Strategic Direction for New Pesticide Testing and Assessment Approaches
- May 24-26, 2011: SAP Consultation on OPP's Use of 21st Century Science
- PPDC 21st Century Toxicology/ New Integrated Testing Strategies Workgroup
- In the Spotlight
- Glossary of Terms
- ToxCast™ Research Program
- Overview of National Research Council Toxicity Testing Strategy
- National Academy of Sciences Report on Toxicology Testing in the 21st Century
- DRAFT FOR 60-day PUBLIC COMMENT - Process for Establishing & Implementing Alternative Approaches to Traditional in vivo Acute Toxicity Studies (8 pp, 136 kb)
- Guiding Principles for Data Requirements (PDF) (6 pp, 190k)
- Test Guidelines/Acute Toxicity - Acute Oral Toxicity Up-And-Down-Procedure
- Guidance for Waiving or Bridging of Mammalian Acute Toxicity Tests for Pesticides and Pesticide Products (PDF)(17 pp, 113k)
- Guidance for Neurotoxicity Battery, Subchronic Inhalation, Subchronic Dermal and Immunotoxicity Studies (PDF) (11 pp, 244k)
- Genetic Toxicology: Integration of in vivo Testing into Standard Repeat Dose Studies
- Use of an Alternate Testing Framework for Classification of Eye Irritation Potential of EPA Pesticide Products
- Update on the Use of the Local Lymph Node Assay for End Use Pesticide Products and Adoption of the Reduced Dose Protocol for LLNA (rLLNA)
- Guidance for Identifying, Selecting and Evaluating Open Literature Studies
To better protect human health and the environment, EPA is developing and evaluating new technologies in molecular, cellular, computational sciences to supplement or replace more traditional methods of toxicity testing and risk assessment.
This Web page illustrates the approach EPA’s Pesticide Program is using to pursue new technologies that predict and characterize potential human health and environmental hazards and exposures from pesticides. This page describes the current status as well as future plans for this rapidly changing area of research and regulatory science.
On this page:
- Vision for Enhancing Integrated Approaches to Testing and Assessment
- Understanding Integrated Approaches to Testing and Assessment
- Tools Matrix
The new technologies will result in:
- A broader suite of computer-aided methods to better predict potential hazards and exposures, and to focus testing on likely risks of concern,
- Improved approaches to more traditional toxicity tests to minimize the number of animals used while expanding the amount of information obtained (See Tools Matrix (PDF) (7 pp, 92k, About PDF) for examples),
- Improved understanding of toxicity pathways to allow development of non-animal tests that better predict how exposures relate to adverse effects, and
- Improved diagnostic biomonitoring and surveillance methods to detect chemical exposures and identify causes of toxic effects
- A suite of spatial databases and geographic information tools, which will aid in developing more spatially explicit risk assessments that identify geographic areas of concern for both human health and ecological exposure
No single new technology can address all situations. However, by using a suite of tools and approaches in combination, EPA’s Pesticide Program will be able to improve hazard and exposure assessments that form the basis for understanding potential pesticide risks. With these improvements EPA can better achieve its goal of ensuring reliable protection of human health and the environment from adverse effects resulting from pesticide use.
Over the next several years, EPA’s Office of Pesticide Programs (OPP) will improve and transform our approach to pesticide risk management by enhancing our ability to use integrated approaches to testing and assessment.
In this section:
Why a paradigm shift now?
What are the benefits of this paradigm shift?
OPP is committed to protecting human health and the environment through application of the latest scientific tools to increase reliability and effectiveness in assessing and managing potential pesticide risks.
Our critical path focuses on fully utilizing an integrated approach to testing and assessment. The goal is to move toward a new paradigm where in vivo (animal) testing is targeted to the most likely hazards of concern. This progressive, tiered-testing approach starts with hazard-based hypotheses about the plausible toxicological potential of a pesticide or group of pesticides based on their physical-chemical properties. Existing exposure and toxicity information is then combined with computer modeling and ‘new’ diagnostic in vitro (non-animal) assays to target toxicity testing to the specific data needed for human health and ecological risk assessments.
