History and Timeline
- The term “endocrine disruptor” is popularized by the book Our Stolen Future. Co-authored by environmental activist and now former World Wildlife Fund senior scientist Theo Colborn, the book sought to implicate synthetic chemicals as the root of problems ranging from reproductive anomalies in wildlife to neuro-developmental deficits in human children. However, according to an editorial in the journal Scientific American, “The book is not scientific. … The authors present a very selective segment of the data that have been gathered about chemicals that might affect hormonal functions. They carefully avoid evidence and interpretations that are not in accord with their thinking.”
- In response to pressure from environmental groups, the U.S. Congress enacts the Food Quality Protection Act (FQPA), which requires the Environmental Protection Agency (EPA) to “develop a screening program, using appropriate validated test systems and other scientifically relevant information, to determine whether certain substances may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen or such other endocrine effect as the [agency] may designate.”
- The EPA establishes an Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) to “provide advice and counsel to the Agency on a strategy to screen and test chemicals and pesticides that may be the cause of endocrine disruption in humans, fish, and wildlife.” According to the EDSTAC Convening Report, “affected interests” that should be represented in EDSTAC included the EPA and other federal and state agencies, industry, water providers, labor/worker health and safety organizations, and environmental, environmental justice, and public-health organizations––everyone except the animal protection community.
- EDSTAC issues its final report to the EPA.
- On EDSTAC’s advice, the EPA significantly expands the scope of its Endocrine Disruptor Screening Program (EDSP) to examine not only estrogen-like effects but also effects on androgen and thyroid hormones. The EPA further expands the program to include toxicity testing on birds, fish, amphibians, and invertebrates, even though the law only calls for the determination of possible chemical effects in humans.
- The Natural Resources Defense Council (NRDC) sues the EPA for failing to implement its endocrine program within a three-year timeframe (by August 1999) as required by the FQPA.
- At its March meeting, the U.S. National Toxicology Program’s former Advisory Committee on Alternative Toxicological Methods (ACATM) makes a unanimous recommendation that all proposed test methods for the EPA’s endocrine program should be validated through the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). Although the EPA does indeed require all non-animal tests to be validated through ICCVAM with very rigorous and thorough standards, it insists on an arbitrary double standard by not requiring this same validation for the animal tests.
- The EPA disbands its Endocrine Disruptor Standardization and Validation Taskforce in response to PETA’s complaints that the panel was not appropriately balanced (it had no representation from the animal protection community) and that the task force was holding its meetings behind closed doors––both violations of the Federal Advisory Committee Act.
- The following motion is passed unanimously by the ACATM at its November meeting, reiterating its position even more strongly: “The ACATM expresses grave concern at the bifurcated approach being taken with review of methods for evaluation of endocrine disruption activity, with ICCVAM considering in vitro [non-animal] methods and with the US EPA proposing to review in vivo [animal] methods using an ICCVAM-like approach. The Committee’s primary concern is that both in vitro and in vivo methods be subjected to the same rigorous peer review and validation process to ensure the highest likelihood of acceptance by the regulatory agencies, the scientific community and the public.”
- PETA intervenes in the endocrine portion of the NRDC’s lawsuit, challenging the EPA’s expansion of the endocrine program, its almost total reliance on animal testing, and its plan for a “bifurcated” validation process.
- The EPA and the NRDC enter into a settlement agreement under which the EPA agrees, among other things, to use best efforts to complete validation of certain screening and testing methodologies that are proposed for use in the program by specific dates and to use best efforts to start requiring screening and testing of certain chemicals by specific dates or explain why it is not able to meet those deadlines.
- The EPA establishes the Endocrine Disruptor Methods Validation Subcommittee (EDMVS) under the EPA’s National Advisory Council for Environmental Policy and Technology (in accordance with the Federal Advisory Committee Act (5 U.S.C. App. 2 Section 9c)). The EDMVS provides technical advice and counsel to the EPA on scientific issues associated with test method validation, including the development and choice of initial protocols and pre-validation/validation study designs. The first and second EDMVS plenary meetings are held in October and December. PETA’s input is reflected in the Pesticide & Toxic Chemical News article “Endocrine Panel Tackles Assays and Obstacles.“
- PETA presents comments at the December 10-12 meeting of the EPA’s EDMVS.
