OMB Control Number 2070-0060; EPA ICR Number 0277.15 

ICR ATTACHMENT F 

40 CFR part 158: Data Requirements For Registration 
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Title 40: Protection of Environment

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PART 158—DATA REQUIREMENTS FOR PESTICIDES

Section Contents

Subpart A—General Provisions

§ 158.1 Purpose and scope.

§ 158.3 Definitions.

§ 158.5 Applicability.

§ 158.30 Flexibility.

§ 158.32 Format of data submissions.

§ 158.33 Confidential data.

§ 158.34 Flagging of studies for potential adverse effects.

§ 158.45 Waivers.

§ 158.60 Minor use data policies.

§ 158.70 Satisfying data requirements.

§ 158.75 Requirements for additional data.

§ 158.80 Use of other data.

Subpart B—How To Use Data Tables

§ 158.100 Pesticide use patterns.

§ 158.110 Required and conditionally required data.

§ 158.120 Determining data requirements.

§ 158.130 Purposes of the registration data requirements.

Subpart C—Experimental Use Permits

§ 158.200 Experimental use permit data requirements tables.

§ 158.210 Experimental use permit data requirements for product chemistry.

§ 158.220 Experimental use permit data requirements for product performance.

§ 158.230 Experimental use permit data requirements for toxicology.

§ 158.240 Experimental use permit data requirements for ecological effects.

§ 158.243 Experimental use permit data requirements for terrestrial and aquatic nontarget organisms.

§ 158.250 Experimental use permit data requirements for human exposure.

§ 158.260 Experimental use permit data requirements for environmental fate.

§ 158.270 Experimental use permit data requirements for residue chemistry.

§§ 158.280-158.290 [Reserved]

Subpart D—Product Chemistry

§ 158.300 Definitions.

§ 158.310 Product chemistry data requirements table.

§ 158.320 Product identity and composition.

§ 158.325 Description of materials used to produce the product.

§ 158.330 Description of production process.

§ 158.335 Description of formulation process.

§ 158.340 Discussion of formation of impurities.

§ 158.345 Preliminary analysis.

§ 158.350 Certified limits.

§ 158.355 Enforcement analytical method.

Subpart E—Product Performance

§ 158.400 Product performance data requirements table.

Subpart F—Toxicology

§ 158.500 Toxicology data requirements table.

§ 158.510 Tiered testing options for nonfood pesticides.

Subpart G— Ecological Effects

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§ 158.630 Terrestrial and aquatic nontarget organisms data requirements table.

§ 158.660 Nontarget plant protection data requirements table.

Subparts H–J [Reserved]

§§ 158.700-158.900 [Reserved]

Subpart K—Human Exposure

§ 158.1000 Applicator exposure—general requirements.

§ 158.1010 Applicator exposure—criteria for testing.

§ 158.1020 Applicator exposure data requirements table.

§ 158.1050 Post-application exposure—general requirements.

§ 158.1060 Post-application exposure—criteria for testing

§ 158.1070 Post-application exposure data requirements table.

Subpart L—Spray Drift

§ 158.1100 Spray drift data requirements table.

Subpart M [Reserved]

§§ 158.1200 -158.1299 [Reserved]

Subpart N—Environmental Fate

§ 158.1300 Environmental fate data requirements table.

Subpart O—Residue Chemistry

§ 158.1400 Definitions.

§ 158.1410 Residue chemistry data requirements table.

Subparts P–T [Reserved]

§§ 158.1500-158.1900 [Reserved]

Subpart U—Biochemical Pesticides

§ 158.2000 Biochemical pesticides definition and applicability.

§ 158.2010 Biochemical pesticides data requirements.

§ 158.2030 Biochemical pesticides product chemistry data requirements table.

§ 158.2040 Biochemical pesticides residue data requirements table.

§ 158.2050 Biochemical pesticides human health assessment data requirements table.

§ 158.2060 Biochemical pesticides nontarget organisms and environmental fate data requirements table.

§ 158.2070 Biochemical pesticides product performance data requirements.

§ 158.2080 Experimental use permit data requirements—biochemical pesticides.

§ 158.2081 Experimental use permit biochemical pesticides product chemistry data requirements table.

§ 158.2082 Experimental use permit biochemical pesticides residue data requirements table.

§ 158.2083 Experimental use permit biochemical pesticides human health assessment data requirements table.

§ 158.2084 Experimental use permit biochemical pesticides nontarget organisms and environmental fate data requirements table.

Subpart V—Microbial Pesticides

§ 158.2100 Microbial pesticides definition and applicability.

§ 158.2110 Microbial pesticides data requirements.

§ 158.2120 Microbial pesticides product analysis data requirements table.

§ 158.2130 Microbial pesticides residue data requirements table.

§ 158.2140 Microbial pesticides toxicology data requirements table.

§ 158.2150 Microbial pesticides nontarget organisms and environmental fate data requirements table.

§ 158.2160 Microbial pesticides product performance data requirements.

§ 158.2170 Experimental use permit data requirements—microbial pesticides.

§ 158.2171 Experimental use permit microbial pesticides product analysis data requirements table.

§ 158.2172 Experimental use permit microbial pesticides residue data requirements table.

§ 158.2173 Experimental use permit microbial pesticides toxicology data requirements table.

§ 158.2174 Experimental use permit microbial pesticides nontarget organisms and environmental fate data requirements table.

Subpart W—Antimicrobial Pesticides [Reserved]

§ 158.2200 [Reserved]

Subparts X–Z [Reserved]

§§ 158.2300-158.2500 [Reserved]

Authority: 7 U.S.C. 136–136y; 21 U.S.C. 346a.

Source: 72 FR 60957, Oct. 26, 2007, unless otherwise noted.

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Subpart A—General Provisions

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§ 158.1 Purpose and scope.

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(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.

(c) Scope of individual subparts . (1) Conventional pesticides . Subparts A, B, C, D, F, G, K, L, N, and O apply to conventional pesticides.

(2) Biochemical pesticides . Subparts A, B and U apply to biochemical pesticides.

(3) Microbial pesticides . Subparts A, B and V apply to microbial pesticides.

(4) Antimicrobial pesticides . [Reserved]

§ 158.3 Definitions.

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All terms defined in sec. 2 of the Federal Insecticide, Fungicide, and Rodenticide Act apply to this part and are used with the meaning given in the Act. Applicable terms from the

Federal Food, Drug, and Cosmetic Act also apply to this part. Individual subparts may contain definitions that pertain solely to that subpart. The following additional terms apply to

this part:

Applicant means any person or entity, including for the purposes of this part a registrant, who submits, or is required to submit, to the Agency any application, petition, or submission

intended to persuade EPA to grant, modify, or leave unmodified a registration or other approval required as a condition of sale or distribution of a pesticide. Such submissions may

include, but are not limited to, the following:

(1) An application for registration or amended registration of a pesticide product under FIFRA sec. 3 or 24.

(2) A submission of data required in conjunction with reregistration of a currently registered product under FIFRA sec. 4.

(3) An application for an experimental use permit under FIFRA sec. 5.

(4) A submission of data in response to a notice issued by EPA under FIFRA sec. 3(c)(2)(B).

(5) A petition to establish or modify a tolerance or an exemption from the requirement of a tolerance for a pesticide chemical residue under FFDCA sec. 408.

Registration includes a new registration, amended registration and reregistration, unless stated otherwise.

§ 158.5 Applicability.

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(a) The requirements of this part apply to the following submissions:

(1) An application for new or amended registration under FIFRA sec. 3 or 24.

(2) An application for experimental use permit under FIFRA sec. 5.

(3) A submission of data or information to support the continuation of a registration under FIFRA sec. 3, 4, or 24.

(4) A petition to establish, modify or revoke a tolerance or exemption from a tolerance under FFDCA sec. 408.

(b) The information specified in this part must be furnished with each submission described in paragraph (a) of this section if it has not been submitted previously, or if any previous

submission is not accurate or complete.

§ 158.30 Flexibility.

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(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.

§ 158.32 Format of data submissions.

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(a) General . (1) All data submitted under this part must be formatted in accordance with this section.

(2) The requirements of this section do not apply to administrative materials accompanying a data submission, including forms, labeling, and correspondence.

(b) Transmittal document . Each submission in support of a regulatory action must be accompanied by a transmittal document, which includes:

(1) Identity of the submitter.

(2) The transmittal date.

(3) Identification of the regulatory action with which the submission is associated, e.g., the registration or petition number.

(4) A list of the individual documents included in the submission.

(c) Individual documents . Unless otherwise specified by the Agency, each submission must be in the form of individual documents or studies. Previously submitted documents

should not be resubmitted unless specifically requested by the Agency, but should be cited with adequate information to identify the previously submitted document. Each study or

document should include the following:

(1) A title page including the following information:

(i) The title of the study, including identification of the substance(s) tested and the test name or data requirement addressed.

(ii) The author(s) of the study.

(iii) The date the study was completed.

(iv) If the study was performed in a laboratory, the name and address of the laboratory, project numbers or other identifying codes.

(v) If the study is a commentary on or supplement to another previously submitted study, full identification of the other study with which it should be associated in review.

(vi) If the study is a reprint of a published document, all relevant facts of publication, such as the journal title, volume, issue, inclusive page numbers, and date of publication.

(2) The appropriate statement(s) regarding any data confidentiality claims as described in §158.33.

(3) A statement of compliance or non-compliance with respect to Good Laboratory Practice Standards as required by 40 CFR 160.12, if applicable.

(4) A complete and accurate English translation must be included for any information that is not in English.

(5) A flagging statement as prescribed by §158.34, if applicable.

§ 158.33 Confidential data.

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(a) Definitions . For the purposes of this section:

(1) Registered or previously registered pesticide means any pesticide containing an active ingredient contained in a product that is, or has ever been, an active ingredient in a

product registered under sec. 3 of FIFRA. A registered pesticide that is the subject of an application for a new use falls within the category of “registered or previously registered

pesticide.”

(2) Safety and efficacy information means information concerning the objectives, methodology, results, or significance of any test or experiment performed on or with a registered or

previously registered pesticide or its separate ingredients, impurities, or degradation products, and any information concerning the effects of such pesticide on any organism or the

behavior of such pesticide in the environment, including, but not limited to, data on safety to fish and wildlife, humans and other mammals, plants, animals, and soil, and studies on

persistence, translocation and fate in the environment, and metabolism.

(b) Applicability . (1) This section applies to information submitted pursuant to this part. It supplements the general confidentiality procedures in 40 CFR part 2, subpart B, including

FIFRA confidentiality procedures at 40 CFR 2.307. To the extent that provisions in this section conflict with those in 40 CFR part 2, subpart B, the provisions in this section take

precedence. The provisions of 40 CFR 2.308 do not apply to information to which this section applies. In addition to complying with the requirements of this section, any

confidentiality claims for information subject to 40 CFR part 174 (plant-incorporated protectants) must be substantiated at the time of submission as described in §174.9 of this

chapter.

(2) FFDCA sec. 408(i) protects confidential information submitted in connection with an application for a tolerance or exemption to the same extent as FIFRA sec. 10. References in

this section to FIFRA sec. 10 are deemed to apply equally to information submitted pursuant to FFDCA sec. 408, pursuant to the authority in sec. 408(i).

(c) Method of asserting business confidentiality claims —(1) Claim required . Information to which this section applies (and which is submitted on or after the effective date of this

regulation) will be deemed as not subject to a confidentiality claim unless a claim for that information is made in accordance with the procedures specified in this paragraph.

Information not subject to a confidentiality claim may be made available to the public without further notice, subject to the requirements of FIFRA sec. 10(g).

(2) Statement required . Upon submission to EPA, each document must be accompanied by a signed and dated document containing either the statements in paragraph (c)(2)(i) or

(ii) of this section. No claims or markings on the document or any attachments, other than these statements and attachments submitted in accordance with paragraph (c)(3) of this

section, will be recognized as asserting a claim of confidentiality. The format of data submissions is set forth in §158.32.

(i) No claim of confidentiality .

No claim of confidentiality, on any basis whatsoever, is made for any information contained in this document. I acknowledge that information not designated as

within the scope of FIFRA sec. 10(d)(1)(A), (B), or (C) and which pertains to a registered or previously registered pesticide is not entitled to confidential treatment

and may be released to the public, subject to the provisions regarding disclosure to multinational entities under FIFRA sec. 10(g).

(ii) Claim of confidentiality .

Information claimed as confidential has been removed to a confidential attachment.

(3) Confidential attachment . (i) All information claimed as confidential must be submitted in a separate confidential attachment to the document and cross referenced to the specific

location in the document from which it was removed. The confidential attachment must have its own title page and be paginated separately from the non-confidential document.

(ii) All information in the confidential attachment that consists of (or whose disclosure would in turn disclose) manufacturing or quality control processes must be individually

identified in the confidential attachment as a claim for information within the scope of FIFRA sec. 10(d)(1)(A).

(iii) All information in the confidential attachment that consists of (or whose disclosure would in turn disclose) the details of any methods for testing, detecting, or measuring the

quantity of any deliberately added inert ingredient of a pesticide, must be individually identified in the confidential attachment as a claim for information within the scope of FIFRA

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sec. 10(d)(1)(B).

(iv) All information in the confidential attachment that consists of (or whose disclosure would in turn disclose) the identity or percentage quantity of any deliberately added inert

ingredient of a pesticide must be individually identified in the confidential attachment as a claim for information within the scope of FIFRA sec. 10(d)(1)(C).

(v) Information in the confidential attachment that is designated in accordance with paragraphs (c)(3)(ii) - (iv) of this section must be on a separate page from information that is not

so designated.

(4) Voluntary release of information to States and foreign governments. (i) Submitters are encouraged to include with the statement required under paragraph (c)(2) of this section

an additional statement to allow EPA to share information with State and foreign governments. EPA will not consider such a statement to be a waiver of confidentiality or proprietary

claims for the information. The statement is as follows:

I authorize the Environmental Protection Agency to release any information contained in this document to State or foreign governments, without relinquishing

proprietary rights or any confidentiality claims asserted above.

(ii) Information designated as releasable to state or foreign governments in accordance with this section may be released to such a government

without further notice to the submitter. EPA will inform the State or foreign government of any of the confidentiality claims associated with the

information.

(d) Release of information . (1) Safety and efficacy information that was submitted to EPA on or after May 4, 1988 and that has not been designated

by the submitter as FIFRA sec. 10(d)(1)(A), (B), or (C) information in accordance with the applicable requirements of this section is not entitled to

confidential treatment and may be disclosed to the public without further notice to the submitter, in accordance with paragraph (d)(2) of this section.

Safety and efficacy information which has been designated by the submitter as FIFRA sec. 10(d)(1) (A), (B), or (C) information is entitled to

confidential treatment only to the extent provided by FIFRA sec. 10(b), this section, and 40 CFR 2.208.

(2) Information that is not entitled to be protected as confidential in accordance with FIFRA sec. 10(b), this section and with EPA confidentiality

regulations at 40 CFR part 2, subpart B, may be released to the public without the affirmation of non-multinational status provided under FIFRA sec.

10(g), provided that the information does not contain or consist of any complete unpublished report submitted to EPA, or excerpts or restatements of

any such report which reveal the full methodology and complete results of the study, test, or experiment, and all explanatory information necessary

to understand the methodology or interpret the results.

§ 158.34 Flagging of studies for potential adverse effects.

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(a) Any applicant who submits a study of a type listed in paragraph (b) of this section must submit with the study a statement in accordance with

paragraph (c) of this section.

(b) The following table indicates the study types and the criteria to be applied to each. Column 1 lists the study types by name. Column 2 lists the

associated Pesticide Assessment Guideline number. Column 3 lists the criteria applicable to each type of study. Column 4 lists the reporting code to

be included in the statement specified in paragraph (c) of this section when any criterion is met or exceeded.

Table—Flagging Criteria

Study Type(s)

Guideline

No. Criteria: Treated animals show any of the following:

Criteria

No.

Carcinogenicity or combined

carcinogenicity/chronic feeding

study

870.4200

870.4300

An incidence of neoplasms in males or females which increases with dose (positive

trend p≤ 0.05); or

1

 A statistically significant (pairwise p≤ 0.05) increase of any type of neoplasm in any test

group, males or females at any dose level, compared to concurrent control animals of

the same sex; or

2

 An increase in any type of uncommon or rare neoplasms in any test group, males or

females animals at any dose level, compared to concurrent controls of the same sex; or

3

 A decrease in the time to development of any type of neoplasms in any test group, males

or females at any dose level, compared to concurrent controls of the same sex.

4

Prenatal developmental toxicity

Reproduction and fertility

Developmental neurotoxicity

870.3700

870.3800

870.6300

When compared to concurrent controls, treated offspring show a dose-related increase

in malformations, pre- or post-natal deaths, or persistent functional or behavioral

changes on a litter basis in the absence of significant maternal toxicity at the same dose

level.

5

Neurotoxicity 870.6100

870.6200

When compared to concurrent controls, treated animals show a statistically or

biologically significant increase in neuropathological lesions or persistent functional or

behavioral changes.

6

Chronic feeding

Carcinogenicity

Reproduction and fertility

Prenatal developmental toxicity

Developmental neurotoxicity

Acute or 90–day neurotoxicity

870.4100

870.4200

870.3800

870.3700

870.6300

870.6200

The no observed adverse effect level (NOAEL) from one of these studies is less than the

NOAEL currently used by the Agency as the basis for either the acute or chronic

reference dose.

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(c) Identification of studies . For each study of a type identified in paragraph (b) of this section, the applicant shall include the appropriate one of the

following two statements, together with the signature of the authorized representative of the company, and the date of signature:

(1) Study does not meet or exceed criteria.

I have applied the criteria of 40 CFR 158.34 for flagging studies for potential adverse effects to the results of the attached study. This study neither meets nor exceeds any of the

applicable criteria.

(2) Study meets or exceeds criteria.

I have applied the criteria of 40 CFR 158.34 for flagging studies for potential adverse effects to the results of the attached study. This study meets or exceeds the criteria numbered

[insert all applicable reporting codes].

§ 158.45 Waivers.

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(a) The data requirements specified in this part as applicable to a category of products will not always be appropriate for every product in that

category. Some products may have unusual physical, chemical, or biological properties or atypical use patterns which would make particular data

requirements inappropriate, either because it would not be possible to generate the required data or because the data would not be useful in the

Agency's evaluation of the risks or benefits of the product. The Agency will waive data requirements it finds are inappropriate, but will ensure that

sufficient data are available to make the determinations required by the applicable statutory standards.

(b)(1) Applicants are encouraged to discuss a data waiver request with the Agency before developing and submitting supporting data, information, or

other materials.

(2) All waiver requests must be submitted to the Agency in writing. The request must clearly identify the data requirement(s) for which a waiver is

sought along with an explanation and supporting rationale why the applicant believes the data requirement should be waived. In addition, the

applicant must describe any unsuccessful attempts to generate the required data, furnish any other information which the applicant(s) believe(s)

would support the request, and when appropriate, suggest alternative means of obtaining data to address the concern which underlies the data

requirement.

(c) The Agency will review each waiver request and subsequently inform the applicant in writing of its decision. If the decision could apply to more

than the requested product, the Agency, in its discretion, may choose to send a notice to all registrants or publish a notice in theFederal

Registerannouncing the decision. An Agency decision denying a written request to waive a data requirement is a final Agency action.

§ 158.60 Minor use data policies.

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FIFRA sec. 2(ll) defines the term “minor use”and FIFRA provides a number of statutory provisions concerning minor uses. In addition, EPA has

established policies with respect to minor uses of pesticides, including, but not limited to, the following:

(a) A new data requirement pertinent to both an unregistered minor use and a registered major use will not be applied to a minor use applicant until it

is applied to the major use registration.

(b) EPA will accept appropriate and adequate extrapolations and regional data to support establishment of individual minor use tolerances.

§ 158.70 Satisfying data requirements.

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(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.

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(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.

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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.

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(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.

Subpart B—How To Use Data Tables

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§ 158.100 Pesticide use patterns.

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(a) General use patterns . There are six broad use categories used in the data tables. The six broad categories include terrestrial outdoor uses, aquatic

outdoor uses, greenhouse uses, forestry uses, residential outdoor uses, and indoor uses of all types. The 6 broad use categories are further subdivided

into 12 general use patterns which are the bases for data requirements established by use pattern. Within the data tables, general use patterns have

been combined into single columns when the data requirements are the same for the combined uses. If there are no data requirements for a specific

use, the column for that use is not included in the table. The 12 general use pattern groups used in the data table in this part are:

(1) Terrestrial food crop use.

(2) Terrestrial feed crop use.

(3) Terrestrial nonfood crop use.

(4) Aquatic food crop use.

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(5) Aquatic nonfood use.

(6) Greenhouse food crop use.

(7) Greenhouse nonfood crop use.

(8) Forestry use.

(9) Residential outdoor use.

(10) Residential indoor use.

(11) Indoor food use.

(12) Indoor nonfood use.

(b) Pesticide use site index . The Pesticide Use Site Index is a comprehensive list of specific pesticide use sites. The index is alphabetized separately

by site for all agricultural and all nonagricultural uses. The Pesticide Use Site Index associates each pesticide use site with one or more of the 12

general use patterns. It may be used in conjunction with the data tables to determine the applicability of data requirements to specific uses. The

Pesticide Use Site Index, which will be updated periodically, is available from the Agency or may be obtained from the Agency's website at

http://www.epa.gov/pesticides .

(c) Applicants unsure of the correct use pattern for their particular product should consult the Agency.

§ 158.110 Required and conditionally required data.

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The tables in this part use the descriptors R (required), CR (conditionally required), and NR (not required) as a general indication of the applicability

of a data requirement. In all cases, the test notes referred to in the table must be consulted to determine the actual applicability of the data

requirement.

(a) EPA requires data designated as “required”(R) for products with a given use pattern in order to evaluate the risks or benefits of a product having

that use pattern under any conditions established by the test notes.

(b) Data designated as “conditionally required” (CR) for products with a given use pattern are required by EPA to evaluate the risks or benefits of a

product having that use pattern if the product meets the conditions specified in the notes accompanying the requirement. The determination of

whether the data must be submitted is based on the product's use pattern, physical or chemical properties, expected exposure of nontarget organisms,

and/or results of previous testing (for example, tier testing). Applicants must evaluate each applicable test note for the conditions and criteria to be

considered in determining whether conditionally required data must be submitted.

(c) Data not required for the Agency's assessment of the risks and benefits of a particular use pattern are designated “not required” (NR) in data

tables.

§ 158.120 Determining data requirements.

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As with current practice, the actual data and studies required may be modified on an individual basis to fully characterize the use and properties of

specific pesticide products under review. While EPA is attempting to assist the applicant in this subpart, it is important to emphasize that it is the

applicant's obligation under FIFRA to demonstrate that an individual product meets the standard under FIFRA and/or FFDCA. Accordingly,

applicants are encouraged to consult with the Agency on the appropriate data requirements as set forth here as they relate to their specific product

prior to and during the registration process.

(a) Finding the appropriate data table . (1) Pesticide data requirements for conventional chemical active ingredients and related substances are

presented in subparts D, E, F, G, K, L, N, and O of this part in the form of a series of data tables, each addressing a particular scientific discipline or

data topic. Data requirements for biochemical and microbial pest control agents are contained and are described separately within subparts U and V

of this part, respectively.

