From animal models to NAMs: a paradigm shift in developmental immunotoxicity testing.

Area of Science:

• Toxicology
• Immunology
• Developmental Biology

Background:

• The developing immune system is uniquely susceptible to environmental toxins.
• Exposure during critical windows can cause lifelong immune dysfunction and disease risk.

Purpose of the Study:

• To review immune system development and identify sensitive periods for toxicant exposure.
• To explore advances in testing frameworks for developmental immunotoxicology (DIT).

Main Methods:

• Literature review integrating mechanistic insights and methodological advances.
• Analysis of New Approach Methodologies (NAMs) for immune ontogeny modeling.
• Integration of physiological maps and multi-omics data.

Main Results:

• NAMs show promise but require validation for critical developmental mechanisms.
• Multi-omics and epidemiological data enhance mechanistic understanding and biomarker discovery.
• Challenges include limited human data, lack of standardization, and need for validated test batteries.

Conclusions:

• Advances in DIT are improving predictive tools and testing frameworks.
• Addressing data gaps and standardization is key for regulatory acceptance.
• Ethically sound, mechanistically informed DIT strategies are essential.