- PETA’s input on the EDMVS March meeting is reflected in the Pesticide & Toxic Chemical News article “PETA Links ‘Body Counts’ to EPA Endocrine Program.“
- The EDMVS meets again in June at the EDMVS Fourth Plenary Meeting. The meeting covers the presentation and discussion of the Steroidogenesis Detailed Review Paper (DRP). PETA comments that the DRP provides an excellent overview of information on steroidogenesis but voiced agreement with several EDMVS members that the DRP did not make an overwhelming case for the relevance of testicular histopathology. PETA requests that the EPA pursue further efforts with cell lines, particularly H295R. PETA also asks for the EPA’s position regarding the lack of metabolism in in vitro assays.
- A special session of the Organization for Economic Cooperation and Development’s (OECD) Task Force on Endocrine Disrupters Testing and Assessment (EDTA) is held in Tokyo, Japan. Thanks to the strong animal protection representation at this meeting, the OECD’s “conceptual framework“ for the testing and assessment of chemicals for potential endocrine disrupting effects is revised to give much greater emphasis to non-animal screening and testing approaches. The EDTA also endorses the formation of a “Validation Management Group” to focus on the development and validation of non-animal screening and testing methods.
- PETA’s science advisor presents the paper “Ideology Masquerading as Science: The Case of Endocrine Disrupter Screening Programmes“ at the Fourth World Congress on Alternatives and Animal Use in the Life Sciences in New Orleans, Louisiana.
- The summer issue of AV Magazine (published by the American Anti-Vivisection Society) states that the animal protection community successfully pressured Congress to require the EPA to allocate $4 million from its current budget on the “research, development, and validation of non-animal, alternative chemical screening and prioritization methods.”
- The EDMVS holds its fifth plenary meeting in December.
- The EPA publishes its proposed approach for selecting the first group of chemicals to be screened under its endocrine program. PETA presents its position in the following public comments and thePesticide & Toxic Chemical News article ”PETA Weighs In on Endocrine Testing Proposal.”
- PETA sends a letter to the head of the EPA office charged with developing the endocrine program to urge the agency to make greater efforts to avoid duplicative testing of chemicals that may be subject to multiple EPA testing programs.
- The first meeting of the OECD’s Validation Management Group for Non-Animal Methods (VMG-NA) is held in Paris, France.
- The EDMVS meets again in June, August, and December. PETA submits public comments on the EPA’s “Detailed Review Paper for an Avian 2-Generation Reproduction Study.”
- The OECD publishes the results of the uterotrophic assay peer review that it organized. The journal Alternatives to Laboratory Animals publishes a critique of the approach taken by the OECD and its member countries to evaluate the validity of the uterotrophic assay.
PETA members in white biohazard suits, along with two hauntingly lifelike “corpses,” hold a protest outside the EPA’s headquarters in response to agency’s continued practice of killing tens of millions of animals in chemical-toxicity tests.
- Instead of renewing the charter for the EDMVS as a subcommittee, the EPA announces its intent to reconstitute the panel as a full advisory committee––the Endocrine Disruptor Methods Validation Advisory Committee (EDMVAC). The EDMVAC is established in accordance with the Federal Advisory Committee Act (5 U.S.C. App. 2 Section 9c)) and is formed to replace EDMVS. The EDMVAC is to continue to function like the EDMVS by providing advice and recommendations to the EPA on scientific and technical aspects of the Tier I screens and Tier II assays being considered for the EDSP. The committee is also to evaluate relevant scientific issues, protocols, data, and interpretations of the data for the assays during the validation process. The EDMVAC is also to provide advice on the composition of the Tier I screening battery.
- The second meeting of the OECD’s VMG-NA is held in Paris, France, in November.
- PETA petitions the EPA to limit the scope of its EDSP to the evaluation of chemical effects in humans, thereby sparing countless birds, frogs and fish from suffering and death in cruel chemical-poisoning experiments. Click here to download PETA’s rulemaking petition.
