Report Date: December 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 The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009.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. DBPs are formed as by-products as a result of the chlorination/ozonization process used to purify water to acceptable drinking water standards. The potential effects of drinking water contaminants to affect adversely the immune system is a concern of both the Environmental Protection Agency and the National Institute of Environmental Health Sciences. Several drinking water DBPs have been identified and selected for evaluation of their potential effects on the immune system in a joint project between the EPA and the NIEHS.
The purpose of these studies was to determine the potential effects of dibromoacetic acid on the immune system when administered in drinking water. These studies were conducted in female B6C3F1 mice. The animals were exposed to DBA based on the concentration of the test article in the drinking water. Three DBA concentrations of 125, 500, and 1000 mg/L for 28 days were utilized. DBA solutions were prepared fresh every two weeks in tap water and stored refrigerated.
Exposure to DBA had minimal effects on the toxicological parameters including body and organ weights and hematological parameters, with the following exceptions. Overall DBA exposure produced a significant increase in weight during the second and third week of exposure and an overall weight gain in two lower dose groups over the study period. A dose-related increase in liver weight was observed in the DBA-exposed animals. While spleen weights were unaffected, a reduction in thymus weights was observed at the two highest dose levels.
Exposure to DBA did not significantly affect splenic subpopulations with the exception of a decrease in the absolute number of natural killer cells and macrophages in animals receiving the middle (500 mg/L) dose. Both of these changes were due in part to the decrease in spleen cell number observed at this dose level. An increase in absolute macrophage number was observed at the high dose level of DBA. Humoral immunity, evaluated in either the IgM antibody forming cell response to the T-dependent antigen sheep erythrocytes (plaque assay) or the IgM enzyme-linked immunosorbent assay to sRBC, was not affected by exposure to DBA. Similarly, cell-mediated immunity as evaluated by the mixed leukocyte response was not affected by exposure to DBA. Innate immunity was evaluated using the ability of peritoneal macrophages to kill B16F10 tumor cells and by evaluating both basal and augmented natural killer cell activity. In animals treated with DBA, no significant difference from the vehicle controls was observed in the ability of macrophages to kill the tumor cells when evaluated with or without a macrophage stimulating factor. Overall, exposure to DBA did not adversely affect natural killer cell activity when measured as basal activity or augmented activity, following stimulation with polyinosinc-polycytidylic acid. In the augment NK cell assay, a decrease response was observed in the low dose (125 mg/L) group at all effector-to-target ratios.
Exposure to DBA did not significantly alter host resistance to either Streptococcus pneumoniae or plasmodium yoelli, two models used to primary evaluate the competence of the humoral immune component of the immune system. Similarly, exposure to DBA did not alter host resistance to the B16F10 melanoma tumor, a model system which evaluates effects on innate immunity, including natural killer cells and macrophages, as well as the cytotoxic T cell population of cell-mediated immunity.
In conclusion, exposure to DBA at concentrations of 125, 500, and 1000 mg/L for 28 days in the drinking water produced minimal changes in the toxicological parameters evaluated. Alterations in liver and thymus weights demonstrate that DBA was being absorbed from the drinking water solutions. Evaluation of the immunological parameters capable of assessing the immunocompetence of the major components of the immune response, including innate immunity, humoral immunity and cell-mediated immunity, was essentially unaffected following exposure to DBA at dose levels as high as 1000 mg/L. The lack of effect of DBA on the various components of the immune system was further demonstrated in that DBA exposure failed to decrease host resistance in any of the bacterial, parasitic, or tumor models evaluated. The results from this study demonstrate that DBA exposure from drinking water at concentrations as high as 1000mg/L does not adversely affect the immune system.