Activities of the In Silico Carcinogenicity Protocol Workgroup

Scientists within the FDA Center for Devices and Radiological Health, FDA Center for Drug Evaluation and Research, and NIEHS participate in an international interdisciplinary consortium to develop publicly available in silico protocols to support the hazard assessment of major toxicological endpoints. Within that consortium, the In Silico Carcinogenicity Protocol Workgroup has focused on developing an in silico protocol for the hazard assessment of carcinogens based on the 10 key characteristics of carcinogens (Smith et al. 2016). The workgroup has published an assessment (Tice et al. 2021) of how current in silico methods address each of the key characteristics and where additional methods or data resources need to be developed. The workgroup is currently developing case studies on four chemicals to determine whether data available for current in silico approaches would be sufficient to generate predictions of in vivo bioassay outcomes. In a related activity, members of the workgroup are compiling a review of receptor-mediated carcinogenesis that will examine the degree to which interaction with nuclear receptors is a key driver of chemically induced carcinogenesis, as opposed to a downstream effect.