Predicting Acute Oral Toxicity Using AcutoX: An Animal Product-Free and Metabolically Relevant Human Cell-Based Test.

Abstract

AcutoX is a human in vitro test method for the evaluation of acute oral toxicity, developed using a library of 67 curated test chemicals. These chemicals cover a wide variety of chemistries, industrial sectors, rodent toxicities, and all EPA and GHS hazard categories. The test uses two different cytotoxicity endpoints (Neutral Red uptake and MTT metabolism), performed both in the presence and absence of a pooled human liver extract (S9), to produce four EC50 values. The EC50 values are used in prediction models to assign a "highly toxic" and "low toxicity" category for both EPA and GHS classification, which can be further refined to assign a hazard category. The binary "highly toxic" / "low toxicity" prediction model has an accuracy of 73.8% and 63.1% for EPA and GHS, respectively, with the subsequent hazard categorization offering a protective prediction (correct or higher category) in 90.0% and 93.3% of cases, respectively. Moreover, the AcutoX test can identify chemicals activated or detoxified by liver metabolism.