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 The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009.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.
Atrazine (2-chloro-4-ethylamino-6-isopropylamino-s-triazine) has been reported to be the most commonly employed herbicide in the United States. Atrazine (ATZ) is routinely used in combating weeds in corn and sorghum crops and is also widely used in combination with other herbicides. As a result of its low biodegradability, it has a high potential for contaminating surface waters. Atrazine's potential environmental hazard for polluting drinking water has led Italy to ban this herbicide. Wide-spread contamination of ground water has been reported in the Midwest of the United States. Prior to these studies, the effect of atrazine on the immune system had only been studied to a limited extent.
Atrazine was nominated to the NTP for toxicological evaluation and was selected for immunotoxicity studies by the chemical manager. Thus, the purpose of these studies was to determine the effect of atrazine on the immune system.
The baseline toxicology studies are summarized in Table ES-1. Mice exposed to atrazine at doses of 500 mg/kg have significant decreases in body weight at the end of the first and second week of exposure. In some studies the decrease in body weight was in excess of 10% of the vehicle control group. Body weight gain when evaluated over the first week period was significantly decreased at all dose levels, and when evaluated over the two week exposure period, both the middle (45%) and high (105%) dose groups were significantly decreased. While the liver weights were unaffected by the atrazine exposure, a dose-dependent decrease was observed in spleen (33%) and thymus (52%) weights. Additionally, kidney weights were decreased (15%) in the atrazine exposure animals at the high dose. No statistically significant effects were observed on leukocyte numbers, leukocyte differentials, reticulocytes or mean corpuscular hemoglobin concentrations. A statistically significant decrease was observed in the erythroid elements: erythrocytes (14%), hemoglobin (5%) and hematocrit (5%). An increase was observed in mean corpuscular hemoglobin which was dose related. However, the significant increase in mean corpuscular volume was observed only in the low dose group, and while the other dose levels were elevated compared to the vehicle control, they did not reach the level of statistical significance (p less than 0.05).
Table ES-2 summarizes the immunology studies. Exposure to atrazine decreased the absolute number of B cells (18%) and decreased the absolute number of CD4+CD8+(40%) T cell subset. Total T cells and the other T cell subsets were not affected. Atrazine had no effect on the humoral immune response to sheep erythrocytes, evaluated either in the plaque-formingcell assay (PFC) or as serum titers. The proliferative response to mitogens, Con A and LPS, were not affected. However, a dose-dependent increase was observed in the proliferative response to allogeneic cells as evaluated in the MLR. The animals receiving the high dose of atrazine had a response which was increased 30% compared to the vehicle controls. Overall, there was no significant effect on the CTL response, natural killer cell activity or the functional activity of the reticuloendothelial system.
The results of the host resistance studies are summarized in Table ES-3. In the two host resistance models evaluated, host resistance to Listeria monocytogenes was not affected, while a decrease in host resistance to the B16F10 Melanoma tumor model was observed.
In summary, although atrazine was administered at dose levels which produced significant decreases in terminal body weights and weight gain as well as effects on various erythroid elements, most of the functional assays used to evaluate immunocompetence were not adversely affected. However, due to the dose-dependent increase in the mixed leukocyte response and the dose-dependent decrease in host resistance to the B16F10 melanoma tumor model, atrazine was found to adversely affect the immune system and, thus, is considered to be an immunotoxic compound when administered under the experimental conditions used in this protocol.