GenEvolutioN is proud to have contributed to a landmark study on the Critical Effect Size (CES) for Quantitative Analysis of Micronucleus In Vitro Concentration-Response Curves, presented at the EMGS 2023 Conference. This research provides crucial data to enhance the benchmark-dose (BMD) approach, a widely recognized method for analyzing dose-response relationships in genotoxicity studies.
A new standard for In Vitro micronucleus testing
While the BMD approach is commonly used, there has been limited data-driven guidance on defining the optimal benchmark-response (CES) for in vitro endpoints, such as the micronucleus assay in cell lines or cultured human lymphocytes. Traditionally, regulatory bodies recommend setting CES values based on historical controls and background variability, but inconsistencies across laboratories have made standardization difficult.
Collaborative research across 17 laboratories
To address this, data from 17 experienced laboratories worldwide, spanning Europe, Japan, and the United States, were analyzed. A total of nearly 5,000 individual studies were reviewed, applying a trimmed historical control approach to define CES thresholds that are both scientifically robust and applicable for regulatory submissions. The study ultimately recommends a 50% increase over concurrent controls as the benchmark CES for in vitro micronucleus studies.
Key findings & implications
- The 50% CES threshold is not meant for binary evaluation (i.e., positive/negative classification), but rather to improve BMDL calculations in tools like PROAST, potentially guiding risk assessment without animal testing.
- The study found no significant impact of cell type, staining method, or geographical location on CES variability, reinforcing the consistency and applicability of the proposed benchmark.
- The results contribute to ongoing discussions within the International Workshops on Genotoxicity Testing (IWGT) and could shape future regulatory guidelines for in vitro toxicology.
A step forward in genotoxicity testing
This research marks a significant advancement in standardizing in vitro genotoxicity assessments, ensuring more reliable, reproducible, and regulatory-compliant results. GenEvolutioN remains at the forefront of scientific innovation, committed to enhancing safety assessments and reducing the need for animal testing.
