Assessment of the sensitizing potency of low molecular weight chemicals : employment of a regression method in vivo and in vitro

Abstract

One of the most important allergic diseases caused by chemicals, contact hypersensitivity (CHS) or skin sensitization, forms a serious problem for individuals experiencing such a reaction. The prevalence of CHS tends to grow proportionally to the increasing exposure to an expanding variety of chemicals. Predictive animal tests to identify sensitizing properties of chemicals are therefore carried out at a large scale. For a better risk assessment, a more quantitative assessment of the sensitizing potency of chemicals is needed. These two current developments result in an increasing number of animals used. The aim of this thesis was to evaluate the risk assessment process for sensitizing potency of contact allergens in a more reliable manner, and to investigate the possibility of developing alternative approaches to in vivo testing, which may ultimately lead to a refinement, reduction, or replacement of animal testing. With the in vivo approach described in this thesis, we are now able to assess the potency of sensitizing chemicals in a more accurate way. This results in a better estimation of the minimal number of test animals needed, which inevitably leads to a decrease in animal use. Another important issue is that this predictive method also provides us with information about the threshold of an allergen. Data on thresholds in humans cannot be derived directly from animal tests. Therefore, we developed an in vitro assay where cytokine responses derived from both murine as human epidermal cells (keratinocytes) were used as read-out for sensitizing strength. The in vitro approach provided us with more insight on the differences in sensitivity between the two species. With these findings it is now possible to interpolate in vivo data towards an estimation of risk in man. The use of cytokines for the assessment of sensitizing potency seems promising and is one of numerous possibilities of in vitro tests for the assessment of sensitizing potency.