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ICR ATTACHMENT F 40 CFR part 158: Data Requi rements For RegistrationHome Page> Executive Branch > Code of Federal Regulations > Electronic Code of Federal Regulations



### e-CFR Data is current as of October 15, 2008

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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10/17/2008 12:07 PM 1 of 62§ 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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10/17/2008 12:07 PM 2 of 62Subpart A—General Provisions
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§ 158.1 Purpose and scope.
top (a) Purpose . The purpose of this part is to specify the kinds of data and in formation EPA requires in order to make regulatory judgments u nder FIFRA secs. 3, 4, and 5 about the risks and benefits of pesticide products. Further, this part specif ies 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 regis tration 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 f or a pesticide chemical residue. (2) This part establishes general policies and procedures associat ed with the submission of data in support of a pesticide regu latory action. (3) This part does not include study protocols, methodology, or standards for conducting or reporting test results; nor does th is part describe how the Agency uses or evaluates the data and information in its risk assessment and risk management deci sions, or the regulatory determinations that may be based u pon 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 appl y to biochemical pesticides. (3) Microbial pesticides . Subparts A, B and V apply to microbial pesticides. (4) Antimicrobial pesticides . [Reserved]
§ 158.3 Definitions.
top All terms defined in sec. 2 of the Federal Insecticide, Fungi cide, 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. I ndividual subparts may contain defi nitions that pertain solely t o that subpart. The following additional terms apply to this part:
A pplicant means any person or entity, including for the purposes of this parta 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 registra tion of a pesticide product under FIFRA sec. 3 or 24. (2) A submission of data required in conjunction with reregist ration 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 exempt ion from the requirement of a tolerance for a pesticide chemical residue under FFDCA sec. 408. Registration includes a new registration, amended registrati on and reregistration, unless stated otherwise.
§ 158.5 Applicability.
top (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 cont inuation of a registration under FIFRA sec. 3, 4, or 24. (4) A petition to establish, modify or revoke a tole rance 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 ifit has not been submitted previously, or if any previous submission is not accurate or complete.
§ 158.30 Flexibility.
top (a) FIFRA provides EPA flexibility to require, or not require, data and information for the purposes of making regulatory judgm ents for pesticide products. EPA has the authority to establish or modify data needs for indivi dual pesticide chemicals. The actual dat a required may be modified on an individual ba sis to fully characterize the use and properties, characteristics, or effects of specific pesticide products un der review. The Agency encourages each applicant to consult with E PA 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 require d in this part may not be sufficient to permit EPA to evaluat e 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 specifi ed 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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10/17/2008 12:07 PM 3 of 62(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 administrati ve 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 submi ssion 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 identif y 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 su bstance(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 c odes. (v) If the study is a commentary on or supplement to another prev iously submitted study, full identification of the other studywith 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, i ssue, 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.
top (a) Definitions . For the purposes of this section: (1) Registered or previously registered pesticide means any pesticide containing an active i ngredient contained in a product that is, orhas 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 with in 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 wi th a registered or previously registered pesticide or its separate ingredients, impurities, or degradation products, and any information concernin g 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 o ther 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 procedure s in 40 CFR part 2, subpart B, including FIFRA confidentiality procedures at 40 CFR 2.307. To the extent t hat provisions in this section conflict with those in 40 CFR p art 2, subpart B, the provisions in this section take precedence. The provisions of 40 CFR 2.308 do not apply to inform ation 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 submi tted in connection with an application for a tolerance or exemptio n to the same extent as FIFRA sec. 10. References in this section to FIFRA sec. 10 are deemed to apply equally to in formation 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 av ailable to the public without further notice, subject to the r equirements 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 sub mitted in accordance with paragraph (c)(3) of this section, will be recognized as asserting a claim of confidentialit y. 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 tha t 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 i s 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 confidenti al 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 confid ential attachment must have its own title page and be paginated s eparately from the non-confidential document. (ii) All information in the confidential attachment that consis ts of (or whose disclosure woul d 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 consis ts 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 ingredi ent of a pesticide, must be individually identified in the confidential attachm ent as a claim for information within the scope of FIFRA 

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10/17/2008 12:07 PM 4 of 62sec. 10(d)(1)(B). (iv) All information in the confidential attachment that consis ts 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 t he 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 secti on 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 stat ement 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 stat ement 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 gover nments, 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 a ssociated 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 sect ion 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 prov ided under FIFRA sec. 10(g), provided that the information does not contain or consist of any complete unpublished report submitted to EPA, or excerp ts or restatements of any such report which reveal the full methodology and complete results of the study, test, or experiment, and all explanatory i nformation necessary to understand the methodology or interpret the results.
§ 158.34 Flagging of studies for potential adverse effects.
top (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 p aragraph (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 nam e. 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. 7 

