Assessing Risks to Endangered and Threatened Species from Pesticides (2013)

Appendix A

Selected Excerpts from 40 CFR Part 158 Data Requirements for Pesticides

158.1 Purpose and scope.

a) Purpose. The purpose of this part is to specify the kinds of data and information EPA requires in order to make regulatory judgments under FIFRA secs. 3, 4, and 5 about the risks and benefits of pesticide products. Further, this part specifies the data and information needed to determine the safety of pesticide chemical residues under FFDCA sec. 408.

b) Scope—

(1) This part describes the minimum data and information EPA typically requires to support an application for pesticide registration or amendment; support the reregistration of a pesticide product; support the maintenance of a pesticide registration by means of the data call-in process, e.g., as used in the registration review program; or establish or maintain a tolerance or exemption from the requirements of a tolerance for a pesticide chemical residue.

(2) This part establishes general policies and procedures associated with the submission of data in support of a pesticide regulatory action.

(3) This part does not include study protocols, methodology, or standards for conducting or reporting test results; nor does this part describe how the Agency uses or evaluates the data and information in its risk assessment and risk management decisions, or the regulatory determinations that may be based upon the data.

§ 158.30 Flexibility.

a) FIFRA provides EPA flexibility to require, or not require, data and information for the purposes of making regulatory judgments for pesticide products. EPA has the authority to establish or modify data needs for individual pesticide chemicals. The actual data required may be modified on an individual

basis to fully characterize the use and properties, characteristics, or effects of specific pesticide products under review. The Agency encourages each applicant to consult with EPA to discuss the data requirements particular to its product prior to and during the registration process.

b) The Agency cautions applicants that the data routinely required in this part may not be sufficient to permit EPA to evaluate the potential of the product to cause unreasonable adverse effects to man or the environment. EPA may require the submission of additional data or information beyond that specified in this part if such data or information are needed to appropriately evaluate a pesticide product.

c) This part will be updated as needed to reflect evolving program needs and advances in science.

§ 158.70 Satisfying data requirements.

a) General policy. The Agency will determine whether the data submitted or cited to fulfill the data requirements specified in this part are acceptable. This determination will be based on the design and conduct of the experiment from which the data were derived, and an evaluation of whether the data fulfill the purpose(s) of the data requirement. In evaluating experimental design, the Agency will consider whether generally accepted methods were used, sufficient numbers of measurements were made to achieve statistical reliability, and sufficient controls were built into all phases of the experiment. The Agency will evaluate the conduct of each experiment in terms of whether the study was conducted in conformance with the design, good laboratory practices were observed, and results were reproducible. The Agency will not reject data merely because they were derived from studies which, when initiated, were in accordance with an Agency-recommended protocol, even if the Agency subsequently recommends a different protocol, as long as the data fulfill the purposes of the requirements as described in this paragraph.

(1) The provisions in this part 158 should be read in conjunction with the provisions in §152.85 to claim eligibility for the formulators' exemption.

(2) [Reserved]

b) Good laboratory practices. Applicants must adhere to the good laboratory practice (GLP) standards described in 40 CFR part 160 when conducting studies. Applicants must also adhere to GLP standards when conducting a study in support of a waiver request of any data requirement which is within the scope of the GLP requirements.

c) Agency guidelines. EPA has published Test Guidelines that contain standards for conducting acceptable tests, guidance on the evaluation and reporting of data, definition of terms, and suggested study protocols. Copies of the Test Guidelines may be obtained by visiting the agency's website at www.epa.gov/pesticides.

d) Study protocols—

(1) General. Any appropriate protocol may be used to generate the data required by this part, provided that it meets the purpose of the test standards specified in the pesticide assessment guidelines, and provides data of suitable quality and completeness as typified by the protocols cited in the guidelines. Applicants should use the test procedure which is most suitable for evaluation of the particular ingredient, mixture, or product. Accordingly, failure to follow a suggested protocol will not invalidate a test if another appropriate methodology is used.

(2) Organization for Economic Co-Operation and Development (OECD) protocols. Tests conducted in accordance with the requirements and recommendations of the applicable OECD protocols can be used to develop data necessary to meet the requirements specified in this part. Applicants should note, however, that certain of the OECD recommended test standards, such as test duration and selection of test species, are less restrictive than those recommended by EPA. Therefore, when using OECD protocols, care should be taken to observe the test standards in a manner such that the data generated by the study will satisfy the requirements of this part.

e) Combining studies. Certain toxicology studies may be combined to satisfy data requirements. For example, carcinogenicity studies in rats may be combined with the rat chronic toxicity study. Combining appropriate studies may be expected to reduce usage of test animals as well as reduce the cost of studies. EPA encourages this practice by including standards for acceptable combined tests in the Pesticide Assessment Guidelines. Registrants and applicants are encouraged to consider combining other tests when practical and likely to produce scientifically acceptable results. Registrants and applicants, however, must consult with the EPA before initiating combined studies.

