Evaluating chemical similarity as a measure to identify potential substances of very high concern.

Evaluating chemical similarity as a measure to identify potential substances of very high concern. Regul Toxicol Pharmacol. 2020 Nov 20;:104834 Authors: Wassenaar PNH, Rorije E, Vijver MG, Peijnenburg WJGM Abstract Due to the large amount of chemical substances on the market, fast and reproducible screening is essential to prioritize chemicals for further evaluation according to highest concern. We here evaluate the performance of structural similarity models that are developed to identify potential substances of very high concern (SVHC) based on structural similarity to known SVHCs. These models were developed following a systematic analysis of the performance of 112 different similarity measures for varying SVHC-subgroups. The final models consist of the best combinations of fingerprint, similarity coefficient and similarity threshold, and suggested a high predictive performance (≥80%) on an internal dataset consisting of SVHC and non-SVHC substances. However, the application performance on an external dataset was not evaluated. Here, we evaluated the application performance of the developed similarity models with a 'pseudo-external assessment' on a set of substances (n = 60-100 for the varying SVHC-subgroups) that were putatively assessed as SVHC or non-SVHC based upon consensus scoring using expert elicitations (n = 30 experts). Expert scores were direct evaluations based on structural similarity to the most similar SVH...
Source: Regulatory Toxicology and Pharmacology : RTP - Category: Toxicology Authors: Tags: Regul Toxicol Pharmacol Source Type: research