Strategic Vision for Adopting New Approach Methodologies - Reduction Strategies
One of EPA’s goals is to reduce laboratory animal studies while maintaining the scientific rigor of pesticide assessments. EPA published its Guiding Principles for Data Requirements on May 31, 2013, to ensure there are sufficient data to support scientifically sound risk characterizations that are health protective while avoiding the generation of data that do not contribute relevant information to a pesticide’s risk profile.
EPA has already taken steps in reducing unnecessary laboratory testing through promoting the use of inter-divisional scientific committees, the publication of guidance documents that allow for the waiving of existing data requirements in certain scenarios, and applying existing toxicological data for chemically similar substances (data bridging).
- Acute Toxicity Waiving and Bridging Guidance
- Acute Dermal Toxicity Tests for Pesticide Single-Active Ingredient
- Acute Dermal Toxicity Waiver Guidance for Pesticide Formulations
- Part 158 Toxicology Data Requirements & Hazard and Science Policy Council (HASPOC)
- Sub-Acute Avian Dietary Test Waiver Guidance
- M010 – Substantially similar determination
- Fish Bioconcentration Data Requirement
- Retrospective Analyses of Dermal Absorption "Triple Pack" Data
Guidance for Waiving or Bridging of Mammalian Acute Toxicity Tests for Pesticides and Pesticide Products
EPA published this guidance document in 2012 to provide a foundation for reducing redundant or unnecessary testing of laboratory animals. This consolidates previous guidance on waivers for acute toxicity tests. Criteria are included for requesting testing waivers.
Guidance for Waiving Acute Dermal Toxicity Tests for Pesticide Single-Active Ingredient and Supporting Retrospective Analysis
In 2020, EPA issued the proposed dermal toxicity guidance for a 30-day public comment period. The guidance will allow waivers for studies on single-active ingredients used to develop end use products to apply for waivers. In developing the guidance, EPA conducted a retrospective analysis and concluded that its requirements for such studies provides little to no added value in regulatory decision making.
Guidance for Waiving Acute Dermal Toxicity Tests for Pesticide Formulations and Supporting Retrospective Analysis
In 2016, EPA completed this document related to the more general guidance document above to provide more specific information on how to waive acute dermal toxicity data requirements for new pesticide formulations. The document includes a policy statement to waive all acute lethality dermal studies for formulated pesticide products.
EPA’s Part 158 Toxicology Data Requirements: Guidance for Neurotoxicity Battery, Subchronic Inhalation, Subchronic Dermal and Immunotoxicity Studies (May 1, 2013) provides guidance on using a weight-of-evidence evaluation to determine data needs in risk assessment. The goal is to only require data that adequately inform regulatory decision-making and avoid unnecessary animal testing.
The Hazard and Science Policy Council (HASPOC) is an inter-divisional forum to address science, policy, hazard data waivers, and risk deliberation and coordination issues in connection to Part 158 data requirements. HASPOC plays an important role in moving toward smarter testing strategies by waiving toxicity studies that do not provide useful information for regulatory decisions. Additionally, HASPOC exercises flexibility by considering a weight-of-evidence approach when determining data needs and safety determinations.
Guidance for Waiving Sub-Acute Avian Dietary Tests for Pesticide Registration and Supporting Retrospective Analysis
This guidance, released in 2020, provides supporting retrospective analysis and additional considerations for pesticide registration when evaluating data waivers for subacute avian dietary tests. Waiving requirements for toxicity studies when they offer little additional scientific information or public health protection is an important component of the document, which emphasizes avoiding unnecessary resource use, data generation costs, and animal testing.
EPA formalized the Chemistry and Acute Toxicology Science Advisory Council (CATSAC) in 2016 to reduce unnecessary animal testing across divisions in OPP by bridging and/or waiving acute toxicity and product chemistry studies that do not provide useful information for product registration. In 2017, the standard operating procedure was finalized and continues to guide internal processes. In 2019, the standard evaluation procedure was finalized to provide guidance on criteria used to determine substantial similarity between pesticide products and allow for bridging or citing existing data.
The M010 PRIA code is a “conditional ruling for a pre-application of product substantial similarity” that EPA established with the enactment of PRIA 4 in 2019. This code allows for a pre-decisional determination indicating whether cited acute toxicity and/or product chemistry studies would adequately address requirements for a new or amended product registration.
Fish Bioconcentration Data Requirement: Guidance for Selection of Number of Treatment Concentrations
In July 2020, EPA released this guidance, which outlines the criteria for the number of treatment concentrations needed for an acceptable Fish Bioconcentration Factor (BCF) study. The guidance is also a supplement to OCSPP Test Guideline 850.1730. The Agency expects that most studies will require only two test concentration levels instead of three, therefore, reducing the number of test animals used by approximately 240 per year.
The “triple pack” approach for dermal absorption combines data from in vivo and in vitro studies to calculate an estimated human dermal absorption factor (DAF). The triple pack typically consists of a rat in vivo study and in vitro studies using rat and human skin. OPP collaborated with NICEATM to perform retrospective analyses of the dermal triple pack data in order to evaluate whether in vivo dermal absorption studies are needed to estimate dermal absorption or if in vitro studies alone could be used to derive DAFs. In July 2021, the results of these analyses were published and demonstrated that the in vitro studies alone provide similar or more protective estimates of dermal absorption, with only limited exceptions. The analyses are available in the following manuscript: Allen et al. (2021). Retrospective Analysis of Dermal Absorption Triple Pack Data. Alternatives to Animal Experimentation.