety and Applied Nutrition, Food and Drug Administration, Washington, DC 20204, USA. VCD@CFSAN.FDA.GOV
V C
VC
Dunkel
R H
RH
San
H E
HE
Seifried
P
P
Whittaker
D000818:Animals; D004305:Dose-Response Relationship, Drug; D007501:Iron / Q000633:toxicity*; D007505:Iron-Dextran Complex / Q000633:toxicity; D007940:Leukemia L5178 / Q000235:genetics* / Q000473:pathology; D051379:Mice; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics*; D014407:Tumor Cells, Cultured
D009153:Mutagens; D007505:Iron-Dextran Complex; D007501:Iron