FutureTox IV Workshop Summary: Predictive Toxicology for Healthy Children

Area of Science:

• Toxicology and Pharmacology
• Developmental Biology
• Computational Biology

Background:

• The Society of Toxicology's FutureTox IV workshop convened to discuss advancements in predictive developmental and reproductive toxicity (DART) assessment.
• High-throughput screening data and mechanistic insights are increasingly available for chemical profiling.
• New Approach Methodologies (NAMs) are emerging as alternatives to traditional animal testing for hazard identification.

Purpose of the Study:

• To review the discussions and outcomes of the FutureTox IV workshop concerning NAMs for DART.
• To identify challenges and opportunities in applying NAMs for assessing risks to embryo-fetal development and postnatal health.
• To highlight the potential of integrated in vitro and in silico approaches for regulatory toxicology.

Main Methods:

• Review of presentations and discussions from the FutureTox IV workshop.
• Analysis of current capabilities in in vitro profiling and in silico modeling for DART.
• Exploration of publicly available high-throughput screening data sets.
• Discussion of advancements in molecular embryology and computational toxicology.

Main Results:

• NAMs provide a framework for evaluating chemical toxicity, drug efficacy, and safety, aiming to reduce or replace animal use.
• Significant challenges remain in applying NAMs for developmental toxicity compared to adult toxicity.
• Opportunities exist for using NAMs to assess risks for adverse pregnancy outcomes and postnatal disorders.
• Novel testing platforms and computational models are being developed to address the complexities of embryonic development and toxicokinetics.

Conclusions:

• Implementing NAMs in DART testing is crucial for leveraging scientific advancements and improving efficiency in hazard detection.
• While regulatory acceptance of NAMs for higher-level decision-making is still developing, the progress in testing platforms and models is substantial.
• Integrated approaches combining in vitro, in silico, and toxicokinetic data are essential for robust DART assessment and extrapolation to in vivo scenarios.