Commentary - In silico acute oral toxicity models are fit for inclusion in GHS and DG Model Regulations...

This commentary advocates for the inclusion of in silico acute oral toxicity (AOT) models within the classification criteria of the Globally Harmonized System (GHS) and Dangerous Goods (DG) Model Regulations. AOT data, traditionally derived from animal studies, are central to hazard classification and regulatory compliance. However, these studies involve severe outcomes including significant toxicity and death as an endpoint and are conducted primarily to support categorical classification rather than for mechanistic understanding. Recent cross-sector evaluations demonstrate that current in silico models provide a high degree of predictivity with accurate or more conservative classification predictions across thousands of chemicals. Incorporating use of these models along with expert review can eliminate the need for routine animal AOT studies while maintaining robust hazard identification and communication practices.