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ICCVAM Biennial Report 2020-2021

Biennial Progress Report 2020-2021 Interagency Coordinating Committee on the Validation of Alternative Methods

Quantification of Variance in Data from Systemic In Vivo Toxicology Studies

NAMs for chemical hazard assessment are often evaluated in comparison to animal studies. However, variability in animal study data represents a barrier to an objective evaluation of NAM accuracy. Data available in EPA’s ToxRefDB enable consideration of such variability in effect levels, measured as the LEL for a treatment-related effect and the LOAEL defined by expert review. These data are available from subacute, subchronic, chronic, and multi-generational reproductive and developmental toxicity studies. EPA scientists reviewed ToxRefDB data to quantify the variance within systemic LEL and LOAEL values and to estimate the upper limit of NAM prediction accuracy (Pham et al. 2020). The analysis enabled both a quantification of the total variance in systemic LEL and LOAEL values and an estimate of the unexplained variance in LEL and LOAEL values. These findings suggest quantitative considerations for building scientific confidence in NAM-based systemic toxicity predictions.