The 2010 report "Toxicity Testing in the 21st Century: A Vision and a Strategy" outlines a new approach to toxicity testing that aims to improve efficiency, reduce animal use, and enhance the relevance of test results for human health. The report emphasizes the need to shift from traditional in vivo testing to in vitro assays using human cells and high-throughput screening with mechanistic parameters. This approach would allow for more accurate risk assessments by focusing on the perturbations of toxicity pathways in humans. Computational models would be used to predict dose-response relationships, and pharmacokinetic models would help extrapolate in vitro results to human conditions. The report highlights the limitations of current testing strategies, including high costs, use of animals, and limited coverage of chemical mixtures and human variability. It proposes a new paradigm based on toxicity pathways, which would allow for more efficient and targeted testing. The report also discusses the importance of integrating new technologies such as genomics, proteomics, and systems biology to improve the accuracy and relevance of toxicity testing. The committee recommends a long-term vision that includes the development of new testing methods, the use of computational models, and the reduction of animal use. The report emphasizes the need for a flexible and adaptable testing strategy that can address the diverse needs of different risk contexts, including the evaluation of new and existing environmental agents, the assessment of site-specific risks, and the identification of environmental contributors to specific diseases. The report concludes that a new toxicity testing paradigm based on human biology is essential for improving public health protection.The 2010 report "Toxicity Testing in the 21st Century: A Vision and a Strategy" outlines a new approach to toxicity testing that aims to improve efficiency, reduce animal use, and enhance the relevance of test results for human health. The report emphasizes the need to shift from traditional in vivo testing to in vitro assays using human cells and high-throughput screening with mechanistic parameters. This approach would allow for more accurate risk assessments by focusing on the perturbations of toxicity pathways in humans. Computational models would be used to predict dose-response relationships, and pharmacokinetic models would help extrapolate in vitro results to human conditions. The report highlights the limitations of current testing strategies, including high costs, use of animals, and limited coverage of chemical mixtures and human variability. It proposes a new paradigm based on toxicity pathways, which would allow for more efficient and targeted testing. The report also discusses the importance of integrating new technologies such as genomics, proteomics, and systems biology to improve the accuracy and relevance of toxicity testing. The committee recommends a long-term vision that includes the development of new testing methods, the use of computational models, and the reduction of animal use. The report emphasizes the need for a flexible and adaptable testing strategy that can address the diverse needs of different risk contexts, including the evaluation of new and existing environmental agents, the assessment of site-specific risks, and the identification of environmental contributors to specific diseases. The report concludes that a new toxicity testing paradigm based on human biology is essential for improving public health protection.