The workplace is one of the most common venues for hazardous chemical contact with skin. Recognition of the dermal exposure hazard is essential for its control. Unfortunately, the present identification of chemicals as skin absorption hazards is inconsistent, poorly documented, and qualitative. As a result, those charged with protecting human health and safety in the workplace are forced to make judgments about safe or dangerous levels, and the type of personal protection required, with little or no information. The ultimate goal of this research effort is to provide occupational safety and health practitioners with improved guidance regarding potentially dangerous levels of occupational dermal exposure. While most occupational exposures of skin involve mixtures of chemicals, the interactions between multiple components and skin remain unknown. The proposed research is directed toward identifying and understanding the ? effect of exposures to chemical mixtures and especially non-aqueous solutions. Understanding that experimental evaluations will be limited to a small fraction of all mixtures encountered occupationally, we propose to develop a fundamental understanding of the underlying mechanisms by combining data with mathematical models. Specifically, we will (i) examine experimentally the extent to which several test solutes in water and in four non-aqueous solutions (toluene, n-octanol, n-octane and a selected chlorinated hydrocarbon) interact with each other or skin to alter the rate ? and/or amount of chemical absorption, (ii) develop computational procedures for estimating dermal absorption from aqueous and non-aqueous solutions containing two or more organic compounds, and (iii) demonstrate and use a new method for measuring electrochemical impedance to characterize skin barrier function and the effect of non-aqueous solutions thereon. Initial studies will involve four solutes (naphthalene, phenanthrene, 1-naphthol, and 1,3-naphthalenediol) in toluene and n-octanol. This combination of solutes and solvents were selected to examine interactions between similar and dissimilar chemicals, and to assess the importance of hydrogen bonding interactions between absorbing chemicals and skin. The ultimate goal of this research effort is a framework for relating dermal absorption measurements and predictions for liquid mixtures to industrial health scientists in the form of useful guidelines. With such information in-hand, it will be possible to plan effective exposure controls and/or interventions. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute for Occupational Safety and Health (NIOSH)
Type
Research Project (R01)
Project #
5R01OH007493-03
Application #
7071783
Study Section
Safety and Occupational Health Study Section (SOH)
Program Officer
Karr, Joan
Project Start
2004-09-01
Project End
2009-03-31
Budget Start
2006-07-01
Budget End
2009-03-31
Support Year
3
Fiscal Year
2006
Total Cost
$244,786
Indirect Cost
Name
Colorado School of Mines
Department
Engineering (All Types)
Type
Schools of Arts and Sciences
DUNS #
010628170
City
Golden
State
CO
Country
United States
Zip Code
80401
White, Erick A; Orazem, Mark E; Bunge, Annette L (2013) Characterization of damaged skin by impedance spectroscopy: chemical damage by dimethyl sulfoxide. Pharm Res 30:2607-24
White, Erick A; Orazem, Mark E; Bunge, Annette L (2013) Characterization of damaged skin by impedance spectroscopy: mechanical damage. Pharm Res 30:2036-49
Bunge, Annette L; Persichetti, John M; Payan, Jean Paul (2012) Explaining skin permeation of 2-butoxyethanol from neat and aqueous solutions. Int J Pharm 435:50-62
White, Erick A; Horne, Alan; Runciman, Jill et al. (2011) On the correlation between single-frequency impedance measurements and human skin permeability to water. Toxicol In Vitro 25:2095-104
White, Erick A; Orazem, Mark E; Bunge, Annette L (2011) A critical analysis of single-frequency LCR databridge impedance measurements of human skin. Toxicol In Vitro 25:774-84
Romonchuk, W J (2010) Mechanism of enhanced dermal permeation of 4-cyanophenol and methyl paraben from saturated aqueous solutions containing both solutes. Skin Pharmacol Physiol 23:152-63