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 fortific ation, were evaluated for mutagenicity in Salmonella typhimurium and L5178Y mouse lymphoma cells. Except for the weak response obtained with ferrous f umarate, 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 element al forms of Fe were divergent. Electrolytic Fe with a relatively larger par ticle 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 mutage nic responses both with and without S9. With ferric chloride (FeCl3) and fe rric 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, so dium Fe(III)EDTA was positive in both the presence and absence of S9. The l owest effective doses (LED) for induction of mutagenicity were identified f or 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 ID50 values obt ained in animal studies. (C) 1999 Wiley Liss, Inc.