Risk assessment in the 21st century: where are we heading?

Area of Science:

• Toxicology
• Chemical Safety Assessment
• Regulatory Science

Background:

• Traditional animal testing for chemical safety faces ethical challenges, regulatory delays, and concerns regarding human relevance.
• New Approach Methodologies (NAMs) are emerging as viable alternatives, requiring updated legislation and validation strategies.
• The British Toxicology Society's 2022 symposium addressed the future of chemical risk assessment and the integration of NAMs.

Purpose of the Study:

• To summarize symposium presentations on the future of chemical risk assessment in the 21st century.
• To explore the application and potential of NAMs in chemical safety evaluations.
• To discuss barriers and opportunities for regulatory implementation of NAMs.

Main Methods:

• Review of symposium presentations and discussions on NAMs in chemical risk assessment.
• Analysis of three case studies showcasing the use of NAMs: read-across with in vitro tests, bioactivity assays with physiologically based kinetic modeling, and in silico models based on adverse outcome pathways (AOPs).

Main Results:

• Case study 1: Read-across and in vitro tests reliably assessed risks for data-poor analogues.
• Case study 2: Bioactivity assays and PBPK modeling established NAM-derived points of departure for risk assessment.
• Case study 3: In silico models using AOP information predicted chemical associations with specific AOPs or networks.

Conclusions:

• NAMs, including in vitro assays, read-across, and in silico modeling, demonstrate significant potential for reliable chemical safety assessment.
• Overcoming regulatory and validation hurdles is crucial for the increased adoption of NAMs.
• Integrating NAMs into regulatory frameworks can enhance efficiency, ethical considerations, and human relevance in chemical risk assessment.