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

The acute and subacute toxicities of several chromium(III) andchromium(VI) compounds were determined in NZC and (CxO) miceinjected i.p. The distal median lethal doses (more than 10 daysafter treatment) averaged (17.9 ± 1.8) x 10^–6 gchromium/g body weight regardless of the oxidation state ofthe chromium compound injected (chromium(III) sulphate may bean exception), but acute toxicity (3 days) was much greaterwith chromium(VI) compounds. Acid digests of entire male micethat were administered i.p. one-sixth of the distal LD₅₀, eitheronce or repeatedly at weekly intervals, were analysed to determinethe whole body persistence and clearance kinetics of chromium.Mice dosed once with chromium(III) retained 6.5 times more chromiumat 21 days than mice treated with chromium(VI). When chromium(III)was given at weeky intervals mice accumulated 6 times more chromiumby 8 weeks than chromium(VI)-treated mice, though only the lattershowed symptoms of chronic toxicity. Whole body chromium concentationscontinued to rise with further chromium(III) treatments, butslowly declined with chromium(VI). Analyses of fecal and urinaryexcretion confirmed most of the urinary chromium clearance occurredsoon after injection, and that chromium excretion from chromium(VI)-treatedanimals was much faster in both urine and feces than from micegiven chromium(III). The differential storage and clearancekinetics of chromium(III) and chromium(VI) compounds may besignificant in experimental chromium carcinogenesis studiesand in the toxicology of chromium in workers exposed industriallyto potentially carcinogenic chromium-containing dusts or aerosols.