Rethinking developmental toxicity testing: Evolution or revolution?

Area of Science:

• Toxicology
• Developmental Biology
• Risk Assessment

Background:

• Current developmental toxicity testing relies on protocols established in 1966, primarily using pregnant laboratory animals.
• Over 50 years of testing have prompted a re-evaluation of these methods for human relevance.

Framework:

• An evolutionary approach involves refining existing protocols with humanized models, disease models, metabolite testing, and informed dose selection.
• A revolutionary approach proposes hypothesis-driven testing based on a compound's known properties and mode of action.

Implementation:

• Hypothesis-driven testing focuses on identifying key molecular or cellular events predicting adverse outcomes.
• Testing can be conducted using in vitro, in silico, or limited in vivo models, leveraging current and developing techniques.

Implications:

• Opportunities exist to refine and replace current developmental toxicity testing protocols.
• Advanced techniques offer more predictive and efficient methods for assessing human developmental toxicity risk.