Scientific publications

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 standardised.

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 formalises the reporting process in a reproducible and standardised 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.

The ASPIS cluster, encompassing ONTOX, PrecisionTox, and RISK-HUNT3R, has published a pivotal paper named Animal-free Safety Assessment of Chemicals: Project Cluster for Implementation of Novel Strategies (ASPIS) definition of new approach methodologies in Environmental Toxicology and Chemistry outlining a comprehensive definition of New Approach Methodologies (NAMs). This effort is a major step toward standardizing animal-free testing strategies in regulatory toxicology, ultimately reducing reliance on animal models while ensuring robust chemical safety assessment.

One of the key contributions of this paper is the clarification of the definition of NAMs. The term has been interchangeably used to mean “new approach methodologies” and “nonanimal methods,” leading to confusion among scientists and regulators. ASPIS proposes an inclusive definition that recognizes NAMs as approaches providing mechanistic toxicological insights through alternative testing platforms such as in vitro, in silico, and computational models.

The paper also highlights the regulatory relevance of NAMs. For these methodologies to replace traditional animal testing, they must provide mechanistic insights into chemical toxicity, determine safe exposure thresholds, and support risk assessments. The authors emphasize how NAMs can contribute to next-generation risk assessment (NGRA) while aligning with international regulatory frameworks.

Another critical aspect explored in the paper is the distinction between predictive and protective applications of NAMs. Predictive NAMs are used to infer potential adverse effects by analyzing mechanistic data, while protective NAMs establish safe exposure limits through in vitro and in vivo extrapolation. By integrating these approaches, ASPIS demonstrates how NAMs can improve the accuracy of chemical risk assessment without relying on animal testing.

This publication is a major step forward in the global effort to transition toward animal-free safety assessment. It provides a clear roadmap for regulatory acceptance of NAMs, reinforcing ASPIS’s role in developing innovative, ethical, and scientifically robust alternatives for evaluating chemical toxicity. By addressing existing challenges and setting a standard for defining NAMs, this paper contributes significantly to shaping the future of nonanimal toxicology.