Mapping the ethical and sustainable transition in toxicology: a bibliometric analysis and a review of new approach methodologies.

Abstract

Toxicology is undergoing a paradigm shift, driven by the ethical imperative to reduce animal testing, the pursuit of sustainability, and regulatory transitions toward new approach methodologies (NAMs). This study systematically maps the integration of ethics and sustainability into NAMs-related toxicological research, using a mixed-methods design that combines bibliometric analysis with a review of scientific and policy literature. Our findings reveal a steep increase in NAMs publications since 2015, with in vitro and in silico approaches at the forefront. Bibliometric clustering identified three dominant thematic domains-regulatory testing, methodological performance factors, and human cell culture innovation-each reflecting varying degrees of engagement with ethical, scientific, and sustainability principles. A qualitative matrix was also developed to link the bibliometric clusters to key ethical and methodological dimensions, highlighting the growing centrality of themes such as the 3Rs, sustainability, and regulatory reform. Notably, the scientific and political discourse is shifting from merely "symbolic" ethics, used primarily to signal alignment with funding priorities or public expectations, toward more deeply embedded and actionable ethical frameworks. Initiatives emphasize operational ethics through concepts such as the fourth R (responsibility), with more expanded models including 12Rs, the 3C model (cell culture, computer simulation, and clinical trials), and ethics-driven AI tools. These developments signal a maturing field where ethics is becoming a methodological imperative. By mapping these shifts, the study offers an integrated perspective on how ethical values shape scientific innovation in toxicology. It provides evidence-based directions for accelerating a responsible transition to animal-free, human-relevant, and resource-efficient risk assessment.