Challenge for Adverse Outcome Pathway (AOP)-based Chemical Safety Assessment

Abstract

The latest chemical management policies require toxicological evaluation of marketed but untested chemicals. Furthermore, in Europe, for animal welfare reasons sales of cosmetics and raw materials for which animal experiments were conducted were totally banned, in 2013. Responding to these regulatory trends, a strong demand exists to develop new in vitro test methods and to improve in silico prediction models for safety assessments. In recent years, the development of adverse outcome pathways (AOPs) has been actively promoted in the Organisation for Economic Co-operation and Development (OECD). Since it is difficult to replace a particular in vivo animal test with a single in vitro test method or in silico prediction model, integrated approaches to testing and assessment (IATA) have been studied based on AOP information. With regard to skin sensitization, several in vitro test methods that measure key events of AOP have been established, and integrated strategies using in vitro tests have been examined using AOP. Currently, numerous AOPs are under development for a wide range of complex toxicity endpoints in the OECD AOP program. The AOPs are expected to contribute to the development of many accurate in vitro test methods and to establish IATA as well as to evaluate safety in humans of many substances, including household chemicals, food-related chemicals, cosmetics, and pharmaceuticals.