EPA Rebuilds Endocrine Disruptor Screening Program by Soliciting Public Comment on New Approach Methodologies to Screen for Endocrine Effects

Released on January 19, 2023

The U.S. Environmental Protection Agency (EPA) is releasing a draft White Paper for public comment, entitled Availability of New Approach Methodologies (NAMs) in the Endocrine Disruptor Screening Program (EDSP), that describes validated NAMs that EPA may now accept as alternatives for certain EDSP tests.

Endocrine systems, also referred to as hormone systems, are found in all mammals, birds, fish, and many other living organisms. These systems are made up of glands located throughout the body, hormones synthesized by these glands and released into the bloodstream or the fluid surrounding cells, and receptors in various organs and tissues that recognize and respond to the hormones. The Federal Food, Drug, and Cosmetic Act (FFDCA) requires that EPA screen pesticide chemicals for their potential to cause endocrine disruption and to protect human health from substances with endocrine effects.

The draft White Paper released today is a key step in EPA’s work to reinvigorate its efforts to meet its requirement for EDSP screening of chemicals and continue to provide transparency of EDSP Tier 1 testing, which is the step in the EDSP that determines the potential for endocrine-disrupting effects and whether there is a need to obtain more data by requiring additional Tier 2 tests. The approaches described in the draft White Paper would accelerate the pace of screening of all chemicals, including pesticide active ingredients, for potential impacts on the endocrine system, add efficiencies and decrease costs in the Agency’s review, and reduce animal testing. By focusing on screening chemicals more efficiently, EPA can also more quickly identify any additional testing needs and regulatory actions to better protect people and communities from pesticides that may impact the endocrine system.

The draft White Paper presents several NAMs that would allow EPA to screen chemicals faster and more efficiently using alternatives to vertebrate animal testing and other in vitro, or in-the-laboratory, assays. NAMs are defined as any technology, methodology, approach, or combination that can provide information on chemical hazard and risk assessment to avoid the use of animal testing. NAMs are technologies and approaches that have been developed by using advances in molecular, cellular, and computational sciences, which can supplement or replace more traditional methods of testing chemicals — such as animal testing — for potential hazards. Advances in testing can lead to quicker analysis and recognition of chemicals that can affect the development, reproduction, and neurological function of people and animals - which in turn will lead to faster efforts to identify and require the implementation of protections for those who need them.

EPA values stakeholder input and is taking comment on the draft White Paper. As science evolves, EPA continues to commit to ensuring that its assessment of pesticides more closely, quickly, and effectively evaluates the potential for endocrine effects.

If EPA finds that data for a particular chemical reveals an effect in humans similar to an effect produced by a naturally occurring estrogen or other endocrine effects, EPA will take action to ensure that any needed protections are implemented.

EDSP White Paper and Next Steps for the Program

EPA has invested in the development of NAMs to more quickly screen chemicals for endocrine disruption, reduce the use of vertebrate animal testing, and ensure that pesticide decisions continue to protect human health and the environment.

The EDSP uses a tiered approach for screening chemicals. Tier 1 screening data is used to identify substances that have potential to interact with the endocrine system. Chemicals that go through Tier 1 screening and are found to exhibit potential to interact with the estrogen, androgen, or thyroid hormone systems will proceed to Tier 2 for testing.

Tier 2 testing data identifies adverse endocrine-related effects caused by the substance and establishes a quantitative relationship between the dose and that adverse effect. The results of Tier 2 testing will be combined with other hazard information and exposure assessments on a given chemical, resulting in a risk assessment. Risk assessments are used to inform risk mitigation measures, and regulatory decisions concerning chemicals to ensure that people who might be exposed to them are protected.

The draft White Paper also identifies NAMs for priority setting and weight-of-evidence (WoE) evaluations. Priority setting is important for EPA to test the chemicals posing the greatest risk first, while WoE is the process by which the strengths and weaknesses of a data collection are judged to render an overall conclusion that may not be evident from considering the data individually. WoE is conducted as part of evaluating EDSP Tier 1 screening data to identify the need for Tier 2 testing.

The current EDSP Tier 1 methods used for screening chemicals for endocrine disruption are expensive, require extensive staff time, and use laboratory animals. Because of the cost (EPA estimated industry costs in conducting a full Tier 1 battery to be approximately $1 million per chemical, largely due to the laboratory animal testing) and time (up to six years) involved in conducting and reviewing the full battery of Tier 1 assays, EPA has only screened a fraction of the thousands of chemicals that are subject to EDSP for their potential endocrine-disrupting effects. These factors delay EPA’s ability to take steps to protect those who may be at risk to these chemicals.

As described in the draft White Paper, EPA has validated NAMs that, when used alongside traditional approaches to chemical testing, will expedite the Tier 1 screening of thousands of chemicals to assess whether they affect the endocrine system. This work will ultimately speed up the risk assessment process and enable EPA to protect people and their communities faster from potentially harmful endocrine effects.

These validated NAMs for screening were reviewed in 2014 and 2017 by the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory Panel (SAP) and are now considered validated alternatives to four EDSP Tier 1 assays. The data derived from these validated models and assays may be used to satisfy specified EDSP data needs, depending on a pesticide’s properties.

Upon publication of the Federal Register notice, public comments on the draft White Paper will be accepted for 60 days in docket ID number EPA-HQ-OPP-2021-0756 at www.regulations.gov. After considering public comments, EPA will issue a finalized document.

Background

EPA has considered previous public input in developing this draft White Paper. In 2015, EPA requested comments on its “Endocrine Disruptor Screening Program: Use of High Throughput Assays and Computational Tools,” which describes how EPA planned to incorporate an alternative scientific approach to screen chemicals for their ability to interact with the endocrine system by integrating high throughput assays and a computational model. EPA’s response to comments it received is now available in docket EPA-HQ-OPPT-2015-0305. Additionally, in 2017, EPA held a FIFRA SAP meeting on the potential use of high-throughput screening for chemicals under the EDSP and the androgen receptor pathway model. EPA’s response is now available in docket EPA-HQ-OPP-2017-0214.

For the entirety of the previous Administration, Presidential budget requests repeatedly proposed to completely eliminate the EDSP. EPA’s focus in the Biden-Harris Administration is to build on the work already done to accelerate the pace and transparency of evaluations done for endocrine disruption. In 2021, EPA also received and responded to 10 recommendations from EPA’s Office of Inspector General (OIG) on the need to make significant improvements to the EDSP and develop an effective system of internal controls. In general, EPA agreed with all of the OIG recommendations, as they are closely aligned with the Agency’s vision for this program. In addition to the issuance of the draft White Paper, EPA is actively working on these recommendations, including those related to List 1 and List 2 chemicals.

Additionally, last year EPA established the Endocrine Disruptor Science Policy Council, an internal group of EPA scientists who will be working to address EDSP science policy issues. EPA is developing a draft strategic plan that will set the future vision for and direction of the EDSP. 

More information on EDSP and NAMs is available on EPA’s website.