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 solvation 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.

Agency
National Institute of Health (NIH)
Institute
National Institute for Occupational Safety and Health (NIOSH)
Type
Research Project (R01)
Project #
5R01OH003669-07
Application #
7249351
Study Section
Safety and Occupational Health Study Section (SOH)
Program Officer
Karr, Joan
Project Start
2000-08-01
Project End
2008-08-31
Budget Start
2007-09-01
Budget End
2008-08-31
Support Year
7
Fiscal Year
2007
Total Cost
$215,118
Indirect Cost
Name
North Carolina State University Raleigh
Department
Anatomy/Cell Biology
Type
Schools of Veterinary Medicine
DUNS #
042092122
City
Raleigh
State
NC
Country
United States
Zip Code
27695
Roux, Lauriane N; Brooks, James D; Yeatts, James L et al. (2015) Skin absorption of six performance amines used in metalworking fluids. J Appl Toxicol 35:520-8
Xu, G; Hughes-Oliver, J M; Brooks, J D et al. (2013) Selection of appropriate training and validation set chemicals for modelling dermal permeability by U-optimal design. SAR QSAR Environ Res 24:135-56
Xu, G; Hughes-Oliver, J M; Brooks, J D et al. (2013) Predicting skin permeability from complex chemical mixtures: incorporation of an expanded QSAR model. SAR QSAR Environ Res 24:711-31
Vijay, Vikrant; White, Eugene M; Kaminski Jr, Michael D et al. (2009) Dermal permeation of biocides and aromatic chemicals in three generic formulations of metalworking fluids. J Toxicol Environ Health A 72:832-41
Yeatts Jr, James L; Baynes, Ronald E; Xia, Xin-Rui et al. (2008) Application of linear solvation energy relationships to a custom-made polyaniline solid-phase microextraction fiber and three commercial fibers. J Chromatogr A 1188:108-17
Baynes, Ronald E; Xia, Xin Rui; Imran, Mudassar et al. (2008) Quantification of chemical mixture interactions modulating dermal absorption using a multiple membrane fiber array. Chem Res Toxicol 21:591-9
Baynes, R E; Xia, X-R; Vijay, V et al. (2008) A solvatochromatic approach to quantifying formulation effects on dermal permeability. SAR QSAR Environ Res 19:615-30