(2) Key to table notations. R = required data; CR = conditionally required data; NR = Not required; MP = manufacturing-use product; EP = end-use

product; TEP = typical end-use product; TGAI = technical grade of the active ingredient; PAI = pure active ingredient; PAIRA = pure active

ingredient, radiolabeled; Choice = choice of several test substances depending on studies required.

(b) Identifying required studies . To determine the specific kinds of data needed to support the registration use of each pesticide product, the

applicant may:

(1) Refer to the applicable subpart(s) of this part. These subparts describe the data requirements including data tables for each subject area.

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(2) Select the general use pattern(s) that best cover the use pattern(s) specified on the pesticide product label as explained in §158.100. All

applicable use patterns must be included.

(3) Proceed down the appropriate general use pattern column in the table and note which tests are required (R), conditionally required (CR), or not

required (NR). Required and conditionally required studies are described in §158.110.

(4) Review the notes for each requirement to determine its applicability to the specific product proposed for registration.

(5)(i) Proceed down the Test substance columns and determine the appropriate test substance needed for that study. If the data are intended to

support a manufacturing-use product, use the MP column. If the data are intended to support an end-use product, use the EP column.

(ii) The test substances columns specify which substance is to be used for testing. Applicants should note that the substance that must be used when

performing the study may or may not be the product itself. For example, the data from a certain study may be required to support the registration of

an end-use product, but the test substance column may state that the particular test shall be performed using the technical grade of the active

ingredient(s) in the end-use product.

(iii) Manufacturing-use products (MP) and end-use products (EP) containing a single active ingredient and no intentionally added inert ingredients

are considered identical in composition to each other, and to the technical grade of the active ingredient (TGAI) from which they were derived.

Therefore, the data from a test conducted using any one of these as the test substance is also suitable to meet the requirement (if any) for the same

test to be conducted using either of the other substances.

(6) Refer to the Pesticide Assessment Guideline reference number for each study located in the first column. See §158.70(c) for information

pertaining to the guidelines and how to obtain copies.

§ 158.130 Purposes of the registration data requirements.

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(a) General . The data requirements for registration are intended to generate data and information necessary to address concerns pertaining to the

identity, composition, potential adverse effects and environmental fate of each pesticide.

(b) Product chemistry —(1) Product composition . Data on product composition are needed:

(i) To support the conclusions expressed in the statement of formula;

(ii) To compare to the composition of materials used in required testing under this part; and

(iii) To determine whether a product is “identical or substantially similar”to another product, a determination that involves the comparison of product

composition.

(2) Nominal concentration and certified limits . The nominal concentration of a product, defined as that concentration that is expected to be present

in a product as a result of the production or formulation process, is used to gauge the acceptability of the certified limits, which define the outer

limits of the range of the product's ingredients. The certified limits are used to enforce the composition of the product and to ensure the accuracy of

hazard assessments.

(3) Physical and chemical characteristics . The physical and chemical characteristics of an active ingredient or product are used:

(i) To confirm or provide supportive information on the identity and composition of the product;

(ii) To assess the hazards of the ingredient or product; and

(iii) To trigger or evaluate certain other studies required by this part.

(c) Product performance . Requirements to develop data on product performance provide a mechanism to ensure that pesticide products will

perform as intended 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 man in any area of the inanimate environment and those pesticides used to control vertebrates (such as rodents, birds, bats and skunks)

that may directly or indirectly transmit diseases to humans.

(d) Toxicology-humans and domestic animals . 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.

(1) Acute studies . 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

farmworker reentry intervals and to develop precautionary label statements pertaining to protective clothing requirements for applicators. They also

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; and determine the need for child resistant packaging. 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.

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(2) Subchronic studies . 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).

(3) Chronic studies . 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 which 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.

(4) Developmental toxicity and reproduction studies . The developmental toxicity study is designed to determine the potential of the test substance

to induce structural and/or other abnormalities to the fetus as the result of exposure of the mother during pregnancy. Two-generation reproduction

testing is designed to provide information concerning the general effects of a test substance on gonadal function, estrus cycles, mating behavior,

conception, parturition, lactation, weaning, and the growth and development of the offspring. The study may also provide information about the

effects of the test substance on neonatal morbidity, mortality, and preliminary data on prenatal developmental toxicity and serve as a guide for

subsequent tests.

(5) Mutagenicity studies . For each test substance a battery of tests is required to assess the potential to affect the mammalian cell's genetic

components. The objectives underlying the selection of a battery of tests for mutagenicity assessment are:

(i) To detect, with sensitive assay methods, the capacity of a chemical to alter genetic material in cells.

(ii) To determine the relevance of these mutagenic changes to mammals.

(iii) When mutagenic potential is demonstrated, to incorporate these findings in the assessment of heritable effects, carcinogenicity, and, possibly,

other health effects.

(6) Metabolism studies . Data from studies on the absorption, distribution, metabolism, and excretion of a pesticide aid in the valuation of test results

from other toxicity studies and in the extrapolation of data from animals to man. The main purpose of metabolism studies is to produce data which

increases the Agency's understanding of the behavior of the chemical when considering the human exposure anticipated from intended uses of the

pesticide.

(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.

(f) Applicator and post-application exposure. Data are used to evaluate exposures to persons in occupational and non-occupational settings,

including agricultural, residential, commercial, institutional and recreational sites. Data include oral, dermal and inhalation exposure data,

post-application residue data, post-application monitoring data, use information, and human activity information. These data, together with

toxicology data, are used to determine whether application or post-application risks are of concern, and, where appropriate, to develop

post-application restrictions such as reentry restrictions.

(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

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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) Metabolism studies . Data generated from aerobic and anaerobic metabolism studies are used to determine the nature and availability of

pesticides to rotational crops and to aid in the evaluation of the persistence of a pesticide.

(4) 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.

(5) Dissipation studies . The data generated from dissipation studies are used to assess potential environmental hazards (under actual field use

conditions) related to: Reentry into treated areas; hazards from residues in rotational crops and other food sources; and the loss of land as well as

surface and ground water resources.

(i) Residue chemistry . (1) Residue chemistry data are used by the Agency 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.

(2) Information on the chemical identity and composition of the pesticide product, the amounts, frequency and time of the pesticide application, and

results of tests on the amount of residues remaining on or in the treated food or feed, are needed to support a finding as to the magnitude and identity

of residues which result in food or animal feed as a consequence of a proposed pesticide usage.

(3) Residue chemistry data are also needed to support the adequacy of one or more methods for the enforcement of the tolerance, and to support

practicable methods for removing residues that exceed any proposed tolerance.

(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 C—Experimental Use Permits

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§ 158.200 Experimental use permit data requirements tables.

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Sections 158.200 through 158.270 describe how to use these tables to determine the experimental use permit data requirements for a particular

pesticide product. Notes that apply to an individual test and include specific conditions, qualifications, or exceptions to the designated test are listed

at the end of each table. Refer to 40 CFR part 172 for further information on experimental use permits.

§ 158.210 Experimental use permit data requirements for product chemistry.

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All product chemistry data, as described in §158.310, must be submitted to support a request for an experimental use permit.

§ 158.220 Experimental use permit data requirements for product performance.

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All product performance data, as described in paragraph (c) of this section, must be submitted to support a request for an experimental use permit.

(a) Use patterns . (1) 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 crop. 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 forestry and residential outdoor uses.

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

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product.

(c) Table . The following table shows the experimental use data requirements for product performance. The test notes are shown in paragraph (d) of

this section.

Table—Data Requirements for Product Performance

Guideline

No. Data Requirement

Use Pattern

Test

substance to

support

Test

Note

No.

Terrestrial Aquatic Greenhouse

Forestry

Residential

Outdoors Indoor MP EP

Food

Crop

Nonfood

Crop

Food

Crop

Nonfood

Crop

Food

Crop

Nonfood

Crop

Efficacy of antimicrobial agents

91–8 Products for treating

water systems

NR NR CR NR NR NR NR NR NR NR EP 1

Efficacy of fungicides and nematicides

93–16 Products for control of

organisms producing

mycotoxins

CR NR CR NR CR NR NR NR NR NR EP 1

Efficacy of vertebrate control agents

96–5 Avian toxicants R R NR NR NR NR NR R R NR EP 1

96–6 Avian repellents R R NR NR NR NR NR R NR NR EP 1

96–7 Avian frightening agents R R NR NR NR NR NR R NR NR EP 1

96–9 Bat toxicants and

repellents

NR NR NR NR NR NR NR NR R NR EP 1

96–10 Commensal

rodenticides

R R NR NR NR NR NR R R TEP EP 1

96–12 Rodenticides on farm

and rangelands

R R NR NR NR NR NR R NR NR EP 1

95–13 Rodent fumigants R R NR NR NR NR NR R R NR EP 1

95–16 Rodent reproductive

inhibitors

R R NR NR NR NR NR R R NR EP 1

95–17 Mammalian predacides R R NR NR NR NR NR R NR NR EP 1

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

1. The Agency has waived the requirement to submit efficacy data unless the pesticide product bears a claim to control pest microorganisms that pose a threat to human health and

whose presence cannot readily be observed by the user including, but not limited to, microorganisms infectious to man in any area of the inanimate environment, or a claim to control

vertebrates (such as rodents, birds, bats, canids, and skunks) that may directly or indirectly transmit diseases to humans. However each registrant must ensure through testing that his

product is efficacious when used in accordance with label directions and commonly accepted pest control practices. The Agency reserves the right to require, on a case-by-case

basis, submission of efficacy data for any pesticide product registered or proposed for registration.

2. [Reserved]

§ 158.230 Experimental use permit data requirements for toxicology.

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All toxicology data, as described in paragraph (c) of this section, must be submitted to support a request for an experimental use permit.

(a) Use patterns . (1) Food use patterns include products classified under the general use patterns of terrestrial food crop use, terrestrial feed crop

use, aquatic food crop use, greenhouse food crop use, and indoor food use.

(2) Nonfood use patterns include products classified under the general use patterns of terrestrial nonfood crop use, aquatic nonfood crop use, aquatic

nonfood outdoor use, greenhouse nonfood crop use, forestry use, residential outdoor use, indoor nonfood use, and indoor residential use.

(b) Key . CR=Conditionally required; NR=Not required; R=Required; EP=End-use product; MP=Manufacturing-use product; PAIRA=Pure active

ingredient radio-labeled; TGAI=Technical grade of the active ingredient.

(c) Table . The following table shows the experimental use data requirements for toxicology. The test notes are shown in paragraph (d) of this

section.

Table—Toxicology Data Requirements

Guideline Number Data Requirement Use Pattern Test substance to support Test Note No.

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Food Nonfood MP EP

Acute Testing

870.1100 Acute oral toxicity - rat R R MP and TGAI TGAI, EP 1

870.1200 Acute dermal toxicity R R MP and TGAI TGAI, EP 1, 2

870.1300 Acute inhalation toxicity - rat R R MP and TGAI TGAI and EP 3

870.2400 Primary eye irritation - rabbit R R MP TGAI and EP 2

870.2500 Primary dermal irritation R R MP TGAI and EP 1, 2

870.2600 Dermal sensitization R R MP TGAI and EP 2, 4

870.6100 Delayed neurotoxicity (acute) - hen CR CR TGAI TGAI 5

Subchronic Testing

870.3100 90–day Oral - rodent R NR TGAI TGAI --

870.3150 90–day Oral - non-rodent R NR TGAI TGAI --

Chronic Testing

870.4100 Chronic oral - rodent R NR TGAI TGAI 6

Developmental Toxicity and Reproduction

870.3700 Prenatal Developmental toxicity - rat and rabbit, preferred R NR TGAI TGAI 7, 8

870.3800 Reproduction R NR TGAI TGAI 6

Mutagenicity Testing

870.5100 Bacterial reverse mutation assay R NR TGAI TGAI 9

870.5300

870.5375

In vitro mammalian cell assay R NR TGAI TGAI 9, 10

870.5385

870.5395

In vivo cytogenetics R NR TGAI TGAI 9, 11

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

1. Not required if test material is a gas or a highly volatile liquid.

2. Not required if test material is corrosive to skin or has a pH of less than 2 or greater than 11.5.

3. Required if the product consists of, or under conditions of use will result in, a respirable material (e.g., gas, vapor, aerosol, or particulate).

4. Required if repeated dermal exposure is likely to occur under conditions of use.

5. Required if the test material is an organophosphorus substance, which includes uncharged organophosphorus esters, thioesters, or anhydrides of organophosphoric,

organophosphonic, or organophosphoramidic acids, or of related phosphorothioic, phosponothioic, or phosphorothioamidic acids, or is structurally related to other substances that

may cause the delayed neurotoxicity sometimes seen in this class of chemicals.

6. These studies are seldom required to support EUPs. They may be required if the dietary exposure for these EUPs occupies a large part, e.g., greater than 50%, of the reference

dose.

7. The oral route, by oral intubation, is preferred unless the chemical or physical properties of the test substance or the pattern of exposure suggests a more appropriate route of

exposure.

8. May be combined with the 2–generation reproduction study in rodents by utilizing a second mating of the parental animals in either generation.

9. At a minimum, an initial battery of mutagenicity tests with possible confirmatory testing is required. Other relevant mutagenicity tests that may have been performed, plus a

complete reference list must also be submitted.

10. Choice of assay using either:

i. Mouse lymphoma L5178Y cells, thymidine kinase (tk) gene locus, maximizing assay conditions for small colony expression or detection;

ii. Chinese hamster ovary (CHO) or Chinese hamster lung fibroblast (V79) cells, hypoxanthine-guanine phosphoribosyl transferase (hgprt) gene locus, accompanied by an

appropriate in vitro test for clastogenicity; or

iii. CHO cells strains AS52, xanthine-guanine phosphoribosyl transferase (xprt) gene locus.

11. The micronucleus rodent bone marrow assay is preferred; however, rodent bone marrow assays using metaphase analysis (aberrations) are acceptable.

§ 158.240 Experimental use permit data requirements for ecological effects.

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All data for terrestrial nontarget organisms and aquatic nontarget organisms as described in §158.243 must be submitted to support a request for an

experimental use permit. No data for nontarget plant protection must be submitted to support a request for an experimental use permit.

§ 158.243 Experimental use permit data requirements for terrestrial and aquatic nontarget organisms.

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All terrestrial and aquatic nontarget organism data, as described in paragraph (c) of this section, must be submitted to support a request for an

experimental use permit.

(a) 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. 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.

(b) Key . CR=Conditionally required; NR=Not required; R=Required; TEP=Typical end-use product; TGAI=Technical grade of the active

ingredient; commas between the test substances (e.g. TGAI, TEP) indicate that data may be required on the TGAI or TEP depending on the

conditions set forth in the test note.

(c) Table . The following table shows the experimental use data requirements for terrestrial and aquatic nontarget organisms. The test notes are

shown in paragraph (d) of this section.

Table—Terrestrial and Aquatic Nontarget Organisms Data Requirements

Guideline

No. Data Requirement

Use Pattern

Test

substance

Test Note

Terrestrial Aquatic Forestry No.

Residential

Outdoor Greenhouse Indoor

Avian and Mammalian Testing

850.2100 Avian oral toxicity R R R R CR CR TGAI 1, 2, 3

850.2200 Avian dietary toxicity R R R R NR NR TGAI 1, 4

Aquatic Organisms Testing

850.1075 Freshwater fish toxicity R R R NR NR NR TGAI, TEP 1, 2, 5, 6,

11

850.1010 Acute toxicity freshwater

invertebrates

R R R NR NR NR TGAI, TEP 1, 2, 6, 7,

11

850.1300 Aquatic invertebrate life cycle

(freshwater)

NR R R NR NR NR TGAI 1, 7, 8

850.1400 Fish early-life stage (freshwater) NR R R NR NR NR TGAI 1, 8, 9

Accumulation Study

850.1730 Fish CR CR CR NR NR NR TGAI or

PAIRA

10

Insect Pollinator Testing

850.3020 Honeybee acute contact toxicity R R R NR NR NR TGAI 1

(d) Test notes . The following test notes apply to the data requirements in the table to paragraph (c) 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. 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.

6. 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.

7. Data are required on one freshwater aquatic invertebrate species.

8. 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.

9. 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

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must also be provided.

10. 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.

11. The freshwater fish test species for the TEP testing is the most sensitive of the species tested with the TGAI. A freshwater invertebrate must also be tested with the EP or TEP

using the same species tested with the TGAI.

§ 158.250 Experimental use permit data requirements for human exposure.

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No data for applicator exposure and post-application exposure must be submitted to support a request for an experimental use permit.

§ 158.260 Experimental use permit data requirements for environmental fate.

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

(a) 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, aquatic nonfood residential, and aquatic

nonfood outdoors. 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.

(b) Key . CR=Conditionally required; NR=Not required; R=Required; PAIRA=Pure active ingredient radio-labeled; TGAI=Technical grade of the

active ingredient.

(c) Table . The following table shows the experimental use data requirements for environmental fate. The test notes are shown in paragraph (d) of

this section.

Table—Environmental Fate Data Requirements

Guideline

No. Data Requirement

Use Pattern

Test

substance

Test Note

Terrestrial Aquatic Greenhouse Indoors Forestry No.

Residential

Outdoors

Degradation Study - Laboratory

835.2120 Hydrolysis R R R NR R R TGAI or

PAIRA

1

Metabolism Studies - Laboratory

835.4100 Aerobic soil R CR NR NR R NR TGAI or

PAIRA

2

835.4300 Aerobic aquatic NR R NR NR NR NR TGAI or

PAIRA

--

Mobility Study

835.1230

835.1240

Leaching and

adsorption/desorption

R NR NR NR R NR TGAI or

PAIRA

3

(d) Test notes . The following test notes apply to the data requirements in the table to paragraph (c) 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. Required for aquatic uses for aquatic sites that are intermittently dry. Such sites include, but are not limited to cranberry bogs and rice paddies.

3. 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.

§ 158.270 Experimental use permit data requirements for residue chemistry.

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All residue chemistry data, as described in §158.1410, are required for an experimental use permit for which a temporary tolerance under FFDCA

section 408(r) is sought. Residue chemistry data are not required for an experimental use permit issued on a crop-destruct basis.

§§ 158.280-158.290 [Reserved]

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Subpart D—Product Chemistry

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§ 158.300 Definitions.

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The following terms are defined for the purposes of this subpart:

Active ingredient means any substance (or group of structurally similar substances, if specified by the Agency) that will prevent, destroy, repel or

mitigate any pest, or that functions as a plant regulator, desiccant, defoliant, or nitrogen stabilizer, within the meaning of FIFRA sec. 2(b).

End-use product means a pesticide product whose labeling:

(1) Includes directions for use of the product (as distributed or sold, or after combination by the user with other substances) for controlling pests or

defoliating, desiccating or regulating growth of plants, or as a nitrogen stabilizer, and

(2) does not state that the product may be used to manufacture or formulate other pesticide products.

Formulation means:

(1) The process of mixing, blending, or dilution of one or more active ingredients with one or more other active or inert ingredients, without an

intended chemical reaction, to obtain a manufacturing-use product or an end-use product, or

(2) The repackaging of any registered product.

Impurity means any substance (or group of structurally similar substances if specified by the Agency), in a pesticide product other than an active

ingredient or an inert ingredient, including unreacted starting materials, side reaction products, contaminants, and degradation products.

Impurity associated with an active ingredient means:

(1) Any impurity present in the technical grade of active ingredient; and

(2) Any impurity which forms in the pesticide product through reactions between the active ingredient and any other component of the product or

packaging of the product.

Inert ingredient means any substance (or group of structurally similar substances if designated by the Agency), other than the active ingredient,

which is intentionally included in a pesticide product.

Integrated system means a process for producing a pesticide product that:

(1) Contains any active ingredient derived from a source that is not an EPA-registered product; or

(2) Contains any active ingredient that was produced or acquired in a manner that does not permit its inspection by the Agency under FIFRA sec.

9(a) prior to its use in the process.

Manufacturing-use product means any pesticide product other than an end-use product. A product may consist of the technical grade of active

ingredient only, or may contain inert ingredients, such as stabilizers or solvents.

Nominal concentration means the amount of an ingredient which is expected to be present in a typical sample of a pesticide product at the time the

product is produced, expressed as a percentage by weight.

Starting material means a substance used to synthesize or purify a technical grade of active ingredient (or the practical equivalent of the technical

grade ingredient if the technical grade cannot be isolated) by chemical reaction.

Technical grade of active ingredient means a material containing an active ingredient:

(1) Which contains no inert ingredient, other than one used for purification of the active ingredient; and

(2) Which is produced on a commercial or pilot plant production scale (whether or not it is ever held for sale).

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§ 158.310 Product chemistry data requirements table.

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(a) General . Sections 158.100 through 158.130 describe how to use this table to determine the product chemistry data requirements for a particular

pesticide product. Notes that apply to an individual test and include specific conditions, qualifications, or exceptions to the designated test are listed

in paragraph (f) of the section.

(b) Use patterns . Product chemistry data are required for all pesticide products and are not use-specific.

(c) Test substance . Data requirements that list only the manufacturing-use product as the test substance apply to products containing solely the

technical grade of the active ingredient and manufacturing-use products to which other ingredients have been intentionally added.

(d) Key . R=Required; CR=Conditionally required; MP=Manufacturing-use product; NR=Not required; EP=End-use product; TGAI=Technical

grade of the active ingredient; PAI=Pure active ingredient.

(e) Table . The following table shows the data requirements for product chemistry. The table notes are shown in paragraph (f) of this section.

Product Chemistry Data Requirements

Guideline

Number Data Requirement

Use

Pattern Test substance to support Test Note

All MP EP No.

Product Identity and Composition

830.1550 Product identity and composition R MP EP 1

830.1600 Description of materials used to produce the product R MP EP 2

830.1620 Description of production process R MP EP 3

830.1650 Description of formulation process R MP EP 4

830.1670 Discussion of formulation of impurities R MP, and possibly

TGAI

EP, and possibly

TGAI

5

830.1700 Preliminary analysis CR MP, and possibly

TGAI

EP, and possibly

TGAI

6, 9, 10

830.1750 Certified limits R MP EP 7

830.1800 Enforcement analytical method R MP EP 8

830.1900 Submittal of samples CR MP, PAI and TGAI EP, PAI, TGAI 9, 11

Physical and Chemical Properties

830.6302 Color R MP and TGAI EP 9

830.6303 Physical state R MP and TGAI EP and TGAI 9

830.6304 Odor R MP and TGAI EP 9

830.6313 Stability to normal and elevated temperatures, metals, and

metal ions

R MP and TGAI EP 9, 12, 26

830.6314 Oxidation/reduction: chemical incompatibility CR MP EP 13

830.6315 Flammability CR MP EP 14

830.6316 Explodability CR MP EP 15

830.6317 Storage stability R MP EP 

830.6319 Miscibility CR MP EP 16

830.6320 Corrosion characteristics R MP EP 

830.6321 Dielectric breakdown voltage CR NR EP 17

830.7000 pH CR MP and TGAI EP and TGAI 9, 18

830.7050 UV/visible light absorption R TGAI or PAI NR --

830.7100 Viscosity CR MP EP 19

830.7200 Melting point/melting range R TGAI or PAI TGAI or PAI 9, 20

830.7220 Boiling point/boiling range R TGAI or PAI TGAI or PA 9, 21

830.7300 Density/relative density/bulk density R MP and TGAI EP and TGAI 9

830.7370 Dissociation constants in water R TGAI or PAI TGAI or PAI 9, 22

830.7520 Particle size, fiber length, and diameter distribution CR TGAI or PAI EP 23

830.7550

830.7560

830.7570

Partition coefficient (n-octanol/water) R TGAI or PAI TGAI or PAI 24

830.7840

830.7860

Water solubility R TGAI or PAI TGAI or PAI 9

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830.7950 Vapor pressure R TGAI or PAI TGAI or PAI 9, 25

(f) Test notes . The following test notes are applicable to the product chemistry data requirements in the table to paragraph (e) of this section:

1. Data must be provided in accordance with §158.320.

2. Data must be provided in accordance with §158.325.

3. Data must be provided in accordance with §158.330.

4. Data must be provided in accordance with §158.335.

5. Data must be provided in accordance with §158.340.

6. Data must be provided in accordance with §158.345.

7. Data must be provided in accordance with §158.350.

8. Data must be provided in accordance with §158.355.

9. If the TGAI cannot be isolated, data are required on the practical equivalent of the TGAI.

10. Data are required if the product is produced by an integrated system.

11. Basic manufacturers are required to provide the Agency with a sample of each TGAI used to formulate a product produced by an integrated system when the new TGAI is first

used as a formulating ingredient in products registered under FIFRA. A sample of the active ingredient (PAI) suitable for use as an analytical standard is also required at this time.

