Improved methods for dermal exposure estimation.
Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, R01-OH-007529, 2008 Jan; :1-28
A mathematical model that closely mimics percutaneous absorption, tissue concentrations and clearance in human skin in vivo was developed. Unique features of this model include an unprecedented level of detail in relating solute transport to the skin microstructure and the ability to simulate a broad variety of exposure conditions and skin hydration states. Completed components include a microscopic model of transport in human stratum corneum, a dermal vascular model including solute exchange in capillary loops, and a disposition model for arbitrary doses of volatile organic compounds contacting the skin. Experimental refinement of the model parameters in our laboratory has included microscopic analysis of stratum corneum structure and skin disposition studies for fragrance ingredients and pesticides deposited from ethanolic solutions. Absorption model development was approached in a stepwise fashion involving five specific aims. Aims 1-4 involved development of the specific model components (stratum corneum transport, dermal clearance, volatiles disposition and skin hydration effect) and Aim 5 involved the synthesis of these components into a comprehensive computer model with a user-friendly interface. At each step a systematic analysis of skin literature data combined with experimental measurements to obtain otherwise unavailable information was used to justify and calibrate the selected approach. Mathematical methods were based on finite difference approximations to diffusive transport involving variable-spaced grids and asymptotic solutions to describe transport in complex geometries. Laboratory methods included in vitro human skin penetration and sorption/desorption studies and volatiles trapping studies with test ingredients applied to human skin in vitro and on the volar forearm in vivo.
Skin-exposure; Skin-absorption; Absorption-rates; Chemical-kinetics; Chemical-properties; Dermatology; Dose-response; Exposure-assessment; Exposure-limits; Mathematical-models; In-vitro-studies; Volatiles
Final Grant Report
NTIS Accession No.
Research Tools and Approaches: Exposure Assessment Methods
National Institute for Occupational Safety and Health
University of Cincinnati