Hexavalent chromium [
Cr(VI)] induces hematological signs of microcytic
anemia in rodents. Considering that
Cr(VI) can oxidize ferrous (Fe(2+)) to ferric (Fe(3+))
iron, and that only the former is transported across the duodenum, we hypothesize that, at high concentrations,
Cr(VI) oxidizes Fe(2+) in the lumen of the small intestine and perturbs
iron absorption. Herein we report that 90-day exposure to
Cr(VI) in
drinking water resulted in dose-dependent decreases in Fe levels in the duodenum, liver, serum, and bone marrow. Toxicogenomic analyses from the duodenum indicate responses consistent with Fe deficiency, including significant induction of divalent
metal transporter 1 (DMT1, Slc11a2) and
transferrin receptor 1 (TFR1, Tfr1). In addition, at ⩾20mg
Cr(VI)/L in
drinking water, Cr RBC:plasma ratios in rats were increased and exceeded unity, indicating saturation of reductive capacity and intracellular absorption of
Cr(VI) into red blood cells (RBCs). These effects occurred in both species but were generally more severe in rats. These data suggest that high concentrations of
Cr(VI) in drinking limit Fe absorption and alter
iron homeostasis. Furthermore, some effects observed at high doses in recent
Cr(VI) chronic and subchronic bioassays may be explained, at least in part, by
iron deficiency and disruption of homeostasis.