Samples of end-use products produced by an integrated system must be submitted on a case-by-case basis.

12. Data on the stability to metals and metal ions are required only if the TGAI is expected to come into contact with either material.

13. Required when the product contains an oxidizing or reducing agent.

14. Required when the product contains combustible liquids.

15. Required when the product is potentially explosive.

16. Required when the product is an emulsifiable liquid and is to be diluted with petroleum solvent.

17. Required when the EP is a liquid and is to be used around electrical equipment.

18. Required when the test substance is soluble or dispersible in water.

19. Required when the product is a liquid.

20. Required when the TGAI is solid at room temperature.

21. Required when the TGAI is liquid at room temperature.

22. Required when the test substance contains an acid or base functionality (organic or inorganic) or an alcoholic functionality (organic).

23. Required for water insoluble test substances (>10-6g/l) and fibrous test substances with diameter of≥0.1 μm.

24. Required if technical chemical is organic and non-polar.

25. Not required for salts.

26. Data on stability of the MP and TGAI to storage at normal temperatures are required. Data on the stability of the TGAI to high temperatures are required if the TGAI is expected

to be subjected to temperatures>50 °C (122 °F) during production or storage.

§ 158.320 Product identity and composition.

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Information on the composition of the pesticide product must be furnished. The information required by paragraphs (a), (b), and (f) of this section

must be provided for each product. In addition, if the product is produced by an integrated system, the information on impurities required by

paragraphs (c) and (d) of this section must be provided.

(a) Active ingredient . The following information is required for each active ingredient in the product:

(1) If the source of any active ingredient in the product is an EPA-registered product:

(i) The chemical and common name (if any) of the active ingredient, as listed on the source product.

(ii) The nominal concentration of the active ingredient in the product, based upon the nominal concentration of active ingredient in the source

product.

(iii) Upper and lower certified limits of the active ingredient in the product, in accordance with §158.350.

(2) If the source of any active ingredient in the product is not an EPA-registered product:

(i) The chemical name according to Chemical Abstracts Society (CAS) nomenclature, the CAS Registry Number, and any common names.

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(ii) The molecular, structural, and empirical formulae and the molecular weight or weight range.

(iii) The nominal concentration.

(iv) Upper and lower certified limits of the active ingredient in accordance with §158.350.

(v) The purpose of the ingredient in the formulation.

(b) Inert ingredients . The following information is required for each inert ingredient (if any) in the product:

(1) The chemical name of the ingredient according to Chemical Abstracts Society nomenclature, the CAS Registry Number, and any common names

(if known). If the chemical identity or chemical composition of an ingredient is not known to the applicant because it is proprietary or trade secret

information, the applicant must ensure that the supplier or producer of the ingredient submits to the Agency (or has on file with the Agency)

information on the identity or chemical composition of the ingredient. Generally, it is not required that an applicant know the identity of each

ingredient in a mixture that he uses in his product. However, in certain circumstances, the Agency may require that the applicant know the identity

of a specific ingredient in such a mixture. If the Agency requires specific knowledge of an ingredient, it will notify the applicant in writing.

(2) The nominal concentration.

(3) Upper and lower certified limits in accordance with §158.350.

(4) The purpose of the ingredient in the formulation.

(c) Impurities of toxicological significance associated with the active ingredient . For each impurity associated with the active ingredient that is

determined by EPA to be toxicologically significant, the following information is required:

(1) Identification of the ingredient as an impurity.

(2) The chemical name of the impurity.

(3) The nominal concentration of the impurity in the product.

(4) A certified upper limit, in accordance with §158.350.

(d) Other impurities associated with the active ingredient . For each other impurity associated with an active ingredient that was found to be present

in any sample at a level≥0.1 percent by weight of the technical grade active ingredient the following information is required:

(1) Identification of the ingredient as an impurity.

(2) The chemical name of the impurity.

(3) The nominal concentration of the impurity in the final product.

(e) Impurities associated with an inert ingredient . [Reserved]

(f) Ingredients that cannot be characterized . If the identity of any ingredient or impurity cannot be specified as a discrete chemical substance (such

as mixtures that cannot be characterized or isomer mixtures), the applicant must provide sufficient information to enable EPA to identify its source

and qualitative composition.

§ 158.325 Description of materials used to produce the product.

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The following information must be submitted on the materials used to produce the product:

(a) Products not produced by an integrated system . (1) For each active ingredient that is derived from an EPA-registered product:

(i) The name of the EPA-registered product.

(ii) The EPA registration number of that product.

(2) For each inert ingredient:

(i) Each brand name, trade name, common name, or other commercial designation of the ingredient.

(ii) All information that the applicant knows (or that is reasonably available to him) concerning the composition (and, if requested by the Agency,

chemical and physical properties) of the ingredient, including a copy of technical specifications, data sheets, or other documents describing the

ingredient.

(iii) If requested by the Agency, the name and address of the producer of the ingredient or, if that information is not known to the applicant, the

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name and address of the supplier of the ingredient.

(b) Products produced by an integrated system . (1) The information required by paragraph (a)(1) of this section concerning each active ingredient

that is derived from an EPA-registered product (if any).

(2) The following information concerning each active ingredient that is not derived from an EPA-registered product:

(i) The name and address of the producer of the ingredient (if different from the applicant).

(ii) Information about each starting material used to produce the active ingredient, as follows:

(A) Each brand name, trade name, or other commercial designation of the starting material.

(B) The name and address of the person who produces the starting material or, if that information is not known to the applicant, the name and

address of each person who supplies the starting material.

(C) All information that the applicant knows (or that is reasonably available to him), concerning the composition (and if requested by the Agency,

chemical or physical properties) of the starting material, including a copy of all technical specifications, data sheets, or other documents describing it.

(3) The information required by paragraph (a)(2) of this section concerning each inert ingredient.

(c) Additional information . On a case-by-case basis, the Agency may require additional information on substances used in the production of the

product.

§ 158.330 Description of production process.

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If the product is produced by an integrated system, the applicant must submit information on the production (reaction) processes used to produce the

active ingredients in the product. The applicant must also submit information about the formulation process, in accordance with §158.335.

(a) Information must be submitted for the current production process for each active ingredient that is not derived from an EPA-registered product.

If the production process is not continuous (a single reaction process from starting materials to active ingredient), but is accomplished in stages or by

different producers, the information must be provided for each such production process.

(b) The following information must be provided for each process resulting in a separately isolated substance:

(1) The name and address of the producer who uses the process, if not the same as the applicant.

(2) A general characterization of the process (e.g., whether it is a batch or continuous process).

(3) A flow chart of the chemical equations of each intended reaction occurring at each step of the process, and of the duration of each step and of

the entire process.

(4) The identity of the materials used to produce the product, their relative amounts, and the order in which they are added.

(5) A description of the equipment used that may influence the composition of the substance produced.

(6) A description of the conditions (e.g., temperature, pressure, pH, humidity) that are controlled during each step of the process to affect the

composition of the substance produced, and the limits that are maintained.

(7) A description of any purification procedures (including procedures to recover or recycle starting materials, intermediates or the substance

produced).

(8) A description of the procedures used to assure consistent composition of the substance produced, e.g., calibration of equipment, sampling

regimens, analytical methods, and other quality control methods.

§ 158.335 Description of formulation process.

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The applicant must provide information on the formulation process of the product (unless the product consists solely of a technical grade of active

ingredient) as required by the following sections:

(a) Section 158.330(b)(2), pertaining to characterization of the process.

(b) Section 158.330(b)(4), pertaining to ingredients used in the process.

(c) Section 158.330(b)(5), pertaining to process equipment.

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(d) Section 158.330(b)(6), pertaining to the conditions of the process.

(e) Section 158.330(b)(8), pertaining to quality control measures.

§ 158.340 Discussion of formation of impurities.

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The applicant must provide a discussion of the impurities that may be present in the product, and why they may be present. The discussion should be

based on established chemical theory and on what the applicant knows about the starting materials, technical grade of active ingredient, inert

ingredients, and production or formulation process. If the applicant has reason to believe that an impurity that EPA would consider toxicologically

significant may be present, the discussion must include an expanded discussion of the possible formation of the impurity and the amounts at which it

might be present. The impurities which must also be discussed are the following, as applicable:

(a) Technical grade active ingredients and products produced by an integrated system . (1) Each impurity associated with the active ingredient

which was found to be present in any analysis of the product conducted by or for the applicant.

(2) Each other impurity which the registrant or applicant has reason to believe may be present in his product at any time before use at a level≥0.1

percent (1,000 ppm) by weight of the technical grade of the active ingredient, based on what he knows about the following:

(i) The composition (or composition range) of each starting material used to produce his product.

(ii) The impurities which the applicant knows are present (or believes are likely to be present) in the starting materials, and the known or presumed

level (or range of levels) of these impurities.

(iii) The intended reactions and side reactions which may occur in the production of the product, and the relative amounts of byproduct impurities

produced by such reactions.

(iv) The possible degradation of the ingredients in the product after its production but prior to its use.

(v) Post-production reactions between the ingredients in the product.

(vi) The possible migration of components of packaging materials into the pesticide.

(vii) The possible carryover of contaminants from use of production equipment previously used to produce other products or substances.

(viii) The process control, purification and quality control measures used to produce the product.

(b) Products not produced by an integrated system . Each impurity associated with the active ingredient which the applicant has reason to believe

may be present in the product at any time before use at a level≥0.1 percent (1,000 ppm) by weight of the product based on what he knows about the

following:

(1) The possible carryover of impurities present in any registered product which serves as the source of any of the product's active ingredients. The

identity and level of impurities in the registered source need not be discussed or quantified unless known to the formulator.

(2) The possible carryover of impurities present in the inert ingredients in the product.

(3) Possible reactions occurring during the formulation of the product between any of its active ingredients, between the active ingredients and inert

ingredients, or between the active ingredient and the production equipment.

(4) Post-production reactions between any of the product's active ingredients and any other component of the product or its packaging.

(5) Possible migration of packaging materials into the product.

(6) Possible contaminants resulting from earlier use of equipment to produce other products.

(c) Expanded discussion . On a case-by-case basis, the Agency may require an expanded discussion of information on impurities:

(1) From other possible chemical reactions.

(2) Involving other ingredients.

(3) At additional points in the production or formulation process.

§ 158.345 Preliminary analysis.

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(a) If the product is produced by an integrated system, the applicant must provide a preliminary analysis of each technical grade of active ingredient

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contained in the product to identify all impurities present at 0. 1 percent or greater of the technical grade of the active ingredient. The preliminary

analysis should be conducted at the point in the production process after which no further chemical reactions designed to produce or purify the

substances are intended.

(b) Based on the preliminary analysis, a statement of the composition of the technical grade of the active ingredient must be provided. If the

technical grade of the active ingredient cannot be isolated, a statement of the composition of the practical equivalent of the technical grade of the

active ingredient must be submitted.

§ 158.350 Certified limits.

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The applicant must propose certified limits for the ingredients in the product. Certified limits become legally binding limits upon approval of the

application. Certified limits will apply to the product from the date of production to date of use. If the product label bears a statement prohibiting use

after a certain date, the certified limits will apply only until that date.

(a) Ingredients for which certified limits are required . Certified limits are required on the following ingredients of a pesticide product:

(1) An upper and lower limit for each active ingredient.

(2) An upper and lower limit for each inert ingredient.

(3) If the product is a technical grade of active ingredient or is produced by an integrated system, an upper limit for each impurity of toxicological

significance associated with the active ingredient and found to be present in any sample of the product.

(4) On a case-by-case basis, certified limits for other ingredients or impurities as specified by EPA.

(b) EPA determination of standard certified limits for active and inert ingredients . (1) Unless the applicant proposes different limits as provided in

paragraph (c) of this section, the upper and lower certified limits for active and inert ingredients will be determined by EPA. EPA will calculate the

certified limits on the basis of the nominal concentration of the ingredient in the product, according to the table in paragraph (b)(2) of this section.

(2) Table of standard certified limits.

Standard Certified Limits

If the nominal concentration (N) for the ingredient and percentage by weight for the

ingredient is:

The certified limits for that ingredient will be as

follows:

Upper Limit Lower Limit

N ≤1.0% N + 10%N N - 10%N

1.0% ≤N ≤20.0% N + 5%N N - 5%N

20.0%≤N≤100.0% N + 3%N N - 3%N

(c) Applicant proposed limits . (1) The applicant may propose a certified limit for an active or inert ingredient that differs from the standard certified

limit calculated according to paragraph (b)(2) of this section.

(2) If certified limits are required for impurities, the applicants must propose a certified limit. The standard certified limits may not be used for such

substances.

(3) Certified limits should:

(i) Be based on a consideration of the variability of the concentration of the ingredient in the product when good manufacturing practices and normal

quality control procedures are used.

(ii) Allow for all sources of variability likely to be encountered in the production process.

(iii) Take into account the stability of the ingredient in the product and the possible formation of impurities between production and sale or

distribution.

(4) The applicant may include an explanation of the basis of his proposed certified limits, including how the certified limits were arrived at (e.g.,

sample analysis, quantitative estimate based on production process), and its accuracy and precision. This will be particularly useful if the range of the

certified limit for an active or inert ingredient is greater than the standard certified limits.

(d) Special cases . If the Agency finds unacceptable any certified limit (either standard, or applicant proposed), the Agency will inform the registrant

or applicant of its determination and will provide supporting reasons. The Agency may also recommend alternative limits to the applicant. The

Agency may require, on a case-by-case basis, any or all of the following:

(1) More precise limits.

(2) More thorough explanation of how the certified limits were determined.

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(3) A narrower range between the upper and lower certified limits than that proposed.

(e) Certification statement . The applicant must certify the accuracy of the information presented, and that the certified limits of the ingredients will

be maintained. The following statement, signed by the authorized representative of the company, is acceptable:

I hereby certify that, for purposes of FIFRA sec. 12(a)(1)(C), the description of the composition of [ insert product name ], EPA Reg. No. [ insert registration number ], refers to

the composition set forth on the Statement of Formula and supporting materials. This description includes the representations that: (1) no ingredient will be present in the product in

an amount greater than the upper certified limit or in an amount less than the lower certified limit (if required) specified for that ingredient in a currently approved Statement of

Formula (or as calculated by the Agency); and (2) if the Agency requires that the source of supply of an ingredient be specified, that all quantities of such ingredient will be obtained

from the source specified in the Statement of Formula.

§ 158.355 Enforcement analytical method.

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An analytical method suitable for enforcement purposes must be provided for each active ingredient in the product and for each other ingredient or

impurity that the Agency determines to be toxicologically significant.

Subpart E—Product Performance

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§ 158.400 Product performance data requirements table.

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(a) General . Sections 158.100 through 158.130 describe how to use this table to determine the product performance 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, which includes both food and nonfood uses.

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

product.

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

section.

Table—Product Performance Data Requirements

Guideline

Number Data Requirement

Use Pattern

Test

substance to

support

Test

Note

No.

Terrestrial Aquatic Greenhouse

Forestry

Residential

Outdoor Indoor MP EP

Food

Crop

Nonfood

Crop Food Nonfood

Food

Crop

Nonfood

Crop

Efficacy of antimicrobial agents

91–2 Products for use on hard

surfaces

NR NR NR NR NR NR NR NR CR NR EP 1

91–3 Products requiring

confirmatory data

NR NR NR NR NR NR NR NR CR NR EP 1

91–4 Products for use on fabrics

and textiles

NR NR NR NR NR NR NR NR CR NR EP 1

91–5 Air sanitizers NR NR NR NR NR NR NR NR CR NR EP 1

91–7 Products for control of

microbial pests associated

with human and animal

wastes

NR NR NR NR NR NR NR NR CR NR EP 1

91–8 Products for treating water

systems

NR NR CR NR NR NR NR NR CR NR EP 1

Efficacy of fungicides and nematicides

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93–16 Products for control of

organisms producing

mycotoxins

CR NR CR NR CR NR NR NR NR NR EP 1

Efficacy of vertebrate control agents

96–5 Avian toxicants R R NR NR NR NR NR R R NR EP 1

96–6 Avian repellents R R NR NR NR NR NR R NR NR EP 1

96–7 Avian frightening agents R R NR NR NR NR NR R NR NR EP 1

96–9 Bat toxicants and repellents NR NR NR NR NR NR NR NR R NR EP 1

96–10 Commensal rodenticides R R NR NR NR NR NR R R TEP EP 1

96–12 Rodenticides on farm and

rangelands

R R NR NR NR NR NR R NR NR EP 1

95–13 Rodent fumigants R R NR NR NR NR NR R R NR EP 1

95–16 Rodent reproductive

inhibitors

R R NR NR NR NR NR R R NR EP 1

95–17 Mammalian predacides R R NR NR NR NR NR R NR NR EP 1

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

1. The Agency has waived the requirement to submit product performance data unless the pesticide product bears a claim to control pest microorganisms that pose a threat to human

health and whose presence cannot readily be observed by the user including, but not limited to, microorganisms infectious to man in any area of the inanimate environment, or a claim

to control vertebrates (such as rodents, birds, bats, canids, and skunks) that may directly or indirectly transmit diseases to humans. However each registrant must ensure through

testing that his product is efficacious when used in accordance with label directions and commonly accepted pest control practices. The Agency reserves the right to require, on a

case-by-case basis, submission of product performance data for any pesticide product registered or proposed for registration.

2. [Reserved]

Subpart F—Toxicology

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§ 158.500 Toxicology data requirements table.

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(a) General . Sections 158.100 through 158.130 describe how to use the data table in paragraph (d) of this section to determine the toxicology data

requirements for a particular pesticide product. Notes that apply to an individual test and include specific conditions, qualifications, or exceptions to

the designated test in the table are listed in paragraph (e) of this section.

(b) Use patterns . (1) Food use patterns include products classified under the general use patterns of terrestrial food crop use, terrestrial feed crop

use, aquatic food crop use, greenhouse food crop use, and indoor food use.

(2) Nonfood use patterns include products classified under the general use patterns of terrestrial nonfood crop use, aquatic nonfood use, greenhouse

nonfood crop use, forestry use, residential outdoor use, and indoor nonfood use.

(c) Key . R=Required; CR=Conditionally required; NR=Not required; MP=Manufacturing-use product; EP=End-use product; TGAI=Technical

grade of the active ingredient; PAI=Pure active ingredient; PAIRA=Pure active ingredient radio-labeled; Choice=Choice of several test substances

depending on study required.

(d) Table . The following table lists the toxicology data requirements. The table notes are shown in paragraph (e) of this section.

Table—Toxicology Data Requirements

Guideline

Number Data Requirements

Use Pattern Test substance to support

Food Nonfood MP EP Test Note No.

Acute Testing

870.1100 Acute oral toxicity - rat R R TGAI and

MP

TGAI, EP, and possibly

diluted EP

1, 2

870.1200 Acute dermal toxicity R R TGAI and

MP

TGAI, EP 1, 2, 3

870.1300 Acute inhalation toxicity - rat R R TGAI and

MP

TGAI and EP 4

870.2400 Primary eye irritation - rabbit R R TGAI and

MP

TGAI and EP 3

870.2500 Primary dermal irritation R R TGAI and

MP

TGAI and EP 1, 3

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870.2600 Dermal sensitization R R TGAI and

MP

TGAI and EP 3, 5

870.6100 Delayed neurotoxicity (acute) - hen CR CR TGAI TGAI 6

870.6200 Acute neurotoxicity - rat R R TGAI TGAI 7

Subchronic Testing

870.3100 90–day Oral - rodent R CR TGAI TGAI 8, 9

870.3150 90–day Oral - non-rodent R CR TGAI TGAI 36

870.3200 21/28–day Dermal R NR TGAI TGAI and EP 10, 11

870.3250 90–day Dermal CR R TGAI TGAI and EP 11, 12

870.3465 90–day Inhalation - rat CR CR TGAI TGAI 13, 14

870.6100 28–day Delayed neurotoxicity-hen CR CR TGAI TGAI 6, 15

870.6200 90–day Neurotoxicity - rat R R TGAI TGAI 7, 16

Chronic Testing

870.4100 Chronic oral - rodent R CR TGAI TGAI 17, 18, 19

870.4200 Carcinogenicity - two rodent species - rat and mouse

preferred

R CR TGAI TGAI 9, 17, 18, 19,

20, 21

Developmental Toxicity and Reproduction

870.3700 Prenatal Developmental toxicity - rat and rabbit,

preferred

R R TGAI TGAI 22, 23, 24, 25,

26

870.3800 Reproduction and fertility effects R R TGAI TGAI 26, 27, 29

870.6300 Developmental neurotoxicity CR CR TGAI TGAI 27, 28, 29

Mutagenicity Testing

870.5100 Bacterial reverse mutation assay R R TGAI TGAI 30

870.5300

870.5375

In vitro mammalian cell assay R R TGAI TGAI 30, 31

870.5385

870.5395

In vivo cytogenetics R R TGAI TGAI 30, 32

Special Testing

870.7485 Metabolism and pharmacokinetics R CR PAI or

PAIRA

PAI or PAIRA 33

870.7200 Companion animal safety CR CR NR TGAI or EP 34

870.7600 Dermal penetration CR CR Choice Choice 35

870.7800 Immunotoxicity R R TGAI TGAI

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

1. Not required if test material is a gas or a highly volatile liquid.

2. Diluted EP testing is required to support the end product registration if results using the EP meet the criteria for restricted use classification under §152.170(b) or special review

consideration under §154.7(a)(1).

3. Not required if the test material is corrosive to skin or has a pH of less than 2 or greater than 11.5.

4. Required if the product consists of, or under conditions of use will result in, a respirable material (e.g., gas, vapor, aerosol, or particulate).

5. Required if repeated dermal exposure is likely to occur under conditions of use.

6. Required if the test material is an organophosphorus substance, which includes uncharged organophosphorus esters; thioesters or anhydrides of organophosphoric,

organophosphonic, or organophosphoramidic acids; or of related phosphorothioic, phosponothioic, or phosphorothioamidic acids; or is structurally related to other substances that

may cause the delayed neurotoxicity sometimes seen in this class of chemicals.

7. As determined by the Agency, additional measurements may also be required, such as cholinesterase activity for certain pesticides, e.g., organophosphates and some carbamates.

The route of exposure must correspond with the primary route of exposure.

