Novel and rigorous methods for identifying cancer hazards: The updated Report on Carcinogens Handbook

Cancer hazard identification is the first step in preventing cancer. Robust and transparent methods for rigorous interrogation of published research are vital for a high-quality assessment of the scientific evidence resulting in cancer hazard identification. The National Toxicology Program publishes cancer hazard assessments for possible listing in the Report on Carcinogens (RoC), which are conducted using a four-part systematic review (SR) process described in the RoC Handbook. This Handbook provides guidance for developing a substance-specific evaluation framework, assessing study informativeness, evaluating and integrating data across studies within each evidence stream (e.g., human, experimental animal, and mechanistic studies) and then integrating across evidence streams to reach a cancer hazard conclusion. The recently updated RoC Handbook incorporates advances in SR methods and provides an updated suite of tools, approaches, and resources to ensure scientific rigor, transparency, and confidence in conclusions reached in cancer hazard evaluations. The most significant advancements include a new fit-for-purpose SR strategy and guidance for assessing and integrating evidence from mechanistic studies, including read-across approaches, and clearer approaches for integrating evidence across evidence streams to reach causal conclusions. We also added toolkits for determining the informativeness of human, animal cancer, and mechanistic studies, and resources related to literature search strings, exposure assessment, and information on biomarkers and assays for the Key Characteristics of Carcinogens. These innovations have significantly enhanced the transparency and scientific integrity of RoC cancer hazard assessments and can be used by the scientific community for their own assessments.