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Application of Modern Toxicology Approaches for Predicting Acute Toxicity for Chemical Defense (2015) / Chapter Skim
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Pages 3-8

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From page 3...
... CONCEPTUAL FRAMEWORK AND STRATEGY As requested by DOD, the committee developed an overall conceptual approach that uses modern approaches for predicting acute, debilitating chemical toxicity. Its approach consisted of three components: (1)
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From page 4...
... If science advances in such a way that adverse outcome pathways of interest to DOD are known, the strategy shown in Figure S-2 could rely on nontesting and biological assay-based approaches that evaluate molecular initiating events or measurable key events in the pathways. NONTESTING APPROACHES FOR PREDICTING ACUTE TOXICITY The committee envisions that nontesting approaches will be an important component of its conceptual framework.
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From page 5...
... SAR models have been developed for predicting in vivo acute toxicity.2 Most have focused on the prediction of acute rodent oral toxicity, such as estimation of oral LD50 values;3 few attempts have been made to derive models for acute toxicity via other exposure routes, such as inhalation and dermal exposure. Nontesting approaches also have been used to predict toxicity end points, such as neurotoxicity or cytotoxicity.
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From page 6...
... BIOLOGICAL ASSAYS FOR PREDICTING ACUTE TOXICITY In vitro assays and nonmammalian in vivo assays are important components of the committee's conceptual framework. Numerous screening assays have been developed to measure specific biological activities.
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From page 7...
... Conversely, the absence of activity could mean that the tested concentration is below the in vitro effective concentration, that the assay does not represent the biological target, or that there are problems with assay reliability. Current efforts in high-throughput screening support the observations noted here, and the committee emphasizes that DOD should use the experience from current high-throughput screening programs to design its screening program to predict acute, debilitating toxicity.
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From page 8...
... ToxCast program and the European ACuteTox program demonstrate that in vitro assays have some value for predicting acute toxicity and provide evidence that an in vitro screening approach is feasible for evaluating the relative threat of a chemical as an acute hazard. However, most of the assays developed and validated for high-throughput screening programs were not developed specifically for acute-toxicity testing and so might be of little use for identifying chemicals that have the potential to cause acute, debilitating injuries in deployed military personnel.
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Key Terms

  • predicting acute
  • nontesting approaches
  • vitro assays
  • prioritization strategy
  • predict acute

  • animal models
  • chemical toxicity
  • tiered prioritization
  • alternative animal
  • exposure routes

  • false negatives
  • toxicology approaches
  • key limitation
  • biological activity
  • pilot studies

  • acute chemical
  • chemical structure
  • committee envisions
  • testing methods
  • allow dod

  • modern approaches
  • dermal exposure
  • screening programs
  • relative threat
  • confidence indicates

  • physicochemical properties
  • category allows
  • biochemical properties
  • low acute
  • evaluate acute


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