8. Required for nonfood use pesticides if oral exposure could occur.

9. The 90–day study is required in the rat for hazard characterization (possibly endpoint selection) and dose-setting for the chronic/carcinogenicity study. It is not required in the

mouse, but the Agency would strongly encourage the registrant to conduct a 90–day range finding for the purposes of dose selection for the mouse carcinogenicity study to achieve

adequate dosing and an acceptable study. The registrant is also encouraged to consult with the Agency on the results of the 90–day mouse study prior to conducting the

carcinogenicity study.

10. Required for agricultural uses or if repeated human dermal exposure may occur. Not required if an acceptable 90–day dermal toxicity study is performed and submitted.

11. EP testing is required if the product, or any component of it, may increase dermal absorption of the active ingredient(s) as determined by testing using the TGAI, or increase toxic

or pharmacologic effects.

12. Required for food uses if either of the following criteria is met:

(i) The use pattern is such that the dermal route would be the primary route of exposure; or

(ii) The active ingredient is known or expected to be metabolized differently by the dermal route of exposure than by the oral route, and a metabolite is the toxic moiety.

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13. Required if there is the likelihood of significant repeated inhalation exposure to the pesticide as a gas, vapor, or aerosol.

14. Based on estimates of the magnitude and duration of human exposure, studies of shorter duration, e.g., 21– or 28–days, may be sufficient to satisfy this requirement. Registrants

should consult with the Agency to determine whether studies of shorter duration would meet this requirement.

15. Required if results of acute neurotoxicity study indicate significant statistical or biological effects, or if other available data indicate the potential for this type of delayed

neurotoxicity, as determined by the Agency.

16. All 90–day subchronic studies in rats can be designed to simultaneously fulfill the requirements of the 90–day neurotoxicity study using separate groups of animals for testing.

Although the subchronic guidelines include the measurement of neurological endpoints, they do not meet the requirement of the 90–day neurotoxicity study.

17. Required if either of the following are met:

(i) The use of the pesticide is likely to result in repeated human exposure over a considerable portion of the human lifespan, as determined by the Agency;

(ii) The use requires a tolerance or an exemption from the requirement of a tolerance.

18. Based on the results of the acute and subchronic neurotoxicity studies, or other available data, a combined chronic toxicity and neurotoxicity study may be required.

19. Studies which are designed to simultaneously fulfill the requirements of both the chronic oral and carcinogenicity studies ( i.e. , a combined study) may be conducted. Minimum

acceptable study durations are:

(i) Chronic rodent feeding study (food use) - 24 months.

(ii) Chronic rodent feeding study (nonfood use) - 12 months.

(iii) Mouse carcinogenicity study - 18 months.

(iv) Rat carcinogenicity study - 24 months.

20. Required if any of the following, as determined by the Agency, are met:

(i) The use of the pesticide is likely to result in significant human exposure over a considerable portion of the human life span which is significant in terms of either frequency,

duration, or magnitude of exposure;

(ii) The use requires a tolerance or an exemption from the requirement of a tolerance; or

(iii) The active ingredient, metabolite, degradate, or impurity (a) is structurally related to a recognized carcinogen, (b) causes mutagenic effects as demonstrated by in vitro or in

vivo testing, or (c) produces a morphologic effect in any organ (e.g., hyperplasia, metaplasia) in subchronic studies that may lead to a neoplastic change.

21. If this study is modified or waived, a subchronic 90–day oral study conducted in the same species may be required.

22. Testing in two species is required for all uses.

23. The oral route, by oral intubation, is preferred unless the chemical or physical properties of the test substance or the pattern of exposure suggests a more appropriate route of

exposure.

24. Additional testing by other routes may be required if the pesticide is determined to be a prenatal developmental toxicant after oral dosing.

25. May be combined with the 2–generation reproduction study in rodents by utilizing a second mating of the parental animals in either generation.

26. Required to support products intended for food uses and to support products intended for nonfood uses if use of the product is likely to result in significant human exposure over a

portion of the human life span in terms of frequency, magnitude or duration of exposure.

27. An information-based approach to testing is preferred, which utilizes the best available knowledge on the chemical (hazard, pharmacokinetic, or mechanistic data) to determine

whether a standard guideline study, an enhanced guideline study, or an alternative study should be conducted to assess potential hazard to the developing animal, or in some cases to

support a waiver for such testing. Registrants should submit any alternative proposed testing protocols and supporting scientific rationale to the Agency prior to study initiation.

28. Study required using a weight-of-evidence approach considering:

(i) The pesticide causes treatment-related neurological effects in adult animal studies ( i.e. , clinical signs of neurotoxicity, neuropathology, functional or behavioral effects).

(ii) The pesticide causes treatment-related neurological effects in developing animals, following pre- and postnatal exposure ( i.e. , nervous system malformations or neuropathy,

brain weight changes in offspring, functional or behavioral changes in the offspring).

(iii) The pesticide elicits a causative association between exposures and adverse neurological effects in human epidemiological studies.

(iv) The pesticide evokes a mechanism that is associated with adverse effects on the development of the nervous system (e.g., SAR relationship to known neurotoxicants, altered

neuroreceptor or neurotransmitter responses).

29. The use of a combined study that utilizes the 2–generation reproduction study in rodents as a basic protocol for the addition of other endpoints or functional assessments in the

immature animal is encouraged.

30. At a minimum, an initial battery of mutagenicity tests with possible confirmatory testing is required. Other relevant mutagenicity tests that may have been performed, plus a

complete reference list must also be submitted.

31. Choice of assay using either:

(i) Mouse lymphoma L5178Y cells, thymidine kinase (tk) gene locus, maximizing assay conditions for small colony expression or detection;

(ii) Chinese hamster ovary (CHO) or Chinese hamster lung fibroblast (V79) cells, hypoxanthine-guanine phosphoribosyl transferase (hgprt) gene locus, accompanied by an

appropriate in vitro test for clastogenicity; or

(iii) CHO cells strains AS52, xanthine-guanine phosphoribosyl transferase (xprt) gene locus.

32. The micronucleus rodent bone marrow assay is preferred; however, rodent bone marrow assays using metaphase analysis (aberrations) are acceptable.

33. Required when chronic or carcinogenicity studies are required. May be required if significant adverse effects are seen in available toxicology studies and these effects can be

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further elucidated by metabolism studies.

34. May be required if the product's use will result in exposure to domestic animals through, but not limited to, direct application.

35. A risk assessment assuming that dermal absorption is equal to oral absorption must be performed to determine if the study is required, and to identify the doses and duration of

exposure for which dermal absorption is to be quantified.

36. A 1–year non-rodent study ( i.e. , 1–year dog study) would be required if the Agency finds that a pesticide chemical is highly bioaccumulating and is eliminated so slowly that it

does not achieve steady state or sufficient tissue concentrations to elicit an effect during a 90–day study. EPA would require the appropriate tier II metabolism and pharmacokinetic

studies to evaluate more precisely bioavailability, half-life, and steady state to determine if a longer duration dog toxicity study is needed.

§ 158.510 Tiered testing options for nonfood pesticides.

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For nonfood use pesticides only, applicants have two options for generating and submitting required toxicology (§158.500) and human exposure

(§158.1020, §158.1070, and §158.1410) studies. Applicants are to select one of the following:

(a) Acute, subchronic, chronic, and other toxicological studies on the active ingredient must be submitted together. The specific makeup of the set of

toxicology study requirements is based on the anticipated exposure to the pesticide as determined by the Agency. If hazards are identified based

upon review of these studies, specific exposure data will be required to evaluate risk.

(b) Certain toxicological and exposure studies must be submitted simultaneously with the toxicology data submitted in a tiered system. Exposure

data must be submitted along with first tier toxicology data. The requirement for additional second and third level toxicology testing will be

determined by the Agency based on the results of the first tiered studies.

(1) The required first-tier toxicology studies consist of:

(i) Battery of acute studies.

(ii) A subchronic 90–day dermal study or a subchronic 90–day inhalation study.

(iii) An acute and subchronic neurotoxicity screening battery in the rat.

(iv) Prenatal developmental toxicity studies in both the rat and rabbit.

(v) Reproduction and fertility studies in rats.

(vi) Battery of mutagenicity studies.

(vii) Immunotoxicity study.

(2) The conditionally required second-tier studies include:

(i) Subchronic 90–day feeding studies in both the rodent and nonrodent.

(ii) Dermal penetration study.

(3) The conditionally required third-tier studies include:

(i) Chronic feeding studies in the rodent.

(ii) Carcinogenicity.

(iii) Metabolism study.

(iv) Additional mutagenicity testing.

Subpart G— Ecological Effects

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§ 158.630 Terrestrial and aquatic nontarget organisms data requirements table.

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(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

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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.

Terrestrial and Aquatic Nontarget Organism Data Requirements

Guideline

Number Data Requirement

Use Pattern

Test substance

Test

Terrestrial Aquatic Forestry Note No.

Residential

Outdoor Greenhouse Indoor

Avian and Mammalian Testing

850.2100 Avian oral toxicity R R R R CR CR TGAI 1, 2, 3

850.2200 Avian dietary toxicity R R R R NR NR TGAI 1, 4

850.2400 Wild mammal toxicity CR CR CR CR NR NR TGAI 5

850.2300 Avian reproduction R R R R NR NR TGAI 1, 4

850.2500 Simulated or actual field testing CR CR CR CR NR NR TEP 6, 7

Aquatic Organisms Testing

850.1075 Freshwater fish toxicity R R R R CR CR TGAI, TEP 1, 2, 8,

9, 26

850.1010 Acute toxicity freshwater

invertebrates

R R R R CR CR TGAI, TEP 1, 2, 9,

10, 26

850.1025

850.1035

850.1045

850.1055

850.1075

Acute toxicity estuarine and marine

organisms

R R R R NR NR TGAI, TEP 1, 9, 11,

12, 26

850.1300 Aquatic invertebrate life cycle

(freshwater)

R R R R NR NR TGAI 1, 10, 12

850.1350 Aquatic invertebrate life cycle

(saltwater)

CR CR CR CR NR NR TGAI 12, 14,

15

850.1400 Fish early-life stage (freshwater) R R R R NR NR TGAI 1, 12, 13

850.1400 Fish early-life stage (saltwater) CR CR CR CR NR NR TGAI 12, 15,

16

850.1500 Fish life cycle CR CR CR CR NR NR TGAI 17, 18

850.1710

850.1730

850.1850

Aquatic organisms bioavailability,

biomagnification, toxicity

CR CR CR CR NR NR TGAI, PAI,

degradate

19

850.1950 Simulated or actual field testing for

aquatic organisms

CR CR CR CR NR NR TEP 7, 20

Sediment Testing

850.1735 Whole sediment: acute freshwater

invertebrates

CR CR CR CR NR NR TGAI 21

850.1740 Whole sediment: acute marine

invertebrates

CR CR CR CR NR NR TGAI 21, 23

Whole sediment: chronic

invertebrates freshwater and marine

CR CR CR CR NR NR TGAI 22, 23

Insect Pollinator Testing

850.3020 Honeybee acute contact toxicity R CR R R NR NR TGAI 1

850.3030 Honey bee toxicity of residues on

foliage

CR CR CR CR NR NR TEP 24

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850.3040 Field testing for pollinators CR CR CR CR NR NR TEP 25

(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.

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

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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 LD50of<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.

§ 158.660 Nontarget plant protection data requirements table.

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(a) General . Sections 158.100 through158.130 describe how to use this table to determine the nontarget plant data requirements for a particular

pesticide product. Notes that apply to an individual test and include 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. The aquatic use pattern includes only the general use patterns of aquatic food crops and aquatic nonfood.

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

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

product.

(d) Table . The following table shows the nontarget plant protection data requirements. The table notes are shown in paragraph (e) of this section.

Table—Nontarget Plant Protection Data Requirements

Guideline

Number Data Requirement

Use Pattern

Test

substance

Test Note

Terrestrial Aquatic No.

Forestry and Residential

Outdoor

Nontarget Area Phytotoxicity - Tier I

850.4100 Seedling emergence R R R TEP 1, 2, 7

850.4150 Vegetative vigor R R R TEP 1, 2, 3, 7

850.4400

850.5400

Aquatic plant growth (algal and aquatic vascular

plant toxicity)

R R R TEP or TGAI 1, 2, 7

Nontarget Area Phytotoxicity - Tier II

850.4100 Seedling emergence CR CR CR TEP 1, 4, 5, 7

850.4150 Vegetative vigor CR CR CR TEP 1, 3, 4, 5, 7

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850.4400

850.5400

Aquatic plant growth (algal and aquatic vascular

plant toxicity)

CR CR CR TEP or TGAI 1, 4, 6, 7

Nontarget Area Phytotoxicity - Tier III

850.4300 Terrestrial field CR CR CR TEP 1, 7, 8, 10

850.4450 Aquatic field CR CR CR TEP 1, 7, 8, 10

Target Area Phytotoxicity

850.4025 Target area phytotoxicity CR CR CR TEP 1, 7, 9, 10

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

1. Not required for contained pesticide treatments such as bait boxes and pheromone traps unless adverse effects reports are received by the Agency.

2. Not required for known phytotoxicants.

3. Generally not required for granular formulations. May be requested on a case-by-case basis.

4. Required for known phytotoxicants such as herbicides, desiccants and defoliants.

5. Required if a tested terrestrial species exhibits a 25 percent or greater detrimental effect in the Tier I study. When Tier II testing is required, the test species should be the species

that showed detrimental effects in the Tier I testing.

6. Required if the tested aquatic species exhibits a 50 percent or greater detrimental effect in the Tier I study. When Tier II testing is required, the test species should be the species

that showed detrimental effects in the tier I testing.

7. Not required for aquatic residential uses.

8. Environmental chemistry methods used to generate data must include the results of a successful confirmatory method trial by an independent laboratory.

9. Tests are required on a case-by-case basis based on the results of lower tier phytotoxicity studies, adverse incident reports, intended use pattern, and environmental fate

characteristics that indicate potential exposure.

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

Subparts H–J [Reserved]

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§§ 158.700-158.900 [Reserved]

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Subpart K—Human Exposure

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§ 158.1000 Applicator exposure—general requirements.

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(a) If EPA determines that industrial standards, such as the workplace standards set by the Occupational Safety and Health Administration (OSHA),

provide adequate protection from risk under FIFRA for a particular pesticide use pattern, exposure data may not be required for that use pattern.

Applicants should consult with the Agency on appropriate testing prior to the initiation of studies.

(b) The Agency may accept surrogate exposure data estimations from other sources to satisfy applicator exposure data requirements if the data meet

the basic quality assurance, quality control, good laboratory practice, and other scientific requirements set by EPA. In order to be acceptable, the

Agency must find that the surrogate exposure data estimations have adequate information to address applicator exposure data requirements and

contain adequate replicates of acceptable quality data to reflect the specific use prescribed on the label and the applicator activity of concern,

including formulation type, application methods and rates, type of activity, and other pertinent information. The Agency will consider using such

surrogate data for evaluating human exposure on a case-by-case basis.

§ 158.1010 Applicator exposure—criteria for testing.

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Applicator exposure data described in paragraph (d) of this section are required based on toxicity and exposure criteria. Data are required if a

product meets, as determined by the Agency, at least one of the toxicity criteria in paragraph (a) of this section and either or both of the exposure

criteria in paragraph (b) of this section.

(a) Toxicity criteria . (1) Evidence of potentially significant adverse effects have been observed in any applicable toxicity study.

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(2) Scientifically sound epidemiological or poisoning incident data indicate that adverse health effects may have resulted from handling of the

pesticide.

(b) Exposure criteria . (1) Dermal exposure may occur during the prescribed use.

(2) Respiratory exposure may occur during the prescribed use.

§ 158.1020 Applicator exposure data requirements table.

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(a) General . Sections 158.100 through 158.130 describe how to use this table to determine the applicator exposure data requirements for a

particular pesticide product. Notes that apply to an individual test and include specific conditions, qualifications, or exceptions to the designated test

are listed in paragraph (e) of this section.

(b) Use patterns . (1) Occupational use patterns include products classified under the general use patterns of terrestrial food crop, terrestrial feed

crop, terrestrial nonfood crop, aquatic food, aquatic nonfood use, forestry, greenhouse food, greenhouse nonfood, indoor food use, and indoor

nonfood use. Occupational use patterns also include commercial (“for hire”) applications to residential outdoor and indoor sites.

(2) Residential use patterns include residential outdoor use and residential indoor use. These use patterns are limited to nonoccupational, i.e. ,

nonprofessional, pesticide applications.

(c) Key . R=Required; CR=Conditionally required; TEP=Typical end-use product.

(d) Table . The data requirements listed pertain to pesticide products that meet the testing criteria outlined in §158.1010. The table notes are shown

in paragraph (e) of this section.

Table—Applicator Exposure Data Requirements

Guideline Number Data requirement

Use pattern

Occupational Residential Test substance Test Note No.

875.1100 Dermal outdoor exposure R R TEP 1, 2, 3

875.1200 Dermal indoor exposure R R TEP 1, 2, 4

875.1300 Inhalation outdoor exposure R R TEP 1, 2, 3

875.1400 Inhalation indoor exposure R R TEP 1, 2, 4

875.1500 Biological monitoring CR CR TEP 1, 2

875.1600 Data reporting and calculations R R TEP 5

875.1700 Product use information R R TEP --

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

1. Protocols must be submitted for approval prior to the initiation of the study. Details for developing protocols are available from the Agency.

2. Biological monitoring data may be submitted in addition to, or in lieu of, dermal and inhalation exposure data, provided the human pharmacokinetics of the pesticide and/or

metabolite/analog compounds ( i.e. , whichever method is selected as an indicator of body burden or internal dose) allow for the back calculation to actual dose.

3. Data are required if the product is applied outdoors.

4. Data are required if the product is applied indoors.

5. Data reporting and calculations are required when handler exposure data are submitted.

§ 158.1050 Post-application exposure—general requirements.

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(a) If EPA determines that industrial standards, such as the workplace standards set by the Occupational Safety and Health Administration, provide

adequate protection for a particular pesticide use pattern, post-application exposure data may not be required for that use pattern. Applicants should

consult with the Agency on appropriate testing before the initiation of studies.

(b) The Agency may accept surrogate exposure data from other sources to satisfy post-application exposure data requirements if the data meet the

basic quality assurance, quality control, good laboratory practice, and other scientific needs of EPA. In order to be acceptable, among other things,

the Agency must find that the surrogate exposure data have adequate information to address post-application exposure data requirements and

contain adequate replicates of acceptable quality data to reflect the specific use prescribed on the label and the post-application activity of concern,

including formulation type, application methods and rates, type of activity, and other pertinent information. The Agency will consider using such

surrogate data for evaluating human exposure on a case-by-case basis.

§ 158.1060 Post-application exposure—criteria for testing

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Exposure data described in §158.1070(d) are required based upon toxicity and exposure criteria. Data are required if a product meets, as determined

by the Agency, either or both of the toxicity criteria in paragraph (a) of this section and either or both of the exposure criteria in paragraph (b) of this

section.

(a) Toxicity criteria . (1) Evidence of potentially significant adverse health effects have been observed in any applicable toxicity study.

(2) Scientifically sound epidemiological or poisoning incident data indicate that adverse health effects may have resulted from post-application

exposure to the pesticide.

(b) Exposure criteria . The need for data from potential exposure resulting from situations not covered by this paragraph should be discussed with

the Agency.

(1) For outdoor uses . (i) Occupational human post-application exposure to pesticide residues on plants or in soil could occur as the result of

cultivation, pruning, harvesting, mowing or other work-related activity. Such uses include agricultural food, feed, and fiber commodities, forest trees,

ornamental plants, and turf grass.

(ii) Residential human post-application exposure to pesticide residues on plants or in soil could occur. Such uses may include turf grass, fruits,

vegetables, and ornamentals grown at sites, including, but not limited to, homes, parks, and recreation areas.

(2) For indoor uses . (i) Occupational human post-application exposure to pesticide residues could occur following the application of the pesticide to

indoor spaces or surfaces at agricultural or commercial sites, such as, but not limited to, agricultural animal facilities and industrial or manufacturing

facilities.

(ii) Residential human post-application exposure to pesticide residues could occur following the application of the pesticide to indoor spaces or

surfaces at residential sites, such as, but not limited to homes, daycare centers, hospitals, schools, and other public buildings.

§ 158.1070 Post-application exposure data requirements table.

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(a) General . Sections 158.100 through 158.130 describe how to use this table to determine the post-application data requirements for a particular

pesticide product. Notes that apply to an individual test and include specific conditions, qualifications, or exceptions to the designated test are listed

in paragraph (e) of this section.

(b) Use patterns . (1) Occupational use patterns include products classified under the general use patterns of terrestrial food crop, terrestrial feed

crop, terrestrial nonfood use, aquatic food, aquatic nonfood use, forestry, greenhouse food, greenhouse nonfood, indoor food, and indoor nonfood.

Occupational use patterns also include commercial (“for hire”) applications to residential outdoor and indoor sites.

(2) Residential use patterns include residential outdoor use and indoor residential use. These use patterns are limited to nonoccupational, i.e. ,

nonprofessional, pesticide applications.

(c) Key . R=Required; CR=Conditionally required; NR=Not required; TEP=Typical end-use product.

(d) Table . The data requirements listed in the following table pertain to pesticide products that meet the testing criteria outlined in §158.1060. The

table notes are shown in paragraph (e) of this section.

Table—Post-Application Exposure Data Requirements

Guideline Number Data Requirement

Use Pattern

Occupational Residential Test Substance Test Note No.

875.2100 Dislodgeable foliar residue and turf transferable residues R R TEP 1, 2, 3, 4, 5

875.2200 Soil residue dissipation R CR TEP 1, 2, 6, 7

875.2300 Indoor surface residue dissipation R R TEP 1, 2, 8, 9

875.2400 Dermal exposure R R TEP 1, 2, 10, 11, 12

875.2500 Inhalation exposure R R TEP 1, 10, 11, 12

875.2600 Biological monitoring CR CR TEP 1, 12, 13

875.2700 Product use information R R TEP --

875.2800 Description of human activity R R TEP --

875.2900 Data reporting and calculations R R TEP 14

875.3000 Nondietary ingestion exposure NR R TEP 1, 11, 15

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

1. Protocols must be submitted for approval prior to the initiation of the study. Details for developing protocols are available from the Agency.

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2. Bridging applicable residue dissipation data to dermal exposure data is required.

3. Turf grass transferable residue dissipation data are required when pesticides are applied to turf grass. Dislodgeable foliar residue dissipation data are required when pesticides

are applied to the foliage of plants other than turf grass.

4. Data are required for occupational sites if (i) there are uses on turf grass or other plant foliage, and (ii) the human activity data indicate that workers are likely to have

post-application dermal contact with treated foliage while participating in typical activities.

5. Data are required for residential sites if there are uses on turf grass or other plant foliage.

6. Data are required for occupational sites, if (i) there are outdoor or greenhouse uses to or around soil or other planting media, and (ii) the human activity data indicate that workers

are likely to have post-application dermal contact with treated soil or planting media while participating in typical activities.

7. Data are required for residential sites if the pesticide is applied to or around soil or other planting media both outdoors and indoors, e.g., residential greenhouse or houseplant

uses.

8. Data are required for occupational sites if the pesticide is applied to or around on non-plant surfaces, e.g., flooring or countertops, and if the human activity data indicate that

workers are likely to have post-application dermal contact with treated indoor surfaces while participating in typical activities.

