A solvatochromatic approach to quantifying formulation effects on dermal permeability†

†Presented at the 13^th International Workshop on QSARs in the Environmental Sciences (QSAR 2008), 8–12 June 2008, Syracuse, USA.

Abstract

Dermal risk assessments are most often concerned with the occupational and environmental exposure to a single chemical and then determining solute permeability through in vitro or in vivo experimentation with various animal models and/or computational approaches. Oftentimes, the skin is exposed to more than one chemical that could potentially modulate dermal permeability of the chemical that could cause adverse health effects. The focus of this article is to demonstrate that these formulation effects on dermal permeability can occur with simple solvent formulations or complex industrial formulations and that these effects can be modeled within the context of a linear solvation energy relationship (LSER). This research demonstrated that formulation-specific strength coefficients (r p a b v) predicted (r ² = 0.75–0.83) changes in the dermal permeability of phenolic compounds when formulated with commercial metal-working fluid (MWF) formulations or 50% ethanol. Further experimentation demonstrated that chemical-induced changes in skin permeability with 50% ethanol are strongly correlated (r ² = 0.91) to similar changes in an inert membrane-coated fiber (MCF) array system consisting of three chemically diverse membranes. Changes in specific strength coefficients pertaining to changes in hydrogen donating ability (Δb) and hydrophobicity (Δv) across membrane systems were identified as important quantitative interactions associated with ethanol mixtures. This solvatochromatic approach along with the use of a MCF array system holds promise for predicting dermal permeability of complex chemical formulations in occupational exposures where performance additives can potentially modulate permeability of potential toxicants.

†Presented at the 13^th International Workshop on QSARs in the Environmental Sciences (QSAR 2008), 8–12 June 2008, Syracuse, USA.

Keywords:

• mixtures
• skin
• membrane-coated fiber
• solvation energy

Acknowledgments

The authors would like to thank the technical staff of the CCTRP, North Carolina State University for conducting the in vitro experiments and data analysis. This research work was funded by the National Institute for Occupational Safety and Health (NIOSH) grants R01-OH-03669 and R01-OH-07555.

Notes

†Presented at the 13^th International Workshop on QSARs in the Environmental Sciences (QSAR 2008), 8–12 June 2008, Syracuse, USA.