- The EPA publishes a Federal Register (FR) Notice that presents the approach that the EPA intends to use for selecting 50 to 100 chemicals for initial screening under the Federal Food, Drug and Cosmetic Act.
- The fourth meeting of the OECD’s VMG-NA is held in Tokyo, Japan, in December. Non-animal assays for estrogen-receptor transcriptional activation and steroidogenesis are in mid-validation.
- The EPA publishes an FR Notice with a draft list of the chemicals for initial screening. Later this year, the EPA publishes two more FR Notices soliciting comments on its draft policies and procedures and its draft Information Collection Request (ICR). The draft ICR describes the information collection activities associated with Tier 1 screening of the first group of chemicals under the EDSP and provides the EPA’s estimates for the related paperwork burden and costs. Click here to view PETA’s comments to the draft list of chemicals in which PETA points out the large amount of existing data for most chemicals on the list, and click here for comments on the draft policies and procedures in which PETA voices concern that there are not sufficient measures to prevent duplicative testing and that the EPA is prohibiting the use of existing data.
- The fifth meeting of the OECD’s VMG-NA is held in Ispra, Italy, in November. A promising Quantitative Structure Activity Relationship decision tree for estrogen receptor binding is presented.
- PETA submits detailed comments to the EPA about the flaws of the individual assays of the Tier 1 battery for the March Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (FIFRA SAP) meeting being held to review the Tier I battery. In spite of critical reviews from several stakeholders and the SAP itself, the EPA decides to continue with Phase I with the Tier 1 battery as is.
- PETA meets with the Office of Management and Budget (OMB) arguing, among other things, that by mandating that all Tier I assays be conducted for Phase I without consideration of existing information and without proper validation of the methods, the EPA is misusing funds of both industry and the EDSP by essentially using the Phase I process to validate the Tier 1 battery.
- PETA sends a letter to the newly appointed administrator of the EPA, Lisa Jackson, summarizing its concerns with the EDSP.
- PETA’s views on the EDSP are mentioned in an article in Chemical and Engineering News.
- The sixth meeting of the VMG-NA is held in Paris, France, in November. PETA is among a small group that initiated a proof-of-principle Performance Based Test Guideline (PBTG), which would streamline validation of non-animal methods and allow use of proprietary methods (much of the non-animal technology is patented and therefore prohibited from use by both the OECD and the EPA).
- The EPA responds to PETA’s 2007 comments on Policies and Procedures, outlining its reasoning for assuming there will be minimal duplicative testing as well as releasing guidance for the submission of Other Scientifically Relevant Information (OSRI).
- The EPA responds to PETA’s 2008 comments on the Tier 1 battery as well as PETA’s comments to the OMB but does not address the most significant issues.
- PETA and others meet with the EPA to discuss concerns about restructuring the Tier 1 battery to include more current non-animal methods as well as non-test methods and OSRI.
- PETA financially supports a workshop through the OECD to review for regulatory acceptance the Quantitative Structure Activity Relationship decision tree for estrogen receptor presented at the fifth VMG-NA meeting. The workshop is successful, and leads to acceptance of this method by the OECD as well as the U.S. EPA (the U.S. EPA holds a SAP review of the method in the fall of 2009).
- PETA meets for a second time with the OMB along with representatives from industry and argues that the cost of the program, in terms of animal lives as well as dollars, grossly exceeds any potential benefit.
- The EPA publishes a new ICR regarding information collection activities associated with Phase I of the EDSP.
- The EPA publishes two related FR Notices describing elements of the EDSP for initial screening and testing:
- Final List of Initial Pesticide Active Ingredients and Pesticide Inert Ingredients to Be Screened under the Federal Food, Drug, and Cosmetic Act. The final list includes 67 chemicals to be screened under Tier 1 of the program.
- Announcement of the Revised Policies and Procedures for the Endocrine Disruptor Screening Program that the EPA is adopting, including the statutory requirements associated with and the format of the test orders as well as the EPA’s procedures for fair and equitable sharing of test costs and data confidentiality.
