Progress in data interoperability to support computational toxicology and chemical safety evaluation

Abstract

New approach methodologies (NAMs) in chemical safety evaluation are being explored to address the current public health implications of human environmental exposures to chemicals with limited or no data for assessment. For over a decade since a push toward "Toxicity Testing in the 21st Century," the field has focused on massive data generation efforts to inform computational approaches for preliminary hazard identification, adverse outcome pathways that link molecular initiating events and key events to apical outcomes, and high-throughput approaches to risk-based ratios of bioactivity and exposure to inform relative priority and safety assessment. Projects like the interagency Tox21 program and the US EPA ToxCast program have generated dose-response information on thousands of chemicals, identified and aggregated information from legacy systems, and created tools for access and analysis. The resulting information has been used to develop computational models as viable options for regulatory applications. This progress has introduced challenges in data management that are new, but not unique, to toxicology. Some of the key questions require critical thinking and solutions to promote semantic interoperability, including: (1) identification of bioactivity information from NAMs that might be related to a biological process; (2) identification of legacy hazard information that might be related to a key event or apical outcomes of interest; and, (3) integration of these NAM and traditional data for computational modeling and prediction of complex apical outcomes such as carcinogenesis. This work reviews a number of toxicology-related efforts specifically related to bioactivity and toxicological data interoperability based on the goals established by Findable, Accessible, Interoperable, and Reusable (FAIR) Data Principles. These efforts are essential to enable better integration of NAM and traditional toxicology information to support data-driven toxicology applications.