The path forward will require an improved ability to predict chemical toxicity and exposure through application of efficient and effective screening tools including new in vitro assays that rapidly provide biological profiles of the toxicological potential of chemicals. New technological advances to support more effective means of screening chemicals for potential effects will include new computer modeling approaches to predict chemical toxicity and exposure as well as the development of new sensitive biomarkers that will enable tracking of pesticide exposures and their early effects in human and wildlife populations. Exposure and biomonitoring surveys of populations will be critical to interpreting toxicity data and for evaluating the effectiveness of the new testing and assessment paradigm.
Our strategic plan also includes the development of increasingly effective laboratory animal tests that are designed to maximize the information generated about the nature of the effects being studied. These advances will be incorporated within a risk assessment framework of problem formulation, hazard, dose response, exposure assessment, and risk characterization to support pesticide registration decisions.
Achieving our objectives will require close collaboration with the scientific community, international organizations, and our government partners to build the foundation for understanding chemically-induced toxicity pathways. This understanding will allow our program to enhance the direct relevance of our risk assessments to people and wildlife by moving toward a paradigm that is based on a chemical’s mode of action and a better understanding of real world exposures to pesticides. Consistent with the 2007 National Research Council (NRC) of the National Academy of Sciences report on Toxicology Testing in the 21st Century (PDF) (4 pp, 418k, About PDF) , this scientific foundation will enable a shift to an integrated testing and assessment approach.
No single tool is intended to be used alone in a regulatory decision, but, rather, in combination with other methods. For chemicals that typically lack extensive existing test data, the new toxicity and exposure approaches will enhance priority-setting and screening approaches that will focus Agency and societal resources on those chemicals with the greatest risk potential. Directing subsequent test data generation on the most probable adverse effects with more effective and focused assays will reduce the time required for testing and also result in the use of fewer laboratory animals in toxicity testing.
Over the next five years, the Pesticide Program will enhance its integrated approach to testing and assessment to better determine what toxicity data are needed to further refine risk assessments for chemicals that do not have extensive toxicity information (e.g., inert ingredients, certain antimicrobial and biochemical pesticides, and metabolites and degradates of pesticide active ingredients).
OPP plans to maximize use of existing data from similar compounds, computer hazard and exposure modeling, and in vitro data to prioritize specific animal toxicity testing that is needed to assess and manage risks appropriately for these chemicals. Additionally, the current status of monitoring or biomarker methods for population surveillance, which can easily measure exposure, susceptibility and biological outcomes, will be assessed and the need for additional research will be identified.
Over the next 10-15 years, as experience is gained and as our understanding of toxicity pathways increases, an enhanced integrated testing and assessment approach will be implemented for all pesticides including conventional agricultural pesticides. The approach will fully integrate hazard and exposure data along with advanced computer modeling based on new in vitro data and an understanding of toxicity pathways to better predict risks and to determine what additional data are necessary to provide a sound basis to characterize risks of concern. Data from improved biomarkers of exposure and biological outcomes from population-based studies will be used to evaluate the effectiveness of this new risk assessment paradigm, to readily identify early effects in exposed populations, and to improve the approach.
It will take time and substantial research to fully realize our vision and strategic direction. To that end, our program has partnered across EPA and with other federal agencies and international organizations to work collaboratively in an open and transparent manner. As we move forward, we will employ external scientific peer review and public participation as new integrated tools are developed and evaluated for inclusion in risk assessment methods. Enhancing the ability to use integrated approaches to testing and assessment holds the potential to usher in a new era of certainty, predictability and timeliness in the assessment of products that the Pesticide Program regulates.
Dr. Steven Bradbury, Director for Programs, Office of Pesticide Programs
The challenge of evaluating the potential effects of thousands of chemicals in the environment cannot be met by the current testing and assessment approach alone. The current approach relies on data from many costly animal tests that can require years to complete.
