Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

Membrane-coated fiber array approach for predicting skin permeability of chemical mixtures from different vehicles.

Authors
Riviere-JE; Baynes-RE; Xia-XR
Source
Toxicol Sci 2007 Sep; 99(1):153-161
NIOSHTIC No.
20032681
Abstract
A membrane-coated fiber (MCF) array approach was developed for quantitative assessment of skin absorption from chemical mixtures, which was based on the similarity in the absorption mechanisms of the MCF membrane and the stratum corneum of the skin. A set of probe compounds were used to detect the relative molecular interaction strengths of chemicals with the vehicle and the membranes, which provided a linkage between the skin permeability (log k) and MCF partition coefficients (log KF). A predictive model was established via multiple linear regression analysis of the data matrix of experimentally measured log k value and log KFm values; log k=a0+a1 log KF1+a2 log KF2+...+an log KFm, where m is the number of diverse MCFs. Twenty-five probe compounds and three MCFs (polydimethylsiloxane for lipophilic, polyacrylate for polarizable, and CarboWax for polar interactions) were used to demonstrate the model development processes in the MCF array approach. The skin permeability of the probe compounds was measured with conventional diffusion cell experiments using dermatomed porcine skin. Three predictive models were established for skin permeability prediction from chemical mixtures in water, 50% ethanol, and 1% sodium lauryl sulfate (SLS) with R2 values of 93, 91, and 83, respectively. The log k and log KF values were considerably altered by the addition of ethanol or SLS into the dose vehicle; however, their correlations to skin permeability remained strong under various conditions. These results suggested that the experimentally based MCF array approach can be used to predict skin absorption from chemical mixtures in different vehicles or formulations.
Keywords
Models; Toxins; Toxic-effects; Risk-analysis; Absorption-rates; Statistical-quality-control; Statistical-analysis; Qualitative-analysis; Quantitative-analysis; Skin-absorption; Skin-exposure; Chemical-composition; Chemical-properties; Chemical-structure
Contact
Jim E. Riviere, Center for Chemical Toxicology Research and Pharmacokinetics (CCTRP), College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606
CODEN
TOSCF2
Publication Date
20070901
Document Type
Journal Article
Email Address
jim_riviere@ncsu.edu
Funding Amount
746428
Funding Type
Grant
Fiscal Year
2007
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-007555; Grant-Number-R01-OH-003669
Issue of Publication
1
ISSN
1096-6080
Priority Area
Work Environment and Workforce: Mixed Exposures
Source Name
Toxicological Sciences
State
NC
Performing Organization
North Carolina State University, Raleigh, North Carolina
TOP