Regulatory Developments

EPA Releases Final Strategic Plan to Promote the Development and Implementation of Alternative Test Methods Within the TSCA Program

June 28, 2018

On June 22, 2018, the U.S. Environmental Protection Agency (EPA) released its Strategic Plan to Promote the Development and Implementation of Alternative Test Methods Within the TSCA Program.  Development of the Strategic Plan was required under Section 4(h)(2)(A) of the Frank R. Lautenberg Chemical Safety for the 21st Century Act with a deadline of not later than two years after enactment.  Release of the final Strategic Plan occurred on the second anniversary of enactment of amendments to the Toxic Substances Control Act (TSCA).
 
The goal of the strategy is to reduce the level of testing in vertebrates for chemicals regulated under TSCA.  EPA describes alternative test methods and strategies as different descriptors that have a common goal.  The former is based on reduction, refinement, and replacement of animal test methods (the 3Rs), while strategies incorporate more than just toxicity test methods to characterize hazard.  The strategy as proposed relies on a range of applications and testing approaches to characterize human health and environmental endpoints. 
 
Collectively, alternative test methods and strategies combine to define a new term: new approach methodologies (NAM).  The NAM designation is used as a broadly descriptive reference to any technology, methodology, approach, or combination thereof that can be used to provide information on chemical hazard and risk assessment that avoids the use of vertebrates. For the purposes of TSCA, EPA recognizes this new term (i.e., NAM) as encompassing any “alternative test methods and strategies to reduce, refine or replace vertebrate animals.”
 
This Strategic Plan was developed by the Office of Pollution Prevention and Toxics (OPPT) in collaboration with EPA’s Office of Pesticide Programs (OPP), the Office of Research and Development (ORD), and the Office of Science Coordination and Policy (OSCP). OPPT also reports that it has worked with members, agencies, and technical workgroups of the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM).
 
EPA recognizes that this Strategic Plan necessarily describes a multi-year process with incremental steps for adoption and integration of NAMs that are appropriate and fit-for-purpose for making TSCA decisions (e.g., identifying candidates for prioritization, prioritization, risk evaluations for new and existing chemicals, and other risk-based decisions). This Strategic Plan should be considered a dynamic, evolving document, considering the best available science at a moment in time. As required by TSCA Section 4(h)(2)(E), EPA will provide a report to Congress every five years (beginning in 2021) describing the progress in implementing this Strategic Plan.
 
There are various sections in TSCA that include provisions related to animal testing.  The Strategic Plan applies most prominently to Sections 4, 5, 6, and 8. Section 4 of TSCA provides EPA with authority to require health and environmental effects testing with the testing in most cases relevant to a determination of an unreasonable risk to health or the environment (Section 4(a)).  Sections 5 and 6 of TSCA pertain to prioritization, hazard, and risk evaluation of new chemicals and existing chemicals, respectively. Section 8(e) requires that EPA be notified of any “substantial risk” information.  In this regard, EPA acknowledges the need to consider updating the TSCA Section 8(e) guidance to reflect the potential role of NAMs in determining substantial risk information that is required to be submitted.
 
EPA’s Strategic Plan has three core components: (1) identifying, developing, and integrating NAMs for TSCA decisions; (2) building confidence that the NAMs are scientifically reliable and relevant for TSCA decisions; and (3) implementing the reliable and relevant NAMs for TSCA decisions.
 
The operational components of the Strategic Plan are organized and described as follows: Chapter 4 -- Identification, Development, and Integration of NAMs; Chapter 5 -- Establishing Scientific Relevance, Reliability and Confidence of NAMs: Development of Criteria for TSCA-related Decisions; Chapter 6 -- The Importance of Education, Training, and Collaboration; Chapter 7 --  Implementation of NAMs Under TSCA; and Chapter 8 -- Conclusions & Next Steps.
 
The TSCA-related NAMs included in Chapter 4 generally fall into four categories: (1) chemical characterization, (2) hazard identification and characterization, (3) dosimetry and in vitro-in vivo extrapolation, and (4) exposure.  EPA released concurrently with the Strategic Plan a List of NAMs as required by Section 4(h)(2)(C).  The TSCA Section 4(h) List relies heavily on historical data sets and their utility depends on, among other considerations, access to the training and test data. EPA supports public access to the data sets used to build the different predictive models as part of building scientific confidence, although, complete access may not be possible in some cases.  EPA/OPPT uses information claimed as confidential business information (CBI) to develop and refine these models because this information, although not public, is critical to the evaluation of TSCA chemicals.  EPA will be performing a retrospective analysis to identify the most requested studies and associated needs for NAMs when assessing new and existing chemicals. The results of this retrospective analysis will be used to inform research and development activities for hazard-related NAMs of most relevance for TSCA chemicals.  EPA proposes to use the Organization for Economic Cooperation and Development’s (OECD) Integrated Approaches to Testing and Assessment (IATA) framework to organize and integrate information from relevant NAMs as part of a weight-of-evidence (WOE) argument.  The IATA can be built starting with the development of Adverse Outcome Pathways as an organizational framework for endpoints and responses relevant to TSCA.
 
