Pragmatic Challenges for the Vision of Toxicity Testing in the 21st Century in a Regulatory Context: Another Ames Test? …or a New Edition of “the Red Book”?

Abstract

Most toxicologists were pleased when the National Research Council appointed a committee in 2004 to review established methodologies and develop a long-range vision and strategy for toxicity testing in the future. This committee reviewed reports from the U.S. Environmental Protection Agency (EPA) and other sources and issued an interim report in 2006 entitled ‘‘Toxicity Testing for Assessment of Environmental Agents’’ (NCR, 2006). This report distinguished general toxicity tests from those designed to evaluate specific health effects and classified such tests as battery, tiered or tailored depending on the approach. It also reviewed the use of human data, alternative approaches and emerging technologies. Three chapters in this report included cogent committee observations and these sections plus the summarized information in boxes, tables and the appendix make this soft-cover report a valuable reference companion for the subsequent hard cover report. One of the many observations in this report is that toxicity testing protocols never die but unlike old soldiers who fade away, ‘‘grow like Topsy’’ (e.g., derived from the character, Topsy, in Harriet Beecher Stowe’s Uncle Tom’s Cabin; to ‘‘grow like Topsy’’ is to grow ‘wild, with neither plan, structure or direction) in response to new perceived or real safety concerns. This approach results in a cookbook/checklist of protocols which is increasingly difficult to apply efficiently in the testing of new agents and is totally inadequate to deal with the substantial backlog of untested existing substances prioritized for consideration in evolving regulatory mandates.