Can case study approaches speed implementation of the NRC report: "Toxicity Testing in the 21st Century: A Vision and...

The 2007 report "Toxicity Testing in the 21st Century: A Vision and a Strategy" argued for a change in toxicity testing for environmental agents and discussed federal funding mechanisms that could be used to support this transformation within the USA. The new approach would test for in vitro perturbations of toxicity pathways using human cells with high-throughput testing platforms. The NRC report proposed a deliberate timeline, spanning about 20 years, to implement a wholesale replacement of current in-life toxicity test approaches focused on apical responses with in vitro assays. One approach to accelerating implementation is to focus on well-studied prototype compounds with known toxicity pathway targets. Through a series of carefully executed case studies with four or five pathway prototypes, the various steps required for implementation of an in vitro toxicity pathway approach to risk assessment could be developed and refined. In this article, we discuss alternative approaches for implementation and also outline advantages of a case study approach and the manner in which the case studies could be pursued using current methodologies. A case study approach would be complementary to recently proposed efforts to map the human toxome, while representing a significant extension toward more formal risk assessment compared to the profiling and prioritization approaches inherent in programs such as the EPA's ToxCast effort.