In the Spotlight
US EPA Adopts Strategic Plan for Evaluating the Toxicity of Chemicals
Published: April 27, 2009
Realizing the ever increasing number of chemicals that need to be evaluated for potential adverse health effects, the emerging new technologies being used to identify toxic effects, and the inability of current regulatory approaches to incorporate the new methods for improved risk assessment, the EPA in 2004 commissioned the National Research Council (NRC) to develop a long-range vision for toxicity testing and risk assessment. The NRC assembled a panel of experts to address this topic, which resulted in the 2007 NRC report, Toxicity Testing in the 21st Century: a Vision and a Strategy.
The intra-agency Future of Toxicity Testing Workgroup under the EPA’s Science Policy Council has now released “The U.S. Environmental Protection Agency’s Strategic Plan for Evaluating the Toxicity of Chemicals that provides a framework for…incorporat[ing] this new scientific paradigm into future toxicity testing and risk assessment practices.” The Plan states that the proposed new approach “will inform and produce more credible decision making with an increased efficiency in design and costs and a reduction in animal usage.” While the NRC report primarily deals with toxicity testing for assessing human health effects, certain statutes or their resulting policies requires the EPA to implement changes that include both human health and environmental risk assessment.
Current regulatory hazard and risk assessments rely on information obtained from exposing animals to a chemical or product in a number of types of experiments. The tests were developed decades ago, and provide crude estimates of biological effects in animals that must be extrapolated to potential human health effects. The vision proposed in the NRC report is based on the application of scientific advances that use molecular, cellular, and computational methods to identify and study toxicity pathways. It describes a “toxicity-testing system that relies mainly on understanding ‘toxicity pathways‘—the cellular response pathways that can result in adverse health effects when sufficiently perturbed. Such a system would evaluate biologically significant alterations without relying on studies of whole animals.”
For a document coming from a regulatory agency, the Strategic Plan is a short and readable paper of only 27 pages, and consists of the following topics:
- Regulatory Applications and Impacts
- Toxicity Pathway Identification and Chemical Screening and Prioritization – research to identify toxicity pathways and use them to facilitate screening and prioritization of chemicals for further testing
- Toxicity Pathway-Based Risk Assessment – using toxicity pathways data in risk assessment
- Institutional Transition – organizational changes needed to implement these practices at the EPA
- Future Steps
The level of effort for each of the three major activities (2-4 above) is expected to change over the 10 to 20-year time frame expected for implementing the Plan. The Plan notes that “other agencies have also recognized the need for this transformative shift,” and describes some of the cooperative and collaborative efforts underway. Implementation of the EPA transformation has been estimated at a cost of $100M per year. A follow-up ‘implementation plan’ was described as the place where the details and practical issues would be addressed. An expected date for this document was not provided. Five years have already elapsed from the commission of the NRC report to the release of the EPA Strategic Plan, so some urgency is due in the development of the implementation plan.
The Strategic Plan, as noted above, is a short overview document, and does not contain details on implementation. Several of the peer review comments echoed my first question/concern which is the lack of clarity about how and when human cell-based assays will become the major basis of toxicity testing compared to the continued use of animals and animal cells. Page 3 of the Plan states that “the overall goal of this strategy is to provide the tools and approaches to move from a near exclusive use of animal tests for predicting human health effects to a process that relies more heavily on in vitro assays, especially those using human cell lines.” However, other statements in the Plan are not as clear, and suggest a long transition using in vivo animal models. So far, -omics research has primarily meant an add-on to animal studies. A few of the other concerns noted by reviewers are the long time frame for implementation and the potential for the plan to get bogged down as a chemical prioritization exercise – teeing up chemicals for testing under the current paradigm rather than investment being truly transformative.