§ 158.75 Requirements for additional data.

The data routinely required by this part may not be sufficient to permit EPA to evaluate every pesticide product. If the information required under this part is not sufficient to evaluate the potential of the product to cause unreasonable adverse effects on man or the environment, additional data requirements will be imposed. However, EPA expects that the information required by this part will be adequate in most cases for an assessment of the properties and effects of the pesticide.

§ 158.80 Use of other data.

a) Data developed in foreign countries. With certain exceptions, laboratory and field study data developed outside the United States may be submitted in support of a pesticide registration. Data generated in a foreign country which the

Agency will not consider include, but are not limited to, data from tests which involved field test sites or a test material, such as a native soil, plant, or animal, that is not characteristic of the United States. Applicants submitting foreign data must take steps to ensure that U.S. materials are used, or be prepared to supply data or information to demonstrate the lack of substantial or relevant differences between the selected material or test site and the U.S. material or test site. Once submitted, the Agency will determine whether or not the data meet the data requirements.

b) Data generated for other purposes. Data developed for purposes other than satisfaction of FIFRA data requirements, such as monitoring studies, may also satisfy data requirements in this part. Consultation with the Agency should be arranged if applicants are unsure about suitability of such data.

§ 158.130 Purposes of the registration data requirements.

e) Hazards to nontarget organisms—

(1) General. 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 which progresses from the basic laboratory tests to the applied field tests. The results of each tier of testing must be evaluated to determine the potential of the pesticide to cause adverse effects, and to determine whether further testing is required. A purpose common to all data requirements is to provide data which determine the need for (and appropriate wording for) precautionary label statements to minimize the potential adverse effects to nontarget organisms.

(2) Short-term studies. The short-term acute and subchronic laboratory studies provide basic toxicity information which 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; to compare toxicity information with measured or estimated pesticide residues in the environment in order to assess potential impacts on fish, wildlife and other nontarget organisms; and to indicate whether further laboratory and/or field studies are needed.

(3) Long-term 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 to 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 adverse effects is high.

g) Pesticide spray-drift evaluation. Data required to evaluate pesticide spray drift are derived from studies of droplet size spectrum and spray drift field evaluations. These data contribute to the development of the overall exposure estimate and, along with data on toxicity for humans, fish and wildlife, or plants, are used to assess the potential hazard of pesticides to these organisms. A purpose common to all these tests is to provide data which will be used to determine the need for (and appropriate wording for) precautionary labeling to minimize the potential adverse effect to nontarget organisms.

h) Environmental fate—

(1) General. The data generated by environmental fate studies are used to: Assess the toxicity to man through exposure of humans to pesticide residues remaining after application, either upon reentering treated areas or from consuming inadvertantly-contaminated food; assess the presence of widely distributed and persistent pesticides in the environment which may result in loss of usable land, surface water, ground water, and wildlife resources; and, assess the potential environmental exposure of other nontarget organisms, such as fish and wildlife, to pesticides. Another specific purpose of the environmental fate data requirements is to help applicants and the Agency estimate expected environmental concentrations of pesticides in specific habitats where threatened or endangered species or other wildlife populations at risk are found.

(2) Degradation studies. The data from hydrolysis and photolysis studies are used to determine the rate of pesticide degradation and to identify pesticides that may adversely affect nontarget organisms.

(3) Mobility studies. These data requirements pertain to leaching, adsorption/desorption, and volatility of pesticides. They provide information on the mode of transport and eventual destination of the pesticide in the environment. This information is used to assess potential environmental hazards related to: Contamination of human and animal food; loss of usable land and water resources to man through contamination of water (including ground water); and habitat loss of wildlife resulting from pesticide residue movement or transport in the environment.

(4) Accumulation studies. Accumulation studies indicate pesticide residue levels in food supplies that originate from wild sources or from rotational crops. Rotational crop studies are necessary to establish realistic crop rotation restrictions and to determine if tolerances may be

needed for residues on rotational crops. Data from irrigated crop studies are used to determine the amount of pesticide residues that could be taken up by representative crops irrigated with water containing pesticide residues. These studies allow the Agency to establish label restrictions regarding application of pesticides on sites where the residues can be taken up by irrigated crops. These data also provide information that aids the Agency in establishing any corresponding tolerances that would be needed for residues on such crops. Data from pesticide accumulation studies in fish are used to establish label restrictions to prevent applications in certain sites so that there will be minimal residues entering edible fish or shellfish. These residue data are also used to determine if a tolerance or action level is needed for residues in aquatic animals eaten by humans.

