A Critical Review of Adverse Outcome Pathway-Based Concepts and Tools for Integrating Information from Nonanimal Testing Methods: The Case of Skin Sensitization

Integrating information from in vitro, in silico, and in chemico methods into toxicity testing strategies has been widely considered the way of phasing out animal testing. At the same time, testing strategies using new approaches and methods shall provide adequate and relevant information about chemicals' hazardous properties. We reviewed objectives and requirements for guiding the process of data integration that are suggested in the scientific literature. Based on the existing approaches, we develop criteria for resource-efficient testing strategies, and we evaluate existing testing strategies for skin sensitization hazard and risk assessment under these criteria. We conclude that existing testing strategies—except two cases—still focus predominantly on maximizing toxicity information, but largely ignore resource efficiency criteria. Balancing information gained from testing strategies with its respective direct and indirect costs (including also welfare losses for society in case of unintended health or environmental damages) is a necessary condition to allow for transparent comparisons of their resource efficiency. Therefore, developing approaches for balancing information gains and costs should become an explicit part of the developmental process of nonanimal testing strategies to ensure that phasing out animal testing complies not only with regulatory information requirements but also with available resources