Correlation of blood Cr(III) and adverse health effects: Application of PBPK modeling to determine non-toxic blood concentrations.

Chromium (Cr) (III) is a trace metal essential to human health and exposure typically occurs via the diet on a daily basis. Some groups of individuals, such as those consuming Cr(III) supplements or patients with Cr-containing implants, may have elevated blood Cr(III) concentrations. Although blood Cr(III) levels are thought to be an accurate metric of exposure, little is known about the relationship between these concentrations and possible adverse health risks. This study evaluated the various effects reported in animal and human epidemiological studies of Cr(III) exposure in an attempt to correlate them with blood Cr(III) concentrations. The target end-points identified in this analysis included the hematological, hepatic, and renal systems. Animal and human physiological-based pharmacokinetic (PBPK) models were used to estimate steady state blood Cr(III) concentrations from a variety of dosing regimens. Based on the animal studies, our results suggest that blood Cr(III) concentrations as high as 480-580 mu g/L are not associated with any responses. For each of the three health endpoints considered in this analysis (hematological, hepatic, and renal) no adverse effects were observed below 3,700 mu g/L. Some hematological responses were observed at 3,700 mu g/L, and adverse effects clearly occurred at 7,500 mu g/L. These findings can be used to assess potential health risks to individuals with elevated blood Cr(III) concentrations.