MIMICKING METABOLISM IN TWO IN VITRO ASSAYS USING HUMAN MICROSOMES TO PREDICT THE SENSITIZATION POTENTIAL OF PROHAPTENS

Abstract

Skin sensitization leads to an allergic reaction caused by acquired immunity from a secondary exposure to a chemical known as a hapten, making skin sensitization an important endpoint for toxicity testing. With legislations to limit the use of animals in scientific research, efforts have been made to develop in vitro alternatives for in vivo toxicity testing. While these assays have proven to be useful alternatives, there are limitations that can lead to false negative results due to a lack of metabolism in the assay systems. To enhance the predictability of the assays, we proposed the addition of human liver microsomes to each assay system as a means of metabolism. In addition, the utility of an in silico tool, OECD Toolbox, was assessed as a way to identify chemicals that may require the addition of microsomes in order to be correctly predicted as sensitizers.