Principles and Procedures for Assessment of Acute Toxicity Incorporating Methods.

Acute models are being used to support an increasing number of application areas including (1) product research and development, (2) product approval and registration as well as (3) the transport, storage and handling of chemicals. The adoption of such models is being hindered, in part, because of a lack of guidance describing how to perform and document an analysis. To address this issue, a framework for an acute toxicity hazard assessment is proposed. This framework combines results from different sources including methods and or experiments. methods that can assist the prediction of outcomes (i.e., LD) are analyzed concluding that predictions obtained using approaches are now well-suited for reliably supporting assessment of LD-based acute toxicity for the purpose of GHS classification. A general overview is provided of the endpoints from studies commonly evaluated for predicting acute toxicity (e.g., cytotoxicity/cytolethality as well as assays targeting specific mechanisms). The increased understanding of pathways and key triggering mechanisms underlying toxicity and the increased availability of data allow for a shift away from assessments solely based on endpoints such as LD, to mechanism-based endpoints that can be accurately assessed or by using prediction models. This paper also highlights the importance of an expert review of all available information using weight-of-evidence considerations and illustrates, using a series of diverse practical use cases, how approaches support the assessment of acute toxicity.