Data Requirements for Pesticide Registration
Before manufacturers can sell pesticides in the United States, EPA must evaluate the pesticides thoroughly to ensure that they meet federal safety standards to protect human health and the environment. We grant a "registration" or license that permits a pesticide's distribution, sale, and use only after the company meets the scientific and regulatory requirements. These data requirements apply to anyone or any company that registers pesticides under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) or seeks a tolerance or tolerance exemption for a pesticide under the Federal Food, Drug, and Cosmetic Act (FFDCA).
In evaluating a pesticide registration application, we assess a wide variety of potential human health and environmental effects associated with use of the product. Potential registrants must generate scientific data necessary to address concerns pertaining to the identity, composition, potential adverse effects, and environmental fate of each pesticide. The data allow us to evaluate whether a pesticide could harm certain nontarget organisms and endangered species, including:
- surface water or ground water
EPA recommends the pesticide registrant provide data from tests conducted according to EPA test guidelines.
FIFRA provides EPA with broad authority to establish or modify data needs and timing for individual pesticide registration actions to achieve statutory and program objectives. Data requirements for pesticide registration actions are found in the Code of Federal Regulations at 40 CFR Part 158. These regulations provide us with substantial discretion to make registration decisions on the basis of what we determine to be the most relevant and important data for each action.
The studies required under Part 158 provide the scientific basis for characterizing the potential risks associated with pesticide exposure. There is considerable flexibility available to us in implementing Part 158. For example:
- Additional data can be required (Section 158.75),
- Alternative approaches can be accepted, and
- Studies can be waived (Section 158.45).
EPA provided pesticide program staff with "Guiding Principles for Data Requirements" to assist them in focusing on the information most relevant to the assessment. EPA's goal is to ensure there is sufficient information to reliably support registration decisions that are protective of human health and the environment, while avoiding the generation and evaluation of data that do not materially influence the scientific certainty of a regulatory decision. It is important to only require data that adequately inform regulatory decision making and thereby avoid unnecessary use of time and resources, data generation costs, and animal testing. As a companion to this guidance, EPA provided OPP staff with "Guidance on Data Compensation Considerations in Connection with Decisions to Waive Typical Data Requirements."
This guidance is consistent with the pesticide program's strategic direction of using integrated approaches to testing and assessment, which promotes a hypothesis-based, systematic, integrative use of exposure and hazard information for assessing pesticide risk. Our strategic direction is consistent with the 2007 and 2008 National Research Council reports, Toxicity Testing in the 21st Century: a Vision and a Strategy and Science and Decisions: Advancing Risk Assessment .
The following sections describe the reasons for each type of test and the kind of information EPA obtains from the results of each test.
Requirements related to product chemistry apply to the manufacturing use product or the end-use product and can include characteristics ranging from odor to flammability. They also include providing information about impurities, submitting an analytical method for enforcement and more.
An alternative test is available for certain aspects of the product chemistry requirements:
Requirements to develop data on product performance provide a mechanism to ensure that pesticide products will control the pests listed on the label and that unnecessary pesticide exposure to the environment will not occur as a result of the use of ineffective products. Specific performance standards are used to validate the efficacy data in the public health areas, including:
- disinfectants used to control microorganisms infectious to humans in any area of the inanimate environment and
- those pesticides used to control vertebrates (such as rodents, birds, bats, and skunks) and invertebrates (ticks, mosquitoes, etc.) that may directly or indirectly transmit diseases to humans.
Data required to assess hazards to humans and domestic animals are derived from a variety of acute, subchronic, and chronic toxicity tests, and tests to assess mutagenicity and pesticide metabolism. EPA is receptive to approaches that effectively incorporate other toxic effects (endpoints) into the battery of routine toxicological studies if they would reduce use of animals while continuing to provide the necessary information within the context of existing toxic effects.
