Alternative methods for developmental toxicity testing: features, status and future directions.

Area of Science:

• Developmental toxicology
• Regulatory science
• In vitro toxicology

Background:

• Early development is critical and sensitive to toxic effects.
• Traditional animal testing for developmental toxicity has limitations (cost, ethics, species differences).
• There is a growing need for reliable alternative methods in drug and chemical safety assessment.

Purpose of the Study:

• To review current alternative methods for developmental toxicity testing.
• To examine institutional efforts in adopting these new approaches.
• To discuss future directions in the field.

Main Methods:

• Review of new approach methodologies (NAMs) including embryoid body tests, organoids, and zebrafish models.
• Integration of in vitro data with predictive models, such as machine learning.
• Examination of regulatory body initiatives (e.g., OECD) promoting method acceptance.

Main Results:

• Alternative methods like embryoid body tests and organoids provide faster, reproducible, and human-relevant toxicity assessments.
• Zebrafish models offer validated endpoints for morphological and behavioral evaluations.
• Predictive models enhance mechanism-based analysis when combined with in vitro data.

Conclusions:

• Alternative methods offer ethical and rational approaches to developmental toxicity assessment.
• Integration into regulatory science aids early safety decisions in clinical development and public health.
• Stakeholder collaboration is crucial for broader adoption and guideline revision.