Range-Finding Report on the Immunotoxicity of Hexavalent Chromium (Sodium Dichromate Dihyrate) in Female F344 Rats (CAS No. 7789-12-0)
Report Date: April 2007
The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of the NTP or the U.S. Government.
Sodium dichromate (hexavalent Cr) is a metal contaminant found in drinking water. The potential for drinking water contaminants to adversely affect the immune system is a concern of the National Institute of Environmental Health Sciences. Several drinking water contaminants, including HCR, have been identified and selected for evaluation of their potential effects on the immune system by NIEHS.
In addition to being a drinking water contaminant, HCR is a potent sensitizer. Individuals can become allergic to HCR by working with it or by being exposed through constant contact of Cr containing stainless steel. HCR has been shown to be immunotoxic in experimental animals. Rats exposed to 25 to 200 µg of Cr(VI)/m3 as sodium dichromate for 28 or 90 days had increased spleen weights and increased response to sheep red blood cells. Changes in immunoglobulin concentration, granulocytes, macrophages and lymphocytes have been observed in bronchoalveolar lavage fluid from animals exposed by inhalation. The concentrations of Cr(VI) in drinking water for animal studies are usually from 0 - 25 parts per million. The US EPA drinking water standard is 100 µg/L (100 ppb).
The National Toxicology Program requested that a dose range-finding study be performed to establish the potential effects of HCR on the immune system. These studies were conducted in female F344 rats. The animals were exposed to HCR based on the concentration of the test substance in the drinking water. Four HCR concentrations of 14.3, 57.3, 172, and 516 mg/L for 28 days were utilized. Animals were evaluated for toxicological and immune functions on day 29.
As in the toxicological parameters, exposure to HCR produced minimal changes in various immunological parameters.
HCR, when administered in the drinking water at doses from 14.3 to 516 mg/L for 28 days, did not produce any signs of overt toxicity. The female F344 rats appeared to have a taste aversion to the two highest dose levels, for which they consumed statistically less drinking water than the vehicle, tap water, control animals. There were no significant effects on body weight or body weight gain in the exposed animals over the entire study period. At the time of sacrifice, no gross pathological lesions were observed in HCR-exposed rats. Overall, exposure to HCR did not produce significant changes in the weights of thymus, liver, spleen, lungs and kidneys. The hemoglobin, hematocrit, MCHC, platelet count, percentage of reticulocytes, total leukocyte count and leukocyte differentials were unaffected by HCR. Increases observed in MCV and MCH were not dose dependent.
As in the toxicological parameters, exposure to HCR produced minimal effects in various immunological parameters. There were no statistically significant changes in the percentage and number of total B cells, T cells, CD4+ T cells, and CD8+ T cells. When evaluated as percent values, a significant increase was observed at the two highest dose levels for natural killer cells, and at the 172 mg/L dose level when evaluated as absolute values. For the splenic macrophage population, an increase was observed at the low dose level when evaluated as absolute values. The effect of HCR on cell-mediated immunity and NK cells was evaluated using anti-CD3 antibody-mediated T cell proliferation and cytotoxic assay of YAC-1 cells, respectively. There were no statistically significant alterations in CD3-mediated proliferation and NK activity after exposure to HCR. Furthermore, no effects were observed in IgM antibody response to the T-dependent antigen keyhole limpet hemocyanin. Exposure to HCR did produce an increase in the IgM antibody-forming cell responses to sheep red blood cells. however, the response only reached the level of statistical significance at one dose level (57.3 mg/L).
In conclusion, when administered in the drinking water for 28 days at doses from 14.3 to 516 mg/L, HCR produced minimal toxicological and immunotoxic effects in female F344 rats.