Determination of acute oral, dermal, and inhalation toxicity is usually the initial step in the assessment and evaluation of the toxic characteristics of a pesticide. These data provide information on health hazards likely to arise soon after, and as a result of, short-term exposure. Data from acute studies serve as a basis for classification and precautionary labeling. For example, acute toxicity data are used to calculate farm worker reentry intervals and to develop precautionary label statements pertaining to protective clothing requirements for applicators.
- provide information used in establishing the appropriate dose levels in subchronic and other studies;
- provide initial information on the mode of toxic action(s) of a substance;
- determine the need for child-resistant packaging; and
- determine the need to restrict use of the pesticide to trained applicators or in other ways to minimize human and environmental hazards.
Information derived from primary eye and primary dermal irritation studies serves to identify possible hazards from exposure of the eyes, associated mucous membranes, and skin.
See documents related to bridging or waiving data requirements: Guidance for Waiving or Bridging of Mammalian Acute Toxicity Tests for Pesticides and Pesticide Products for criteria that registrants can cite to bridge data or support a waiver of the requirement for mammalian acute toxicity testing for pesticide technical active ingredients and pesticide end use formulations. The studies, sometimes referred to as "the six-pack," to which this applies are:
- Acute oral toxicity
- Acute dermal toxicity
- Acute inhalation toxicity
- Primary eye irritation
- Primary dermal irritation
- Dermal sensitization
Guidance for Waiving Acute Dermal Toxicity Tests for Pesticide Formulations and Supporting Retrospective Analysis, published in 2016, expands the potential for data waivers for acute dermal studies for formulated products. The document includes a policy statement to waive all acute lethality dermal studies for formulated pesticide products (see section 3.0).
EPA is seeking comment on the draft interim science policy, Use of Alternative Approaches for Skin Sensitization as a Replacement for Laboratory Animal Testing. This draft policy document describes the science behind the non-animal alternatives that can now be used (in vitro, in silico, in chemico) to identify skin sensitization. EPA currently requires these data to support pesticide registrations. Given the substantial scientific evidence and international activities supporting the new methodologies for skin sensitization testing, EPA will begin accepting these approaches immediately under the conditions described in the draft policy document. Comments can be submitted via www.regulations.gov to docket # EPA-HQ-OPP-2016-0093 until June 9, 2018.
EPA is requesting submission of acute oral and acute inhalation toxicity study data paired with GHS calculations to support the evaluation of pesticide product formulations. The GHS dose additive mixtures equation, used to classify the toxicity of mixtures based on the available data on the individual ingredients in them, could be an alternative to animal testing of pesticide formulations. OPP will use submissions under this pilot to evaluate the utility and acceptability of the GHS dose additive mixtures equation as an alternative to oral and inhalation toxicity studies for pesticide formulations. For information on how to submit data for the pilot and an example submission template, visit our Mixtures Equation Pilot Program page.
In addition, for antimicrobial cleaning products, EPA has provided guidance for testing antimicrobial cleaning products for their potential to cause eye irritation. .
Subchronic tests provide information on health hazards that may arise from repeated exposures over a limited period of time. They provide information on target organs and accumulation potential. The resulting data are also useful in selecting dose levels for chronic studies and for establishing safety criteria for human exposure. These tests are not capable of detecting those effects that have a long latency period for expression (e.g., carcinogenicity).
Chronic toxicity studies (usually conducted by feeding the test substance to the test species) are intended to determine the effects of a substance in a mammalian species following prolonged and repeated exposure. Under the conditions of this test, effects that have a long latency period or are cumulative should be detected. The purpose of long-term carcinogenicity studies is to observe test animals over most of their life span for the development of neoplastic lesions during or after exposure to various doses of a test substance by an appropriate route of administration.
The pesticide program is receptive to waiver requests. Such requests should be made on a case-by-case basis and include a scientifically sound, chemical-specific rationale.
