Sodium dichromate dihydrate is one of a number of inorganic compounds containing
hexavalent chromium (
CR VI) found in
drinking water supplies as a contaminant resulting from various industrial processes including electroplating operations, leather tanning, and textile manufacturing. Because of the lack of adequate experimental data on the toxicity and carcinogenicity of
hexavalent chromium ingested orally, and because
hexavalent chromium has been found in human
drinking water supplies, the California Congressional delegation and the California Environmental Protection Agency nominated
hexavalent chromium to the NTP for study. In study 1, male and female F344/N rats and B6C3F1 mice were exposed to
sodium dichromate dihydrate (greater than 99% pure) in
drinking water for 3 months. In study 2,
sodium dichromate dihydrate was administered in
drinking water to male B6C3F1, BALB/c, and
am3-C57BL/6 mice for 3 months. Genetic toxicology studies were conducted in Salmonella typhimurium, Escherichia coli, and mouse peripheral blood erythrocytes. In study 1, groups of 10 male and 10 female F344/N rats and B6C3F1 mice were given
drinking water containing 0, 62.5, 125, 250, 500, or 1,000 mg
sodium dichromate dihydrate/L for 3 months (equivalent to average daily doses of approximately 5, 10, 17, 32, or 60 mg
sodium dichromate dihydrate/kg
body weight to rats and 9, 15, 26, 45, or 80 mg/kg to mice). On a molecular weight basis, these doses are equivalent to approximately 1.7, 3.5, 5.9, 11.2, and 20.9 mg
hexavalent chromium/kg
body weight per day to rats and 3.1, 5.2, 9.1, 15.7, and 27.9 mg/kg per day to mice. Additional groups of 10 rats per sex were exposed to the same concentrations of
sodium dichromate dihydrate for 4 weeks. All rats and mice survived to the end of the study. Reduced
body weights occurred in 500 and 1,000 mg/L male rats, 1,000 mg/L female rats, and in male and female mice exposed to 125 mg/L or greater. Water consumption by male and female rats exposed to 250 mg/L or greater and male and female mice exposed to 125 mg/L or greater was generally less than that by the control groups, and decreases in urine volume and increases in urine specific gravity in rats were related to reduced water consumption. Exposure to
sodium dichromate dihydrate caused a microcytic
hypochromic anemia in rats and mice, but the severity was less in mice. Serum
cholesterol and
triglyceride concentrations were decreased in rats. Increased
bile acid concentrations in exposed groups of rats may have been due to altered hepatic function. The incidences of histiocytic cellular infiltration were generally significantly increased in the duodenum of rats and mice, the liver of female rats, and the mesenteric lymph node of mice exposed to 125 mg/L or greater. Significantly increased nonneoplastic lesions (focal ulceration, regenerative epithelial
hyperplasia, and squamous epithelial
metaplasia) occurred in the glandular stomach of male and female rats exposed to 1,000 mg/L. Incidences of epithelial
hyperplasia of the duodenum were significantly increased in all exposed groups of mice. In study 2,
sodium dichromate dihydrate was administered in
drinking water to groups of 10 male B6C3F1, 10 male BALB/c, and five male
am3-C57BL/6 mice for 3 months at exposure concentrations of 0, 62.5, 125, or 250 mg/L (equivalent to average daily doses of approximately 8, 15, or 25 mg/kg
sodium dichromate dihydrate or 2.8, 5.2, or 8.7 mg/kg
chromium to B6C3F1, BALB/c, and
am3-C57BL/6 mice). All mice in study 2 survived until study termination. Mean
body weights of 125 and 250 mg/L B6C3F1 and BALB/c mice and all exposed groups of
am3-C57BL/6 mice were less than those of the control groups. Mice exposed to 250 mg/L consumed less water than the control groups. Exposure concentration-related decreases in mean red cell volumes and mean red cell
hemoglobin values were observed in all three mouse strains. Erythrocyte counts were increased in exposed B6C3F1 and BALB/c mice but not in
am3-C57BL/6 mice. Changes in organ weights were generally consistent with reduced
body weights in exposed groups in all mouse strains. No biologically significant differences in reproductive parameters were observed in any strain. Histiocytic cellular infiltration and epithelial
hyperplasia of the duodenum occurred in most mice exposed to 125 or 250 mg/L, and the incidences of these lesions were increased in the 62.5 mg/L group compared to controls. Secretory depletion was present in the pancreas of most mice exposed to 125 or 250 mg/L. The incidences of
glycogen depletion of the liver were significantly increased in male B6C3F1 mice exposed to 125 or 250 mg/L and in all exposed groups of male
am3-C57BL/6 mice. The incidence of histiocytic cellular infiltration in the mesenteric lymph node was significantly increased in the 250 mg/L group of male
am3-C57BL/6 mice.
Sodium dichromate dihydrate was mutagenic in S. typhimurium strains TA100 and TA98 and in E. coli strain WP2 uvrA pKM101 with and without induced rat liver S9
enzymes. The results of four micronucleus tests conducted in the three strains of mice from studies 1 and 2 were mixed. In study 1, no significant increases were seen in micronucleated normochromatic erythrocytes in peripheral blood samples from male or female B6C3F1 mice; there was a decrease in the percentage of polychromatic erythrocytes among total erythrocytes (an indication of bone marrow toxicity), but the changes were small and not well correlated with exposure concentrations. In study 2, a significant exposure concentration-related increase (P<0.001) in micronucleated normochromatic erythrocytes was seen in
am3-C57BL/6 male mice. An equivocal increase in micronucleated erythrocytes was noted in male B6C3F1 mice, based on a small increase in micronucleated normochromatic erythrocytes that did not reach statistical significance. No increase in micronucleated normochromatic erythrocytes was observed in male BALB/c mice. No significant effect of
sodium dichromate dihydrate exposure on the percentage of polychromatic erythrocytes was observed in any of the three micronucleus tests conducted in study 2. In summary, administration of
sodium dichromate dihydrate in the
drinking water to F344/N rats and B6C3F1 mice resulted in focal ulceration,
hyperplasia, and
metaplasia in the glandular stomach at the limiting ridge in rats in the 1,000 mg/L group and evidence of increased histiocytic infiltration in the liver (female), duodenum of the small intestine, and/or pancreatic lymph nodes at concentrations as low as 62.5 mg/L, the lowest concentration studied. In addition, a microcytic,
hypochromic anemia occurred at all exposure concentrations and was considered evidence of a toxic response resulting from absorption of
Cr VI following oral ingestion in rats. A similar, but less severe,
anemia was evident in mice receiving
drinking water containing
sodium dichromate dihydrate; histiocytic infiltration was noted in the duodenum of all three strains studied (B6C3F1, BALB/c, and
am3-C57BL/6) at all concentrations employed, in the mesenteric lymph nodes
at 125 mg/L or greater in the B6C3F1 strain, and at 250 mg/L in the
am3-C57BL/6 strain. There was no consistent evidence of hepatocyte injury in mice in any of the strains tested. Variations in
glycogen content were considered more likely related to diminished food intake than to the toxicity of
sodium dichromate dihydrate. Synonyms:
Chromic acid;
dichromic acid; disodium
salt, dihydrate; disodium dichromate dihydrate;
chromium VI.