Abstract
Skin sensitizer potency assessment based on New Approach Methodologies (NAM) is key to derive a Point of Departure (PoD) for risk assessment. Regression models to predict a PoD based on OECD validated in vitro tests and trained on LLNA data were previously presented and results from human tests were recently compiled. To integrate both data sources, the Reference Chemical Potency List (RCPL) was developed that provides potency values (PV) for 33 chemicals integrating LLNA and human data in a structured weight-of-evidence approach. When calculating regression models vs. PV or LLNA data, different weights for the input parameters were noted. As the RCPL is based on too few chemicals to train robust statistical models, the list of human data was extended to a larger set of PV (n = 139) with associated in vitro data. This database was used to retrain the regression models and to compare regression models trained vs. (i) LLNA, (ii) PV or (iii) human DSA04 values. Using the PV as a target, predictive models of similar predictivity to the LLNA-based models were obtained, which mainly differ in a lower weight for cytotoxicity and a higher weight for cell activation and reactivity parameters. Analysis of the human DSA04 dataset indicates a similar pattern, but also shows that the human dataset appears to be too small and biased as a key dataset for potency prediction. Hence using an enlarged set of PV values appears as a complementary tool to train predictive models next to an LLNA only database.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.