The US Environmental Protection Agency (EPA) is an independent regulatory agency established in 1970 with the mission “to protect human health and the environment.” To this end, EPA develops and enforces regulations that implement environmental statutes enacted by Congress to prevent toxic pollution and to protect human health and the environment from hazarous chemicals.
EPA is organized into a number of central program offices as well as regional offices and laboratories, each with its own regulatory, research, and/or enforcement mandate. In the context of regulatory toxicology, most of EPA’s animal use and/or testing requirements can be linked to the agency’s two largest divisions: the Office of Prevention, Pesticides and Toxic Substances (OPPTS), which regulates industrial chemicals and pesticides, and the Office of Research and Development (ORD), which manages the agency’s intramural and extramural research programs.
More than 80,000 chemicals are currently in commercial use in the US, while an additional 700 or more new chemicals are introduced into commerce each year. Responsibility for the safety evaluation and regulation of these substances lies with EPA’s Office of Pollution Prevention and Toxics, a subdivision of OPPTS, under the authority of the Toxic Substances Control Act (TSCA) and the Pollution Prevention Act.
Before a new chemical is marketed in the US, the TSCA requires that a premanufacture notice be filed with EPA, providing information on the chemical’s identity, intended uses and production volume, and anticipated exposure and emission levels, as well as any toxicity data in the company’s possession. EPA uses the information in premanufacture notices, together with structure-activity relationship modeling, to determine whether there is a need to impose restrictions on the release and/or marketing of a chemical in order to ensure there is “no unreasonable risk of injury to health or the environment.”
With respect to existing chemicals, the TSCA provides EPA with the authority to require companies to submit “all existing data concerning the environmental and health effects of [a chemical] or mixture.” EPA is further empowered to compel companies to generate test data when the agency finds that a chemical (1) may present an unreasonable risk of injury to health or the environment or (2) is or will be produced in substantial quantities and (a) there is or may be significant or substantial human exposure to the chemical or (b) it enters or may reasonably be anticipated to enter the environment in substantial quantities. Recognized testing methods include the TSCA Health Effects Test Guidelines, OPPTS Test Guidelines, and the internationally harmonized Organisation for Economic Co-operation and Development (OECD) Test Guidelines.
EPA also provides administrative support for the TSCA Interagency Testing Committee and has initiated a number of voluntary chemical evaluation and data gathering programs, which are discussed elsewhere on AltTox.
The agency solicits advice from chemical stakeholders through its National Pollution Prevention and Toxics Advisory Committee (NPPTAC).
All products that are designed to manage, destroy, attract, or repel “pests” and that are used, sold, or imported into the US are regulated by the EPA’s Office of Pesticide Programs, a subdivision of OPPTS. These products include synthetic and bio-chemicals, genetically engineered toxins, and even other organisms and are collectively referred to as “pesticides.” EPA’s statutory authority for regulating pesticides is primarily derived from the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA); however, provisions in the Federal Food, Drug and Cosmetic Act and the Endangered Species Act also strongly impact EPA’s activities in the pesticides sector.
EPA registration data requirements for pesticide chemicals are codified under Title 40, Part 158 of the Code of Federal Regulations (40 CFR § 158). In the case of “conventional” chemicals, which operate via a known toxic mode of action, EPA requirements call for dozens of animal tests to evaluate the potential human health and ecotoxicological effects of each “active ingredient” in a pesticide formulation, including:
EPA generally accepts reduced data sets for naturally occurring biochemical and microbial pesticides (e.g., pheromones) and for germ-killing antibacterial cleaning products.
In addition to mandatory testing of each active ingredient in a pesticide formulation, each finished product is also required to undergo separate acute toxicity testing via the oral, dermal, and inhalation routes, skin and eye irritation, and skin sensitization (known as the acute toxicity “six-pack”) for labeling purposes. Recognized testing methods include OPPTS Test Guidelines, as well as the internationally harmonized OECD Test Guidelines. However, FIFRA grants the agency broad discretion to request testing data for any effect(s) of interest under the pesticide program, including by means of “special,” non-guideline studies.
It is estimated that upwards of 12,000 animals may be consumed in the toxicological evaluation of each (conventional) chemical pesticide on the US market. Such high costs prompted the creation of a multi-stakeholder technical committee under the auspices of the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) with a mandate to develop integrated testing strategies for pesticide safety assessments that minimize redundancies, use fewer animals, and use resources more wisely. EPA adopted one of the recommendations of the HESI technical committee––that one-year general toxicity studies in dogs be abolished––in an October 2007 final rule amending Part 158 data requirements for conventional pesticides. At the same time, EPA issued a second rule amending its data requirements for biochemical and microbial pesticides. Both rules introduced a number of new and/or newly codified animal testing requirements.
The Food Quality Protection Act of 1996 required EPA to develop and implement “a screening program, using appropriate validated test systems and other scientifically relevant information, to determine whether certain substances may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or such other endocrine effect as [EPA] may designate.” Responsibility for developing a “toolbox” of validated screens and tests for this “Endocrine Disruptor Screening Program” (EDSP) has been delegated to EPA’s Office of Science Coordination and Policy, whereas EDSP implementation will occur primarily within the purview of the Office of Pesticide Programs.
Animal testing requirements imposed by other EPA program offices are generally more limited than those of OPPTS. However, a certain amount of acute and chronic testing of aquatic organisms is prescribed, for example, under water quality standards and whole effluent toxicity methods promulgated by EPA’s Office of Water.
Research & Development
The mission of EPA’s Office of Research and Development (ORD) is to conduct and fund research “to identify, understand, and solve current and future environmental problems” and to support the regulatory work of EPA program offices. ORD is organized into a number of distinct centers and laboratories; those with an impact on animal use include:
Alternatives Policies & Actions
EPA does not appear to have a specific policy on animal welfare or the 3Rs. However, in written communications with stakeholders, senior officials have expressed the agency’s “… commitment to reducing the number of subjects used in animal testing by not only replacing test methods involving the use of animals but also refining existing test methods to optimize animal use when there is no substitute for animal testing. As part of this commitment, EPA is actively involved in numerous efforts to develop and adopt alternative test methods. EPA is an active participant in working domestically within the framework of the Interagency Coordinating Committee for the Validation of Alternative Methods (ICCVAM) and internationally with the Organization for Economic Cooperation and Development (OECD) to evaluate the scientific adequacy of alternative test methods that are becoming available. We work directly with groups at ICCVAM that are concerned with the development and validation of alternative methods to reduce animal testing. In addition, EPA’s Office of Research and Development is conducting research within its National Center for Computational Toxicology to develop screening technologies that limit or do not require animal testing.”
In February 2008, EPA took an additional step forward by signing a memorandum of understanding with the National Toxicology Program and National Institutes of Health Chemical Genomics Center outlining a strategy for interagency cooperation in “the research, development, validation, and translation of new and innovative test methods that characterize key steps in toxicity pathways.” This represents the first substantive effort by the US federal government to implement the vision of 21st century toxicology articulated in 2007 by the National Research Council.