Assessing similarity for read-across predictions
Updated: Apr 6
The evaluation of the similarity between your target substance and your analogue(s) plays a central role in building your justification of a read-across study. In all evaluations it is imperative the read-across must be both scientifically justified and fully documented to meet the expectations of regulators. I personally evaluate the analogue(s) in five steps:
Step 1: Physicochemical similarity analysis
Step 2: Structural similarity analysis
Step 3: Toxicokinetic similarity analysis
Step 4: Mechanistic similarity analysis
Step 5: Toxicodynamic similarity analysis
The exact content of the analogue evaluation will vary case-by-case. For example you might want to strengthen the initial justification of a read-across initially rejected by a regulator including a toxicokinetic or a toxicodynamic similarity analysis.
A video explaining the read-across workflow in more detail can be viewed:
A recent paper added a new dimension to my Toxicokinetic similarity analysis providing examples on how to assess metabolic similarity using either documented or simulated metabolic maps. The authors of the paper are scientists of the group of Prof. Mekenyan, the developers of the well known OECD (Q)SAR ToolBox, Darina G. Yordanova, Chanita D. Kuseva and Ovanes G. Mekenyan himself, together with Prof. Terry Schultz, emeritus professor at the College of Veterinary Medicine, University of Tennessee whose current research focuses on toxicological read-across.
Yordanova, Darina G., Terry W. Schultz, Chanita D. Kuseva, and Ovanes G. Mekenyan. “Assessing Metabolic Similarity for Read-across Predictions.” Computational Toxicology 18 (May 2021): 100160. https://doi.org/10.1016/j.comtox.2021.100160.