A problem formulation framework for the application of in silico toxicology methods in chemical risk assessment

Arch Toxicol. 2024 Mar 30. doi: 10.1007/s00204-024-03721-6. Online ahead of print.ABSTRACTThe first step in the hazard or risk assessment of chemicals should be to formulate the problem through a systematic and iterative process aimed at identifying and defining factors critical to the assessment. However, no general agreement exists on what components an in silico toxicology problem formulation (PF) should include. The present work aims to develop a PF framework relevant to the application of in silico models for chemical toxicity prediction. We modified and applied a PF framework from the general risk assessment literature to peer reviewed papers describing PFs associated with in silico toxicology models. Important gaps between the general risk assessment literature and the analyzed PF literature associated with in silico toxicology methods were identified. While the former emphasizes the need for PFs to address higher-level conceptual questions, the latter does not. There is also little consistency in the latter regarding the PF components addressed, reinforcing the need for a PF framework that enable users of in silico toxicology models to answer the central conceptual questions aimed at defining components critical to the model application. Using the developed framework, we highlight potential areas of uncertainty manifestation in in silico toxicology PF in instances where particular components are missing or implicitly described. The framework represents the next step i...

Source: Archives of Toxicology - March 30, 2024 Category: Toxicology Authors: Jerry Achar Mark T D Cronin James W Firman Gunilla Öberg Source Type: research