ABSTRACT
In common with other areas of toxicology, there is presently considerable interest in the possibility of developing alternative methods for contact sensitizing testing that have a reduced requirement for experimental animals, that reduce the trauma to which animals are potentially subject, or that eliminate completely the need for animals. As described in the previous chapter, much progress has been made already in defining mouse predictive tests which offer advantages with respect to animal numbers and/or potential trauma. There are, however, additional initiatives and approaches and some of these are discussed below. The objective ultimately is the accurate identification and characterization of skin sensitizing chemicals without the need for animal experimentation. Within this context one can identify two main strategies. Firstly, there is the use of structure-activity relationships (SAR), or quantitative structure-activity relationships (QSAR), linked to the development of expert, rule-based, systems (Barratt et al., 1994, Barratt and Basketter, 1994). This area is explored in detail in Chapter 5. The second approach is the use in predictive toxicology of in vitro models that mirror accurately some important aspect of the skin sensitization process. The goal is laudable; the difficulty of achieving it, however, should not be underestimated. The primary constraints in developing workable models of immune function in vitro are the complexity of the immune system itself, and the requirement of normal immunological activity for complex interactions between cells and molecules that are tightly coordinated and regulated in time and space. Notwithstanding these difficulties, advances have been made in the design of alternative
methods and these are described here under headings that reflect the main areas of activity: allergen-driven T lymphocyte activation, the stimulation of epidermal cell responses and the association of chemical allergens with protein.
Measurement of T Lymphocyte Activation
