An integrated chemical environment with tools for chemical safety testing

Area of Science:

• Toxicology and Chemical Safety Assessment
• Computational Toxicology
• In Silico Modeling

Background:

• Developing reliable, non-animal testing methods for chemical safety assessment is crucial.
• Existing data accessibility and interpretability can hinder the development of new approach methodologies (NAMs).
• The Integrated Chemical Environment (ICE) is a platform designed to support chemical safety assessments.

Purpose of the Study:

• To describe recent updates to the Integrated Chemical Environment (ICE) platform.
• To enhance the accessibility and interpretability of in vitro data for regulatory applications.
• To improve tools for in vitro to in vivo extrapolation (IVIVE) to build confidence in non-animal approaches.

Main Methods:

• Mechanistic target mapping of in vitro assay data using literature-based mode-of-action information and controlled terminology.
• Curation of Tox21 high-throughput screening data with analytical chemistry data and assay-specific parameters.
• Prediction of physicochemical/ADME parameters for over 800,000 chemicals using quantitative structure-activity relationship (QSAR) models.
• Integration of ICE with the U.S. Environmental Protection Agency's httk R package for IVIVE calculations.

Main Results:

• Improved accessibility and interpretability of in vitro data through mechanistic target mapping.
• Curated Tox21 data with artifact elimination for enhanced reliability.
• Physicochemical/ADME parameters for over 800,000 chemicals generated via QSAR.
• A new ICE IVIVE tool enabling estimation of in vivo exposures from in vitro data.

Conclusions:

• The updated ICE platform provides enhanced data and tools to support species-relevant chemical safety assessments.
• These advancements facilitate the exploration of non-animal approaches and build confidence in their regulatory acceptance.
• Improved data interoperability and IVIVE capabilities are key to advancing the use of NAMs in chemical safety.