Data Requirements for Pesticide Registration
Current as of August 2013
- On May 8, 2013, EPA published in the Federal Register the final rule for antimicrobial pesticides, CFR Part158W
- Guidance for Identifying, Selecting and Evaluating Open Literature Studies
- Storage Stability and Corrosion Characteristics Protocol (PDF) (10 pp, 9.6M)
- New Web Page on Genetic Toxicology and Use of New Tests in Standard Repeat Dose Studies
- Data Requirements Checklists
- Study Profile Templates
- Test Guidelines for Data Requirements
- Strategic Direction for New Pesticide Testing and Assessment Approaches
- Test Guidelines/Acute Toxicity - Acute Oral Toxicity Up-And-Down-Procedure
- Use of an Alternate Testing Framework for Classification of Eye Irritation Potential of EPA Pesticide Products
- Update on the Use of the Local Lymph Node Assay for End Use Pesticide Products and Adoption of the Reduced Dose Protocol for LLNA (rLLNA)
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. EPA grants 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, EPA assesses 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 EPA to evaluate whether a pesticide has the potential to cause harmful effects on certain nontarget organisms and endangered species that include:
- 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 (CFR) at 40 CFR Part 158. These regulations provide the Agency with substantial discretion to make registration decisions on the basis of what the Agency determines to be the most relevant and important data for that particular 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 the agency in implementing Part 158. For example,
- Additional data can be required (§158.75),
- Alternative approaches can be accepted, and
- Studies can be waived (§158.45).
EPA provided OPP staff with "Guiding Principles for Data Requirements (PDF)" (6 pp, 159k) 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 public health and the environment while avoiding the generation and evaluation of data that does 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 Requirement (PDF)" (8 pp, 150k) to help ensure that data continue to be protected.
This guidance is consistent with OPP’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. OPP’s strategic direction is consistent with the 2007 and 2009 National Research Council reports, Toxicity Testing in the 21st Century: A Vision and a Strategy and Science and Decisions: Advancing Risk Assessment.
On this page:
- Revised Pesticide Data Requirements
- Changes in the Structure of Part 158
- Types of Studies Required
EPA's pesticide registration data requirements have been restructured. As outlined below under Changes in the Structure of Part 158, the revised tables provided in 40 CFR Part 158, subparts 158.200–158.2500 specify the data requirements for various use patterns and provide references to the test guidelines.
In 2013, the Agency revised the data requirements for antimicrobial pesticides. In 2007, the Agency revised the data requirements that pertain to conventional pesticides, as well as the data requirements for biochemical and microbial pesticides. These revisions improve the Agency's ability to make regulatory decisions about the human health and environmental effects of pesticide products in order to better protect wildlife, the environment, and people, including sensitive subpopulations. EPA also reformatted the requirements and revised its general procedures and policies associated with data submission. By codifying data requirements that have been applied on a case-by-case basis, the Agency enables the pesticide industry to better understand and prepare for the pesticide registration process. Revision of data requirements for the registration of pesticide products will occur through five separate rulemakings:
(1) Conventional Pesticides - Final Rule Published October 26, 2007
The final rule for data requirements for conventional pesticides published in the Federal Register (October 26, 2007) eliminated certain data requirements and added a few new studies to provide new scientific information for risk assessment purposes in areas not previously addressed. The majority of changes were modifications based on current risk assessment data needs. Few of the additions represent truly new requirements.
(2) Biochemical and Microbial Pesticides - Final Rule Published Oct. 26, 2007
The final rule for biochemical and microbial pesticides, published in the Federal Register, (October 26, 2007) reduces regulatory burden for the pesticide industry. The majority of changes are modifications based on current risk assessment data needs, technical revisions, clarifications in test notes, and regulatory experience during the many years since EPA published the original rule.
(3) Antimicrobial Pesticides
The final rule for antimicrobial pesticides, published in the Federal Register on May 8, 2013, revises use patterns and data requirements for antimicrobial pesticides.
(4) Product Performance Data Requirements
The Agency will be developing a proposed rule in the future to address product performance data requirements for conventional pesticides and biochemical and microbial pesticides.
