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On October 7, 2020, the U.S. Environmental Protection Agency (EPA) announced that it is requesting comments on its draft guidance that would allow registrants, in certain circumstances, to forgo testing chemicals on animal skin to determine whether a pesticide would lead to adverse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 This new draft guidance is part of EPA’s continued efforts to reduce animal testing and achieve its goal of eliminating all EPA requests for studies and EPA funding of studies on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 The new draft guidance also allows EPA to harmonize with the Pest Management Regulatory Agency (PMRA) of Canada, which published guidance on acute dermal toxicity waivers for both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 The draft guidance is in addition to the final guidance for waiving acute dermal toxicity tests published by EPA in November 2016 for pesticide formulations.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.
By Lara A. Hall, MS, RQAP-GLP and Barbara A. Christianson
On December 17, 2019, the U.S. Environmental Protection Agency (EPA) will host its first annual conference in Washington, D.C., to discuss alternative test methods and strategies to reduce animal testing. EPA states that its conference “will bring together some of the leading voices in environmental and health research to discuss efforts to reduce testing on mammals.” The conference will focus on the New Approach Methods (NAM), which include “any technologies, methodologies, approaches or combinations thereof that can be used to provide information on chemical hazard and potential human exposure that can avoid or significantly reduce the use of testing on animals,” and will have U.S. and international scientific experts present information on advancements in the field. On-site participants attending the conference will have an opportunity to exchange information about scientific advancements in the NAMs field to develop a better understanding of the state of the science, discuss approaches for developing scientific confidence in using alternatives, and summarize existing studies characterizing the uncertainties in results from animal testing.
This conference is part of Administrator Wheeler’s “Directive to Prioritize Efforts to Reduce Animal Testing,” issued on September 10, 2019, which outlines EPA’s pursuit to aggressively reduce animal testing. In his directive, Administrator Wheeler calls for EPA to reduce its requests for, and funding of, mammalian studies by 30 percent by 2025 and eliminate all mammalian study requests and funding by 2035. Any mammalian studies requested or funded by EPA after 2035 will require Administrator approval on a case-by-case basis. The directive also supports scientific advancements that allow scientists to predict potential hazards for risk assessments without using traditional animal testing methods.
Information on how to register to participate in the conference by webinar is available here.
By Carla N. Hutton
On April 10, 2018, the U.S. Environmental Protection Agency (EPA) announced the availability of a draft Science Policy document intended to reduce the use of animals in testing chemicals to evaluate whether they cause an allergic reaction, inflammation, or sensitization of the skin. According to EPA, the document, Draft Interim Science Policy: Use of Alternative Approaches for Skin Sensitization as a Replacement for Laboratory Animal Testing, “describes the science behind the non-animal alternatives that can now be used (in vitro, in silico, in chemico) to identify skin sensitization.” The draft Science Policy states that the Office of Pesticide Programs (OPP) and Office of Pollution Prevention and Toxics (OPPT) will immediately begin to accept submissions of new approach methodologies (NAM) and defined approaches (DA) as described in the draft Science Policy. EPA notes that there are multiple domestic and international activities ongoing that will allow for refinement and expansion of this draft Science Policy to other DAs and additional NAMs and support global harmonization of DAs for skin sensitization. According to the draft Science Policy, OPP and OPPT “will continue to be active participants in these activities to ensure regulatory acceptance and will continue to support cross-sector collaborations that enhance animal welfare, and accelerate the implementation of NAMs.” Comments on the draft Science Policy document must be submitted to Docket Number EPA-HQ-OPP-2016-0093 by June 9, 2018.
The draft Science Policy is the result of national and international collaboration between the Interagency Coordinating Committee on the Validation of Alternative Methods, the National Toxicology Program’s Interagency Center for the Evaluation of Alternative Toxicological Methods, the European Union Reference Laboratory for Alternatives to Animal Testing, and Health Canada’s Pest Management Regulatory Agency.
By Lisa M. Campbell, Lara A. Hall, and Margaret R. Graham
On May 8, 2016, the U.S. Environmental Protection Agency (EPA) announced its invitation for public input regarding the “Strategic Roadmap: New Approaches to Evaluate the Safety of Chemicals and Medical Products” (Roadmap), the development of which was coordinated by the National Toxicology Program’s (NTP) Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). ICCVAM states that the vision of the Roadmap is to “establish new approaches for evaluating the safety of chemicals and medical products in the United States that will increase confidence in alternative methods and improve their relevance to human health outcomes while maximizing efficiency and maintaining a commitment to replace, reduce, and refine animal use.” ICCVAM’s Roadmap effort was introduced in March 2016. A detailed presentation on the development of the Roadmap is available here.
ICCVAM, a permanent committee of the National Institute of Environmental Health Sciences (NIEHS) under the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), is composed of representatives from 16 U.S. federal regulatory and research agencies that require, use, generate, or disseminate toxicological and safety testing information. As a participating member of ICCVAM, EPA states that its role is to “encourage the development and use of alternatives to animal test methods, ensure that new methods are valid, review test method recommendations, and as appropriate, adopt these alternatives in our own regulatory programs.”
There are also three upcoming public meetings that will provide additional opportunities to comment on topics relevant to this effort:
- ICCVAM Public Forum: May 23, 2017, National Institutes of Health (NIH), Bethesda, Maryland;
- NTP Board of Scientific Counselors meeting: June 29, 2017, NIEHS, Research Triangle Park, North Carolina; and
- Scientific Advisory Committee on Alternative Toxicological Methods meeting: September 18-19, 2017, NIH, Bethesda, Maryland.
As ICCVAM’s commitment to replace, reduce, and refine animal use continues to draw public comment and gain support, there is an increasing need to demonstrate the utility and harmonization of predictive approaches in toxicology testing with the conventional safety evaluation of chemicals and medical products. Bergeson & Campbell, P.C. (B&C®) continues to monitor the development, validation, and implementation of alternative in vitro and in silico test methods, high throughput screening assays, and computational models as they are integrated into global regulatory frameworks.
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.
By Lynn L. Bergeson
On January 30, 2015, the U.S. Environmental Protection Agency (EPA) released drafts of new guidelines for animal testing of the endocrine disrupting effects of pesticides and other chemicals. The proposed guidelines outline how scientists can use Japanese quail, medaka fish, or amphibian larvae to conduct various endocrine tests. EPA reportedly also considered including mysid crustaceans on its list of non-mammals acceptable to use in endocrine testing, but did not because the data were not deemed "fully reliable" across all endpoints. Comments are due March 31, 2015.