9. Data are required for residential sites if the pesticide is applied to or around non-plant surfaces, e.g., flooring and countertops.

10. Data are required for occupational sites if the human activity data indicate that workers are likely to have post-application exposures while participating in typical activities.

11. Data are required for residential sites if post-application exposures are likely.

12. Biological monitoring data may be submitted in addition to, or in lieu of, dermal and inhalation exposure data provided the human pharmocokinetics of the pesticide and/or

metabolite/analog compounds ( i.e. , whichever method is selected as an indicator of body burden or internal dose) allow for a back-calculation to the total internal dose.

13. Data are required when passive dosimetry techniques are not applicable for a particular exposure scenario, such as a swimmer exposure to pesticides.

14. Data reporting and calculations are required when any post-application exposure monitoring data are submitted.

15. The selection of a sampling method will depend on the nondietary pathway(s) of interest. Data must be generated to consider all potential pathways of nondietary ingestion

exposure that are applicable (e.g., soil ingestion, hand-to-mouth transfer, and object-to-mouth transfer of surface residues).

Subpart L—Spray Drift

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§ 158.1100 Spray drift data requirements table.

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(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.

Table—Spray Drift Data Requirements

Guideline

Number

Data

Requirement

Use Pattern

Test

substance

Test

Note No.

Terrestrial Aquatic Greenhouse

Forestry

Residential

Outdoor Indoor MP EP

Food

Crop

Nonfood

Crop Food Nonfood

Food

Crop

Nonfood

Crop

201–1 Droplet size

spectrum

CR CR CR CR NR NR CR NR NR TEP TEP 1

202–1 Droplet size

spectrum

CR CR CR CR NR NR CR NR NR TEP TEP 1

(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.

2. [Reserved]

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Subpart M [Reserved]

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§§ 158.1200 -158.1299 [Reserved]

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Subpart N—Environmental Fate

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§ 158.1300 Environmental fate data requirements table.

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(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.

Table—Environmental Fate Data Requirements

Guideline

Number Data Requirement

Use Pattern

Test

substance

Test Note

Terrestrial Aquatic Greenhouse Indoor Forestry No.

Residential

Outdoor

Degradation Studies - Laboratory

835.2120 Hydrolysis R R R CR R R TGAI or

PAIRA

1

835.2240 Photodegradation in water R R NR NR R NR TGAI or

PAIRA

2

835.2410 Photodegradation on soil R NR NR NR R NR TGAI or

PAIRA

3

835.2370 Photodegradation in air CR NR CR NR CR CR TGAI or

PAIRA

4

Metabolism Studies - Laboratory

835.4100 Aerobic soil R CR R NR R R TGAI or

PAIRA

5

835.4200 Anaerobic soil R NR NR NR NR NR TGAI or

PAIRA

--

835.4300 Aerobic aquatic R R NR NR R NR TGAI or

PAIRA

--

835.4400 Anaerobic aquatic R R NR NR R NR TGAI or

PAIRA

--

Mobility Studies

835.1230

835.1240

Leaching and

adsorption/desorption

R R R NR R R TGAI or

PAIRA

6

835.1410 Volatility - laboratory CR NR CR NR NR NR TEP 4

835.8100 Volatility - field CR NR CR NR NR NR TEP --

Dissipation Studies - Field

835.6100 Terrestrial R CR NR NR CR R TEP 5, 7, 12

835.6200 Aquatic (sediment) CR R NR NR NR NR TEP 7, 8

835.6300 Forestry NR NR NR NR CR NR TEP 7, 9, 12

835.6400 Combination and tank mixes CR CR NR NR NR NR TEP 10

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Ground Water Monitoring

835.7100 Ground water monitoring CR NR NR NR CR CR TEP 7, 9, 11

(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 dissipation 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 study will be required.

Subpart O—Residue Chemistry

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§ 158.1400 Definitions.

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The following terms are defined for the purposes of this subpart:

Livestock , for the purposes of this section, includes all domestic animals that are bred for human consumption, including, but not limited to, cattle,

swine, sheep, and poultry.

Plant or animal metabolite means a pesticide chemical residue that is the result of biological breakdown of the parent pesticide within the plant or

animal.

Residue of concern means the parent pesticidal compound and its metabolites, degradates, and impurities of toxicological concern.

Tolerance , for the purposes of this section, includes the establishment of a new tolerance or tolerance exemption, or amended tolerance or tolerance

exemption.

§ 158.1410 Residue chemistry data requirements table.

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(a) General . Sections 158.100 through 158.130 describe how to use this table to determine the residue chemistry data requirements for a particular

pesticide product. Notes that apply to an individual test and include specific conditions, qualifications, or exceptions to the designated test are listed

in paragraph (e) of this section.

(b) Use patterns . (1) Data are required or conditionally required for all pesticides used in or on food and for residential outdoor uses where food

crops are grown. Food use patterns include products classified under the general use patterns of terrestrial food crop use, terrestrial feed crop use,

aquatic food crop use, greenhouse food crop use, and indoor food use.

(2) Data may be required for nonfood uses if pesticide residues may occur in food or feed as a result of the use. Data requirements for these nonfood

uses will be determined on a case-by-case basis. For example, most products used in or near kitchens require residue data for risk assessment

purposes even though tolerances may not be necessary in all cases.

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(c) Key . R=Required; CR=Conditionally required; NR=Not required; TGAI=Technical grade of the active ingredient; PAI=Pure active ingredient;

PAIRA=Pure active ingredient radio-labeled; Residue of concern= the active ingredient and its metabolites, degradates, and impurities of

toxicological concern; TEP=Typical end-use product.

(d) Table . The following table list the data requirements for residue chemistry related to food uses. The table notes are shown in paragraph (e) of

this section.

Table—Residue Chemistry Data Requirements for Food Uses

Guideline

Number Data Requirement

Use Pattern

Test substance

Test

Note No.

Terrestrial

Food or Feed

Aquatic

Food

Greenhouse

Food

Indoor

Food

Residential

Outdoor

Supporting Information

860.1100 Chemical identity R R R R R TGAI --

860.1200 Directions for use R R R R R -- --

860.1550 Proposed tolerance R R R CR NR -- 1

860.1560 Reasonable grounds in

support of petition

R R R CR NR -- 1

860.1650 Submittal of analytical

reference standards

R R R CR NR PAI and residue of

concern

1, 2, 25

Nature of the residue

860.1300 Nature of the residue in

plants

R R R CR CR PAIRA 3, 4, 25

860.1300 Nature of the residue in

livestock

CR CR CR CR NR PAIRA or radiolabeled

plant metabolite

1, 6, 25

860.1850 Confined rotational

crops

CR CR NR NR NR PAIRA 7

Analytical methods

860.1340 Residue analytical

methods

R R R CR CR Residue of concern 1, 3, 8, 9,

10, 25

860.1360 Multiresidue method R R R CR NR Residue of concern 1, 11, 25

Magnitude of the residue

860.1380 Storage stability R R R CR CR TEP or residue of

concern

1, 3, 10,

12, 25

860.1500 Crop field trials R R R CR CR TEP 3, 10, 14,

24, 25

860.1520 Processed food or feed CR CR CR CR NR TEP 1, 15, 25

860.1480 Meat/milk/poultry/eggs CR CR CR CR NR TGAI or plant

metabolite

1, 16, 17,

18, 25

860.1400 Potable water NR R NR NR NR TEP 19, 25

860.1400 Fish NR R NR NR NR TEP 5, 25

860.1400 Irrigated crops NR CR NR NR NR TEP 20, 25

860.1460 Food handling NR NR NR CR NR TEP 1, 21, 25

860.1540 Anticipated residues CR CR CR CR NR Residue of concern 1, 13, 22,

26

860.1900 Field rotational crops CR CR NR NR NR TEP 23, 25

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

1. Required if indoor use could result in pesticide residues in or on food or feed.

2. Material safety data sheets must accompany standards as specified by OSHA in 29 CFR 1910.1200.

3. Required for residential outdoor uses on food crops if the corresponding agricultural use is not approved or the residential use is expected to produce higher residues based on the

label directions.

4. Required for indoor uses where the pesticide is applied directly to food, in order to determine metabolites and/or degradates. Not required when only indirect contact with food

would occur (e.g., crack and crevice treatments).

5. Data for fish are required for all pesticides applied directly to water inhabited, or which will be inhabited, by fish that may be caught or harvested for human consumption.

6. Required when a pesticide is to be applied directly to livestock, to livestock premises, to livestock drinking water, or to crops used for livestock feed. If results from the plant

metabolism study show differing metabolites in plants from those found in animals, an additional livestock metabolism study involving dosing with the plant metabolite(s) may also

be required.

7. Required when the Agency determines that it is reasonably foreseeable that a food or feed crop could be subsequently planted on the site of pesticide application after harvest or

failure of the treated crop. Typically not required for pesticide uses in permanent food crops (e.g., various tree crops, vines) or semi-permanent crops (e.g., asparagus, pineapples).

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8. A residue analytical method suitable for enforcement purposes is required whenever a numeric tolerance (including temporary and time-limited tolerances) is proposed.

9. New analytical methods to be used for enforcement purposes must include results from an independent laboratory validation.

10. A residue method, storage stability data, and crop field trials are required for the nonfood crop tobacco (green, freshly harvested). Depending on the level of residues found on

the green tobacco, additional data may be required on cured/dried tobacco and pyrolysis products.

11. Data are required to determine whether FDA/USDA multiresidue methodology would detect and identify the pesticides and any metabolites.

12. Data are required for any magnitude of the residue study unless analytical samples are stored frozen for 30 days or less, and the active ingredient is not known to be volatile or

labile.

13. Studies using single serving samples of a raw agricultural commodity may be needed for acutely toxic pesticides and/or their metabolites. These residue studies must be

conducted using a statistical design accepted by the Agency.

14. Required for indoor uses which are direct postharvest treatments of raw agricultural commodities (e.g., fungicidal waxes or stored grain fumigants).

15. Data on the nature and level of residues in processed food/feed are required if residues could potentially concentrate on processing thus requiring the establishment of a separate

tolerance higher than that of the raw agricultural commodity.

16. Required when the pesticide use is a direct application to livestock.

17. Data are required if pesticide residues are present in or on livestock feed items or intentionally added to drinking water. These studies, however, may not be required in cases

where the livestock metabolism studies indicate negligible transfer of the pesticide's residues of concern to tissues, milk, and eggs at the maximum expected exposure level for the

animals.

18. If results from the plant metabolism study show differing metabolites in plants from those found in animals, an additional livestock feeding study involving dosing with the plant

metabolite(s) may also be required.

19. Data are required whenever a pesticide may be applied directly to water, unless it can be demonstrated that the treated water would not be available for human or livestock

consumption.

20. Data are required when a pesticide is to be applied directly to water that could be used for irrigation or to irrigation facilities such as irrigation ditches.

21. Data are required whenever a pesticide may be used in a food handling or feed handling establishment.

22. Required when residues at the tolerance level may result in a risk of concern. These data may include washing, cooking, processing or degradation studies as well as market

basket surveys for a more precise residue determination.

23. Typically required if pesticide residues of concern greater than 0.01 ppm are found in crops at the appropriate plant back intervals (taking into account plant back restrictions on

product labels) in the confined rotational crop study. If residues of concern in the confined study are greater than 0.01 ppm but less than the limit of quantitation of the analytical

method to be used on field trial samples, the Agency will consider not requiring, on a case-by-case basis, the limited field trials. If there are particular toxicological concerns with

the parent pesticide or any metabolites, limited field studies may be needed if such residues are identified at levels below 0.01 ppm in the confined study.

24. Crop field trials are required to establish tolerances on rotational crops when quantifiable residues of concern are observed in the field rotational crops study.

25. Not required for an exemption from a tolerance provided that dietary exposure estimates are not needed due to low toxicity or that theoretical estimates of exposure are adequate

to assess dietary risk.

26. Not required for an exemption from a tolerance.

Subparts P–T [Reserved]

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§§ 158.1500-158.1900 [Reserved]

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Subpart U—Biochemical Pesticides

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Source: 72 FR 61002, Oct. 26, 2007, unless otherwise noted.

§ 158.2000 Biochemical pesticides definition and applicability.

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This subpart applies to all biochemical pesticides as defined in paragraphs (a), (b), and (c) of this section.

(a) Definitions . The following terms are defined for the purposes of subpart U of this part.

(1) A biochemical pesticide is a pesticide that:

(i) Is a naturally-occurring substance or structurally-similar and functionally identical to a naturally-occurring substance;

(ii) Has a history of exposure to humans and the environment demonstrating minimal toxicity, or in the case of a synthetically-derived biochemical

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pesticides, is equivalent to a naturally-occurring substance that has such a history; and

(iii) Has a non-toxic mode of action to the target pest(s).

(2) A Pheromone is a compound produced by a living organism or is a synthetically derived substance that is structurally similar and functionally

identical to a naturally-occurring pheromone, which, alone or in combination with other such compounds, modifies the behavior of other individuals

of the same species.

(i) An Arthropod Pheromone is a pheromone produced by a member of the taxonomic phylum Arthropoda.

(ii) A Lepidopteran Pheromone is an arthropod pheromone produced by a member of the insect order Lepidoptera.

(iii) A Straight Chain Lepidopteran Pheromone is a lepidopteran pheromone consisting of an unbranched aliphatic chain (between 9 and 18

carbons) ending in an alcohol, aldehyde, or acetate functional group and containing up to three double bonds in the aliphatic backbone.

(b) Examples . Biochemical pesticides include, but are not limited to:

(1) Semiochemicals (insect pheromones and kairomones),

(2) Natural plant and insect regulators,

(3) Naturally-occurring repellents and attractants, and

(4) Enzymes.

(c) Applicability . The Agency may review, on a case-by-case basis, naturally-occurring pesticides that do not clearly meet the definition of a

biochemical pesticide in an effort to ensure, to the greatest extent possible, that only the minimum testing sufficient to make scientifically sound

regulatory decisions would be conducted. The Agency will review applications for registration of naturally-occurring pesticides to determine whether

to review the pesticide under this subpart U.

§ 158.2010 Biochemical pesticides data requirements.

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(a) Sections 158.2030 through 158.2070 identify the data requirements that are required to support registration of biochemical pesticides. Sections

158.2080 through 158.2084 identify the data requirements that are required to support Experimental Use Permits (EUPs). Variations in the test

conditions are identified within the test notes. Definitions that apply to all biochemical data requirements can be found in §158.2000.

(b) Each data table includes “use patterns” under which the individual data are required, with variations including food and nonfood uses for

terrestrial and aquatic applications, greenhouse, indoor, forestry, and residential outdoor applications under certain circumstances.

(c) The categories for each data requirement are “R”, which stands for required, and “CR” which stands for conditionally required. Generally, “R”

indicates that the data are more likely required than for those data requirements with “CR.” However, in each case, the regulatory text preceding the

data table and the test notes following the data table must be used to determine whether the data requirement must be satisfied.

(d) Each table identifies the test substance that is required to be tested to satisfy the data requirement. Test substances may include: technical grade

active ingredient (TGAI), manufacturing-use product (MP), end-use product (EP), typical end-use product (TEP), residue of concern, and pure

active ingredient (PAI) or all of the above (All). Commas between the test substances ( i.e. , TGAI, EP) indicate that data may be required on the

TGAI or EP or both depending on the conditions set forth in the test note.

(e) The data requirements are organized into a tier-testing system with specified additional studies at higher tiers being required if warranted by

adverse effects observed in lower tier studies. The lower tier studies are a subset of those required for conventional pesticides, and the studies overall

are generally selected from those required for conventional pesticides.

(f) Two sets of guideline numbers are provided for some of the environmental fate data requirements. For ease of understanding, the current

guidelines will be used as an interim measure until the new guidelines (in parentheses) are finalized.

§ 158.2030 Biochemical pesticides product chemistry data requirements table.

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(a) General . (1) Sections 158.100 through 158.130 describe how to use this table to determine the product chemistry data requirements for a

particular pesticide product. Notes that apply to an individual test and include specific conditions, qualifications, or exceptions to the designated test

are listed in paragraph (e) of the section.

(2) Definitions in §158.300 apply to data requirements in this section.

(b) Use patterns . Product chemistry data are required for all pesticide products and are not use specific.

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

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product; TGAI=Technical grade of the active ingredient; Residue of concern=the active ingredient and its metabolites, degradates, and impurities of

toxicological concern; All=All of the above.

(d) Table . The following table shows the data requirements for biochemical pesticides product chemistry. The test notes are shown in paragraph (e)

of this section.

Table—Biochemical Pesticides Product Chemistry Data Requirements

Guideline Number Data Requirement All Use Patterns

Test Substance

MP EP Test Notes

Product Identity and Composition

880.1100 Product identity and composition R TGAI, MP TGAI, EP 1, 2

880.1200 Description of starting materials, production and formulation process R TGAI, MP TGAI, EP 2, 3

880.1400 Discussion of formation of impurities R TGAI and MP TGAI and EP 4

Analysis and Certified Limits

830.1700 Preliminary analysis CR TGAI and MP TGAI and EP 5, 8

830.1750 Certified limits R MP EP 6

830.1800 Enforcement analytical method R MP EP 7

Physical and Chemical Characteristics

830.6302 Color R TGAI TGAI 8

830.6303 Physical state R TGAI and MP TGAI and EP 8

830.6304 Odor R TGAI TGAI 8

830.6313 Stability to normal and elevated temperatures, metals and metal ions R TGAI TGAI 8, 17

830.6315 Flammability CR MP EP 9

830.6317 Storage stability R MP EP --

830.6319 Miscibility CR MP EP 10

830.6320 Corrosion characteristics R MP EP --

830.7000 pH CR TGAI and MP TGAI and EP 8, 11

830.7050 UV/Visible light absorption R TGAI TGAI --

830.7100 Viscosity CR MP EP 12

830.7200 Melting point/melting range CR TGAI TGAI 8, 13

830.7220 Boiling point/boiling range CR TGAI TGAI 8, 14

830.7300 Density/relative density/bulk density R TGAI and MP TGAI and EP 8, 18

830.7520 Particle size, fiber length, and diameter distribution CR TGAI TGAI 8, 15

830.7550

830.7560

830.7570

Partition coefficient (n-Octanol /Water) CR TGAI TGAI 16

830.7840 Water solubility R TGAI TGAI 8

830.7950 Vapor pressure R TGAI TGAI 8, 19

(e) Test notes . The following test notes are applicable to the data requirements for biochemical pesticides product chemistry and are referenced in

the last column of the table in paragraph (d) of this section.

1. Data must be provided in accordance with §158.320.

2. If the MP and EP are produced by an integrated formulation system (non-registered source), these data are also required on TGAI.

3. Data must be provided in accordance with §§158.325, 158.330, and §158.335.

4. Data must be provided in accordance with §158.340.

5. Data must be provided in accordance with §158.345. Also, required to support the registration of each manufacturing-use product (including registered TGAIs) and end-use

products produced by an integrated formulation system. Data on other end-use products would be required on a case-by-case basis.

6. Data must be provided in accordance with §158.350.

7. Data must be provided in accordance with §158.355.

8. If the TGAI cannot be isolated, data are required on the practical equivalent of the TGAI. EP testing may also be appropriate.

9. Required if the product contains combustible liquids.

10. Required if the product is an emulsifiable liquid and is to be diluted with petroleum solvents.

11. Required if the test substance is soluble or dispersible in water.

12. Required if the product is a liquid.

13. Required when the technical chemical is a solid at room temperature.

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14. Required when the technical chemical is a liquid at room temperature.

15. Required for water insoluble test substances (>10-6g/l) and fibrous test substances with diameter≥0.1 μm.

16. Required for organic chemicals unless they dissociate in water or are partially or completely soluble in water.

17. Data on the stability to metals and metal ions is required only if the active ingredient is expected to come in contact with either material during storage.

18. True density or specific density are required for all test substances. Data on bulk density is required for MPs or EPs that are solid at room temperature.

19. Not required for salts.

§ 158.2040 Biochemical pesticides residue data requirements table.

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(a) General . Sections 158.100 through 158.130 describe how to use this table to determine the biochemical pesticides residue data requirements for

a particular pesticide product and the substance that needs to be tested. These data requirements apply to all biochemical pesticides, i.e. , naturally

occurring insect repellents and attractants, semiochemicals (e.g., insect pheromones), natural and plant growth regulators. Notes that apply to an

individual test and include specific conditions, qualifications, or exceptions to the designated test are listed in paragraph (e) of this section.

(b) Use patterns . (1) Data are required or conditionally required for all pesticides used in or on food and for residential outdoor uses where food

crops are grown. Food use patterns include products classified under the general use patterns of terrestrial food crop use, terrestrial feed crop use,

aquatic food crop use, greenhouse food crop use, and indoor food use. Data are also conditionally required for aquatic nonfood use if there is direct

application to water that could subsequently result in exposure to food.

(2) Data are conditionally required for nonfood uses if pesticide residues may occur in food or feed as a result of the use. Data requirements for these

nonfood uses would be determined on a case-by-case basis. For example, most products used in or near kitchens require residue data for risk

assessment purposes even though tolerances may not be necessary in all cases.

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

end-use product; TGAI=Technical grade of the active ingredient; Residue of concern=the active ingredient and its metabolites, degradates, and

impurities of toxicological concern; All=All of the above. Specific conditions, qualifications, or exceptions to the designated test procedures appear

in paragraph (e) of this section, and apply to the individual tests in the following table:

(d) Data requirements table . The following table shows the data requirements for biochemical pesticides residue. The test notes are shown in

paragraph (e) of this section.

Table—Biochemical Residue Data Requirements for Specific Uses

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Guideline

Number Data Requirement

Use Patterns

Test Substance Test Notes

Terrestrial Aquatic Greenhouse

Food

Indoor

Food/Feed Food Food

Supporting Information

860.1100 Chemical identity CR CR CR CR TGAI 1, 2, 4

860.1200 Directions for use CR CR CR CR -- 1, 3, 4

Nature of the Residue

860.1300 Nature of the residue in plants CR CR CR CR TGAI 1, 4, 5, 6

860.1300 Nature of the residue in livestock CR CR CR CR TGAI or plant metabolite 1, 7, 8, 10,

13

860.1340 Residue analytical method CR CR R CR Residue of concern 4, 9, 10

860.1360 Multiresidue method CR CR R CR Residue of concern 10, 11

Magnitude of the Residue

860.1400 Potable water NR CR NR NR TGAI 1, 12

860.1400 Fish NR CR NR NR TGAI 1, 13

860.1400 Irrigated crops NR CR NR NR TGAI 1, 14

860.1460 Food handling NR NR NR CR TGAI 1, 15

860.1480 Meat/milk/poultry/eggs CR CR CR CR TGAI or plant

metabolites

1, 7, 8, 10

860.1500 Crop field trials CR CR CR CR TEP 1, 3, 4

860.1520 Processed food/feed CR CR CR CR TEP 1, 16

860.1540 Anticipated residues CR CR CR CR Residue of concern 1, 10, 17

860.1550 Proposed tolerances CR CR CR CR -- 1, 18

860.1560 Reasonable grounds in support of the

petition

CR CR CR CR -- 1, 10

860.1650 Submittal of analytical reference

standards

CR CR CR CR TGAI and residue of

concern

10, 19

(e) Test notes . The following test notes are applicable to the data requirements for biochemical pesticides product chemistry and are in the last

column of the table contained in paragraph (d) of this section.

1. Residue chemistry data requirements apply to biochemical pesticide products when Tier II or Tier III toxicology data are required, as specified for biochemical agents in the

biochemical human health assessment data requirements, §158.2050.

