Expert Report

Each report is produced by a committee of experts selected by the Academy to address a particular statement of task and is subject to a rigorous, independent peer review; while the reports represent views of the committee, they also are endorsed by the Academy. Learn more on our expert consensus reports.

Toxicity testing in laboratory animals provides much of the information used by the Environmental Protection Agency (EPA) to assess the hazards and risks associated with exposure to environmental agents that might harm public health or the environment. The data are used to establish maximum acceptable concentrations of environmental agents in drinking water, set permissible limits of exposure of workers, define labeling requirements, establish tolerances for pesticides residues on food, and set other kinds of limits on the basis of risk assessment. Because the number of regulations that require toxicity testing is growing, EPA called for a comprehensive review of established and emerging toxicity-testing methods and strategies. This interim report reviews current toxicity-testing methods and strategies and near-term improvements in toxicity-testing approaches proposed by EPA and others. It identifies several recurring themes and questions in the various reports reviewed. The final report will present a long-range vision and strategic plan to advance the practices of toxicity testing and human health assessment of environmental contaminants.

Key Messages

  • A new strategy is needed to improve efficiency, reduce animal use, increase the number of chemicals screened for toxicity, and address some of the data gaps identified.
  • Generally little information is available on pharmacokinetics, including possible differences across life stages. It is critically important to define the purpose of pharmacokinetic studies to avoid the creation of data that are unlikely to be used and therefore represent a waste of animals, time, and resources.
  • The REACH program has the advantage of generating at least some toxicity data on chemicals that are not now subject to testing in the United States.
  • The committee found that the NTP's near-term efforts to refine and extend its toxicity tests and to improve the use of pharmacokinetic information promise to increase the depth of toxicity information on chemicals assayed and to provide greater insight in applying the findings to humans.
  • The committee found that the REACH program focuses more on screening large numbers of chemicals than on generating in-depth information that is often needed for quantitative risk assessment. However, the REACH program does allow for greater depth of testing to be triggered on the basis of initial results.
  • The committee notes that the ILSI-HESI evaluation may have overlooked redundancy of testing as a critical part of the weight-of-evidence approach.
  • The committee supports the general ILSI-HESI approach of using existing databases to evaluate the importance of specific toxicity tests or their contribution to the dataset and endorses further broad retrospective reviews.
  • The existing protocols for acute toxicity testing focus on lethal effects and gross observations and generally do not provide adequate information for acute and short-term RfDs or reference concentrations (RfCs).
  • The relevant exposure route and exposure durations should be considered in developing a testing strategy.
  • There are numerous data gaps in life stages and specific health effects evaluated in current toxicity-testing approaches. Few data are available to determine the degree to which those gaps have practical significance for risk assessment or whether they are primarily of theoretical or academic concern.