The Problem Being Addressed
Cardiovascular diseases are increasingly linked to environmental exposure to toxic chemicals. Yet Europe lacked standardised devices, protocols, and regulatory applications to reliably assess chemical mixture toxicity. Traditional animal-based testing cannot capture complex mixture effects and poorly reflects human physiology, especially in vulnerable groups such as the elderly. There was therefore a clear need for innovative, human-relevant tools to improve chemical safety and risk assessment.
Importance for Society
- Cardiovascular diseases remain a leading cause of morbidity and mortality worldwide.
- Citizens are exposed to mixtures of chemicals and pharmaceuticals, often without clear knowledge of long-term risks.
- Improved testing tools can reduce reliance on animal models, lower costs, and accelerate regulatory decisions.
- By focusing on aged cardiac tissue, the project directly addresses vulnerable populations, ensuring risk assessments are inclusive and protective.
The societal benefits include stronger public health protection, greater consumer safety, and enhanced trust in regulatory systems, while reinforcing Europe’s leadership in sustainable and ethical innovation.
Overall Objectives
The ALTERNATIVE project aimed to design and validate an in vitro system mimicking human-aged cardiac tissue to test the toxicity of chemical mixtures and their biotransformation products. This was achieved through a high-throughput monitoring system based on multi-omics analyses and integrated into a machine learning risk assessment tool. Specifically, the project delivered:
- An integrated system (ALTERNATIVE platform) for evaluating cardiac toxicity of chemicals and mixtures.
- An aged cardiac tissue model reproducing biological responses of living organisms.
- Omics markers of toxicity to support mechanistic understanding and in silico modelling.
- An in-silico cloud system for mixture risk assessment, hosting validated ML models and Big Data pipelines.
- Proof-of-concept validation against selected chemicals and mixtures.
- Regulatory guidance and stimulation of acceptance, including novel AOPs, IATA concepts, and validation roadmaps.
- Long-lasting impact through dissemination, exploitation, and raising citizen awareness of chemical co-exposure risks.
Conclusions of the Action
The project successfully delivered a validated, human-relevant platform combining in vitro and in silico methods for cardiotoxicity testing. It demonstrated that:
- The platform can reduce and replace animal testing while providing more realistic toxicity data.
- It enables early detection of cardiotoxicity through novel biomarkers and omics analyses.
- It supports regulatory innovation, with AOPs submitted to OECD and guidance documents drafted for uptake.
- Dissemination and exploitation ensured visibility to regulators, industry, and the scientific community, while IPR management and exploitation plans pave the way for future use.
Overall, ALTERNATIVE introduced a new paradigm for chemical mixture risk assessment, with significant scientific, regulatory, socio-economic, and societal impacts. It strengthens Europe’s position in advancing Next Generation Risk Assessment (NGRA) and contributes to safer, more sustainable chemical management.
