Bridging Toxicological Silos with Organoids: A Systems Approach to Human-Relevant Risk Assessment.

Area of Science:

• Environmental Toxicology
• Biomedical Engineering
• Regenerative Medicine

Background:

• Conventional toxicity testing using animal models and 2D cell cultures fails to capture human complexity and variability.
• Organoid technology offers a 3D, heterogeneous, and donor-specific platform for more accurate toxicity assessments.
• Organoids provide a human-relevant and ethically superior alternative for studying environmental contaminants.

Purpose of the Study:

• To highlight the application of organoids in developmental and organ-specific toxicity assessments.
• To explore patient-derived organoids (PDOs) for personalized susceptibility and gene-environment interaction studies.
• To discuss emerging strategies and challenges in organoid-based environmental health assessment.

Main Methods:

• Utilizing organoids to model organ-specific toxicity (liver, brain, thyroid) and developmental toxicity.
• Employing patient-derived organoids (PDOs) for personalized risk assessment.
• Integrating emerging strategies like vascularized organoids, multiorgan platforms, cocultures, high-throughput screening, and single-cell omics.

Main Results:

• Organoids enable identification of vulnerable cell populations and mechanistic mapping of adverse outcomes.
• Emerging strategies allow pollutant effect mapping from molecular to organ levels.
• Organoid approaches, coupled with computational frameworks, advance predictive and mechanistic toxicology.

Conclusions:

• Organoid technology is transforming environmental toxicology by providing a human-relevant, integrative, and predictive platform.
• This technology facilitates improved chemical risk assessment and regulatory decision-making.
• Addressing challenges in standardization, scalability, and predictive modeling is crucial for widespread adoption.