Computational Toxicology

Chapter 10Computational Approaches to Predicting Dermal Absorption of Complex Topical Mixtures

Jim E. Riviere and Jason Chittenden

Center for Chemical Toxicology Research; Pharmacokinetics Biomathematics Program, North Carolina State University, Raleigh, NC, USA

Chapter Menu

1. Introduction
2. Principles of Dermal Absorption
3. Dermal Mixtures
4. Model Systems
5. Local Skin Versus Systemic Endpoints
6. QSAR Approaches to Model Dermal Absorption
7. Pharmacokinetic Models
8. Conclusions

10.1 Introduction

The skin is a primary route of exposure for chemicals in environmental and occupational settings; it also serves as a portal for systemic drug delivery using transdermal patches or is useful for local therapy of dermatological diseases using topical formulations. Exposure may also occur with the use of cosmetics and many personal care products. The skin is also a target for toxicity by these same agents owing to secondary or direct chemical action or as a result of immunological detection with amplification due to previous chemical sensitization. Because of this almost universal exposure of the skin to chemicals and drugs and because the toxicity is manifested in very visible and noticeable reactions, a great deal of attention has been focused on the effects of chemical exposure to this organ.

There are two major types of studies that comprise the field of dermatotoxicology: chemical absorption and irritation/sensitization. Computational approaches in this field have been focused on the former owing ...