Developing context appropriate toxicity testing approaches using new alternative methods (NAMs).

Area of Science:

• Toxicology
• Risk Assessment
• Computational Biology

Background:

• The scientific community advocates for replacing traditional animal testing with New Approach Methodologies (NAMs) for hazard identification and risk assessment.
• NAMs leverage advancements in biological sciences for more human-relevant in vitro and in silico chemical safety evaluations.
• A gap exists in establishing clear decision criteria for selecting and implementing NAMs within various risk assessment contexts.

Purpose of the Study:

• To propose application scenarios for NAMs across different risk contexts.
• To introduce a tiered framework (Levels 1-4) categorizing NAMs and conventional testing approaches.
• To foster discussion on context-dependent NAM utilization for chemical safety decisions and provide a roadmap for their adequacy.

Main Methods:

• Categorization of NAMs and traditional methods into four distinct levels based on complexity and data output.
• Description of each level, including computational screening, in vitro assays, fit-for-purpose assays, and complex multi-dimensional assays.
• Integration of decision-appropriate exposure assessment tools within each level.

Main Results:

• A structured, four-level framework for applying NAMs in risk assessment is presented.
• Each level is defined by the type of assays used and their suitability for different risk assessment needs.
• The framework aims to guide the selection of appropriate NAMs for specific chemical safety decision-making scenarios.

Conclusions:

• The proposed framework facilitates the strategic application of NAMs in chemical risk assessment.
• It addresses the need for context-specific decision criteria to guide NAM implementation.
• This approach supports the efficient and human-relevant evaluation of chemical safety, moving beyond traditional animal testing.