(5) Plant-Incorporated Protectants (PIPs)
EPA is developing a proposed rule for data requirements for the registration of plant-incorporated protectants. The proposed rule will also contain an exemption that would lessen regulatory hurdles for cisgenic PIPs. [EPA is coordinating with our federal partners (Federal Register Notice, March 16, 2011). When we publish the proposed rule, there will be a public comment period. EPA will announce the proposed rule on the PIPs web page and through the Office of Pesticide Programs email list.]
The data requirements in the final rules for conventional, biochemical, and microbial pesticides were effective December 26, 2007.
The data requirements for antimicrobial chemicals (PDF) will be effective July 8, 2013. EPA developed guidance for registrants on the implementation of this new rule (Coming Soon!).
Changes in the Structure of Part 158
EPA has reorganized Part 158 of Title 40 by creating a series of new subparts to address an individual scientific discipline or data type. The table below shows new subparts and reserved (future) subparts. Appendix A to Part 158, the Use Pattern Index, has been removed and replaced with the Pesticide Use Site Index that can be updated regularly.
40 CFR Part 158 (New Structure)
Subpart G: Ecological Effects
Subpart H: Reserved 158.700
Subpart I: Reserved 158.800
Subpart J: Reserved 158.900
Subpart M: Reserved 158.1200
Subpart P: Reserved 158.1500
Subpart Q: Reserved 158.1600
Subpart R: Reserved 158.1700
Subpart S: Reserved 158.1800
Subpart T: Reserved 158.1900
Subpart X: Reserved 158.2300
Subpart Y: Reserved 158.2400
Subpart Z: Reserved 158.2500
The following sections describe the reasons for each type of test and the kind of information EPA obtains from the results of each test.
- 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.
- 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
- 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.
- 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.
- 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.
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. The Agency is receptive to approaches that effectively incorporate other endpoints into the battery of routine toxicology studies if it would reduce animal usage while still providing the necessary information within the context of other toxicological endpoints.
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. They also:
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 Guidance for Waiving or Bridging of Mammalian Acute Toxicity Tests for Pesticides and Pesticide Products (PDF) - (17 pp, 112.63k, about PDF) criteria that can be cited by registrants to bridge data for or support a waiver of the requirement for mammalian acute toxicity data for pesticide technical active ingredients and pesticide end use formulations (Acute Oral, Acute Dermal, Acute Inhalation, Primary Eye, Primary Dermal, and Dermal Sensitization).
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 (usually conducted by feeding the test substance to the test species) studies 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.
EPA conducted an extensive analysis of dog toxicity studies on 110 chemicals representing over 50 different classes of pesticides. EPA concluded from this analysis that extending a dog toxicity study beyond a 13-week duration does not provide additional essential toxicity information; eliminating the 1-year dog toxicity study does not compromise the data needed for the determination of chronic RfDs and margins of exposure (MOE). Thus, reliance on the required chronic rodent studies, 2-generation rat reproductive study, and the 13-week dog toxicity study provides an adequate basis for chronic RfD derivation in pesticide risk assessment. See A Retrospective Analysis of Toxicity Studies in Dogs and Impact on the Chronic Reference Dose for Pesticide Chemicals (PDF) (21 pp, 136k, about PDF).
OPP 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 the weight-of-the-evidence-based (WOE) determination of data needs for neurotoxicity, subchronic inhalation, subchronic, dermal and immunotoxicity studies (PDF) (11 pp, 240k). This guidance will assist registrants in developing for data waiver requests for these kinds of studies. OPP accepts and reviews waiver requests on a case-by-case basis for other types of studies, such as chronic or developmental toxicity studies, also. The guidance provided on Immunotoxicity study needs was based, in part, on a Retrospective Analysis of the Immunotoxicity Study (PDF) (OSCPP Test Guideline No. 870.7800) (26 pp, 2.5M, about PDF)
The information required to assess hazards to nontarget organisms are 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:
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:
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.
Data required to assess hazard to farm employees resulting from reentry into areas treated with pesticides are derived from studies on toxicity, residue dissipation, and human exposure. Monitoring data generated during exposure studies are used to determine how much pesticide people may be exposed to after application and to establish how long workers must wait before reentering a treated area.
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.
EPA uses the data generated by environmental fate studies to:
EPA uses 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: