In the Spotlight
The US EPA’s Endocrine Disruptor Screening Program: Part II
Published: August 6, 2012
In May 2011, the EPA Office of Inspector General (OIG) issued an Evaluation Report on the EDSP, EPA’s Endocrine Disruptor Screening Program Should Establish Management Controls to Ensure More Timely Results, as a result of concern over delays in meeting program milestones. The OIG report noted that the 1998 EPA’s Proposed Statement of Policy reported the need to screen thousands of chemicals (p.4), but fourteen years later “has not determined whether any chemical is a potential endocrine disruptor” (p. 9). The EDSP had not developed a management plan, had missed milestones for assay validation and chemical selection, and target dates were missed by about 4½ to 6 years (p. 9). One of the six recommendations made to the EPA in the OIG Evaluation Report was for the development of a comprehensive management plan for the EDSP (p.19).
This article describes two EPA publications that have been released since the OIG report: 1) the Endocrine Disruptor Screening Program for the 21st Century: EDSP21 Work Plan (September 30, 2011), and 2) the EDSP Comprehensive Management Plan (June 2012).
EDSP21 Work Plan
In 2012, the EPA will begin to transition from EDSP to EDSP21. The EDSP21 Work Plan, describes the rationale and framework for how this transition will take place. EDSP21 is aligned with the recommendations proposed in the 2007 National Research Council report, Toxicity Testing in the 21st Century: A Vision and a Strategy (Tox21). The Work Plan lays out an approach to screening chemicals for their potential to interact with the endocrine system using in silico modeling and in vitro high-throughput (HTP) assays. According to the EPA, “the development and validation of these new tools will be a multiyear process.”
The EDSP21 Work Plan proposes the use of these innovative technologies for prioritizing and screening the backlog of previously registered pesticide ingredients for which the EPA is mandated to complete a first round of registration review by October 1, 2022 (p.2). Under the existing EDSP, many active pesticide ingredients have yet to undergo Tier 1 screening. The EPA claims that “Using this current process [EDSP] to continue to identify chemicals for screening, having them screened, and making decisions about more definitive testing, is not sustainable to evaluate the tens of thousands of chemicals that fall within the purview of EPA” (p.25).
As explained in the EPA’s FY2012 Budget in Brief, EPA is reorganizing its research into four new research programs. The Chemical Safety for Sustainability Research Program (CSS) will be “integrating a diversity of scientific disciplines to develop new prediction techniques, pioneering the use of innovative technologies for chemical toxicity testing, and designing tools to advance the management of chemical risks.” Research on endocrine disrupting chemicals to improve the efficiency of EPA’s EDSP will be conducted under the CSS program. More information on the CSS program can be found in the AltTox article EPA’s New Chemical Safety for Sustainability Research Program.
The EDSP21 Work Plan describes the EPA’s statutory obligations, defines the universe of chemicals for screening for potential endocrine effects, and explains implementation and the timeline of the EDSP21 Work Plan. Table 1 in the Work Plan, “The numerical estimates of chemicals associated with each authority,” estimates the universe of chemicals for prioritization and screening to be 6,000 to 9,700 (p.3).
EDSP21 approaches will be used to increase efficiencies for testing both pesticide and non-pesticide active ingredients. “For pesticides, EPA’s strategy is to coordinate the timing of issuance of EDSP Tier 1 test orders with the timing of the registration review program” (p.4). The time required to complete the current battery of Tier 1 assays makes it difficult to integrate the Tier 1 data into the pesticide registration reviews. “It is envisioned that the EDSP21 program, along with a combination of existing data, and in silico and in vitro methodologies, will enable the agency to prioritize and identify EDSP Tier 1 information needs for pesticide active ingredient cases entering the registration review program over the next several (1-3) years” (p.4). The same methods are proposed for prioritizing non-pesticide chemicals for Tier 1 screening.
A three-stage timeline and the goals at each stage are described as follows (pp.4-5):
- The short-term goal (< 2 years) is prioritization: to use existing data, computational models, and HTP screening assays to prioritize chemicals for screening in the EDSP Tier 1 assays.
- The intermediate-term goal (2-5 years) is screening: “to replace current validated in vitro screening assays with validated in vitro HTP assays; use the results to inform and target current in vivo estrogen- or androgen-specific screening assays; and, where possible, reduce the use of animals for screening purposes.”
- The longer-term goal (> 5 years) is replacement: to replace the in vivo Tier 1 screening assays with validated HTP assays (eliminate the use of animals for screening purposes). A weight-of-evidence approach will also be employed to determine which chemicals require further testing (in vivo EDSP Tier 2 testing).
EDSP Comprehensive Management Plan
The EDSP Comprehensive Management Plan (CMP), the plan requested in the May 2011 OIG Evaluation Report, was released by the EPA on June 28, 2012.
The EPA starts out by describing the purpose of the CMP as providing strategic guidance for EPA staff on “internal activities associated with EDSP” through fiscal year (FY) 2017, and that the plan will be “evaluated for revision on an annual basis.” They also emphasize that the CMP “is not intended to establish any policy or procedures or impose any requirements…nothing in this plan is binding on either the EPA or others” (pp. 2-4).
This 27-page report includes the following sections: Introduction, Scope of the Document, Program Organization, Technical Review Processes, Consolidated IT Infrastructure, Resource Requirements and Performance Management, and Training Plans. The content of selected sections will be examined further.
The objectives of the EDSP for the next 5 years are outlined in this section of the CMP (see Table 1, pp.4-5). These objectives include expanding Tier 1 test orders to the second list of chemicals (List 2 Chemicals) (2013-16), validating Tier 2 in vivo assays (2012-14), and starting to release Tier 2 test orders for the List 1 Chemicals (2014-15). Since the Tier 1 screening includes ~5 in vitro and 7-8 in vivo assays, and Tier 2 includes 5-6 in vivo assays, implementation of these objectives will enormously expand EDSP animal testing over the next decade.
The CMP confirms the EPA’s plans over this period to implement Tox21 tools to “allow the agency to better optimize the ability to prioritize chemicals for review under the EDSP” (p. 3).
The performance of the Tier 1 assays and battery and weight-of-evidence (WoE) approach for a subset of List 1 Chemicals will be externally reviewed by a Federal Insecticide, Fungicide, and Rodenticide (FIFRA) Scientific Advisory Panel in 2013-14. However, the full set of scientific data reviews and data evaluations for Tier 1 and Tier 2 test results from the List 1 Chemicals (test orders issued October 29, 2009) are not proposed to be completed until 2018. Following this schedule, the List 2 Chemicals will be in Tier 1 testing (2013-16) before the performance assessment of the Tier 1 assays and battery is completed, and before the EDSP21 (Tox21) battery is fully implemented. Thus, delays in the EDSP will result in lost opportunities to reduce animal use in this testing program.
Furthermore, the WoE approach that will be used to determine the need for Tier 2 testing will be performed during the same year (2014) as the Tier 1 data for the first subset of List 1 Chemicals are being reviewed. EPA has issued a guidance document on WoE; however, the details of the approach as it will be applied to the EDSP have not been articulated and examples of WoE use by EPA are not yet available.
This more than 4-page section focuses on describing the EDSP organizational structure, communication and coordination processes, and roles and responsibilities of different EPA offices. Communication and coordination among the many EPA groups involved in EDSP are only briefly described. It is unclear whether or not a communication plan has actually been developed.
A “Policies and Procedures” subsection mentions that over the next 5 years the draft policies and procedures established in 2009 will be updated, and that electronic submission will be provided for agency orders.
Technical Review Processes
To implement the program, the following 5 steps were described as the overall “EDSP technical review process” (pp.11-13):
1. Universe of chemicals for prioritization
“Priority setting in EDSP refers to identifying which chemicals will undergo Tier 1 Screening first.”
The CMP explains that the statutes mandating EDSP (Food Quality Protection Act and Safe Drinking Water Act) identify the scope for the universe of chemicals under EDSP. The Priority Setting Activities webpage referenced in the CMP provides historical information on EDSP priority setting activities, however, the supplemental document mentioned in the CMP, Endocrine Chemical Prioritization, was not found.
2. Issuance of test orders for the Tier 1 screening assays
Test orders for the first list of 67 chemicals for Tier 1 screening were issued on October 29, 2009. Issuance of test orders for a second list of chemicals is proposed for 2013.
3. Review of Tier 1 assay data
“…pending the availability of complete Tier 1 assay data sets for a sufficient and representative number of chemicals,” the functionality of each Tier 1 assay and the battery will be submitted for external scientific peer review in FY 2013.
4. Develop weight-of-evidence determination
Following Tier 1 screening, the approach described in the WoE guidance document will be used to determine whether additional information is needed for a particular chemical.
5. Issuance of test orders for Tier 2 assays
Test orders will be issued for Tier 2 testing when the WoE determination suggests possible endocrine disruptor activity for a chemical. The Tier 2 tests are not a battery, so targeted testing could be ordered.
The “Technical Review Processes” section of the CMP also describes how the EPA will incorporate the new EDSP21 technologies (described above in EDSP21 Work Plan section).
Resource Requirements and Performance Management
As a result of annual planning, three performance measures were identified for EDSP, and the current results and targets reported by the EPA are provided in the table below.
EDSP performance measures with FY 2011 performance results and FY 2011-2013 performance targets.
Number of chemicals for which EDSP decisions have been completed.
Number of chemicals for which EDSP Tier 1 test orders have been issued.
Number of screening and testing assays for which validation decisions have been reached.
The EPA is also developing additional performance measures to address the OIG recommendation that the EPA: “Develop short-term, intermediate, and long-term outcome performance measures, and additional output performance measures, with appropriate targets and timeframes, to measure the progress and results of the program” (p.19). Additional performance measures will be needed to cover the transition to EDSP21.
The development of computational and HTP approaches for endocrine disruptor testing are supported by the Endocrine Disruptors Research Program (EDRP) rather than as part of EDSP. The EDRP under the EPA’s Office of Research and Development’s CSS program is funded under a different appropriation than EDSP, and so over the next 5 years resources for EDSP will decrease as they increase for EDRP.
This section of the CMP also describes a vision for the future where CSS research will lead to alternative methodologies replacing “part or all of the current Tier 1 screening battery” with a longer-term goal to “replace whole animal testing in Tier 1” (p.22).
The CMP describes organizational and coordination plans for managing these transitions which involve multiple EPA programs and offices. The EPA Office of Chemical Safety and Pollution Prevention (OCSPP) will also conduct an annual review of EDSP as recommended by the OIG.
A representative of the EPA (not identified) is scheduled to present an “Update on EDSP21 Activities at EPA” on September 5, 2012 at the NTP’s annual Scientific Advisory Committee on Alternative Toxicological Methods (SACATM) meeting.