Subpart G – Ecological Effects

§ 158.630 Terrestrial and aquatic nontarget organisms data requirements table.

a) General. Sections 158.100 through 158.130 describe how to use this table to determine the terrestrial and aquatic nontarget data requirements for a particular pesticide product. Notes that apply to an individual test including specific conditions, qualifications, or exceptions to the designated test are listed in paragraph (e) of this section.

b) Use patterns.

(1) The terrestrial use pattern includes products classified under the general use patterns of terrestrial food crop, terrestrial feed crop, and terrestrial nonfood crop. The aquatic use pattern includes products classified under the general use patterns of aquatic food crop and aquatic nonfood use patterns. The greenhouse use pattern includes products classified under the general use patterns of greenhouse food crop and greenhouse nonfood crop. The indoor use pattern includes products classified under the general use patterns of indoor food and indoor nonfood use.

(2) Data are also required for the general use patterns of forestry and residential outdoor use.

(3) In general, for all outdoor end-uses, including turf, the following studies are required: Two avian oral LD₅₀, two avian dietary LC₅₀, two avian reproduction studies, two freshwater fish LC₅₀, one freshwater invertebrate EC₅₀, one honeybee acute contact LD₅₀, one freshwater fish early-life stage, one freshwater invertebrate life cycle, and three estuarine acute LC₅₀/EC₅₀studies—fish, mollusk and invertebrate. All other outdoor residential uses, i.e., gardens and ornamental will not usually require the freshwater fish early-life stage, the freshwater invertebrate life-cycle, and the acute estuarine tests.

c) Key. R = Required; CR = Conditionally required; NR = Not required; TGAI = Technical grade of the active ingredient; TEP = Typical end-use product; PAI = Pure active ingredient; EP = end-use product. Commas between the test substances (i.e., TGAI, TEP) indicate that data may be required on the TGAI or the TEP depending on the conditions set forth in the test note.

d) Table. The following table shows the data requirements for nontarget terrestrial and aquatic organism. The table notes are shown in paragraph (e) of this section.

e) Test notes. The following test notes apply to terrestrial and aquatic nontarget organisms data requirements in the table to paragraph (d) of this section:

(1) Data using the TGAI are required to support all outdoor end-use product uses including, but not limited to turf. Data are generally not required to support end-use products in the form of a gas, a highly volatile liquid, a highly reactive solid, or a highly corrosive material.

(2) For greenhouse and indoor end-use products, data using the TGAI are required to support manufacturing-use products to be reformulated into these same end-use products or to support end-use products when there is no registered manufacturing-use product. Avian acute oral data are not required for liquid formulations for greenhouse and indoor uses. The study is not required if there is no potential for environmental exposure.

(3) Data are required on one passerine species and either one waterfowl species or one upland game bird species for terrestrial, aquatic, forestry, and residential outdoor uses. Data are preferred on waterfowl or upland game bird species for indoor and greenhouse uses.

(4) Data are required on waterfowl and upland game bird species.

(5) Tests are required based on the results of lower tier toxicology studies, such as the acute and subacute testing, intended use pattern, and environmental fate characteristics that indicate potential exposure.

(6) Higher tier testing may be required for a specific use pattern when a refined risk assessment indicates a concern based on laboratory toxicity endpoints and refined exposure assessments.

(7) Environmental chemistry methods used to generate data associated with this study must include results of a successful confirmatory method trial by an independent laboratory. Test standards and procedures for independent laboratory validation are available as addenda to the guideline for this test requirement.

(8) Data are required on one coldwater fish and one warmwater fish for terrestrial, aquatic, forestry, and residential outdoor uses. For indoor and greenhouse uses, testing with only one of either fish species is required.

Terrestrial and Aquatic Nontarget Organism Data Requirements

(9) EP or TEP testing is required for any product which meets any of the following conditions:

i. The end-use pesticide will be introduced directly into an aquatic environment (e.g., aquatic herbicides and mosquito larvicides) when used as directed.

ii. The maximum expected environmental concentration (MEEC) or the estimated environmental concentration (EEC) in the aquatic environment is ≥one-half the LC₅₀or EC₅₀of the TGAI when the EP is used as directed.

iii. An ingredient in the end-use formulation other than the active ingredient is expected to enhance the toxicity of the active ingredient or to cause toxicity to aquatic organisms.

