TOXICOLOGICAL PROFILE FOR CHROMIUM - Davidborowski.com

CHROMIUM 1612. HEALTH EFFECTSincorporation of chromium into actively mineralizing bone. It also includes the reductive process forconversion of chromium(VI) to chromium(III) and takes into account differences in their absorptionthrough tissues of the body as well as in the lung and gastrointestinal tract. The chromium model neededto be modified to include two lung compartments. Chromium via inhalation or intratracheal routes entersthe lung in compartment A where it can be systemically absorbed, transferred to the second lungcompartment B, or cleared by mucociliary action and enter the digestive tract. Chromium enteringcompartment B can only be cleared by mucociliary action, and no chromium re-enters compartment Afrom B. In order to account for the urinary excretion delay observed in the experimental data, a urinaryretention compartment was added. Because the absorption of chromium compounds into the body andvarious tissues depends on the type and solubility of the complexes formed with ligands, adjustments tothe model must be made based on physicochemical characteristics of individual chromium compounds.Validation of the model. The model was run with the exposure regimen of an inhalation study ofchromium(VI) as zinc chromate dust in Wistar rats (Langård et al. 1978). This study was chosen forvalidation because none of the studies used to develop the model were inhalation studies. Rats wereexposed to 2.1 mg chromium(VI)/m 3 for 6 hours/day for 4 days, blood chromium was measured beforeand after each exposure and 4 times over the next 37 days post-exposure. The model tended tooverpredict chromium blood levels during the 4-day exposure period, but agreement during the postexposureperiod was good. The exposure conditions of a drinking water exposure to potassiumchromate(VI) for 1 year at concentrations of 045, 2.2, 4.5, 7.7, 11.2, and 25 ppm in Sprague-Dawley ratswere also simulated (MacKenzie et al. 1958).The model overestimated final liver chromium concentrations, but bone and kidney concentrations werewell-predicted. This was not a completely independent test of the model’s validity since data from thisstudy were used to set parameters for fractional uptake of chromium into bone.Target tissues. Tissue levels of chromium(III) and chromium(VI) in the rat lung, erythrocyte, liver,and kidney can be predicted by this model.Species extrapolation. No species extrapolation was attempted in this model. The model is basedentirely on data from rat kinetic studies.