The long-term goal is to understand physicochemical and chemical-biological interactions in a mixture in order to predict quantitatively how cutting fluid additives influence dermal absorption of biocides often associated with irritant dermatitist in workers. Previous dermal risk assessments only evaluated absorption of single chemicals and given the multitude of diverse laboratory methodologies, robust extrapolation is limited, which ultimately impacts risk characterization. The primary objective of this project is to utilize the membrane-coated fiber (MCF) technique to characterize the partitioning behavior of biocides between a defined mixture such as cutting fluids and an inert membrane and to relate this phase distribution to solvatochromatic parameters within a linear salvation energy relationship (LSER) framework. The central hypothesis to be tested is that the presence of cutting fluid additives will alter the phase distribution of biocides between the mixture and the MCF. These changes in biocide distribution can be expressed in terms of interaction coefficients that can be extrapolated to a defined mixture. The rationale for this approach is that additives used in cutting fluid formulations can modulate bicocide absorption by discrete biological mechanism, but very little is known about the embedded physicochemical interactions. The MCF approach within the LSER framework allows for a mechanistic examination of these solvation effects using a non-biological membrane system. The following three specific aims will be pursued to accomplish the stated objectives: 1) Identify and quantify physicochemical parameters that influence solute transport from aqueous solution systems to the membrane-coated fibers (MCF). This first involves calibration of a diverse series of MCFs so as to capture as many physicochemical attributes of solute-membrane interaction. 2) Identify and quantify additive effects influencing biocide transport between mixtures and the MCF. This will provide interaction coefficients for a given mixture scenario. 3) Identify chemical biological interactions in a biological membrane system. Dermal in vitro experiments will calibrate permeability in the biological system and determine interaction coefficients in related mixtures. Comparative analysis of interaction coefficients between the MCF and biological systems will provide some insight into dominant physicochemical interactions influencing dermal absorption of biocides in chemical mixtures. ? ?
