Propanil is a post emergent herbicide. Wheat and rice have high levels of arylamidase which allows them to detoxify propanil, and thus become resistant to its herbicide effects, while common weeds are unable to detoxify the agent and are killed. Because of these characteristics, farmers can control common weeds throughout the growing season with multiple applications of propanil. The US EPA estimates that 7 9 million pounds of propanil is applied during an annual growing season. The toxicity of propanil to animals has been the subject of several studies. Earlier studies showed a neurotoxic as well as a hematotoxic effects, i.e., propanil causes anemia and methemoglobin formation. The immunotoxic effects of propanil have been documented by Barnett and his coworkers. Propanil causes a reduction in T dependent and T independent antibody production, and reduced macrophage, natural killer cell, and T helper (TH) cell function but does not appear to affect cytotoxic T lymphocyte function. The investigator's preliminary data also indicate that propanil, and not a metabolite, is the primary immunotoxicant. The thrust of this project is focused on T cell and macrophage cytokine production. The investigator's preliminary data indicates that propanil causes a significant reduction in IL 2, IFN gamma, GM CSF and IL 6 production in T cells and IL 6 and TNF alpha in macrophages. Cytokine production is a critical step in the immune response and a selective reduction in cytokine production could account for many of the immunotoxic effects seen. Newer preliminary data allow them to focus on the mechanism the effect of propanil on cytokine production on mouse cells through 3 specific aims, the effect of propanil on: 1) macrophage signaling processes, 2) T cell signaling processes, and 3) IL 2 message stability. A fourth specific aim will extend the mechanistic findings to human cell lines, thus, providing a basis for extrapolating animal data to human exposure risk. The final specific aim will provide data essential for correlating in vivo exposure levels with in vitro exposure levels.
