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ICCVAM Biennial Report 2020-2021

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

Variability Analysis of In Vivo Acute Oral Systemic Toxicity Data

There is a pressing need to develop reliable and robust reference acute systemic toxicity data sets to contextualize results, to set expectations regarding NAM performance, and to train and evaluate computational models. To meet these needs, EPA and NICEATM compiled and curated rat acute oral LD50 data from multiple databases (Karmaus et al. 2022). More than 2,000 chemicals with LD50 values from at least two independently conducted rat acute oral systemic toxicity assays were subjected to comprehensive manual review to curate all data. Variability could not be attributed to any chemical-specific characteristics, and thus it was concluded that inherent biological or protocol variability is likely underlying the variance in the results. Understanding the challenges with reproducibility of the rat acute systemic toxicity test helps to better inform appropriate evaluation of future NAM performance assessments.