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Adopting 21st-Century Science Methodologies - Replacement Strategies

One of EPA’s goals is to replace complex laboratory animal studies with new approach methodologies (NAMs) while maintaining the scientific defensibility of pesticide assessments. NAMs include alternative test methods and strategies, and refer to any non-animal technology, methodology, approach or combination thereof that can be used to provide information on chemical hazard and risk assessment.

EPA has already taken steps to replace in vivo animal studies through engagement with the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) to draft documents and strategies moving towards eye irritation and skin sensitization testing based on in silico Helpin silico A general term used to mean "performed on computer or via computer simulation.", in chemico and in vitro Helpin vitro Experiments or tests done under controlled experimental conditions outside of the body, such as in a test tube or laboratory dish. These tests tend to focus on organs, tissues, cells, cellular components, proteins, and/or biomolecules. approaches.

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Skin Sensitization Policy

EPA continues to work with the National Toxicology Program’s Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) (headquartered at the National Institute of Environmental Health Sciences),  other Federal agencies, the European Union Joint Research Centre, and Health Canada to develop a defined approach for skin sensitization as presented and discussed in international settings such as the Organisation for Economic Co-operation and Development (OECD).

EPA released a new draft interim science policy, Use of Alternative Approaches for Skin Sensitization as a Replacement for Laboratory Animal Testing, in April 2018. This draft policy document describes the science behind the non-animal alternatives that can be used (in vitro, in silico, in chemico) to identify skin sensitization.

Given the substantial scientific evidence and international activities supporting the NAMs for skin sensitization testing, EPA began accepting these approaches under the conditions described in the draft policy document immediately upon its release.

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Mixtures Equations Pilot

EPA established the mixtures equations pilot program to evaluate the utility and acceptability of a mathematical tool (GHS Mixtures Equation) as an alternative to animal oral and inhalation toxicity studies for pesticide formulations. The Mixtures Equation is used in the Globally Harmonized System of Classification and Labeling of Chemicals (GHS).

Under this pilot, registrants had the option of submitting calculations (GHS Mixtures Equation data), paired with the required acute oral and inhalation acute toxicity data, to support the evaluation of pesticide toxicity. In FY 2019, OPP closed the submission period for new data and began working with NICEATM to perform the analysis.

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Alternative Testing Framework for Classification of Eye Irritation Potential of EPA-Regulated Pesticide Products

In May 2015, EPA released updated guidance for testing antimicrobial cleaning products for their potential to cause eye irritation. The updated guidance describes a testing framework for assessing eye irritation potential using three in vitro/ex vivo assays: Bovine Corneal Opacity and Permeability assay, EpiOcular assay, and the Cytosensor Microphysiometer assay. The same testing approach is considered on a case-by-case basis for other classes of pesticides and pesticide products.

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New Approach Methodology (NAM) for Inhalation Risk Assessments

In December 2018, EPA presented the document Evaluation of a Proposed Approach to Refine the Inhalation Risk Assessment for Point of Contact Toxicity: A Case Study Using a New Approach Methodology (NAM) to the FIFRA Scientific Advisory Panel (SAP). The SAP’s report was released in April 2019.

Throughout FY 2019, OPP has continued to work with Syngenta Crop Protection on science activities to address the SAP’s recommendations, such as evaluation of in vitro repeat dosing, determination of appropriate particle size distributions for dosimetry modeling, and updates to human equivalent concentration calculations. 

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Collaborative Acute Toxicity Modelling Suite (CATMos)

EPA continues to collaborate with NICEATM and the Humane Society on the use of the CATMos computational model for acute mammal toxicity endpoints in mammalian wildlife ecological risk assessment for pesticides. This effort involves a retrospective analysis of the effect on wild mammal risk assessment conclusions when replacing the routinely required acute oral rat toxicity study-derived effects endpoint with one generated by CATMos. 

EPA will determine if direct replacement provides a consistent and protective acute wild mammal risk assessment conclusion, the most quantitative use of the acute mammal toxicity data in OPP.

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CompTox Chemicals Dashboard

EPA’s Office of Research and Development (ORD)’s CompTox Chemicals Dashboard is a tool that provides risk assessors access to in vivo toxicity and in vitro bioassay data for thousands of substances searchable by chemical structures.