Range-Finding Report on the Immunotoxicity of Dibromoacetic Acid in Female Sprague Dawley Rats (CAS No. 631-64-1)
Report Date: September 2006
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 The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009.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.
Disinfection by-products are contaminants found in drinking water and are formed as by-products of the chlorination/ozonization processes that are used to purify water to acceptable drinking water standards. At the present time, five haloacetic acids, including dibromoacetic acid, are regulated by the United States Environmental Protection Agency (EPA) such that their total concentration does not exceed 60 parts per billion (ppb) (= 60 µg/L) (Boorman, 1999; Richardson et al., 2007). The potential for drinking water contaminants to adversely affect the immune system is a concern of both the EPA and the National Institute of Environmental Health Sciences. Previous studies in B6C3F1 mice evaluating the effects of DBA exposure at doses of 125, 500, and 1000 mg/L for 28 days in the drinking water demonstrated no effects on immune function, although thymus weight was decreased at the two highest dose levels (Smith et al., 2010).
The National Toxicology Program requested that a dose range-finding study be conducted to establish the potential effects of DBA on the immune system. These studies were conducted in female Sprague Dawley Rats. Five DBA concentrations (125, 250, 500, 1000, and 2000 mg/L) were utilized and administered for 28 days via the drinking water.
Female Sprague Dawley rats demonstrated significant decreases in both terminal body weights and in body weight gain when exposed for 28 days to DBA via the drinking water. In animals exposed at 1000 mg/L, body weight was decreased 5% and body weight gain was decreased 13% after 28 days of exposure. In animals exposed to 2000 mg/L DBA, body weight and body weight gain were decreased by 9% and 31%, respectively, following 28 days of exposure. The decreases in weight at the 2000 mg/L dose were due, in part, to decreased water consumption by the animals in this dose group. The weights of major organs of the immune system, i.e., the thymus and the spleen, were unaffected overall following DBA exposure, while liver weights were significantly increased in a dose-related manner. Effects on several hematological parameters were also observed, suggesting that DBA exposure produces anemia in female Sprague Dawley rats. Specifically, hemoglobin concentration was decreased at doses ≥ 500 mg/L, mean corpuscular hemoglobin was decreased at doses ≥ 1000 mg/L, and hematocrit and mean corpuscular volume were each significantly decreased at the 2000 mg/L treatment level.
Total splenocyte numbers were decreased at the 1000 mg/L and 2000 mg/L dose groups in one study but unaffected in two other studies. The latter is consistent with the lack of effects on spleen weight and there was no apparent reason for the differential results. The absolute values of splenic total T cells, TH, and natural killer cells were all significantly decreased at doses ≥ 1000 mg/L, while TCTL cells were decreased at 2000 mg/L DBA only. Absolute numbers of B cells and macrophages were unaffected. When evaluated as a percentage of total cell numbers, splenic B cells, TCTL cells, NK cells, and macrophages were unaffected by DBA exposure. In contrast, the percentages of T cells and TH cells were significantly decreased following DBA exposure.
No effects were observed on either the antibody-forming cell response to sheep erythrocytes or the serum IgM antibody levels to keyhole limpet hemocyanin, suggesting that DBA exposure does not adversely affect humoral immunity. In addition, cell-mediated immunity was unaffected, as evidenced by a lack of effect on both the anti-CD3 proliferative response and the delayed-type hypersensitivity response to Candida albicans. Furthermore, no effects on innate immunity were observed in either natural killer cell activity or the activity of the fixed tissue macrophages of the mononuclear phagocytic system. While hematological, body weight, and liver weight effects were observed, the results of the immunology studies suggest that DBA does not affect immune function when administered to female Sprague Dawley rats for 28 days via the drinking water.
Boorman G.A. (1999). Drinking water disinfection byproducts: review and approach to toxicity evaluation. Environ Health Perspect, 107 Suppl 1:207-217.
Richardson S.D., Plewa M.J., Wagner E.D., Schoeny R., & Demarini D.M. (2007). Occurrence, genotoxicity, and carcinogenicity of regulated and emerging disinfection byproductes in drinking water: A review and roadmap for research. Mutat Res., 636:178-242.
Smith M.J., Germolec D.R., Luebke R.W., Sheth C.M., Auttachoat W., Guo T.L., & White K.L. (2010). Immunotoxicity of dibromoacetic acid administered via drinking wter to female B6C3F1 mice. J Immunotoxicol 7(4):333-43.