INFLUENCE OF METAL-WORKING FLUID FORMULATIONS ON DERMAL ABSORPTION OF BIOCIDES

AbstractThe long-term goal is to understand physicochemical and chemical-biologicalinteractions in a metal-working fluid (MWF) formulation in order to be able to predictquantitatively how these formulations influence dermal absorption of industrial biocidesused as additives in these chemically complex formulations. Current dermal riskassessments only evaluate dermal absorption of single chemicals which has limited usein occupational exposure to chemically complex MWF formulations. The primaryobjective of this research project is to utilize the membrane-coated fibers (MCF) tocharacterize the distribution behavior between a defined MWF formulation, a MWFbiocide, and an inert membrane and to relate this phase distribution to solvationparameters within a linear solvation energy relationship (LSER) framework that is alsoapplicable to dermal permeability. The central hypothesis to be tested is that thepresence of MWF formulations will alter the phase distribution of biocides between theformulation and the MCF and/or skin. These changes in biocide distribution can beexpressed in terms of interaction coefficients ( values) that can be used in futureextrapolations to a defined formulation scenario and thus can be of value to MWFformulators and metal fabrication workers by indicating what formulations are more likelyto promote skin penetration and possibly adverse occupational effects. The rationale forthis approach is that MWF formulations can modulate biocide partitioning and diffusionby quantifiable physicochemical interactions ( values). The MCF approach within theLSER framework allows for a physicochemical examination of these formulation effectsusing a multi-fiber MCF array system and validated in porcine skin diffusion cells andfinally validated in vivo for systemic absorption. The following three specific aims will bepursued to accomplish the stated objectives: 1) To quantify mixture interactionsinfluencing transport of MWF biocides between MWF formulations and themembrane coated fibers (MCF). This first involves calibration of a diverse series offibers followed by exposure of a 5-component MCF array to MWF formulations toprovide interaction coefficients ( values) for a defined formulation. 2) To quantifychemical-biological interactions in a biological membrane system followingexposure to MWF formulations in porcine skin flow-through diffusion cell. Dermalin vitro experiments will calibrate permeability in the biological system and validateformulation interaction coefficients in the MCF array for the biocides. 3) To quantify theeffect of MWF formulations on the in vivo dermal absorption of MWF biocides.This involves comparative analysis of interaction coefficients between the MCF arrayand the two biological systems (in vitro and in vivo) and will validate the proposed MCF-array approach within the LSER framework to predict the dermal permeability ofoccupationally relevant toxicants such as MWF biocides in a defined in MWFformulations.