Cardiovascular diseases remain the predominant cause of death globally, with indications that environmental pollutants play a significant role in their exacerbation. Despite this, cardiotoxicity is not yet a primary focus in the prevailing regulatory standards for chemicals, biocides, and pesticides, which lean heavily on animal testing-based evaluations.

In the context of the EU-H2020 Project ALTERNATIVE (www.alternative-project.eu), our mission is to rethink the evaluation of cardiotoxicity by: (1) Spotlighting the existing regulatory constraints, (2) combining diverse lines of evidence related to heart failure induced by environmental pollutants using the Adverse Outcome Pathway (AOP) framework (3) identifying non-animal testing methods and Biomarkers of Effect (BoEs) to evaluate key events within the AOP, and (4) conceptualizing an Integrated Approach to Testing and Assessment (IATA).

Our research has highlighted gaps in the current cardiotoxicity evaluation process, the limited predictability of both animal and in vitro methods as per existing regulatory guidelines, and the importance of considering the older, more susceptible population. We've established a novel AOP network (incorporating AOPs #479 & #480) that systematically integrates human epidemiological data (from 15 studies) and experimental evidence (from 362 studies) on heart failure triggered by environmental pollutants. These AOPs are set to form the foundation for an IATA addressing organ toxicity, including cardiotoxicity, aiming to reduce the reliance on animal testing.