Last year, the Department of Defense (DoD) commissioned the National Research Council (NRC) to develop an approach for the use of modern methods for predicting the acute systemic toxicity of substances. A NRC-convened committee has released their findings and recommendations, which highlight the importance of non-animal test methods. The report Application of Modern Toxicology Approaches for Predicting Acute Toxicity for Chemical Defense notes that the traditional approach of testing chemicals on animals raises concerns about animal welfare, is of questionable applicability to humans, and is time-consuming, expensive, and impractical for evaluating a large number of chemicals. The NAP Committee suggested integrating nontesting methods (including use of existing data, structural alerts, grouping and (Q)SARs) with high- and medium-throughput in vitro assays in a tiered testing strategy. The report also highlighted the importance of accounting for pharmacokinetic characteristics, such as metabolism, and good cell culture techniques for in vitro studies. Additionally, there was emphasis on the importance of knowledge about the mechanism of action, or adverse outcome pathways, leading to acute systemic toxicity when designing an integrated testing strategy.