Toxicity Testing in the 21st Century: A View from the Chemical Industry

The rapid onset of the science and experimental tools of molecular biology and genomics has presented the toxicology community with an unprecedented opportunity to reexamine, and potentially significantly restructure, many of the decadeslong principles and practices guiding translation of conventional animal toxicology data to scientifically informed assessments of adverse human health risks. Implementation of this energizing and transformational technology into toxicology has of course been recently catalyzed by the report of the U.S. National Research Council (NRC) report, Toxicity Testing in the 21st Century: A Vision and a Strategy (National Research Council, Committee on Toxicity Testing and Assessment of Environmental Agents, Board of Environmental Studies and Toxicology, Institute for Laboratory Animal Research, 2007a), and was overviewed in Part I of this Forum series (Andersen and Krewski, 2009). The NRC report outlined the promise that the new technologies could dramatically increase both the number of chemicals comprehensively evaluated as well as broadening and improving the human relevance of toxicity end points assessed. Such outcomes, if successfully achieved, would significantly improve and inform science-based health assessments on a broad range of environmental chemicals. It has long been recognized that the ability to fully characterize the potential hazard properties of the many thousands of environmental chemicals associated with chemical production by conventional toxicity test methods is pragmatically constrained by laboratory, animal, financial, and expertise resource limitations. And, of course, there are yet many thousands more chemicals originating as by-products of other human endeavors or as natural substances in the environment, all of which cannot be ignored if we are truly interested in understanding the contributions of environmental chemicals to adverse public health outcomes. The resource limitations associated with conventional toxicity testing are further emphasized when examining the testing resources necessary to develop pharmaceutical or pesticide products. Testing of these agents mandate use of an extensive and regulatory-proscribed core battery of sequential tests that cost millions of dollars per chemical and 4–5 years at a minimum to complete (and consume many thousands of animals). The chemical industry, facing the challenge of testing many thousands of more chemicals (to which human exposures may already be occurring) relative to the limited numbers of drug and pesticide products, has generally applied a tier-based testing framework for evaluation of chemicals and by-products of