By Lara A. Hall, MS, RQAP-GLP and Heather F. Collins, M.S.

On March 17, 2021, the U.S. Environmental Protection Agency (EPA) announced the issuance of the final guidance document entitled "Guidance for Waiving Acute Dermal Toxicity Tests for Pesticide Technical Chemicals & Supporting Retrospective Analysis" (EPA 705-G-2020-3722; Docket ID: EPA-HQ-OPP-2016-0093) that expands the potential for data waivers for acute dermal studies to single technical active ingredients (AI) used to formulate end-use products. This new guidance builds upon the final guidance for waiving acute dermal toxicity tests for pesticide formulations published by EPA on November 9, 2016, and is an example of EPA’s continued efforts to reduce animal testing and achieve its goal of eliminating all EPA requests for studies and EPA funding of studies on mammals by 2035.  EPA states that this guidance is expected to reduce the number of test animals used annually by approximately 750, as well as save EPA, industry, and laboratory resources.

The new final guidance document also allows EPA to harmonize with the Pest Management Regulatory Agency (PMRA) of Canada, which published guidance on acute dermal toxicity waivers for both end-use product formulations and technical chemicals in 2017. 

In developing the new guidance, EPA states that the Office of Pesticide Programs (OPP) and the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) conducted a retrospective analysis of rat acute oral and acute dermal LD50 studies for 249 AIs across numerous chemical classes and toxicity categories in the EPA pesticide categorization scheme.  The overall purpose of this analysis was to address the utility of the acute dermal toxicity study for single AIs in pesticide labeling, such as the signal word and precautionary statements. Fumigants and rodenticides were excluded from this retrospective analysis based on their physical state and/or anticipated exposures to them. EPA concluded that:

• For 67 percent of the 249 technical chemicals, the results of both oral and dermal acute toxicity studies fall within the same Toxicity Category; 
• For 32 percent of the chemicals, the oral study falls within a lower (i.e., more protective) Toxicity Category;
• Thus, for 99 percent of the chemicals in the analysis, if the dermal study had not been available and labeling had been based only on the Toxicity Category for the oral acute toxicity study, the labeling requirements would have been equally or more protective; 
• For the two remaining chemicals (less than 1 percent), factors other than the dermal acute toxicity may influence labeling requirements; and
• The acute dermal toxicity studies provide little to no added value in regulatory decision making. 

EPA states that it believes the retrospective analysis fully supports the conclusion that waivers may be granted for acute dermal toxicity studies for pesticide technical chemicals, except for fumigants and rodenticides.  Waivers may be accepted for fumigants and rodenticides on a case-by-case basis with appropriate scientific rationale. EPA maintains the ability to request acute dermal toxicity data on a case-by-case basis, but states that it anticipates granting the waiver in most cases.

Additional information on EPA’s efforts to reduce animal testing is available here.

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By Lisa M. Campbell, Lara A. Hall, MS, RQAP-GLP, and Heather F. Collins, M.S.

On October 7, 2020, the U.S. Environmental Protection Agency (EPA) announced that it is requesting comments on its draft guidance that would allow registrants, in certain circumstances, to forgo testing chemicals on animal skin to determine whether a pesticide would lead to adverse effects.  This new draft guidance is part of EPA’s continued efforts to reduce animal testing and achieve its goal of eliminating all EPA requests for studies and EPA funding of studies on mammals by 2035.

According to EPA, the draft dermal toxicity guidance would allow applicants to request waivers for acute dermal toxicity studies on single-active ingredients used to develop end-use products.  The new draft guidance also allows EPA to harmonize with the Pest Management Regulatory Agency (PMRA) of Canada, which published guidance on acute dermal toxicity waivers for both formulations and technical chemicals in 2017.  The draft guidance is in addition to the final guidance for waiving acute dermal toxicity tests published by EPA in November 2016 for pesticide formulations.