(10) Data are required on one freshwater aquatic invertebrate species.

(11) Data are required on one estuarine/marine mollusk, one estuarine/marine invertebrate and one estuarine/marine fish species.

(12) Data are generally not required for outdoor residential uses, other than turf, unless data indicate that pesticide residues from the proposed use(s) can potentially enter waterways.

(13) Data are required on one freshwater fish species. If the test species is different from the two species used for the freshwater fish acute toxicity tests, a 96-hour LC₅₀on that species must also be provided.

(14) Data are required on one estuarine/marine invertebrate species.

(15) Data are required on estuarine/marine species if the product meets any of the following conditions:

i. Intended for direct application to the estuarine or marine environment. ii. Expected to enter this environment in significant concentrations because of its expected use or mobility patterns.

iii. If the acute LC₅₀or EC₅₀ <1 milligram/liter (mg/l).

iv. If the estimated environmental concentration (EEC) in water is ≦0.01 of the acute EC₅₀or LC₅₀or if any of the following conditions exist:

A. Studies of other organisms indicate the reproductive physiology of fish and/or invertebrates may be affected.

B. Physicochemical properties indicate bioaccumulation of the pesticide.

C. The pesticide is persistent in water (e.g., half-life in water >4 days).

(16) Data are required on one estuarine/marine fish species.

(17) Data are required on estuarine/marine species if the product is intended for direct application to the estuarine or marine environment, or the product is expected to enter this environment in significant concentrations because of its expected use or mobility patterns.

(18) Data are required on freshwater species if the end-use product is intended to be applied directly to water, or is expected to be transported

to water from the intended use site, and when any of the following conditions apply:

i. If the estimated environmental concentration (EEC) is ≥0.1 of the no-observed-effect level in the fish early-life stage or invertebrate life cycle test;

ii. If studies of other organisms indicate that the reproductive physiology of fish may be affected.

(19) Not required when:

i. The octanol/water partition coefficients of the pesticide and its major degradates are <1,000; or

ii. There are no potential exposures to fish and other nontarget aquatic organisms; or

iii. The hydrolytic half-life is <5 days at pH 5, 7 and 9.

(20) Data are required based on the results of lower tier studies such as acute and chronic aquatic organism testing, intended use pattern, and environmental fate characteristics that indicate significant potential exposure.

(21) Data are required if:

i. The half-life of the pesticide in the sediment is ≤10 days in either the aerobic soil or aquatic metabolism studies and if any of the following conditions exist:

A. The soil partition coefficient (Kd) is ≥50.

B. The log Kow is ≥3.

C. The Koc ≥1,000.

ii. Registrants must consult with the Agency on appropriate test protocols prior to designing the study.

(22) Data are required if:

i. The estimated environmental concentration (EEC) in sediment is >0.1 of the acute LC₅₀/EC₅₀values and ii. The half-life of the pesticide in the sediment is >10 days in either the aerobic soil or aquatic metabolism studies and if any of the following conditions exist:

A. The soil partition coefficient (Kd) is ≥50.

B. The log Kow is ≥3.

C. The Koc ≥1,000.

iii. Registrants must consult with the Agency on appropriate test protocols prior to designing the study.

(23) Sediment testing with estuarine/marine test species is required if the product is intended for direct application to the estuarine or marine environment or the product is expected to enter this environment in concentrations which the Agency believes to be significant, either by runoff or erosion, because of its expected use or mobility pattern.

(24) Data are required only when the formulation contains one or more active ingredients having an acute LD₅₀ of <11 micrograms per bee as

determined in the honey bee acute contact study and the use pattern(s) indicate(s) that honey bees may be exposed to the pesticide.

(25) Required if any of the following conditions are met:

i. Data from other sources (Experimental Use Permit program, university research, registrant submittals, etc.) indicate potential adverse effects on colonies, especially effects other than acute mortality (reproductive, behavioral, etc.);

ii. Data from residual toxicity studies indicate extended residual toxicity.

iii. Data derived from studies with terrestrial arthropods other than bees indicate potential chronic, reproductive or behavioral effects.

(26) The freshwater fish test species for the TEP testing is the most sensitive of the species tested with the TGAI. Freshwater invertebrate and acute estuarine and marine organisms must also be tested with the EP or TEP using the same species tested with the TGAI.

