8. In vitro sensitization tests

Under the REACh Regulation, tests on vertebrate animals (i.e., rats, other mammals, or fish, for example) may only be used as a last resort to meet information requirements for registration purposes.

Four key events occur during skin sensitization.

• The first initiating molecular event (the first key event is the establishment of a covalent bond between electrophilic chemicals and the nucleophilic centers of skin proteins.

• The second key event takes place in keratinocytes and involves inflammatory responses and changes in gene expression linked to specific cell signaling pathways such as those dependent on the antioxidant response element (ARE).

• The third key event is the activation of dendritic cells, usually assessed based on the expression of specific...