In developing the guidance, EPA states that it conducted a retrospective analysis of rat acute oral and acute dermal LD50 studies for 249 active ingredients across numerous chemical classes and toxicity categories.  Fumigants and rodenticides were excluded from this analysis, based on their physical state and/or anticipated exposures to them.  EPA concluded that for 67 percent of the 249 technical chemicals, the results of both oral and dermal acute toxicity studies fall within the same Toxicity Category.  For 32 percent of the chemicals, the oral study falls within a lower (i.e., more protective) Toxicity Category; thus, for 99 percent of the chemicals in the analysis, if the dermal study had not been available and labeling had been based only on the Toxicity Category for the oral acute toxicity study, the labeling requirements would have been equally or more protective.  For the two remaining chemicals (less than 1 percent), factors other than the dermal acute toxicity may influence labeling requirements.  EPA concluded that its requirements for such acute dermal toxicity studies provide little to no added value in regulatory decision making.  EPA states that this guidance, when finalized, is expected to reduce the number of test animals used annually by approximately 750, as well as save EPA, industry, and laboratory resources.

EPA states that it believes the retrospective analysis fully supports the conclusion that waivers may be granted for acute dermal toxicity studies for pesticide technical chemicals, except for fumigants and rodenticides.  Waivers may be accepted for fumigants and rodenticides on a case-by-case basis with appropriate scientific rationale.  Once the guidance is issued in final form, EPA states that applicants who wish to pursue waivers for these studies would submit formal waiver requests as part of the registration application through existing processes and cite the guidance as support for the requests.  EPA maintains the ability to request acute dermal toxicity data on a case-by-case basis, but states that it anticipates granting the waiver in most cases.

Comments on the draft guidance are due on or before November 9, 2020, and can be submitted at http://www.regulations.gov under Docket ID No. EPA-HQ-OPP-2016-0093.

EPA also announced the launch of its new webpage that provides metrics and strategies for reducing and replacing animal testing, including links and resources to all pertinent guidance and work plans tied to the larger Toxicology in the 21st Century Initiative across the federal government.  The directive, issued by EPA Administrator Andrew Wheeler in September 2019, calls for EPA to reduce animal testing and to reduce funding 30 percent by 2025 and eliminate it by 2035.  EPA states that its actions to date to support these efforts include:

• In September 2019, EPA announced $4.25 million in funding for five universities to research and develop alternative test methods for evaluating chemical safety.
• In December 2019, EPA convened a conference for achieving reduced animal testing in chemical safety research and updated its list of New Approach Methodologies (NAM) that could be used in EPA’s work under the amended Toxic Substances Control Act, including adding 21 new test guidelines related to health and ecological effects and six additional EPA policies that reduce the use of animal testing.
• In June 2020, EPA released a NAMs work plan that details how EPA plans to develop, test, and apply chemical safety testing approaches without the use of animals.
• In February 2020, EPA issued final guidance waiving the subacute dietary testing of pesticides on birds when the additional information is unnecessary to support a pesticide registration decision, which is expected to save 720 test animals annually.
• In July 2020, EPA announced new guidance to reduce unnecessary testing on fish, which is expected to save 240 test animals annually.

EPA will host its Second Annual Conference on the State of the Science on Development and Use of NAMs for Chemical Safety Testing virtually on October 19 and 20, 2020.  Additional information on EPA’s efforts to reduce animal testing is available here.

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By Lisa M. Campbell, Lisa R. Burchi and Barbara A. Christianson

On February 28, 2020, the U.S. Environmental Protection Agency (EPA) announced the availability of a new web portal that is available to the public to search for EPA guidance documents.  The EPA Guidance Portal (Portal) was created under Executive Order 13891, “Promoting the Rule of Law Through Improved Agency Guidance Documents,” where agencies are to develop a central web portal for the public to review active guidance documents and the ability to request for modification or withdrawal of the guidance documents. 

Information available about each guidance document listed on the Portal includes:

• A concise name for the guidance document;
• The date on which the guidance document was issued;
• The date on which the guidance document was posted to the web portal
• An agency unique identifier;
• A hyperlink to the guidance document;
• The general topic addressed by the guidance document; and
• A summary of the guidance documents’ content.

