Differential toxicity and clearance kinetics of chromium(III) or (VI) in mice

The acute and subacute toxicities of several chromium(III) and chromium(VI) compounds were determined in NZC and (CxO) mice injected i.p. The distal median lethal doses (more than 10 days after treatment) averaged (17.9 +/- 1.8) X 10(-6) g chromium/g body weight regardless of the oxidation state of the chromium compound injected (chromium(III) sulphate may be an exception), but acute toxicity (3 days) was much greater with chromium(VI) compounds. Acid digests of entire male mice that were administered i.p. one-sixth of the distal LD50, either once or repeatedly at weekly intervals, were analysed to determine the whole body persistence and clearance kinetics of chromium. Mice dosed once with chromium(III) retained 6.5 times more chromium at 21 days than mice treated with chromium(VI). When chromium(III) was given at weekly intervals mice accumulated 6 times more chromium by 8 weeks than chromium(VI)-treated mice, though only the latter showed symptoms of chronic toxicity. Whole body chromium concentrations continued to rise with further chromium(III) treatments, but slowly declined with chromium(VI). Analyses of fecal and urinary excretion confirmed most of the urinary chromium clearance occurred soon after injection, and that chromium excretion from chromium(VI)-treated animals was much faster in both urine and feces than from mice given chromium(III). The differential storage and clearance kinetics of chromium(III) and chromium(VI) compounds may be significant in experimental chromium carcinogenesis studies and in the toxicology of chromium in workers exposed industrially to potentially carcinogenic chromium-containing dusts or aerosols.