Health problems associated with exposure to arsenic (As) from chromated copper arsenate (CCA)-treated wood continue to command world attention. It has been demonstrated that, in addition to As, chromium (Cr) and copper (Cu) also leach at levels potentially toxic to aquatic organisms. Although considerable progress has been made in studying the toxicity of As, the harmful effects of these three elements in mixtures, leached simultaneously are currently unknown. The lack of this information remains one of the major obstacles to assess the potential effects of CCA-treated wood on human health. Our longterm goal is to characterize and ultimately reduce the human health risks associated with exposure to CCA. The principal objective of this research is to understand the leaching and human physiological effects (cell behavior and metabolism) of As, Cr, and Cu associated with CCA-treated wood. The objective will be accomplished by pursuing the following specific aims: (1) Investigate the leaching characteristics of all three toxic elements, As, Cr, and Cu from CCA-treated wood and from the affected soils; (2) Evaluate the effects on aspects of cell physiology of As, Cr, and Cu alone or in mixtures using a model based on human nerve cell cultures (cell lines such as NSC-34, SH-SY5Y, CATH.a, D384 and SK-N-MC); and 3) Determine the effects of soil properties on the cell effects of soil leachate. This study will be guided by the following hypotheses: (1) The potential physiological effects of the leachates associated with CCA-treated wood to human beings is affected by the presence of the three metals derived from CCA and interactions between them and low concentrations of As, Cr, and Cu in these leachates will affect critical aspects of cell metabolism; and (2) The leaching and potential effects of these elements from soils affected by CCA are altered by soil properties. It is expected that this research will provide new and essential information for assessing the effects of the leachates associated with CCA on human beings. These results will allow improved predictions of leaching of As, Cr, and Cu from CCA-treated wood and their transport through soils and, ultimately, evaluations of possible human health impacts associated with the release of these elements. Our results will, therefore, enable us to more accurately assess the environmental and human health impacts of As, Cr, and Cu pollution resulting from CCA applications.