Integrated approaches to testing and assessment will increase the information available to EPA for risk management decisions and accomplish this in less time with less animal testing. Implementing this approach requires scientists to make initial predictions of toxicity to create a tailored toxicity testing strategy for each chemical, including carefully targeted animal tests when needed for decision-making. This will be achieved by:
- combining different types of existing information on a similar chemical or group of similar compounds;
- using predictive computer modeling (e.g., quantitative structure activity relationships); and
- non-animal toxicology testing such as in vitro and high-throughput screening assays.
The key goals of integrated approaches to testing and assessment are to:
- improve our ability to set priorities for what data to require,
- ensure that the data requirements are focused on the right issues, and
- efficiently reach the end result of effective risk assessment.
This approach will help us focus testing on pesticide chemicals and the effects that could most likely result in harm. As a result, testing would:
- use fewer animals,
- take less time,
- be less expensive for data generation and review, and
- explore a broader range of potential adverse effects.
For the Pesticide Program, these new approaches over time will allow better use of government and societal resources for evaluation of pesticide active and inert ingredients to consider a broader range of potential toxic effects that may not have been considered previously, and to provide a better understanding of the mechanisms underlying potential areas of concern.
The ultimate outcome of this new approach will be enhancement of the quality of risk assessments and risk management decisions.
EPA has developed a set of tables that describe plans to incorporate new scientific tools for integrated approaches to testing and assessment (PDF) (7 pp, 92k, About PDF) into the pesticide program. These tools reflect current as well as both near-term and long-term approaches.
To advance integrated testing and assessment and enhance the capacity for priority-setting, screening, and evaluation of pesticide hazards, there are a wide variety of activities that involve various partners. These activities are part of an evolving process.
Partnerships Within EPA
OPP is working closely with partners across EPA to define the research and to evaluate new tools to improve the efficiency and reliability of testing and assessment. These partners include:
- other programs in the Office of Chemical Safety and Pollution Prevention, and
- the Office of Research and Development.
For example, the U.S. Environmental Protection Agency’s Strategic Plan for Evaluating the Toxicity of Chemicals will serve as a blue print for implementing the 2007 NAS recommendations on Toxicity Testing in the 21st Century.
Partnerships With Other Federal Agencies
- EPA and two National Institutes of Health Institutes (National Institute of Environmental Health Science’s National Toxicology Program and National Human Genome Research Institute) signed a five-year Memorandum of Understanding (MOU). This MOU leverages the strengths of each organization to advance high-speed, automated screening tools to test chemicals in vitro instead of in laboratory animals.
- EPA is also partnering with the U.S. Food and Drug Administration to exchange toxicity data to build better predictive models.
- EPA is partnering with the Pest Management Regulatory Agency of Health Canada to test the predictive performance of selected (Q)SAR models for pesticides and develop guidance for the application of (Q)SAR models to pesticide risk assessments.
- The Agency is working with the Organization for Economic Cooperation and Development (OECD) on a number of activities including the application of toxicogenomic methods, development of non-animal testing methods (e.g., in vitro and (Q)SAR approaches for endocrine disrupting chemicals), and on reducing and refining animal testing approaches.
- In December 2007, EPA hosted an OECD workshop in Washington, DC to discuss integrated testing and assessment approaches (PDF) (97 pp, 558k, About PDF) .
- EPA has also contributed to several of OECD’s reports and guidance documents on practical applications of (Q)SARs in specific regulatory contexts by governments and industry and to the development of the OECD (Q)SAR Application Toolbox .
The ways in which computer-aided approaches are used to predict effects on human health and the environment depends on the requirements of the specific legislation and needs of the regulatory authority. There is global interest in facilitating and expanding the role of predictive computer approaches in regulatory settings (for example see Joint Meeting of the Chemicals Committee and the Working Party on Chemicals, Pesticides and Biotechnology (PDF) (79 pp, 558k, About PDF)) .