The path via pathway-based approaches towards safety assessment: A concise review

Area of Science:

• Toxicology
• Computational Biology
• Regulatory Science

Background:

• The need to replace animal testing in chemical safety assessment has driven the development of alternative methods.
• Integrated Testing Strategies (ITS) in Europe and the in vitro toxicity testing paradigm in the US (since 2007) represent key shifts.
• The Adverse Outcome Pathway (AOP) framework, introduced in 2010, advanced pathway-based approaches in regulatory toxicology.

Purpose of the Study:

• To review achievements in pathway-based chemical assessment since 2007.
• To discuss potential pitfalls and challenges in mechanism-driven chemical assessment.
• To present future perspectives on safety assessment utilizing computational systems biology.

Main Methods:

• Review of scientific literature and regulatory initiatives.
• Analysis of advancements in computational modeling, high-throughput screening, and high-content omics.
• Discussion of conceptual frameworks like AOPs.

Main Results:

• Significant progress has been made in developing pathway-based chemical assessment frameworks.
• Computational modeling and omics technologies are crucial for facilitating these advancements.
• The field is moving towards a more mechanism-driven approach to chemical safety.

Conclusions:

• Pathway-based chemical assessment, integrating various data sources and advanced technologies, is the future of toxicology.
• Overcoming challenges in mechanism-driven assessment is key to realizing a paradigm shift.
• Computational systems biology offers promising avenues for future safety evaluations.