Building confidence in NAMs rests on the relevance and reliability of the test methods included in the approach.  Relevance is defined in EPA’s strategy as the ability of a test method to measure or predict an effect/target of interest as well as the regulatory need, usefulness of the alternative method(s), and associated limitations of the test method.  EPA continues that the definition of relevance incorporates fit-for-purpose and utilization as a contextual evaluation and application of the NAM or integrated NAMs, and may include a WOE analysis of their use, based on all available evidence, for use in making qualitative or quantitative predictions. Reliability is defined in a 2005 OECD guidance document as the extent of reproducibility of results within (intra-) and among (inter-) laboratories over time.  Because some in vitro NAMs are not amenable to transfer into naïve laboratories, the demonstration of reliability is therefore confined to assessment of within laboratory reproducibility.

Under Chapter 6, The Importance of Education, Training, and Collaboration, EPA is undertaking and plans to continue an active and engaged dialogue with researchers, the regulated community, and other stakeholders as NAMs and their use are developed. For example, the development of information technology tools provides an efficient means to assemble and integrate NAM information related to health and environmental hazard, exposure, and risk. The general engagement of the scientific community will be augmented by the development of customized training sessions for stakeholders. Education and training will cover both use and interpretation of the information, as well as the specific tools such as dashboards and workflows. EPA specifically envisions internal training/education of EPA staff and managers.
 
Chapter 7 describes the activities that EPA expects to undertake to implement this Strategic Plan. The activities are centered on three core components and for which timelines are provided that are sensitive to the requirements in the law. EPA recognizes that this Strategic Plan is a multi-year process with incremental steps for adoption and integration of NAMs for TSCA decisions (e.g., identifying candidates for prioritization, prioritization, risk evaluation, and other risk-based decisions). As such, a key activity in this Strategic Plan will be to identify evolving NAMs and prioritize further development (leading to regulatory acceptance) of NAMs that are of potential interest to TSCA regulatory outcomes (i.e., fit-for-purpose).  EPA has identified current/near-term (<three years) needs and activities. Completing these activities will result in moving towards five intermediate-term (three to five years) objectives. These time frames, needs, and activities provide the basis for developing NAMs, establishing reliability and relevance criteria for the NAMs, and implementing NAMs to inform decisions made under TSCA.  To facilitate a successful deployment of the Strategic Plan, EPA established a TSCA NAM Team (TNT) to oversee implementation activities.  The TNT draws resources and experts from different offices within EPA.  EPA indicates that at this time membership in the TNT will be limited to EPA personnel largely because of the need for CBI clearance of potential members and to establish a system and process to manage internal information.  EPA will continue to engage with stakeholders for insight and advice on the milestones of the Strategic Plan.  The TNT will consist of EPA staff/managers from across the Office of Chemical Safety and Pollution Prevention (OCSPP) and ORD.  The TNT will be chaired by OPPT and the team will report to the OPPT Office Director.
 
EPA identified near term activities as follows:

  • Ongoing
    • Continue to implement NAMs to evaluate hazard, exposure, and environmental fate for new and existing chemicals.
    • Use of NAMs to identify candidates for prioritizing existing chemicals for TSCA risk evaluation.
    • Begin development of scientific information technology platforms.
    • Collaborate with partners and stakeholders to identify NAMs for further development.
  • Third Quarter 2018
    • Launch TSCA NAM website.
  • First Quarter 2019
    • Maintain and regularly update a list of NAMs pursuant to Section 4(h)(2)(C).
  • Second Quarter 2019
    • Identify and maintain a list of most requested/needed studies for new and existing chemicals under TSCA.
    • Identify and curate available existing TSCA information on NAMs (and traditional test data).
  • Intermediate (three to five years)
    • The intermediate-term objectives identified by EPA represent essentially a continuation, refinement, and expansion of the short-term activities. 
  • Long-Term
    • The long-term goal expressed by EPA is the reduction and eventual elimination of vertebrate animal testing.
Commentary

EPA is to be commended for the timely release of the final Strategic Plan, thereby meeting yet another deadline under TSCA.  The design reflects EPA’s cautionary observation that the Strategic Plan represents a multi-year process with gradual, incremental steps for adoption and integration into the chemicals program. The program outlines near-term, intermediate (three to five years), and long-term goals with unspecified time frames.  The final version reflects largely editorial changes and clarifications relative to the discussion found in the proposed Strategic Plan. Perhaps the most important change in the final version is the “elevation” of the List of NAMs. The List was originally an appendix in the draft version and the List was published concurrent with but separate from the Strategic Plan.  The final Plan incorporates the List and devotes two new sections to it -- maintenance and the unveiling of the List website.
 
The new term adopted by EPA, New Approach Methodologies or NAMs, identifies the different methodologies that will be used to characterize the different aspects of the life cycle of an industrial chemical.  The NAMs listed in the Plan include estimation and predictive tools that EPA is currently using for assessment of new and existing chemicals.  The tools include all areas of the assessment process: physicochemical properties, exposure, and environmental fate, as well as aquatic and mammalian hazard. Although no explicit statement is made in the document, the implication is that the NAMs listed meet the criteria for relevance and reliability. 
 
EPA also established an internal group, the TNT, to oversee implementation of the Strategic Plan.  The TNT, consisting of staff from OPPT, OPP, and ORD, will be responsible for interactions with stakeholders and the public; communications, outreach, and training; technical aspects; and collaborations.  The size of the group is not specified but this is a critical aspect of the Team’s success given that the near-term milestones listed in the Strategic Plan are likely to require a significant investment of time and resources.


 
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