TOXICOLOGICAL PROFILE FOR CHROMIUM - Davidborowski.com

CHROMIUM 1362. HEALTH EFFECTSThe distribution of potassium chromate(VI) was compared in male Fisher rats and C57BL/6J miceexposed either by drinking water (8 mg chromium(VI)/kg/day for 4 and 8 weeks) or by intraperitonealinjection (0.3 and 0.8 mg chromium(VI)/kg/day for 4 or 14 days) (Kargacin et al. 1993). Theconcentrations of chromium (µg/g wet tissue) after drinking water exposures for 8 weeks in mice were:liver 13.83, kidney 4.72, spleen 10.09, femur 12.55, lung 1.08, heart 1.02, muscle 0.60, and blood 0.42.These concentrations were not markedly different than for 4-week exposures. For rats, the concentrationswere liver 3.59, kidney 9.49, spleen 4.38, femur 1.78, lung 0.67, heart 1.05, muscle 0.17, and blood 0.58.These results demonstrate that considerable species differences exist between mice and rats and need tobe factored into any toxicological extrapolations across species even if the routes of administration are thesame. In the drinking water experiments, blood levels in rats and mice were comparable, but in intraperitonealinjection experiments, rats’ levels were about 8-fold higher than mice after 4 days of exposure.This difference appeared to be due to increased sequestering by rat red blood cells, since accumulation inwhite blood cells was lower in rats than mice. The higher incidence of red cell binding was alsoassociated with greater binding of chromium to rat hemoglobin.The feeding of five male Wistar rats at 0.49 mg chromium(III)/kg/day as chromium(III) chloride for10 weeks resulted in increased chromium levels in liver, kidney, spleen, hair, heart, and red blood cells(Aguilar et al. 1997). Increases were highest in kidney (0.33 µg/g wet tissue in controls versus 0.83 µg/gin treated animals) and erythrocytes (1.44 µg/g wet tissue in controls versus 3.16 µg/g in treated animals).The higher tissue levels of chromium after administration of chromium(VI) than after administration ofchromium(III) (MacKenzie et al. 1958; Maruyama 1982; Witmer et al. 1989, 1991) reflect the greatertendency of chromium(VI) to traverse plasma membranes and bind to intracellular proteins in the varioustissues, which may explain the greater degree of toxicity associated with chromium(VI). In anexperiment to determine the distribution of chromium in red and white blood cells, rats were exposedorally to 0.0031 mg/kg of 51 chromium(VI) as sodium chromate. The 51 chromium content of thefractionated blood cells was determined either 24 hours or 7 days after exposure. After 24 hours, thewhite blood cells contained much more 51 chromium (.250 pg chromium/billion cells) than did the redblood cells (.30 pg chromium/billion cells). After 7 days, the 51 chromium content of the white bloodcells was reduced only 2.5-fold, while that of the red blood cells was reduced 10-fold. Thus, white bloodcells preferentially accumulated chromium(VI) and retained the chromium longer than did the red bloodcells. As discussed in Section 2.3.2.4, a small amount of chromium(III) entered red blood cells of ratsafter intravenous injection of 51 chromium trichloride, but no 51 chromium was detectable in white bloodcells (Coogan et al. 1991b).