Subpart L – Spray Drift

§ 158.1100 Spray drift data requirements table.

a) General. Sections 158.100 through 158.130 describe how to use this table to determine the spray drift data requirements for a particular pesticide product. Notes that apply to an individual test, including specific conditions, qualifications, or exceptions to the designated test are listed in paragraph (e) of this section.

b) Use patterns. The terrestrial use pattern includes products classified under the general use patterns of terrestrial food crop and terrestrial nonfood crop. The aquatic use pattern includes products classified under the general use patterns of aquatic food crop and aquatic nonfood. The greenhouse use pattern includes products classified under the general use patterns of greenhouse food crop and greenhouse nonfood crop. Data are also required for the general use patterns of forestry use, residential outdoor use, and indoor use.

c) Key. CR = Conditionally required; NR = Not required; TEP = Typical end-use product; MP = Manufacturing use product; EP = End-use product.

d) Table. The following table lists the data requirements that pertain to spray drift. The table notes are shown in paragraph (e) of this section.

Subpart N – Environmental Fate

§ 158.1300 Environmental fate data requirements table.

a) General. All environmental fate data, as described in paragraph (c) of this section, must be submitted to support a request for registration.

b) Use patterns.

(1) The terrestrial use pattern includes products classified under the general use patterns of terrestrial food crop, terrestrial feed crop, and terrestrial nonfood. The aquatic use pattern includes the general use patterns of aquatic food crop, and aquatic nonfood. The greenhouse use pattern includes both food and nonfood uses. The indoor use pattern includes food, nonfood, and residential indoor uses.

(2) Data are also required for the general use patterns of forestry use and residential outdoor use.

c) Key. CR = Conditionally required; NR = Not required; R = Required; PAIRA = Pure active ingredient radio-labeled; TGAI = Technical grade of the active ingredient; TEP = Typical end-use product.

d) Table. The following table shows the data requirements for environmental fate. The test notes are shown in paragraph (e) of this section.

e) Test notes. The following test notes apply to the requirements in the table to paragraph (d) of this section:

(1) Study is required for indoor uses in cases where environmental exposure is likely to occur. Such sites include, but are not limited to, agricultural premises, in or around farm buildings, barnyards, and beehives.

(2) Not required when the electronic absorption spectra, measured at pHs 5, 7, and 9, of the chemical and its hydrolytic products, if any, show no absorption or tailing between 290 and 800 nm.

(3) Not required when the chemical is to be applied only by soil injection or is incorporated in the soil.

(4) Requirement based on use patterns and other pertinent factors including, but not limited to, the Henry’s Law Constant of the chemical. In view of methodological difficulties with the study of photodegradation in air, prior consultation with the Agency regarding the protocol is recommended before the test is performed.

(5) Required for aquatic food and nonfood crop uses for aquatic sites that are intermittently dry. Such sites include, but are not limited to, cranberry bogs and rice paddies.

(6) Adsorption and desorption using a batch equilibrium method is preferred. However in some cases, for example, where the pesticide degrades rapidly, soil column leaching with unaged or aged columns may be more appropriate to fully characterize the potential mobility of the parent compound and major transformation products.

(7) Environmental chemistry methods used to generate data associated with this study must include results of a successful confirmatory method trial by an independent laboratory. Test standards and procedures for independent laboratory validation are available as addenda to the guideline for this test requirement.

(8) Requirement for terrestrial uses is based on potential for aquatic exposure and if pesticide residues have the potential for persistence, mobility, nontarget aquatic toxicity or bioaccumulation. Not required for aquatic residential uses. Field testing under the terrestrial field dissipa-

tion requirement may be more appropriate for some aquatic food crops, such as rice and cranberry uses, that are managed to have a dry-land period for production. The registrant is encouraged to consult with the Agency on protocols.

(9) Agency approval of a protocol is necessary prior to initiation of the study.

(10) This study may be triggered if there is specific evidence that the presence of one pesticide can affect the dissipation characteristics of another pesticide when applied simultaneously or serially.

(11) Required if the weight-of-evidence indicates that the pesticide and/or its degradates is likely to leach to ground water, taking into account other factors such as the toxicity of the chemicals(s), available monitoring data, and the vulnerability of ground water resources in the pesticide use area.

(12) If the terrestrial dissipation study cannot assess all of the major routes of dissipation, the forestry.

Table—Spray Drift Data Requirements

e) Test notes. The following notes apply to the requirements in the table to paragraph (d) of this section:

(1) This study is required when aerial applications (rotary and fixed winged) and mist blower or other methods of ground application are proposed and it is estimated that the detrimental effect level of those nontarget organisms expected to be present would be exceeded. The nontarget organisms include humans, domestic animals, fish and wildlife, and nontarget plants.

Table—Environmental Fate Data Requirements