- The EPA publishes two related Federal Register Notices on October 21:
- PETA’s views on the EPA’s announcements are highlighted in an article in Pesticide and Toxic Chemical News.
- PETA submits comments to the EPA and the OMB outlining the lack of utility of the EDSP Phase I.
- To avoid unnecessary costs and duplicate assays that will be of no value, the OMB sends a letter to the EPA mandating that they promote and encourage test order recipients to submit existing chemical data to the EPA in lieu of performing all or some of the Tier 1 assays and that the EPA should accept this data as sufficient to satisfy the test orders to the greatest extent possible. PETA responds to this mandate by sending a letter of agreement to the OMB.
- PETA unveils an alternative to the EDSP at the Society of Toxicology meeting.
- The OECD approves the first non-animal test for endocrine disruption: Japan’s ER transcriptional activation assay. This assay becomes one of the required Tier 1 tests. The OECD also endorses development of the PBTG as a formal project.
- The OECD Countries Activities Regarding Testing, Assessment and Management of Endocrine Disrupters Workshop is held in Copenhagen, Denmark, in September. This workshop begins the process of reviewing all endocrine-related activities at the OECD and developing guidance on how to assess endocrine activity of chemicals, focusing on, among other things, reducing the use of animals.
- The seventh VMG-NA meeting is held in Arlington, Virginia, in November. The EPA presents its validation efforts for the non-animal methods to be included in the EDSP Tier 1.
- PETA submits comments to the EPA using existing data to address the test orders for 12 of the Phase I chemicals.
- In a presentation at the 2010 Society of Toxicology meeting, PETA applies the OSRI in an integrated strategy to address data requirements for five of the Phase I chemicals.
- The first meeting of the newly reorganized OECD Advisory Group on Testing and Assessment (EDTA-AG) is held in Paris, France, in March. The EDTA-AG is responsible for completing the endocrine assessment guidance document.
- PETA is invited to present validation strategies for non-animal methods pertaining to assessment of endocrine activity at the Workshop on 21st Century Validation for 21st Century Tools presented by the Center for Alternatives to Animal Testing at the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, in July.
- At the 2010 European Society for Toxicology In Vitro and European Society for Alternatives to Animal Testing Joint Congress, PETA presents a detailed integrated strategy for risk assessment for two Phase I chemicals.
- The EPA announces that it intends to submit a request to the OMB to expand the ICR from the List 1 chemicals to include the testing of additional chemicals under the Safe Drinking Water Act (SDWA). PETA responds with comments reiterating its numerous concerns about the original ICR, most of which had not yet been addressed, and once again urging adoption of an integrated, tiered strategy for identifying endocrine disruptors.
- The EPA publishes its second list of 134 chemicals in November, which includes a large number of pesticides and an array of other chemicals, ranging from those used in industrial manufacturing processes to those used in the production of pharmaceutical and personal-care products. PETA submits extensive comments and includes existing data on 17 of the List 2 chemicals that provide a basis for exemption from EDSP testing.
- In response to draft policies and procedures issued by the EPA for the List 2 chemicals, PETA submits comments urging the EPA to require manufacturers of the same chemical to form consortia to minimize duplicative testing; to focus only on those chemicals for which mitigation measures are feasible (for example, those no longer being produced or imported into the U.S. or those that are not persistent in the environment); and to clarify the terms used to define a chemical’s inclusion on the SDWA list.
- A “Petition to Maximize Practical Utility of List 1 Chemicals Screened through EPA’s Endocrine Disruptor Screening Program” is submitted jointly to the EPA by CropLife America, the Consumer Specialty Products Association, and the Responsible Industry for a Sound Environment requesting that the Agency develop and publish guidance “explaining the criteria by which EPA will make its decisions on data received in response to the test orders issued under the Endocrine Disruptor Screening Program.” Specifically, the petition asks that 1) a scientifically valid, peer-reviewed critical process be developed and procedure guidance documents for Tier I screening be provided; 2) sufficient time be provided for the List 1 chemical test order recipients to prepare and submit their Tier 1 screening results in compliance with the guidance, once developed; and 3) the EPA fully analyze the List 1 chemical EDSP screening data and revise the program guidance based on lessons learned prior to the issuance of List 2 chemical test orders. PETA issues comments to the EPA in support of the petition.