EPA states that the “guidance documents lack the force and effect of law, unless expressly authorized by statute or incorporated into a contract” and EPA “may not cite, use, or rely on any guidance that is not posted on this web area, except to establish historical facts.”

The portal is broken down by office, including regional offices:

• Office of Air and Radiation (OAR)
• Office of Chemical Safety and Pollution Prevention (OCSPP)
• Office of Enforcement and Compliance Assurance (OECA)
• Office of General Counsel (OGC)
• Office of International and Tribal Affairs (OITA)
• Office of Land and Emergency Management (OLEM)
• Office of Mission Support (OMS)
• Office of Research and Development (ORD)
• Office of Water (OW)
• All EPA Regional offices

Currently, there are a total of 1,735 guidance documents listed under OCSPP.  Within the 1,735 documents, 117 appear to be specific to FIFRA. Examples of guidance documents included in the portal are:

• Inert Ingredients Overview and Guidance;
• Exporting Unregistered Pesticides: Foreign Purchaser Acknowledgement Statements;
• EPA's Regulation of Biotechnology for Use in Pest Management;
• CPARD USER GUIDE: For State Lead Agency (SLA) and Tribal Representatives with Certification Plans (CPs);
• Frequent Questions for the 2018 Series 810 – Product Performance Test Guidelines: Antimicrobial Efficacy Test Guidelines;
• Pesticide Registration Manual;
• Guidance on FIFRA 24(c) Registrations;
• Design for the Environment Logo for Antimicrobial Pesticide Products;
• Draft Guidance for Plant Regulator Label Claims, Including Plant Biostimulants;
• Structured Product Labeling (SPL) Draft Implementation Guide with Validation Procedures and User Guide;
• Reregistration and Other Review Programs Predating Pesticide Registration Review;
• FIFRA Pesticides Export Policy: Questions & Answers Issue: Research and Development Pesticides; Active Ingredient Concentrations;
• State FIFRA Issues, Research, and Evaluation Group Final Guidance for State Lead Agencies for the Development and Implementation of Managed Pollinator Protection Plans; and
• E-FAST, Down the Drain Assessment Model.

Under OECA, there are six documents specific to FIFRA.  The guidance documents included in this portal are:

• Compliance Advisory: High Number of Complaints Related to Alleged Misuse of Dicamba Raises Concerns;
• Good Laboratory Practices - Questions and Answers;
• EPA and Association of American Pesticide Control Officials (AAPCO) Advisory Notice on Pesticide-related E-Commerce;
• Fact Sheet on Pesticides Sales in E-Commerce;
• Documents with Questions and Answers on FIFRA Pesticides Export Policy; and
• FIFRA Pesticide Export Policy: Interpretive Guidance: Multilingual Labeling.

Of note, the portal sets forth an option for petitioning EPA to modify or withdraw a guidance document from the Portal by completing an online form.  The required information to submit using the online form is name, email address, unique identifier of the guidance document, the office and/or region, and comments related to the withdrawal or modification of the guidance document.

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By Margaret R. Graham

On November 29, 2016, the U.S. Environmental Protection Agency (EPA) announced the issuance of its new guidance for testing pesticides designed to reduce animal testing for acute dermal toxicity for pesticides, Guidance for Waiving Acute Dermal Toxicity Tests for Pesticide Formulations & Supporting Retrospective Analysis, in final.  This guidance was issued as part of the Office of Pesticide Programs’ (OPP) Strategic Vision for implementing the 2007 National Research Council’s report on Toxicity Testing in the 21st Century.

OPP states that it “receives about 200-300 dermal formulation toxicity tests annually, each of which generally use 10 animals per test,” and “[w]e expect this waiver guidance to save 2,500 or more laboratory animals every year.”  Further, as described in OPP Director Jack Housenger’s March 17, 2016, letter to stakeholders, “[t]his new policy represents significant progress toward EPA’s goal of significantly reducing the use of animals in acute effects testing.”

More information on OPP’s Strategic Direction for Adopting 21st Century Science Methodologies is available on EPA’s website and in our blog item EPA’s OPP Releases Guidance Documents Related to Strategic Vision for Adopting 21st Century Science Methodologies.

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