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A2.2-UNJM: Determination of the Optimal Physico-Chemical Parameters to Use in a QSAR Approach to Predict Skin Permeation Rate

Principal Investigator

Dr. Mark Cronin
Liverpool John Moores University
Byrom street
UK - L3 3AF Liverpool
m.t.cronin@livjm.ac.uk
Tel: +44 151 231 2066
Fax: +44 151 231 2170

Collaborators

LRI Monitor: Dr. Wil ten Berge - DSM
wil.berge-ten@dsm.com

Description

Many toxic chemicals can enter the body via the skin. Measuring a chemical’s ability to cross the skin is difficult, time-consuming and costly. One solution is to develop models relating skin permeability to chemical structure – known as a quantitative structure-activity relationships (QSARs) – which can be used to predict permeability from chemical structure alone. In this approach, skin is considered to be a lipid (fatty) layer, with pores or channels (holes), through which chemicals can pass. Studies have related the ability of a chemical to enter the skin to its affinity for lipids and its molecular size: small molecules, which are readily soluble in lipids will generally pass through the skin more easily than large ones which are less soluble in lipids. Methods traditionally used to assess lipid solubility and molecular size is rather crude. This study will use more sophisticated methods. For instance, molecular size will be calculated more accurately using 3-D computational modelling. Such measures will be used in QSARs to predict the ability of a chemical to cross the skin, based solely on knowledge of its chemical structure.

Related Publications

H Patel, W ten Berge, MTD Cronin.Quantitative structure-activity relationships (QSARs) for the prediction of skin permeation of exogenous chemicals. Chemosphere : Vol. 48, Issue 6, 603-613, August 2002. GP Moss, JC Dearden, H Patel, MTD Cronin. Quantitative structure-permeability relationships (QSPRs) for percutaneous absorption. Toxicology in Vitro, Vol. 16, Issue 3, 299-317, June 2002. H Patel, TW Schultz, MTD Cronin. Physico-chemical interpretation and prediction of the dimyristoyl phosphatidyl choline-water partition coefficient. Journal of Molecular Structure (Theochem) Vol. 593, Issues 1-3, 9-18, September 2002.

H Patel, MTD Cronin. A novel index for the description of molecular linearity. Journal of Chemical Information and Computer Sciences : Vol. 41, Issue 5, 1228-1236, 2001.

H Patel, MTD Cronin, JC Dearden. The prediction of L-a-dimyristoyl phosphatidylcholine - water partition coefficients. British Pharmaceutical Conference 2001 Abstract Book, p. 228. (Published in association with the Journal of Pharmacy and Pharmacology). Hiren Patel and Mark Cronin. Determination of the optimal physico-chemical parameters to use in a QSAR-approach to predict skin permeation rate. QSAR and Modelling Research Group. School of Pharmacy and Chemistry. Liverpool John Moores University. Final report June 2001.

LRI funding: €34,068

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