Chemistry Based Nonanimal Predictive Modeling for Skin Sensitization

Skin sensitization is a significant environmental and occupational health concern. The possibility of workers and consumers becoming sensitized is a major problem for individuals, employers and marketing certain products. Consequently, there exists an important need to accurately identify chemicals that have the potential to cause skin sensitization. Under Registration, Evaluation, Authorization and Restriction of Chemicals (REACH), the sensitizing potential needs to be assessed for substances manufactured or imported at levels of 1 ton or greater per annum. Assessment of skin sensitization has traditionally relied on animal testing, but there are now strong pressures to reduce and ultimately eliminate the use of animals for this purpose. Building on research dating back at least 7 decades, a quite detailed mechanistic understanding of skin sensitization, both in terms of the underlying biological processes and the underlying chemistry, has been developed, with significant advances being made in the present century. This chapter presents an overview of the current biological and chemical mechanistic understanding, and reviews recent progress in nonanimal predictive modeling for skin sensitization, with an emphasis on how the understanding of these mechanisms can be applied in combination with in chemico and in silico approaches to hazard and risk assessment.