2. The same chemical identity data are required for biochemical product chemistry data requirements, §158.2030, with an emphasis on impurities.

3. Required information includes crops to be treated, rate of application, number and timing of applications, preharvest intervals, and relevant restrictions.

4. Required for residential outdoor uses on food crops if the corresponding agricultural use is not approved or the residential use is expected to produce higher residues based on the

label directions.

5. Required unless it is an arthropod pheromone applied at a rate less than or equal to 150 grams active ingredient per acre.

6. Required for indoor uses where the pesticide is applied directly to food, in order to determine metabolites and/or degradates. Not required when only indirect contact with food

would occur (e.g., crack and crevice treatments).

7. Required when a pesticide is to be applied directly to livestock, to livestock premises, to livestock drinking water, or to crops used for livestock feed.

8. If results from the plant metabolism study show differing metabolites in plants from those found in animals, an additional livestock metabolism study involving dosing with the

plant metabolite(s) may also be required.

9. A residue analytical method suitable for enforcement of tolerances is required whenever a numeric tolerance (including temporary and time-limited tolerances) is proposed.

10. Required if indoor use could result in pesticide residues in or on food or feed.

11. Data are required to determine whether FDA/USDA multiresidue methodology would detect and identify the pesticides and any metabolites.

12. Data are required whenever a pesticide may be applied directly to water, unless it can be demonstrated that the treated water would not be available for human or livestock

consumption.

13. Data on fish are required for all pesticides applied directly to water inhabited, or which will be inhabited by fish that may be caught or harvested for human consumption.

14. Data are required when a pesticide is to be applied directly to water that could be used for irrigation or to irrigation facilities such as irrigation ditches.

15. Data are required whenever a pesticide may be used in food/feed handling establishments.

16. Data on the nature and level of residue in processed food/feed are required when detectible residues could potentially concentrate on processing thus requiring the establishment

of a separate tolerance higher than that of the raw agricultural commodity.

17. Required when residues at the tolerance level may result in risk of concern. These data may include washing, cooking, processing, or degradation studies as well as market

basket surveys for a more precise residue determination.

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18. The proposed tolerance must reflect the maximum residue likely to occur in crops, in meat, milk, poultry, or eggs.

19. Required when a residue analytical method is required.

§ 158.2050 Biochemical pesticides human health assessment data requirements table.

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(a) General . (1) Sections 158.100 through 158.130 describe how to use this table to determine the biochemical human health assessment data

requirements for a particular biochemical pesticide product.

(2) The data in this section are not required for straight chain lepidopteran pheromones when applied up to a maximum use rate of 150 grams active

ingredient/acre/year.

(b) Use patterns . (1) Food use patterns, in general, include products classified under the following general uses: terrestrial food crop use; terrestrial

feed crop use; aquatic food crop use; greenhouse food crop use.

(2) Nonfood use patterns include products classified under the general use patterns of terrestrial nonfood crop use; aquatic nonfood residential use;

aquatic nonfood outdoor use; aquatic nonfood industrial use; greenhouse nonfood crop use; forestry use; residential outdoor use; residential indoor

use; indoor food use; indoor nonfood use; indoor medical use.

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

product; TGAI=Technical grade of the active ingredient; Residue of concern=the active ingredient and its metabolites, degradates, and impurities of

toxicological concern; All=All of the above. Specific conditions, qualifications, or exceptions to the designated test procedures appear in paragraph

(e) of this section, and apply to the individual tests in the following table:

(d) Table . The following table shows the data requirements for biochemical pesticides human health assessment. The test notes are shown in

paragraph (e) of this section.

Table—Biochemical Pesticides Human Health Assessment Data Requirements

Guideline Number Data Requirement

Use Patterns Test Substance

Food Nonfood MP EP Test Notes

Tier I

Acute Testing

870.1100 Acute oral toxicity - rat R R TGAI and MP TGAI and EP 1

870.1200 Acute dermal toxicity R R TGAI and MP TGAI and EP 1, 2

870.1300 Acute inhalation toxicity - rat R R TGAI and MP TGAI and EP 3

870.2400 Primary eye irritation - rabbit R R TGAI and MP TGAI and EP 2

870.2500 Primary dermal irritation R R TGAI and MP TGAI and EP 1, 2

870.2600 Dermal sensitization R R TGAI and MP TGAI and EP 2, 4

none Hypersensitivity incidents R R All All 5

Subchronic Testing

870.3100 90-day oral (one species) R CR TGAI TGAI 6

870.3250 90-day dermal - rat CR CR TGAI TGAI 7

870.3465 90-day inhalation - rat CR CR TGAI TGAI 8

Developmental Toxicity

870.3700 Prenatal developmental - rat preferably R CR TGAI TGAI 9

Mutagenicity Testing

870.5100 Bacterial reverse mutation test R CR TGAI TGAI 10

870.5300

870.5375

In vitro mammalian cell assay R CR TGAI TGAI 10, 11

Tier II

Mutagenicity Testing ( In vivo cytogenetics)

870.5385

870.5895

In vivo Mammalian Cytogenetics CR CR TGAI TGAI 13

Developmental Toxicity

870.3700 Prenatal developmental CR CR TGAI TGAI 9

Special Tests

880.3550 Immunotoxicity CR CR TGAI TGAI 12, 13

Applicator/User Exposure

875.1100 Dermal outdoor exposure CR CR TGAI TGAI 15

875.1200 Dermal indoor exposure CR CR TGAI TGAI 15

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875.1300 Inhalation outdoor exposure CR CR TGAI TGAI 15

875.1400 Inhalation indoor exposure CR CR TGAI TGAI 15

875.1500 Biological monitoring CR CR TGAI TGAI 15

Tier III

Chronic Testing/Special Testing

880.3800 Immune response CR CR TGAI TGAI 14

870.3800 Reproduction and fertility effects CR CR TGAI TGAI 16

870.4100 Chronic oral - rodent and nonrodent CR CR TGAI TGAI 17

870.4200 Carcinogenicity - two species - rat and mouse preferred CR CR TGAI TGAI 18

870.5380 Mammalian spermatogonial chromosome aberration test CR CR TGAI TGAI 19

Special Testing

870.7200 Companion animal safety CR CR NR TGAI or EP 20

(e) Test notes . The following test notes are applicable to the data requirements for biochemical pesticides human health assessment as referenced in

the last column of the table in paragraph (d) of this section.

1. Required unless the test material is a gas or highly volatile (vapor pressure>10-4torr (mm/Hg)).

2. Required unless the test material is corrosive to skin or has pH<2 or>11.5.

3. Required when the pesticide, under conditions of use, would result in respirable material (e.g., gas, volatile substance or aerosol/particulate), unless it is a straight chain

lepidopteran pheromone.

4. Required if repeated contact with human skin is likely to occur under conditions of use.

5. Hypersensitivity incidents must be reported as adverse effects data.

6. Required for non-food uses that are likely to result in repeated oral exposure to humans.

7. Required to support uses involving purposeful application to the human skin or which would result in comparable prolonged human exposure to the product (e.g., insect repellents)

and if any of the following criteria are met:

i. Data from a 90–day oral study are not required.

ii. The active ingredient is known or expected to be metabolized differently by the dermal route of exposure than by the oral route and the metabolite is of toxicological concern.

iii. The use pattern is such that the dermal route would be the primary route of exposure.

8. Required if there is a likelihood of significant levels of repeated inhalation exposure to the pesticide as a gas, vapor, or aerosol.

9. Required if the use of the product under widespread and commonly recognized practice may reasonably be expected to result in significant exposure to female humans (e.g.,

occupational exposure or repeated application of insect repellents directly to the skin). Tier II data is required on a different test species from Tier I data when developmental effects

are observed in the first study and information on species-to-species extrapolation is needed.

10. Required to support nonfood uses if either:

i. The use is likely to result in significant human exposure; or

ii. The active ingredient (or its metabolites) is structurally related to a known mutagen or belongs to any chemical class of compounds containing a known mutagen. Additional

mutagenicity tests that may have been performed plus a complete reference list must also be submitted. Subsequent testing may be required based on the available evidence.

11. Choice of assay using either:

i. Mouse lymphoma L5178Y cells, thymidine kinase (tk) gene locus, maximizing assay conditions for small colony expression or detection;

ii. Chinese hamster ovary (CHO) or Chinese hamster lung fibroblast (V79) cells, hypoxanthine-guanine phosphoribosyl transferase (hgprt) gene locus, accompanied by an

appropriate in vitro test for clastogenicity; or

iii. CHO cells strains AS52, xanthine-guanine phosphoribosyl transferase (xprt) gene locus.

12. Required if there are effects on hematology, clinical chemistry, lymphoid organ weights, and histopathology are observed in the 90–day studies.

13. The micronucleus rodent bone marrow assay is preferred; however, rodent bone marrow assays using metaphase analysis (aberrations) are acceptable.

14. Required if adverse effects are observed in the Tier II immunotoxicity study. The protocol for evaluating adverse effects to the immune response should be developed after

evaluating the effects noted in the immunotoxicity study.

15. These data are required when the data used for the human health assessment indicates that the biochemical may pose a potential hazard to the applicator/user.

16. Required if there is evidence of:

i. Endocrinological effects from the subchronic toxicity studies.

ii. Developmental effects in the prenatal developmental toxicity study(s), or

iii. Genotoxicity to mammals based on results from the mutagenicity tests.

The use of a combined study that utilizes the two-generation reproduction study in rodents (guideline 870.3800) as a basic protocol for the addition of other endpoints or functional

assessments in the immature animal is encouraged.

17. Required if the potential for adverse chronic effects is indicated based on any of the following:

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i. The subchronic effect level established in the following Tier I studies: 90–day oral toxicity study, 90–day dermal toxicity study, or 90–day inhalation toxicity study.

ii. The pesticide use pattern (e.g., rate, frequency, and site of application).

iii. The frequency and level of repeated human exposure that is expected.

18. Required if the product meets either of the following criteria:

i. The active ingredient (or any of its metabolites, degradation products, or impurities) produce(s) in Tier I subchronic studies a morphologic effect (e.g., hyperplasia or metaplasia)

in any organ that potentially could lead to neoplastic change.

ii. Adverse cellular effects suggesting carcinogenic potential are observed in Tier II immunotoxicity and Tier III immune response study or in Tier II mammalian mutagenicity assays.

In addition, a 90–day range finding study in both rats and mice is required to determine the dose levels if carcinogenicity studies are required. If the mouse carcinogenicity study is

not required, the 90–day mouse subchronic study is likewise not required.

19. Required if results from lower tiered mutation or reproductive studies indicate there is potential for chromosomal aberration to occur.

20. May be required if the product's use will result in exposure to domestic animals through, but not limited to, direct application or consumption of treated feed.

§ 158.2060 Biochemical pesticides nontarget organisms and environmental fate data requirements table.

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(a) General . (1) Sections 158.100 through 158.130 describe how to use this table to determine the terrestrial and aquatic nontarget organisms and

fate data requirements for a particular biochemical 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. In general, for all outdoor end-use products including

turf, the following studies are required: one avian acute oral, one avian dietary, one acute freshwater fish, one acute freshwater invertebrate study,

plant toxicity testing, and a honeybee acute contact study.

(2) The data in this section are not required for arthropod pheromones when applied at up to a maximum use rate of 150 grams active

ingredient/acre/year except when the product is expected to be available to avian species ( i.e. , granular formulation).

(b) Use patterns . The terrestrial use pattern includes products classified under the general use patterns of terrestrial food crop, terrestrial feed crop,

and terrestrial nonfood/nonfeed crop. 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 nonfood

use. The remaining terrestrial uses include: forestry and residential outdoor use. Data are also required for the general use patterns of aquatic food

and nonfood crop use.

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

product; TGAI=Technical grade of the active ingredient; Residue of concern=the active ingredient and its metabolites, degradates, and impurities of

toxicological concern; All=All of the above. Specific conditions, qualifications, or exceptions to the designated test procedures appear in paragraph

(e) of this section, and apply to the individual tests in the following table:

(d) Table . The following table shows the data requirements for biochemical pesticides nontarget organisms and environmental fate. The test notes

are shown in paragraph (e) of this section.

Table—Biochemical Pesticides Nontarget Organisms and Environmental Fate Data Requirements

Guideline

Number Data Requirement

Use Patterns

Test

Substance

Test

Notes

Terrestrial Aquatic Greenhouse Forestry,

Residential

Outdoor

Indoor

Food/Feed

/Nonfood Food/Nonfood Food/Nonfood Food/Nonfood

Tier I

Avian Testing

850.2100 Avian acute oral toxicity R R CR R CR TGAI, EP 1, 2, 3,

4

850.2200 Avian dietary toxicity R R CR R CR TGAI, EP 1, 2, 3,

4

Aquatic Organism Testing

850.1075 Fish acute toxicity, freshwater R R CR R CR TGAI, EP 2, 3, 4,

5

850.1010 Aquatic invertebrate acute

toxicity, freshwater

R R CR R CR TGAI, EP 2, 3, 5

Nontarget Plant Testing

850.4100 Terrestrial Plant Toxicity,

Seedling emergence

R R NR R NR TGAI, EP 5

850.4150 Terrestrial Plant Toxicity,

Vegetative vigor

R R NR R NR TGAI, EP 5

Insect Testing

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880.4350 Nontarget Insect Testing R R R R NR TGAI 14

Tier II

Environmental Fate Testing

163-1

(835.1230)

Sediment and soil

adsorption/desorption for parent

and degradates

CR CR CR CR NR TGAI 6

163-1

(835.1240)

Soil column leaching CR CR CR CR NR TGAI 6

163-2

(835.1410)

Laboratory volatilization from

soil

CR NR CR CR NR TEP 7

161-1

(835.2120)

Hydrolysis CR CR CR CR NR TGAI 6

161-1

(835.4100)

Aerobic soil metabolism CR NR CR CR NR TGAI 6

161-2

(835.2240)

Photodegradation in water CR CR CR CR NR TGAI 6

161-3

(835.2410)

Photodegradation on soil CR NR CR CR NR TGAI 6

162-2

(835.4200)

Anaerobic soil metabolism CR NR NR NR NR TGAI 6

162-4

(835.4300)

Aerobic aquatic metabolism CR CR CR CR NR TGAI 6

162-3

(835.4400)

Anaerobic aquatic metabolism CR CR NR NR NR TGAI 6

880.4425 Dispenser - water leaching CR NR CR CR NR EP 8

Nontarget Plant

850.4225 Seedling emergence R R NR R NR TGAI 9

850.4250 Vegetative vigor R R NR R NR TGAI 9

Tier III

Aquatic Fauna Chronic, Life Cycle, and Field Studies

850.1300

850.1400

850.1500

Freshwater fish/invertebrate

testing

CR CR NR CR NR TGAI 10

850.1025

850.1035

850.1045

850.1055

850.1350

850.1400

850.1500

Marine/Estuarine

fish/invertebrate animal testing

CR CR NR CR NR TGAI 10

850.1950 Aquatic field fish/invertebrate

testing

CR CR NR CR NR EP 10

Terrestrial Wildlife

850.2300 Avian Reproduction CR CR NR CR NR TGAI 11

850.2400 Wild mammal acute toxicity CR CR NR CR NR TGAI 11

850.2500 Terrestrial field testing CR CR NR CR NR EP 11

Beneficial Insects

850.3040 Field testing for Pollinators CR CR NR CR NR TEP 12

Nontarget Plants

850.4225

850.4250

850.4300

850.4450

Nontarget plant CR CR NR CR NR TGAI 13

(e) Test notes . The following test notes are applicable to the data requirements for biochemical pesticides nontarget organisms and environmental

fate as referenced in the last column of the table contained in paragraph (d) of this section.

1. Required for the EP when any end-use formulation may contain other ingredients that may be toxic to nontarget organisms or to support arthropod pheromones that would be

available to avian wildlife, (e.g., a granular product).

2. Tests for pesticides intended solely for indoor application would be required on a case-by-case basis, depending on use pattern, physical/chemical properties, production volume,

and other pertinent factors.

3. Not required for any use groups if the pesticide is highly volatile (estimated volatility>5 X 10-5atm m3

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4. Preferred test species are Upland game, waterfowl, or passerine for avian acute oral toxicity studies; Upland game and waterfowl for avian dietary studies; and coldwater fish

species for acute freshwater fish studies.

5. Required for the EP when the end-use formulation may contain other ingredients that may be toxic to nontarget organisms.

6. Required on a case-by-case basis when results from Tier I studies indicate adverse effects.

7. Required when results of any one or more of the nontarget organism studies in Tier I indicate potential adverse effects on nontarget organisms and the pesticide is to be applied on

land. In view of methdological difficulties with the study of photodegradation in air, prior consultation with the Agency regarding the protocol is recommended before the test is

performed.

8. Required when results of any one or more of the nontarget organism studies in Tier I indicate potential adverse effects on nontarget organisms and the pesticide is to be applied in

a passive dispenser.

9. Required to support registration of known phytotoxicants, i.e. , herbicides, desiccants, defoliants, and plant growth regulators.

10. Required if environmental fate characteristics indicate that the estimated environmental concentration of the pesticide in the aquatic environment is>0.01 of any EC50or

LC50determined in the aquatic nontarget organism testing.

11. Required if either of the following criteria are met:

i. Environmental fate characteristics indicate that the estimated concentration of the pesticide in the terrestrial environment is>0.20 the avian dietary LC50or equal to>0.20 the avian

oral single dose LD50(converted to ppm).

ii. The pesticide or any of its metabolites or degradation products are stable in the environment to the extent that potentially toxic amounts may persist in the avian or mammalian

feed.

12. Required when results of Tier I nontarget organism studies indicate potential adverse effects on nontarget insects and results of Tier II tests indicate exposure of nontarget insects.

Additional insect species may have to be tested if necessary to address issues raised by use patterns and potential exposure of important nontarget insect species, (e.g., threatened or

endangered species).

13. Required if the product is expected to be transported from the site of application by air, soil, or water. The extent of movement would be determined by the results of the Tier II

environmental fate studies.

14. Required depending on pesticide mode of action, method and timing of application, and results of any available efficacy data. Typically the honeybee acute toxicity guideline

(guideline 850.3020) satisfies this requirement, however, additional nontarget insect species may have to be tested if necessary to address issues raised by use patterns and potential

exposure of important nontarget insect species, (e.g., endangered species.)

§ 158.2070 Biochemical pesticides product performance data requirements.

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Product performance data must be developed for all biochemical pesticides. However, the Agency typically does not require applicants to submit

such efficacy data unless the pesticide product bears a claim to control public health pests, such as pest microorganisms infectious to man in any area

of the inanimate environment or a claim to control vertebrates (including but not limited to: rodents, birds, bats, canids, and skunks) or invertebrates

(including but not limited to: mosquitoes and ticks) that may directly or indirectly transmit diseases to humans. However, each registrant must ensure

through testing that his products are efficacious when used in accordance with label directions and commonly accepted pest control practices. The

Agency reserves the right to require, on a case-by-case basis, submission of efficacy data for any pesticide product registered or proposed for

registration.

§ 158.2080 Experimental use permit data requirements—biochemical pesticides.

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(a) Sections 158.2081 through 158.2084 describe the experimental use permit (EUP) data requirements for biochemical pesticides. Variations in the

test conditions are identified within the test notes. Definitions that apply to all biochemical data requirements can be found in §158.2000.

(b) For general information on the data requirement tables, see §158.2010(b)-(f).

§ 158.2081 Experimental use permit biochemical pesticides product chemistry data requirements table.

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(a) General . (1) Sections 158.100 through 158.130 describe how to use this table to determine the product chemistry data requirements for a

particular biochemical pesticide product. Notes that apply to an individual test and include specific conditions, qualifications, or exceptions to the

designated test are listed in paragraph (e) of the section.

(2) Depending on the results of the required product chemistry studies, appropriate use restrictions, labeling requirements, or special packaging

requirements may be imposed.

(b) Use patterns . Product chemistry data are required for all pesticide products and are not use specific.

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

product; TGAI=Technical grade of the active ingredient; Residue of concern=the active ingredient and its metabolites, degradates, and impurities of

toxicological concern; All=All of the above. Specific conditions, qualifications, or exceptions to the designated test procedures appear in paragraph

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(e) of this section, and apply to the individual tests in the following table:

(d) Table . The following table shows the data requirements for experimental use permit biochemical pesticides product chemistry. The test notes are

shown in paragraph (e) of this section.

Table—EUP Biochemical Pesticides Product Chemistry Data Requirements

Guideline Number Data Requirement All Use Patterns

Test Substance

MP EP Test Notes

Product Identity and Composition

880.1100 Product identity and composition R TGAI, MP TGAI, EP 1, 2

880.1200 Description of starting materials, production and formulation process R TGAI, MP TGAI, EP 2, 3

880.1400 Discussion of formation of impurities R TGAI and MP TGAI and EP 4

Analysis and Certified Limits

830.1700 Preliminary analysis CR TGAI and MP TGAI and EP 5, 8

830.1750 Certified limits R MP EP 6

830.1800 Enforcement analytical method R MP EP 7

Physical and Chemical Characteristics

830.6302 Color R TGAI TGAI 8

830.6303 Physical state R TGAI and MP TGAI and EP 8

830.6304 Odor R TGAI TGAI 8

830.6313 Stability to normal and elevated temperatures, metals and metal ions R TGAI TGAI 8, 17

830.6315 Flammability CR MP EP 9

830.6317 Storage stability R MP EP --

830.6319 Miscibility CR MP EP 10

830.6320 Corrosion characteristics R MP EP --

830.7000 pH CR TGAI and MP TGAI and EP 8, 11

830.7050 UV/Visible light absorption R TGAI TGAI --

830.7100 Viscosity CR MP EP 12

830.7200 Melting point/melting range CR TGAI TGAI 8, 13

830.7220 Boiling point/boiling range CR TGAI TGAI 8, 14

830.7300 Density/relative density/bulk density R TGAI and MP TGAI and EP 8, 18

830.7520 Particle size, fiber length, and diameter distribution CR TGAI TGAI 8, 15

830.7550

830.7560

830.7570

Partition coefficient (n-Octanol /Water) CR TGAI TGAI 16

830.7840 Water solubility R TGAI TGAI 8

830.7950 Vapor pressure R TGAI TGAI 8, 19

(e) Test notes . The following test notes are applicable to the data requirements for experimental use permit biochemical pesticides product chemistry

and are referenced in the last column of the table in paragraph (d) of this section.

1. Data must be provided in accordance with §158.320.

2. If the MP and EP are produced by an integrated formulation system (non-registered source), these data are also required on TGAI.

3. Data must be provided in accordance with §158.325, §158.330, and §158.335.

4. Data must be provided in accordance with §158.340.

5. Data must be provided in accordance with §158.345. Also, required to support the registration of each manufacturing-use product (including registered TGAIs) and end-use

products produced by an integrated formulation system. Data on other end-use products would be required on a case-by-case basis. For pesticides in the production stage, a

preliminary product analytical method and data would suffice to support an experimental use permit.

6. Data must be provided in accordance with §158.350.

7. Data must be provided in accordance with §158.355.

8. If the TGAI cannot be isolated, data are required on the practical equivalent of the TGAI. EP testing may also be appropriate.

9. Required if the product contains combustible liquids.

10. Required if the product is an emulsifiable liquid and is to be diluted with petroleum solvents.

11. Required if the test substance is soluble or dispersible in water.

12. Required if the product is a liquid.

13. Required when the technical chemical is a solid at room temperature.

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14. Required when the technical chemical is a liquid at room temperature.

