EPA’s Office of Pesticide Programs (OPP) and Office of Pollution Prevention and Toxics (OPPT) have jointly released for public comment an interim science policy titled Use of Alternative Approaches for Skin Sensitization as a Replacement for Laboratory Animal Testing.
The document explains the Agency’s provisional approach to accepting three types of nonanimal testing of pesticides and other commercial chemicals to develop data required by federal statutes, primarily the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Toxic Substances Control Act (TSCA).
The 2016 amendments to TSCA included a new section directing the EPA to “… reduce and replace, to the extent practicable (and) scientifically justified … the use of vertebrate animals in the testing of chemical substances or mixtures….” The law also requires the Agency to “… develop a strategic plan to promote the development and implementation of alternative test methods and strategies to reduce, refine, or replace vertebrate animal testing and provide information of equivalent or better scientific quality and relevance for assessing risks of injury to health or the environment….”
The current interim science policy is part of that strategy. While the policy is a draft, the EPA says that given the substantial scientific evidence and international activity supporting new approach methodologies (NAMs) for skin sensitization, OPP/OPPT will begin accepting these approaches immediately provided conditions described in the policy are met.
Strong International Support
Acceptance of nonanimal testing of chemicals has been growing among science organizations and regulators for more than a decade. In a 2007 report, the National Research Council endorsed computational modeling as a means to test the toxic effects of chemicals, an approach that is potentially more accurate than animal (in vivo) testing. The interim policy also acknowledges progress made by international agencies such as the Organisation for Economic Co-operation and Development (OECD), European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM), and Health Canada.
“Over the last several years, OPP has worked intensively and collaboratively with numerous domestic and international stakeholders to develop and refine NAMs for use in modernizing the 6-pack,” says the EPA. (The 6 pack refers to six uses of animals in laboratory testing of chemicals—acute oral, dermal, and inhalation lethality toxicity testing along with skin irritation, eye irritation, and skin sensitization testing.)
KEs and DAs
The policy states that several nonanimal methods with internationally recognized test guidelines (TGs) adopted by OECD member countries assess the ability of chemicals to activate what are called key events (KEs), which are basically interactions of chemicals with skin proteins that indicate reactions such as inflammation. The next step is called a defined approach (DA), which consists of a fixed data interpretation procedure (DIP) (e.g., statistical, mathematical models) applied to data (e.g., in silico predictions, in chemico, in vitro data) generated with a defined set of information sources to derive a prediction. “The reproducibility of a DA should provide a level of confidence no less than that provided by the reproducibility of the reference animal test,” states the EPA.
The policy emphasizes that all toxicity tests—animal and nonanimal—have limitations, and therefore, nonanimal testing should not be expected to provide more accurate predictions than animal testing. However, at a minimum, a nonanimal test should provide an equivalent level of information as the reference animal test method.
Three Acceptable Tests
The interim policy lists three OECD TGs that will be accepted in submissions to the Agency for single chemicals (e.g., pesticide active ingredients or pesticide inert ingredients).
“Formulations will not yet be accepted under this interim policy,” says the Agency. “However, EPA expects expansion of this interim policy in the near term to include some pesticide formulations or other mixtures evaluated by OPPT, upon completion of ongoing testing.”
The interim policy is here.