An Alternative Safety Profiling Algorithm (ASPA) to transform next generation risk assessment into a structured and transparent process

Next generation risk assessment (NGRA) strategies use animal-free new approach methodol­ogies (NAMs) to generate information concerning chemical hazard, toxicokinetics (ADME), and exposure. The information from these major pillars of data gathering is used to inform risk assessment and classification decisions. While the required types of data are widely agreed upon, the pro­cesses for data collection, integration and reporting, as well as several decisions on the depth and granularity of required data, are poorly standardized. Here, we present the Alternative Safety Pro­filing Algorithm (ASPA), a broad-purpose, transparent, and reproducible risk assessment workflow that allows documentation and integration of all types of information required for NGRA. ASPA aims to make safety assessments fully traceable for the recipient (e.g., a regulator), delineating which steps and decisions have led to the final outcome and why certain decisions were made. An overarching objective of ASPA is to ensure that identical data input yields identical outcomes in the hands of independent assessors. Therefore, ASPA is not just a data gathering workflow; it also considers data interdependencies and requires precise justification of intermediate decisions. This includes the monitoring and assessment of uncertainties. To assist users, the ASPA-assist software was developed. It formalizes the reporting process in a reproducible and standardized fashion. By guiding an operator step-by-step through the ASPA workflow, a complete and comprehensive report is assembled, whereby all data, methods, operator activities, and intermediate decisions are recorded. Practical examples illustrating the broader applicability of ASPA across various regula­tions and problem formulations are provided through case studies.