15. Required for water insoluble test substances (>10-6g/l) and fibrous test substances with diameter≥0.1 μm.

16. Required for organic chemicals unless they dissociate in water or are partially or completely soluble in water.

17. Data on the stability to metals and metal ions is required only if the active ingredient is expected to come in contact with either material during storage.

18. True density or specific density are required for all test substances. Data on bulk density is required for MPs or EPs that are solid at room temperature.

19. Not required for salts.

§ 158.2082 Experimental use permit biochemical pesticides residue data requirements table.

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(a) General . Sections 158.100 through 158.130 describe how to use this table to determine the biochemical pesticides residue data requirements for

a particular pesticide product and the substance that needs to be tested. These data requirements apply to all biochemical pesticides, i.e. , naturally

occurring insect repellents and attractants, semiochemicals (e.g., insect pheromones), natural and plant growth regulators. Notes that apply to an

individual test and include specific conditions, qualifications, or exceptions to the designated test are listed in paragraph (e) of this section.

(b) Use patterns . (1) Data are required or conditionally required for all pesticides used in or on food and for residential outdoor uses where food

crops are grown. Food use patterns include products classified under the general use patterns of terrestrial food crop use, terrestrial feed crop use,

aquatic food crop use, greenhouse food crop use, and indoor food use. Data are also conditionally required for aquatic nonfood use if there is direct

application to water that could subsequently result in exposure to food.

(2) Data are conditionally required for nonfood uses if pesticide residues may occur in food or feed as a result of the use. Data requirements for these

nonfood uses would be determined on a case-by-case basis. For example, most products used in or near kitchens require residue data for risk

assessment purposes even though tolerances may not be necessary in all cases.

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

end-use product; TGAI=Technical grade of the active ingredient; Residue of concern=the active ingredient and its metabolites, degradates,and

impurities of toxicological concern. All=All of the above. Specific conditions, qualifications, or exceptions to the designated test procedures appear

in paragraph (e) of this section, and apply to the individual tests in the following table:

(d) Data table . The following table shows the data requirements for biochemical pesticides residue. The test notes are shown in paragraph (e) of this

section.

Table—EUP Biochemical Pesticides Residue Data Requirements

Guideline

Number Data Requirement

Use Patterns

Test Substance Test Notes

Terrestrial Aquatic Greenhouse

Food

Indoor

Food/Feed Food Food

Supporting Information

860.1100 Chemical identity CR CR CR CR TGAI 1, 2, 4

860.1200 Directions for use CR CR CR CR -- 1, 3, 4

Nature of Residue

860.1300 Nature of the residue in plants CR CR CR CR TGAI 1, 4, 5, 6

860.1300 Nature of the residue in livestock CR CR CR CR TGAI or plant metabolite 1, 7, 8, 9,

13

Magnitude of the Residue

860.1400 Potable water NR CR NR NR TGAI 1, 11

860.1400 Fish NR CR NR NR TGAI 1, 12

860.1400 Irrigated crops NR CR NR NR TGAI 1, 13

860.1460 Food handling NR NR NR CR TGAI 1, 14

860.1480 Meat/milk/poultry/eggs CR CR CR CR TGAI or plant

metabolites

1, 7, 8, 9

860.1500 Crop field trials CR CR CR CR TEP 1, 3, 4

860.1520 Processed food/feed CR CR CR CR TEP 1, 15

860.1540 Anticipated residues CR CR CR CR Residue of concern 1, 9, 16

860.1550 Proposed tolerances CR CR CR CR -- 1, 17

860.1560 Reasonable grounds in support of the

petition

CR CR CR CR -- 1, 9

860.1650 Submittal of analytical reference

standards

CR CR CR CR TGAI and residue of

concern

9, 18

(e) Test notes . The following test notes are applicable to the data requirements for biochemical pesticides product chemistry and are referenced

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referenced in the last column of the table contained in paragraph (d) of this section.

1. Residue chemistry data requirements apply to biochemical pesticide products when Tier II or Tier III toxicology data are required, as specified for biochemical agents in the

biochemical human health assessment data requirements, §158.2050.

2. The same chemical identity data are required for biochemical product chemistry data requirements,§158.2030 with an emphasis on impurities.

3. Required information includes crops to be treated, rate of application, number and timing of applications, preharvest intervals, and relevant restrictions.

4. Required for residential outdoor uses on food crops if the corresponding agricultural use is not approved or the residential use is expected to produce higher residues based on the

label directions.

5. Required unless it is an arthropod pheromone applied at a rate less than or equal to 150 grams active ingredient per acre.

6. Required for indoor uses where the pesticide is applied directly to food, in order to determine metabolites and/or degradates. Not required when only indirect contact with food

would occur (e.g., crack and crevice treatments).

7. Required when a pesticide is to be applied directly to livestock, to livestock premises, to livestock drinking water, or to crops used for livestock feed. If results from the plant

metabolism study show differing metabolites in plants form those found in animals, an additional livestock metabolism study involving dosing with the plant metabolite(s) may also

be required.

8. Livestock feeding studies are required whenever a pesticide residue is present in livestock feed or when direct application to livestock uses occurs.

9. Required if indoor use could result in pesticide residues in or on food or feed.

10. Data are required to determine whether FDA/USDA multiresidue methodology would detect and identify the pesticides and any metabolites.

11. Data are required whenever a pesticide may be applied directly to water, unless it can be demonstrated that the treated water would not be available for human or livestock

consumption.

12. Data on fish are required for all pesticides applied directly to water inhabited, or which will be inhabited, by fish that may be caught or harvested for human consumption.

13. Data are required when a pesticide is to be applied directly to water that could be used for irrigation or to irrigation facilities such as irrigation ditches.

14. Data are required whenever a pesticide may be used in food/feed handling establishments.

15. Data on the nature and level of residue in processed food/feed are required when detectible residues could potentially concentrate on processing thus requiring the establishment

of a separate tolerance higher than that of the raw agricultural commodity.

16 Anticipated residue data are required when the assumption of tolerance level residues would result in predicted exposure at an unsafe level of exposure. Data, using single

serving samples of a raw agricultural commodity, on the level or residue in food as consumed would be used to obtain a more precise estimate of potential dietary exposure. These

data may also include washing, cooking, processing or degradation studies as well as market basket surveys for a more precise residue determination.

17. The proposed tolerance must reflect the maximum residue likely to occur in crops, in meat, milk, poultry, or eggs.

18. Required when a residue analytical method is required.

§ 158.2083 Experimental use permit biochemical pesticides human health assessment data requirements table.

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(a) General . (1) Sections 158.100 through 158.130 describe how to use this table to determine the human health assessment data requirements for a

particular biochemical pesticide product.

(2) The data in this section are not required for straight chain lepidopteran pheromones when applied up to a maximum use rate of 150 grams active

ingredient/acre/year.

(b) Use patterns . (1) Food use patterns, in general, include products classified under the following general uses: terrestrial food crop use; terrestrial

feed crop use; aquatic food crop use; greenhouse food crop use.

(2) Nonfood use patterns include products classified under the general use patterns of terrestrial nonfood crop use; aquatic nonfood residential use;

aquatic nonfood outdoor use; aquatic nonfood industrial use; greenhouse nonfood crop use; forestry use; residential outdoor use; residential indoor

use; indoor food use; indoor nonfood use; indoor medical use.

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

product; TGAI=Technical grade of the active ingredient; Residue of concern=the active ingredient and its metabolites, degradates, and impurities of

toxicological concern; All=All of the above. Specific conditions, qualifications, or exceptions to the designated test procedures appear in paragraph

(e) of this section, and apply to the individual tests in the following table:

(d) Table . The following table shows the data requirements for experimental use permit biochemical pesticides human health assessment. The test

notes are shown in paragraph (e) of this section.

Table—EUP Biochemical Pesticides Human Health Assessment Data Requirements

Guideline Number Data Requirement

Use Patterns Test Substance

Food Nonfood MP EP Test Notes

Tier I

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Acute Testing

870.1100 Acute oral toxicity - rat R R TGAI and MP TGAI and EP 1

870.1200 Acute dermal toxicity R R TGAI and MP TGAI and EP 1, 2

870.1300 Acute inhalation toxicity - rat R R TGAI and MP TGAI and EP 3

870.2400 Primary eye irritation - rabbit R R TGAI and MP TGAI and EP 2

870.2500 Primary dermal irritation R R TGAI and MP TGAI and EP 1, 2

none Hypersensitivity incidents R R All All 4

Subchronic Testing

870.3100 90-day oral (one species) R NR TGAI TGAI --

Developmental Toxicity

870.3700 Prenatal developmental - rat preferably R CR TGAI TGAI 5

Mutagenicity Testing

870.5100 Bacterial reverse mutation test R CR TGAI TGAI 6

870.5300 In vivo mammalian cell assay R CR TGAI TGAI 6, 7

Tier II

Developmental Toxicity

870.3700 Prenatal developmental CR CR TGAI TGAI 5

(e) Test notes . The following test notes are applicable to the data requirements for experimental use permit biochemical pesticides human health

assessment as referenced in the last column of the table in paragraph (d) of this section.

1. Required unless the test material is a gas or highly volatile (vapor pressure>10-4torr (mm/Hg)).

2. Required unless the test material is corrosive to skin or has pH<2 or>11.5.

3. Required when the pesticide, under conditions of use, would result in respirable material (e.g., gas, volatile substance or aerosol/particulate), unless it is a straight chain

lepidopteran pheromone.

4. Hypersensitivity incidents must be reported as adverse effects data.

5. Required if the use of the product under widespread and commonly recognized practice may reasonably be expected to result in significant exposure to female humans (e.g.,

occupational exposure or repeated application of insect repellents directly to the skin). Tier II data is required on a different test species from Tier I data when developmental effects

are observed in the first study and information on species-to-species extrapolation is needed.

6. Required to support nonfood uses if either:

i. The use is likely to result in significant human exposure; or

ii. The active ingredient (or its metabolites) is structurally related to a known mutagen or belongs to any chemical class of compounds containing a known mutagen.

Additional mutagenicity tests that may have been performed plus a complete reference list must also be submitted. Subsequent testing may be required based on the available

evidence.

7. Choice of assay using either:

i. Mouse lymphoma L5178Y cells, thymidine kinase (tk) gene locus, maximizing assay conditions for small colony expression or detection;

ii. Chinese hamster ovary (CHO) or Chinese hamster lung fibroblast (V79) cells, hypoxanthine-guanine phosphoribosyl transferase (hgprt) gene locus, accompanied by an

appropriate in vivo test for clastogenicity; or

iii. CHO cells strains AS52, xanthine-guanine phosphoribosyl transferase (xprt) gene locus.

§ 158.2084 Experimental use permit biochemical pesticides nontarget organisms and environmental fate data requirements table.

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(a) General . (1) Sections 158.100 through 158.130 describe how to use this table to determine the terrestrial and aquatic nontarget organisms and

fate data requirements for a particular biochemical 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. In general, for all outdoor end-use products including

turf, the following studies are required: one avian acute oral, one avian dietary, one acute freshwater fish, and one acute freshwater invertebrate

study.

(2) The data in this section are not required for arthropod pheromones when applied at up to a maximum use rate of 150 grams active

ingredient/acre/year except when the product is expected to be available to avian species ( i.e. , granular formulation).

(b) Use patterns . The terrestrial use pattern includes products classified under the general use patterns of terrestrial food crop, terrestrial feed crop,

and terrestrial nonfood/nonfeed crop. 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 nonfood

use. The remaining terrestrial uses include forestry and residential outdoor use. Data are also required for the general use patterns of aquatic food

and nonfood crop use.

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

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product; TGAI=Technical grade of the active ingredient; Residue of concern=the active ingredient and its metabolites, degradates, and impurities of

toxicological concern; All=All of the above. Specific conditions, qualifications, or exceptions to the designated test procedures appear in paragraph

(e) of this section, and apply to the individual tests in the following table:

(d) Table . The following table shows the data requirements for experimental use permit biochemical pesticides nontarget organisms and

environmental fate. The test notes are shown in paragraph (e) of this section.

Table—EUP Biochemical Pesticides Nontarget Organisms and Environmental Fate Data Requirements

Guideline

Number Data Requirement

Use Patterns

Test

Substance

Test

Notes

Terrestrial Aquatic Greenhouse Forestry,

Residential

Outdoor

Indoor

Food/Feed

/Nonfood Food/Nonfood Food/Nonfood Food/Nonfood

Tier I

Avian Testing

850.2100 Avian acute oral toxicity R R NR R NR TGAI, EP 1, 2, 3

850.2200 Avian dietary toxicity R R NR R NR TGAI, EP 1, 2, 3

Aquatic Organism Testing

850.1075 Fish acute toxicity,

freshwater

R R NR R NR TGAI, EP 2, 3, 4

850.1010 Aquatic invertebrate acute

toxicity, freshwater

R R NR R NR TGAI, EP 2, 4

(e) Test notes . The following test notes are applicable to the data requirements for experimental use permit biochemical pesticides nontarget

organisms and environmental fate as referenced in the last column of the table contained in paragraph (d) of this section.

1. Required for the EP when any end-use formulation may contain other ingredients that may be toxic to nontarget organisms or to support arthropod pheromones that would be

available to avian wildlife, (e.g., a granular product).

2. Not required for any use groups if the pesticide is highly volatile (estimated volatility>5 X 10-5atm m3

 /mol).

3. Preferred test species are: upland game, waterfowl, or passerine for avian acute oral toxicity studies; upland game or waterfowl for avian dietary studies; and coldwater fish for

acute freshwater fish studies.

4. Required for the EP when the end-use formulation may contain other ingredients that may be toxic to nontarget organisms.

Subpart V—Microbial Pesticides

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Source: 72 FR 61002, Oct. 26, 2007, unless otherwise noted.

§ 158.2100 Microbial pesticides definition and applicability.

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(a) This subpart applies to all living or dead microbial pesticides as described in paragraphs (b) and (c) of this section.

(b) Definition . Microbial pesticide is a microbial agent intended for preventing, destroying, repelling, or mitigating any pest, or intended for use as a

plant regulator, defoliant, or desiccant, that:

(1) Is a eucaryotic microorganism including, but not limited to, protozoa, algae, and fungi;

(2) Is a procaryotic microorganism, including, but not limited to, Eubacteria and Archaebacteria; or

(3) Is a parasitically replicating microscopic element, including, but not limited to, viruses.

(c) Applicability . (1) This part applies to microbial pesticides as specified in paragraphs (c)(2), (3) and (4) of this section.

(2) Each new isolate of a microbial pesticide is treated as a new strain and must be registered independently of any similar registered microbial

pesticide strain and supported by data required in this subpart.

(3) Genetically modified microbial pesticides may be subject to additional data or information requirements on a case-by-case basis depending on the

particular microbial agent and/or its parental strains, the proposed pesticide use pattern, and the manner and extent to which the organism has been

genetically modified.

(4) Pest control organisms such as insect predators, nematodes, and macroscopic parasites are exempt from the requirements of FIFRA as authorized

by section 25(b) of FIFRA and specified in §152.20 (a) of this chapter.

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§ 158.2110 Microbial pesticides data requirements.

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(a) For all microbial pesticides. (1) The following §158.2120 through §158.2150 identify the data requirements that are required to support

registration of microbial pesticides. The variations in the test conditions are identified within the test notes.

(2) Each data table includes “use patterns” under which the individual data are required, with variations including all use patterns, food and nonfood

uses for terrestrial and aquatic applications, greenhouse, indoor, forestry, and residential outdoor applications under certain circumstances.

(3) The categories for each data requirement are “R,” which stands for required, and “CR” which stands for conditionally required. If a bracket

appears around the “R” or “CR,” the data are required for both the registration and experimental use permit requests. Generally, “R” indicates that

the data are more likely required than for those data requirements with “CR.” However, in each case, the regulatory text preceding the data table

and the test notes following the data table must be used to determine whether the data requirement must be satisfied.

(4) Each table identifies the test substance that is required to be tested to satisfy the data requirement. Test substances may include: technical grade

active ingredient (TGAI), manufacturing-use product (MP), end-use product (EP), typical end-use product (TEP), residue of concern, and pure

active ingredient (PAI) or all of the above (All). Commas between the test substances ( i.e. , TGAI, EP) indicate that data may be required on the

TGAI or EP or both depending on the conditions set forth in the test note. Data requirements which list two test substances ( i.e. , TGAI and EP)

indicate that both are required to be tested. Data requirements that list only MP as the test substance apply to products containing solely the

technical grade of the active ingredient and manufacturing-use products to which other ingredients have been intentionally added. Data requirements

listing the EP as the test substance apply to any EP with an ingredient in the end-use formulation other than the active ingredient that is expected to

enhance the toxicity of the product.

(b) Additional data requirements for genetically modified microbial pesticides. Additional requirements for genetically modified microbial pesticides

may include but are not limited to: genetic engineering techniques used; the identity of the inserted or deleted gene segment (base sequence data or

enzyme restriction map of the gene); information on the control region of the gene in question; a description of the “new” traits or characteristics

that are intended to be expressed; tests to evaluate genetic stability and exchange; and selected Tier II environmental expression and toxicology

tests.

§ 158.2120 Microbial pesticides product analysis data requirements table.

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(a) General . Sections 158.100 through 158.130 describe how to use this table to determine the product analysis data requirements and the substance

to be tested for a particular microbial pesticide. Specific conditions, qualifications, or exceptions to the designated test are identified in paragraph (d)

of this section, and the test notes appear in paragraph (e) of this section.

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

product; TGAI=Technical grade of the active ingredient; All=All of the above. Specific conditions, qualifications, or exceptions to the designated

test procedures appear in paragraph (e) of this section, and apply to the individual tests in the following table:

(c) Table . The following table shows the data requirements for microbial pesticides product analysis. The test notes are shown in paragraph (d) of

this section.

Table—Microbial Pesticides Product Analysis Data Requirements

Guideline Number Data Requirement All Use Patterns

Test Substance

MP EP Test Notes

Product Chemistry and Composition

885.1100 Product Identity R MP EP --

885.1200 Manufacturing process R TGAI and MP TGAI and EP --

Deposition of a sample in a nationally recognized culture collection R TGAI TGAI --

885.1300 Discussion of formation of unintentional ingredients R TGAI and MP TGAI and EP --

Analysis and Certified Limits

885.1400 Analysis of samples R TGAI and MP TGAI and EP 1

885.1500 Certification of limits R MP EP --

Physical and Chemical Characteristics

830.6302 Color R TGAI TGAI --

830.6303 Physical state R TGAI TGAI --

830.6304 Odor R TGAI TGAI --

830.6313 Stability to normal and elevated temperatures, metals and metal ions R TGAI TGAI --

830.6317 Storage stability R TGAI and MP TGAI and EP --

830.6319 Miscibility R MP EP 2

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830.6320 Corrosion Characteristics R MP EP 3

830.7000 pH R TGAI TGAI --

830.7100 Viscosity R MP EP 4

830.7300 Density/relative density/bulk density (specific gravity) R TGAI TGAI --

(d) Test notes . The following test notes are applicable to the data requirements for microbial pesticides product analysis as referenced in the last

column of the table contained in paragraph (c) of this section.

1. Required to support registration of each manufacturing-use product and end-use product. This analysis must be conducted at the point in the production process after which there

would be no potential for microbial contamination or microbial regrowth. For full registration, generally an analysis of samples is a compilation of batches, over a period of time,

depending on the frequency of manufacturing.

2. Only required for emulsifiable liquid forms of microbial pesticides.

3. Required when microbial pesticides are packaged in metal, plastic, or paper containers.

4. Only required for liquid forms of microbial pesticides.

§ 158.2130 Microbial pesticides residue data requirements table.

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(a) General . Sections 158.100 through 158.130 describe how to use this table to determine the residue chemistry data requirements and the

substance to be tested for a particular microbial pesticide. Specific conditions, qualifications, or exceptions to the designated test appear in paragraph

(d) of this section, and the procedures appear in paragraph (e) of this section.

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

product; TGAI=Technical grade of the active ingredient; All=All of the above. Specific conditions, qualifications, or exceptions to the designated

test procedures appear in paragraph (d) of this section, and apply to the individual tests in the following table:

(c) Table . The following table shows the data requirements for microbial pesticides residue. The test notes are shown in paragraph (d) of this

section.

Table—Microbial Pesticides Residue Data Requirements

Guideline

Number Data Requirement

All Use

Patterns

Test Substance Data to Support MP or

EP

Test

Notes

885.2100 Chemical Identity CR EP 1

885.2200 Nature of the Residue in plants CR EP 1

885.2250 Nature of the Residue in animals CR EP 1

885.2300 Analytical methods - plants CR TGAI 1

885.2350 Analytical methods - animals CR TGAI 1

885.2400 Storage Stability CR EP 1

885.2500 Magnitude of residue in plants CR EP 1

885.2550 Magnitude of residues in meat, milk, poultry, eggs CR EP 1

885.2600 Magnitude of residues in potable water, fish, and irrigated

crops

CR EP 1

(d) Test notes . The following test note is applicable to the data requirements for microbial pesticides residue as referenced in the last column of the

table contained in paragraph (c) of this section.

1. Required when the results of testing:

i. Indicate the potential to cause adverse human health effects or the product characterization indicates the microbial pesticide has a significant potential to produce a mammalian

toxin; and

ii. The use pattern is such that residues may be present in or on food or feed crops.

§ 158.2140 Microbial pesticides toxicology data requirements table.

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(a) General . Sections 158.100 through 158.130 describe how to use this table to determine the toxicology data requirements for a particular

pesticide product. Notes that apply to an individual test and include specific conditions, qualifications, or exceptions to the designated test are listed

in paragraph (d) of this section.

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

product; TGAI=Technical grade of the active ingredient; All=All of the above. Specific conditions, qualifications, or exceptions to the designated

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test procedures appear in paragraph (d) of this section, and apply to the individual tests in the following table:

(c) Table . The following table shows the data requirements for microbial pesticides toxicology. The test notes are shown in paragraph (d) of this

section.

Table—Microbial Pesticides Toxicology Data Requirements

Guideline Number Data Requirement All Use Patterns Test Substance Test Notes

Tier I

885.3050 Acute oral toxicity/pathogenicity R TGAI 1

885.3150 Acute pulmonary toxicity/pathogenicity R TGAI --

885.3200 Acute injection toxicity/pathogenicity/(intravenous)

Acute injection toxicity/pathogenicity/(intraperitoneal)

R TGAI 2

885.3400 Hypersensitivity incidents R All 3

885.3500 Cell culture R TGAI 4

870.1100 Acute oral toxicity R MP , EP 1, 5

870.1200 Acute dermal toxicity R MP , EP 5

870.1300 Acute inhalation toxicity R MP , EP 5, 6

870.2400 Acute eye irritation R MP , EP 5

870.2500 Primary dermal irritation R MP , EP 5

Tier II

885.3550 Acute toxicology CR TGAI 7

885.3600 Subchronic toxicity/pathogenicity CR TGAI 8

Tier III

885.3650 Reproductive fertility effects CR TGAI 9, 13

870.4200 Carcinogenicity CR TGAI 10, 13

870.7800 Immunotoxicity CR TGAI 11, 13

885.3000 Infectivity/pathogenicity analysis CR TGAI 12, 13

(d) Test notes . The following test notes are applicable to the data requirements for microbial pesticides toxicology as referenced in the last column

of the table contained in paragraph (c) of this section:

1. The acute oral toxicity/pathogenicity study is required to support the TGAI. However, it can be combined with the unit dose portion of the acute oral toxicity study, with an EP or

MP test material to fulfill the requirement for the TGAI and the MP or EP in a single study, if the new protocol is designed to address the endpoints of concern.

