Host: The Japanese Society of Toxicology
Name : The 49th Annual Meeting of the Japanese Society of Toxicology
Date : June 30, 2022 - July 02, 2022
In 2021, several defined approaches (DAs) were adopted as the OECD Guideline 497, which provide information that is equivalent to animal studies. On the other hand, there are common limitations, such as lipophilic chemicals (e.g. LogKow>3.5) and pre/pro-haptens, in the existing DAs. To overcome these issues, we have developed RhE based Testing Strategy (RTS) as a novel DA in which both EpiSensA and TIMES-SS are utilized. It is a simple score-based DA as well as ITS v1/v2 and showed 78.7% potency accuracy for LLNA results based on GHS sub-categorization (1A, 1B, NC), which is higher than 71.2% potency accuracy of ITS v1. On the other hand, in quantitative risk assessment, EC3 values derived from LLNA results are useful. However, DA alone cannot determine a specific EC3 value because it predicts sensitization potency as three categories. Moreover, it is also important to avoid underprediction in quantitative risk assessment, but previous studies have confirmed that RTS alone underpredicts 18 chemicals among the chemical dataset of EpiSensA. Therefore, we aimed to construct a strategy that can predict sensitization potency precisely and avoid underpredictions by combining read-across, which predicts toxicity from similar compounds. In order to confirm the utility of this strategy, it was applied to EpiSensA dataset, and it was confirmed that this strategy can predict sensitization potency precisely and avoid the underpredictions for all 18 chemicals, indicating the usefulness of this strategy for sensitization risk assessment.
