Assessment of immunotoxicity in female Fischer 344/N and Sprague Dawley rats and female B6C3F1 mice exposed to hexavalent chromium via the drinking water |
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| Authors: | Kelly A. Shipkowski Christopher M. Sheth Matthew J. Smith Michelle J. Hooth Kimber L. White Jr. Dori R. Germolec |
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| Affiliation: | 1. Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA;2. Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA;3. Richard Bland College of William &4. Mary, Petersburg, VA, USA;5. Department of Pharmacology and Toxicology (retired), Virginia Commonwealth University, Richmond, VA, USA |
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| Abstract: | Sodium dichromate dihydrate (SDD), an inorganic compound containing hexavalent chromium (Cr(VI)), is a common environmental contaminant of groundwater sources due to widespread industrial use. There are indications in the literature that Cr(VI) may induce immunotoxic effects following dermal exposure, including acting as both an irritant and a sensitizer; however, the potential immunomodulatory effects of Cr(VI) following oral exposure are relatively unknown. Following the detection of Cr(VI) in drinking water sources, the National Toxicology Program (NTP) conducted extensive evaluations of the toxicity and carcinogenicity of SDD following drinking water exposure, including studies to assess the potential for Cr(VI) to modulate immune function. For the immunotoxicity assessments, female Fischer 344/N (F344/N) and Sprague Dawley (SD) rats and female B6C3F1 mice were exposed to SDD in drinking water for 28 consecutive days and evaluated for alterations in cellular and humoral immune function as well as innate immunity. Rats were exposed to concentrations of 0, 14.3, 57.3, 172, or 516?ppm SDD while mice were exposed to concentrations of 0, 15.6, 31.3, 62.5, 125, or 250?ppm SDD. Final mean body weight and body weight gain were decreased relative to controls in 250?ppm B6C3F1 mice and 516?ppm SD rats. Water consumption was significantly decreased in F344/N and SD rats exposed to 172 and 516?ppm SDD; this was attributed to poor palatability of the SDD drinking water solutions. Several red blood cell-specific parameters were significantly (5–7%) decreased in 250?ppm mice; however, these parameters were unaffected in rats. Sporadic increases in the spleen IgM antibody response to sheep red blood cells (SRBC) were observed, however, these increases were not dose-dependent and were not reproducible. No significant effects were observed in the other immunological parameters evaluated. Overall, exposure to Cr(VI) in drinking water had limited effects on the immune system in both rats and mice. |
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| Keywords: | Hexavalent chromium immunotoxicity Fischer 344/N Sprague Dawley rats B6C3F1 mice antibody-forming cell response natural killer cell activity |
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