EPA developed guidance for assessors on determining data needs for neurotoxicity, subchronic inhalation, dermal and immunotoxicity studies using the weight-of-the-evidence methods. This guidance will assist registrants in developing data waiver requests. The guidance on immunotoxicity study needs was based in part on Retrospective Analysis of the Immunotoxicity Study (OCSPP Test Guideline No. 870.7800).
The information required to assess hazards to nontarget organisms is derived from tests to determine pesticidal effects on birds, mammals, fish, terrestrial and aquatic invertebrates, and plants. These tests include short-term acute, subacute, reproduction, simulated field, and full field studies arranged in a hierarchical or tier system that progresses from the basic laboratory tests to the applied field tests.
The results of each tier of tests must be evaluated to determine the potential of the pesticide to cause harmful effects and to determine whether further testing is required. A purpose common to all data requirements is to help determine the need for (and appropriate wording for) precautionary label statements to minimize the potential harm to nontarget organisms.
Acute and Subacute Studies
The short-term acute and subacute laboratory studies provide basic toxicity information that serves as a starting point for the hazard assessment. These data are used to:
- establish acute toxicity levels of the active ingredient to the test organisms;
- compare toxicity information with measured or estimated pesticide residues in the environment in order to assess potential effects on fish, wildlife, plants, and other nontarget organisms; and
- indicate whether further laboratory and/or field studies are needed.
Chronic and Field Studies
Additional studies (i.e., avian, fish, and invertebrate reproduction; life cycle studies; and plant field studies) may be required when basic data and environmental conditions suggest possible problems. Data from these studies are used to:
- estimate the potential for chronic effects, taking into account the measured or estimated residues in the environment; and
- determine if additional field or laboratory data are necessary to further evaluate hazards.
Simulated field and/or field data are used to examine acute and chronic adverse effects on captive or monitored fish and wildlife populations under natural or near-natural environments. Such studies are required only when predictions as to possible adverse effects in less extensive studies cannot be made, or when the potential for harmful effects is high.
EPA requires applicator/user exposure data for all pesticides to evaluate the potential risks to people applying the pesticide, i.e., those who may be exposed to higher concentrations of the pesticide through handling, including mixing or applying.
Data required to evaluate pesticide spray drift are derived from studies on the range of droplet sizes and spray drift field evaluations. These data contribute to development of the overall exposure estimate. Along with data on toxicity for humans, fish, and wildlife, or plants, data on spray drift are used to assess the potential exposure of these organisms to pesticides. A purpose common to all these tests is to provide data to help determine the need (and appropriate wording) for precautionary labeling to minimize the potential harm to nontarget organisms.
We use the data generated by environmental fate studies to:
- assess the presence of widely distributed and persistent pesticides in the environment that may result in loss of usable land, surface water, ground water, and wildlife resources;
- assess the potential environmental exposure of other nontarget organisms, such as fish, wildlife, and plants, to pesticides; and
- help estimate expected environmental concentrations of pesticides in specific habitats where threatened or endangered species or other wildlife populations at risk are found.
We use residue chemistry data to estimate the exposure of the general population to pesticide residues in food and for setting and enforcing tolerances for pesticide residues in food or feed. The Agency can estimate the amount and nature of residues likely to be present in food or animal feed because of a proposed pesticide usage by evaluating information on:
- the chemical identity and composition of the pesticide product;
- the amounts, frequency, and time of pesticide application; and
- test results on the amount of residues remaining on or in the treated food or feed.
EPA’s regulation "Data Requirements for Registration," which was issued in 1984 as 40 CFR Part 158, specifies the types of data and information generally required to make sound regulatory judgments under FIFRA for each pesticide proposed for experimental use, registration, amended registration, or reregistration with respect to a pesticide product’s potential for causing unreasonable adverse effects. On May 08, 2013, EPA promulgated final rules (EPA-HQ-OPP-2008-0110-0111) to update the data requirements for antimicrobial pesticides. These final rules include the new Part 158W.
EPA has provided additional guidance on the data requirements under Part 158W, including a letter to pesticide registrants describing how we have been implementing 158W.