2. Data not required for products whose active ingredient is a virus. For test materials whose size or consistency may prevent use of an intravenous injection, the intraperitoneal

injection procedure may be employed.

3. Hypersensitivity incidents, including immediate type and delayed-type reactions of humans or domestic animals, occur during the testing or production of the TGAI, MP, or EP, or

are otherwise known to the applicant must be reported if they occur.

4. Data must be submitted only for products whose active ingredient is a virus.

5. The 870 series studies for the MP and EP are intended to provide data on the acute toxicity of the product. Waivers for any or all of these studies may be granted when the

applicant can demonstrate that the combination of inert ingredients is not likely to pose any significant human health risks. Where appropriate, the limit dose approach to testing is

recommended.

6. Required when the product consists of, or under conditions of use would result in, an inhalable material (e.g., gas, volatile substances, or aerosol particulate).

7. Data required when significant toxicity, in the absence of pathogenicity and significant infectivity, is observed in acute oral, injection, or pulmonary studies (Tier I). Route(s) of

exposure correspond to route(s) where toxicity was observed in Tier I studies. The toxic component of the TGAI is to be tested.

8. Data required when significant infectivity and/or unusual persistence is observed in the absence of pathogenicity or toxicity in Tier I studies. Routes of exposure (oral and/or

pulmonary) correspond to routes in Tier I studies where adverse effects were noted. Data may also be required to evaluate adverse effects due to microbial contaminants or to toxic

byproducts.

9. Data are required when one or more of the following criteria are met:

i. Significant infectivity of the microbial pest control agent (MPCA) was observed in test animals in the Tier II subchronic study and in which no significant signs of toxicity or

pathogenicity were observed.

ii. The microbial pesticide is a virus which can persist or replicate in mammalian cell culture lines.

iii. The microbial pesticide is not amenable to thorough taxonomic classification, and is related to organisms known to be parasitic for mammalian cells.

iv. The microbial pesticide preparation is not well purified, and may contain contaminants which are parasitic for mammals.

10. Data may be required for products known to contain or suspected to contain carcinogenic viruses or for microbial components that are identified as having significant toxicity in

Tier II testing.

11. Data may be required for products known to contain or suspected to contain viruses that can interact in an adverse manner with components of the mammalian immune system.

12. An analysis of human infectivity/pathogenicity potential using scientific literature, genomic analysis, and/or actual specific cell culture/animal data may be required for products

known to contain or suspected of containing intracellular parasites of mammalian cells for products that exhibit pathogenic characteristics in Tier I and/or Tier II, for products which

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are closely related to known human pathogens based on the product analysis data, or for known human pathogens that have been “disarmed” or rendered non-pathogenic for humans.

13. Test standards may have to be modified depending on the characteristics of the microorganism. Requirements may vary for these studies depending on the active ingredient being

tested. Consultation with the Agency is advised before performing these Tier III studies.

§ 158.2150 Microbial pesticides nontarget organisms and environmental fate data requirements table.

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(a) General . Sections 158.100 through 158.130 describe how to use this table to determine the terrestrial and aquatic nontarget organisms data

requirements for a particular microbial 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 . Aquatic uses include: food and feed, nonfood uses (e.g., outdoor, residential, and industrial). Terrestrial uses include: Food, Feed,

Non-Food, Forestry, Residential outdoor, greenhouse (food and food), Indoor (food and nonfood), and Industrial.

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

product; TGAI=Technical grade of the active ingredient; All=All of the above. Specific conditions, qualifications, or exceptions to the designated

test procedures appear in paragraph (e) of this section, and apply to the individual tests in the following table:

(d) Table . The following table shows the data requirements for microbial pesticides nontarget organisms and environmental fate. The test notes are

shown in paragraph (e) of this section.

Table—Microbial Pesticides Nontarget Organisms and Environmental Fate Data Requirements

Guideline

Number Data Requirement

Use Patterns

Test

Substance

Test

Notes

Aquatic Terrestrial

Food/Feed Nonfood

Food/Feed

/Nonfood Forestry

Residential Greenhouse Indoor

Outdoor Food/Nonfood Food/Nonfood Industrial

Tier I

885.4050 Avian oral toxicity R R R R R CR CR CR TGAI 1, 2

885.4100 Avian inhalation

toxicity/pathogenicity

CR CR CR CR CR CR CR CR TGAI 1, 2,

3

885.4150 Wild mammal

toxicity/pathogenicity

CR CR CR CR CR NR NR CR TGAI 1, 4

885.4200 Freshwater fish

toxicity/

pathogenicity

R R R R CR CR CR CR TGAI or

TEP

1, 2,

5

885.4240 Freshwater

invertebrate

toxicity/pathogenicity

R R R R CR CR CR CR TGAI or

TEP

1, 2,

5

885.4280 Estuarine/Marine fish

testing

Estuarine and marine

invertebrate testing

CR CR CR CR CR NR NR CR TGAI 1, 6

885.4300 Nontarget plant

testing

CR CR CR R CR NR CR CR TEP 1, 7

885.4340 Nontarget insect

testing

R R R R R CR NR CR TGAI 1, 8

885.4380 Honey bee testing R R R R R CR NR CR TGAI 1

Tier II

885.5200 Terrestrial

environmental

expression tests

CR CR CR CR CR NR NR CR TGAI or

TEP

9

885.5300 Freshwater

environmental

expression tests

CR CR CR CR CR NR NR CR TGAI or

TEP

10

885.5400 Marine or estuarine

environmental

expression tests

CR CR CR CR CR NR NR CR TGAI or

TEP

11,

12

Tier III

885.4600 Avian chronic

pathogenicity and

reproduction test

CR CR CR CR CR NR NR CR TGAI 12,

13

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885.4650 Aquatic invertebrate

range testing

CR CR CR CR CR NR NR CR TGAI 12,

14

885.4700 Fish life cycle studies CR CR CR CR CR NR NR CR TGAI 12,

14

885.4750 Aquatic ecosystem

test

CR CR CR CR CR NR NR CR TGAI 15

Tier IV

850.2500

850.1950

Field testing for

terrestrial wildlife

and Field testing for

aquatic organisms

CR CR CR CR CR NR NR CR TGAI or

TEP

11,

16

850.2500 Simulated or actual

field tests (birds,

mammals)

CR CR CR CR CR NR NR CR TEP 16,

17,

20

850.1950 Simulated or actual

field test (aquatic

organisms)

CR CR CR CR CR NR NR CR TEP 16,

18,

19,

20

850.2500 Simulated or actual

field tests (insect

predators, parasites)

CR CR CR CR CR NR NR CR TEP 16,

18,

19,

20

850.3040 Simulated or actual

field tests (insect

pollinators)

CR CR CR CR CR NR NR CR TEP 16,

18,

19,

20

850.4300 Simulated or actual

field tests (plants)

CR CR CR CR CR NR NR CR TEP 16,

18,

19,

20

(e) Test notes . The following test notes are applicable to the data requirements for microbial pesticides nontarget organism and environmental fate as

referenced in the last column of the table contained in paragraph (d) of this section.

1. Tests for pesticides intended solely for indoor application would be required on a case-by-case basis, depending on use pattern, production volume, and other pertinent factors.

2. The preferred species for the avian oral study is either the upland game or waterfowl. The preferred species for the avian inhalation toxicity/pathogenicity study and the avian

chronic toxicity/pathogenicity study is the upland game. There is also the option to test the passerine if there is a concern. The coldwater fish is preferred for freshwater fish testing.

However, two species (coldwater and warmwater fish species are the preferred species) must be tested for uses involving direct freshwater exposure. Freshwater invertebrate

testing is also required.

3. Data required when the nature of the microbial pesticide and/or its toxins indicates potential pathogenicity to birds.

4. Required on a case-by-case basis if results of tests required by §158.2140 are inadequate or inappropriate for assessment of hazards to wild mammals.

5. Required when there will be significant exposure to aquatic organisms (fish and invertebrates).

6. Required if the product is intended for direct application into the estuarine or marine environment or expected to enter this environment in significant concentrations because of

expected use or mobility pattern.

7. Required if the microbial pesticide is taxonomically related to a known plant pathogen.

8. Data are not required unless an active microbial ingredient controls the target insect pest by a mechanism of infectivity; i.e. , may create an epizootic condition in nontarget insects.

9. Required if toxic or pathogenic effects are observed in one or more of the following tests for microbial pesticides:

i. Avian acute oral or avian inhalation studies.

ii. Wild mammal studies.

iii. Nontarget plant studies (terrestrial).

iv. Honey bee studies.

v. Nontarget insect studies.

10. Required when toxic or pathogenic effects are observed in any of the following Tier I tests for microbial pest control agents:

i. Freshwater fish studies.

ii. Freshwater invertebrate studies.

iii. Nontarget plant studies (aquatic).

11. Required if product is applied on land or in fresh water or marine/estuarine environments and toxic or pathogenic effects are observed in any of the following Tier I tests for

microbial pesticides:

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i. Estuarine and marine animal toxicity and pathogenicity.

ii. Plant studies - estuarine or marine species.

12. An appropriate dose-response toxicity test is required when toxic effects on nontarget terrestrial wildlife or aquatic organisms (including plants) are reported in one or more Tier

I tests and results of Tier II tests indicate exposure of the microbial agent to the affected nontarget terrestrial wildlife or aquatic organisms. The protocols for these tests may have to

be modified in accordance with results from the nontarget organism and environmental expression studies.

13. Required when one or more of the following are present:

i. Pathogenic effects are observed in Tier I avian studies.

ii. Tier II environmental expression testing indicate that long-term exposure of terrestrial animals is likely.

14. Required when product is intended for use in water or expected to be transported to water from the intended use site, and when pathogenicity or infectivity was observed in Tier

I aquatic studies.

15. Required if, after an analysis of the microbial pesticide's ability to survive and multiply in the environment and what ecological habitat it would occupy, the intended use

patterns, and the results of previous nontarget organisms and environmental expression tests, it is determined that use of the microbial agent may result in adverse effects on the

nontarget organisms in aquatic environments. Testing is to determine if applications of the microbial pest control would be expected to disrupt the balance of populations in the target

ecosystem.

16. Tier IV studies may be conducted as a condition of registration as post-registration monitoring if the potential for unreasonable adverse effects appears to be minimal during that

period of use due to implementation of mitigation measures.

17. Required when both of the following conditions occur:

i. Pathogenic effects observed at actual or expected field residue exposure levels are reported in Tier III; and

ii. The Agency determines that quarantine methods would not prevent the microbial pesticide from contaminating areas adjacent to the test area.

18. Short term simulated or actual field studies are required when it is determined that the product is likely to cause adverse short-term or acute effects, based on consideration of

available laboratory data, use patterns, and exposure rates.

19. Data from a long-term simulated field test (e.g., where reproduction and growth of confined populations are observed) and/or an actual field test (e.g., where reproduction and

growth of natural populations are observed) are required if laboratory data indicate that adverse long-term, cumulative, or life-cycle effects may result from intended use.

20. Since test standards would be developed on a case-by-case basis, consultation with the Agency and development of a protocol is advised before performing these Tier IV

studies.

§ 158.2160 Microbial pesticides product performance data requirements.

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Product performance data must be developed for all microbial pesticides. However, the Agency has waived all requirements to submit efficacy data

unless the pesticide product bears a claim to control public health pests, such as pest microorganisms infectious to man in any area of the inanimate

environment or a claim to control vertebrates (including but not limited to: rodents, birds, bats, canids, and skunks) or invertebrates (including but

not limited to: mosquitoes and ticks) that may directly or indirectly transmit diseases to humans. However, each registrant must ensure through

testing that his products are efficacious when used in accordance with label directions and commonly accepted pest control practices. The Agency

reserves the right to require, on a case-by-case basis, submission of efficacy data for any pesticide product registered or proposed for registration.

§ 158.2170 Experimental use permit data requirements—microbial pesticides.

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(a) For all microbial pesticides. (1) The following §158.2171 through §158.2174 identify the data requirements that are required to support

experimental use permits for microbial pesticides. The variations in the test conditions are identified within the test notes.

(2) For general information on the data requirement tables, see §158.2110(a)(2)-(4).

(b) Additional data requirements for genetically modified microbial pesticides. Additional requirements for genetically modified microbial pesticides

may include but are not limited to: genetic engineering techniques used; the identity of the inserted or deleted gene segment (base sequence data or

enzyme restriction map of the gene); information on the control region of the gene in question; a description of the “new” traits or characteristics

that are intended to be expressed; tests to evaluate genetic stability and exchange; and selected Tier II environmental expression and toxicology

tests.

§ 158.2171 Experimental use permit microbial pesticides product analysis data requirements table.

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(a) General . Sections 158.100 through 158.130 describe how to use this table to determine the product analysis data requirements and the substance

to be tested for a particular microbial pesticide. Specific conditions, qualifications, or exceptions to the designated test are identified in (d) of this

section, and the test notes appear in paragraph (e) of this section.

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

product; TGAI=Technical grade of the active ingredient; All=All of the above. Specific conditions, qualifications, or exceptions to the designated

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test procedures appear in paragraph (e) of this section, and apply to the individual tests in the following table:

(c) Table . The following table shows the data requirements for experimental use permit microbial pesticides product analysis. The test notes are

shown in paragraph (d) of this section.

Table—EUP Microbial Product Analysis Data Requirements

Guideline Number Data Requirement All Use Patterns

Test Substance

MP EP Test Notes

Product Chemistry and Composition

885.1100 Product Identity R MP EP --

885.1200 Manufacturing process R TGAI and MP TGAI and EP 1, 2

Deposition of a sample in a nationally recognized culture collection R TGAI TGAI --

885.1300 Discussion of formation of unintentional ingredients R TGAI and MP TGAI and EP 2

Analysis and Certified Limits

885.1400 Analysis of samples R TGAI and MP TGAI and EP 2, 3

885.1500 Certification of limits R MP EP --

Physical and Chemical Characteristics

830.6302 Color R TGAI TGAI --

830.6303 Physical state R TGAI TGAI --

830.6304 Odor R TGAI TGAI --

830.6313 Stability to normal and elevated temperatures, metals and metal ions R TGAI TGAI --

830.6317 Storage stability R TGAI and MP TGAI and EP --

830.6319 Miscibility R MP EP 4

830.6320 Corrosion Characteristics R MP EP 5

830.7000 pH R TGAI TGAI --

830.7100 Viscosity R MP EP 6

830.7300 Density/relative density/bulk density (specific gravity) R TGAI TGAI --

(d) Test notes . The following test notes are applicable to the data requirements for experimental use permit microbial pesticides product analysis as

referenced in the last column of the table contained in paragraph (c) of this section.

1. If an experimental use permit is being sought, and if the pesticide is not already under full-scale production, a schematic diagram and/or description of the manufacturing process

suffices.

2. If an experimental use permit is being sought, and if the product is not already under full-scale production, a discussion of unintentional ingredients is required to be submitted to

the extent this information is available.

3. Required to support registration of each manufacturing-use product and end-use product. This analysis must be conducted at the point in the production process after which there

would be no potential for microbial contamination or microbial regrowth. For pesticides in the production stage, a preliminary product analytical method and data would suffice to

support an experimental use permit. For full registration, generally an analysis of samples is a compilation of batches, over a period of time, depending on the frequency of

manufacturing.

4. Only required for emulsifiable liquid forms of microbial pesticides.

5. Required when microbial pesticides are packaged in metal, plastic, or paper containers.

6. Only required for liquid forms of microbial pesticides.

§ 158.2172 Experimental use permit microbial pesticides residue data requirements table.

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(a) General . Sections 158.100 through 158.130 describe how to use this table to determine the residue chemistry data requirements and the

substance to be tested for a particular microbial pesticide. Specific conditions, qualifications, or exceptions to the designated test appear in (d) of this

section, and the procedures appear in paragraph (e) of this section.

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

product; TGAI=Technical grade of the active ingredient; All=All of the above. Specific conditions, qualifications, or exceptions to the designated

test procedures appear in paragraph (d) of this section, and apply to the individual tests in the following table:

(c) Table . The following table shows the data requirements for experimental use permit microbial pesticides residue. The test notes are shown in

paragraph (d) of this section.

Table—EUP Microbial Pesticides Residue Data Requirements

Guideline

Data Requirement

All Use Test Substance Data to Support MP or Test

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Number Patterns EP Notes

885.2100 Chemical Identity CR EP 1

885.2200 Nature of the Residue in plants CR EP 1

885.2250 Nature of the Residue in animals CR EP 1

885.2300 Analytical methods - plants CR TGAI 1

885.2350 Analytical methods-animals CR TGAI 1

885.2400 Storage Stability CR EP 1

885.2500 Magnitude of residue in plants CR EP 1

885.2550 Magnitude of residues in meat, milk, poultry, eggs CR EP 1

885.2600 Magnitude of residues in potable water, fish, and irrigated

crops

CR EP 1

(d) Test notes . The following test note is applicable to the data requirements for experimental use permit microbial pesticides residue as referenced

in the last column of the table contained in paragraph (c) of this section.

1. Required when the results of testing:

i. Indicate the potential to cause adverse human health effects or the product characterization indicates the microbial pesticide has a significant potential to produce a mammalian

toxin; and

ii. The use pattern is such that residues may be present in or on food or feed crops.

§ 158.2173 Experimental use permit microbial pesticides toxicology data requirements table.

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(a) General . Sections 158.100 through 158.130 describe how to use this table to determine the toxicology data requirements for a particular

microbial pesticide product. Notes that apply to an individual test and include specific conditions, qualifications, or exceptions to the designated test

are listed in paragraph (d) of this section.

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

product; TGAI=Technical grade of the active ingredient; All=All of the above. Specific conditions, qualifications, or exceptions to the designated

test procedures appear in paragraph (d) of this section, and apply to the individual tests in the following table:

(c) Table . The following table shows the data requirements for microbial pesticide toxicology. The test notes are shown in paragraph (d) of this

section.

Table—EUP Microbial Pesticides Toxicology Data Requirements

Guideline Number Data Requirement All Use Patterns Test Substance Test Notes

885.3050 Acute oral toxicity/pathogenicity R TGAI 1

885.3150 Acute pulmonary toxicity/pathogenicity R TGAI --

885.3200 Acute injection toxicity/pathogenicity/(intravenous)

Acute injection toxicity/pathogenicity/(intraperitoneal)

R TGAI 2

885.3400 Hypersensitivity incidents R All 3

885.3500 Cell culture R TGAI 4

870.1100 Acute oral toxicity R MP, EP 1, 5

870.1200 Acute dermal toxicity R MP, EP 5

870.1300 Acute inhalation toxicity R MP, EP 5, 6

870.2400 Acute eye irritation R MP, EP 5

870.2500 Primary dermal irritation CR MP, EP 5

(d) Test notes . The following test notes are applicable to the data requirements for experimental use permit microbial pesticides toxicology as

referenced in the last column of the table contained in paragraph (c) of this section:

1. The acute oral toxicity/pathogenicity study is required to support the TGAI. However, it can be combined with the unit dose portion of the acute oral toxicity study, with an EP or

MP test material to fulfill the requirement for the TGAI and the MP or EP in a single study, if the new protocol is designed to address the endpoints of concern.

2. Data not required for products whose active ingredient is a virus. For test materials whose size or consistency may prevent use of an intravenous injection, the intraperitoneal

injection procedure may be employed.

3. Hypersensitivity incidents, including immediate type and delayed type reactions of humans or domestic animals occur during the testing or production of the TGAI, MP, or EP, or

are otherwise known to the applicant must be reported if they occur.

4. Data must be submitted only for products whose active ingredient is a virus.

5. The 870 series studies for the MP and EP are intended to provide data on the acute toxicity of the product. Waivers for any or all of these studies may be granted when the

applicant can demonstrate that the combination of inert ingredients is not likely to pose any significant human health risks. Where appropriate, the limit dose approach to testing is

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recommended.

6. Required when the product consists of, or under conditions of use that would result in an inhalable material (e.g., gas, volatile substances, or aerosol particulate).

§ 158.2174 Experimental use permit microbial pesticides nontarget organisms and environmental fate data requirements table.

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(a) General . Sections 158.100 through 158.130 describe how to use this table to determine the terrestrial and aquatic nontarget organisms data

requirements for a particular microbial 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 . Aquatic uses include: food and feed, nonfood uses (e.g., outdoor, residential, and industrial). Terrestrial uses include: Food, Feed,

Non-Food, Forestry, Residential outdoor, greenhouse (food and food), Indoor (food and nonfood), and Industrial.

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

product; TGAI=Technical grade of the active ingredient; All=All of the above. Specific conditions, qualifications, or exceptions to the designated

test procedures appear in paragraph (e) of this section, and apply to the individual tests in the following table:

(d) Table . The following table shows the data requirements for experimental use permit microbial pesticides nontarget organisms and environmental

fate. The test notes are shown in paragraph (e) of this section.

Table—EUP Microbial Pesticides Nontarget Organisms and Environmental Fate Data Requirements

Guideline

Number Data Requirement

Use Patterns

Test

Substance

Test

Notes

Aquatic Terrestrial

Food/Feed Nonfood

Food/Feed

/Nonfood Forestry

Residential Greenhouse Indoor

Outdoor Food/Nonfood Food/Nonfood Industrial

885.4050 Avian oral

toxicity

NR R R R R NR NR NR TGAI 1, 2

885.4200 Freshwater fish

toxicity/pathogenicity

NR R R R NR NR NR NR TGAI 1, 2,

3

885.4240 Freshwater

invertebrate

toxicity/pathogenicity

NR R R R NR NR NR NR TGAI 1, 2,

3

885.4300 Nontarget plant

testing

NR NR NR R NR NR NR NR TEP 1, 4

885.4340 Nontarget insect

testing

R R R R NR NR NR NR TGAI 1, 5

885.4380 Honey bee testing R R R R NR NR NR NR TGAI 1

(e) Test notes . The following test notes are applicable to the data requirements for microbial pesticides nontarget organism and environmental fate as

referenced in the last column of the table contained in paragraph (d) of this section.

1. Tests for pesticides intended solely for indoor application would be required on a case-by-case basis, depending on use pattern, production volume, and other pertinent factors.

Tests to support EUP's are based on the application timing and acreage.

2. The preferred species for the avian oral study is either the upland game or waterfowl. The preferred species for the avian inhalation toxicity/pathogenicity study and the avian

chronic toxicity/pathogenicity study is the upland game. There is also the option to test a passerine species if there is a concern. The coldwater fish is preferred for freshwater fish

testing. However, two species (coldwater and warmwater fish are the preferred species) must be tested for uses involving direct freshwater exposure. Freshwater invertebrates are

preferred for invertebrate testing.

3. Required when there will be significant exposure to aquatic organisms (fish and invertebrates).

4. Required if the microbial pesticide is taxonomically related to a known plant pathogen.

5. Data are not required unless an active microbial ingredient controls the target insect pest by a mechanism of infectivity; i.e. , may create an epizootic condition in nontarget insects.

Subpart W—Antimicrobial Pesticides [Reserved]

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§ 158.2200 [Reserved]

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Subparts X–Z [Reserved]

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§§ 158.2300-158.2500 [Reserved]

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