- In September, the EPA releases a draft guidance document on the weight-of-evidence (WoE) approach it plans to use in analyzing Tier 1 assay results and the OSRI submitted by chemical companies seeking test waivers. PETA submits comments pointing out the inadequacy of the proposed WoE guidance in providing a transparent, clearly articulated method for assessing test results and existing data.
- PETA authors a paper in the peer-reviewed journal Toxicological Sciences titled “Application of an Integrated Testing Strategy to the U.S. EPA Endocrine Disruptor Screening Program.”
- PETA gives a presentation at the 8th World Congress on Alternatives and Animal Use in the Life Sciences, “A Strategy for Reducing Animal Use in the U.S. EPA’s Endocrine Disruption Screening Program.”
- PETA joins with the Chemical Producers & Distributors Association and the Halogenated Solvents Industry Alliance, Inc., to submit a petition to the EPA requesting that the Agency abide by the Paperwork Reduction Act and the OMB’s Terms of Clearance for the approved ICR of the first list of 67 chemicals to receive test orders under the EDSP by demonstrating that the information being sought has practical utility and is not duplicative before proceeding with Tier 1 test orders for additional chemicals.
- The EPA releases a summary work plan titled “Endocrine Disruptor Screening Program for the 21st Century: EDSP21 Work Plan—The Incorporation of In Silico Models and In Vitro High Throughput Assays in the Endocrine Disruptor Screening Program for Prioritization and Screening.” This document outlines the approach to adopting advanced computer models and non-animal methods for use in the EDSP that the EPA plans to implement over a multiyear period. See Non-Animal Methods for a more detailed description of EDSP21 goals.
- The EPA releases a new Comprehensive Management Plan for the EDSP in June, which outlines a number of new directions that the agency plans to take over the coming five years. These include evaluating, incorporating, and validating new Tox21 methods for use in the EDSP with the eventual goal of replacing the Tier 1 assays; developing a transparent methodology for building confidence in the reliability and applicability of new methods; forming an internal EDSP21 workgroup with senior-level scientists to ensure cross-agency and international interaction with Tox21 efforts and OECD endocrine disruptor testing activities; and general reorganization of the EDSP within the EPA to ensure better interaction and coordination among decisionmakers.
- Because of the length of time it had taken the EPA to collect information about the first list of EDSP chemicals, the initial ICR was expiring, so the agency submits a renewal request to the OMB to continue data-collection activities. The renewal document remains largely unchanged from the original, with the exception of some minor changes to paperwork-burden estimates and costs of data collection. PETA submits comments urging the EPA to fully evaluate the results of Tier 1 testing on the first list of chemicals before continuing with the program in order to reevaluate the use of Tier 1 assays in light of promising new non-animal methods and the announcement of EDSP21 and to assess the current program to determine its effectiveness in identifying endocrine disruptors.
- AV Magazine publishes a short article by PETA on ways to reduce animal testing in the EDSP.
- In November, a meeting of the FIFRA SAP is announced to consider and review scientific issues associated with a draft methodology for “Prioritization of the Endocrine Disruptor Screening Program Universe of Chemicals for an Estrogen Receptor Adverse Outcome Pathway Using Computational Toxicology Tools.” This document describes in detail the steps that the EPA had taken thus far in developing a non-animal method based on high throughput in vitro screening assays and computational toxicology tools to prioritize and screen chemicals for interaction with the estrogen hormone receptor system.
- The FIFRA SAP meets in January and considers PETA’s comments on the methodology developed for the estrogen receptor system. In general, PETA is highly supportive of this move toward the development and adoption of a non-animal method for screening chemicals for the potential to interact with the estrogen hormone system.
- PETA presents a poster at the 2013 Society of Toxicology Annual Meeting that analyzes the use of OSRI by recipients of the List 1 chemicals test orders, the EPA’s level of acceptance of this OSRI, and the resulting impact on saving animal lives.