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10/17/2008 12:07 PM 5 of 62(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 signatur e: (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.
top (a) The data requirements specified in this part as applicable to a category of products will not always be appropriate for eve ry 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 d ata, 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) f or 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 applic ant(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 decisio n 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 act ion.
§ 158.60 Minor use data policies.
top FIFRA sec. 2(ll) defines the term “minor use”and FIFRA provides a number of statutory provisions concerning minor uses. In addi tion, 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 mino r 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.
top (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 wh ether 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 conduct ed 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 subseque ntly 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 f ormulators' 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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10/17/2008 12:07 PM 6 of 62(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 visitin g 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 p urpose of the test standards specified in the pesticide assessment guidelines, and provides data of suitable quality and comple teness 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 meth odology 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 th is part. Applicants should note, however, that certain of the OECD recommended test standards, such as test duration and selection of te st 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 scientificallyacceptable results. Registrants and applicants, however, must consult with the EPA before initiating combined studies.
§ 158.75 Requirements for additional data.
top 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 enviro nment, additional data requirements will be imposed. However, EPA expects that the information required by this part will be adequate in most cases fo r an assessment of the properties and effects of the pesticide.
§ 158.80 Use of other data.
top (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 includ e, 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 ch aracteristic of the United States. Applicants submitting foreign data must take steps to ensure that U.S. materials are used, or be prepared to supply dat a 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.
top (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 categorie s are further subdivided into 12 general use patterns which are the bases for data requirements established by use pattern. Within the data tables, gene ral use patterns have been combined into single columns when the data requirements are the same for the combined uses. If there are no data requireme nts 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 par t 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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10/17/2008 12:07 PM 7 of 62(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 withone 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 tospecific uses. The Pesticide Use Site Index, which will be updated periodically, is available from the Agency or may be obtained from the Agency'swebsite 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.
top The tables in this part use the descriptors R (required), CR (conditionally required), and NR (not required) as a general indic ation of the applicability of a data requirement. In all cases, the test notes referred toin the table must be consulted to determine the actual applicab ility 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 benef its 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 p roduct having that use pattern if the product meets the conditions specified in the notes accompanying the requirement. The det ermination 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 req uired” (NR) in data tables.
§ 158.120 Determining data requirements.
top 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 e mphasize 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 p rior 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 p resented 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 with in 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 prod uct; EP = end-use p roduct; 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 ea ch subject area. 

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10/17/2008 12:07 PM 8 of 62(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 r equired (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 p erforming the study may or may not be the product itself. For example, the data fro m 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 gra de 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 adde d inert ingredients are considered identical in composition to each other, and to the technical grade of the active ingredient (TGAI) from which th ey 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 p ertaining to the guidelines and how to obtain copies.
§ 158.130 Purposes of the registration data requirements.
top (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 t o 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 p erform as intended and that unnecessary pesticide exposure to the environment will not occur as a result of the use of ineffect ive products. Specific p erformance 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, b irds, 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 us ed to calculate farmworker reentry intervals and to develop precautionary label statements pertaining to protective clothing requirements for a pplicators. They also p rovide information used in establishing the appropriate dose levels in subchronic and other studies; provide initial informatio n on the mode of toxic action(s) of a substance; and determine the need for child resistant packaging. Information derived from primary eye and primar y dermal irritation studies serves to identify possible hazards from exposure of the eyes, associated mucous membranes and skin. 

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10/17/2008 12:07 PM 9 of 62(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 dos e 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, eff ects 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-gene ration reproduction testing is designed to provide information concerning the general effects of a test substance on gonadal function, estrus cycle s, 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 ser ve 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, carcinoge nicity, 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 inten ded uses of the p esticide. (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 sho rt-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 fo r 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 predict ions 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, p ost-application residue data, post-application monitoring data, use information, an dhuman activity information. These data, together with toxicology data, are used to determine whether application or post-application risks are of concern, and, where appropriate, todevelop p ost-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 f or humans, fish and wildlife, or plants, are used to assess the potential hazard of pesticides to these organisms. A purpose common to all these te sts is to provide data which will be used to determine the need for (and appropriate wording for) precautionary labeling to minimize the potential adv erse 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 env ironmental 

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10/17/2008 12:07 PM 10 of 62concentrations 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 p esticides 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 p esticides 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 potentia l environmental hazards related to: Contamination of human and animal food; loss of usable land and water resources to man through contamination of wat er (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 p racticable 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 take n up by representative crops irrigated with water containing pesticide residues. These studies allow the Agency to establish label restrictions regarding application of p esticides on sites where the residues can be taken up by irrigated crops. These data also provide information that aids the Age ncy 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.
top Sections 158.200 through 158.270 describe how to use these tables to determine the experimental use permit data requirements fo r a particular p esticide 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.
top 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.
top All product performance data, as described in paragraph (c) of this section, must be submitted to support a request for an expe rimental use permit. (a) Use patterns . (1) The terrestrial use pattern includes products classified under the general use patterns of terrestrial food crop and terr estrial 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 nonfo od 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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10/17/2008 12:07 PM 11 of 62p roduct. (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 mic roorganisms 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 ar ea 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. How ever each registrant must ensure thro ugh testing that his product is efficacious when used in accordance with label directions and commonly accepted pest control practices. The Agency r eserves 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.
top 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 fe ed 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 no nfood 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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10/17/2008 12:07 PM 12 of 62Food 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, aer osol, 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, o r 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 pat tern 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 mutage nicity 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 de tection; 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.
top All data for terrestrial nontarget organisms and aquatic nontarget organisms as described in §158.243 must be submitted to supp ort 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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10/17/2008 12:07 PM 13 of 62All terrestrial and aquatic nontarget organism data, as described in paragraph (c) of this section, must be submitted to suppor t 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 nonf ood 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 no tes 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 No. Terrestrial Aquatic Forestry 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 g enerally 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 ref ormulated 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 liqu id 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 u ses. 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 larvici des) 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 LC 50 or EC 50 of 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 activ e 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 LC 50 on that species 

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10/17/2008 12:07 PM 14 of 62must 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 freshwate r 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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N o 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.
top 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 paragrap h (d) of this section. Table—Environmental Fate Data Requirements

Guideline No. Data Requirement Use Pattern Test substance Test Note No. Terrestrial Aquatic Greenhouse Indoors Forestry 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 pest icide 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 tr ansformation products.
§ 158.270 Experimental use permit data requirements for residue chemistry.
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10/17/2008 12:07 PM 15 of 62All 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 basi s.
§§ 158.280-158.290 [Reserved]
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Subpart D—Product Chemistry
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§ 158.300 Definitions.
top The following terms are defined for the purposes of this subpart:
A ctive 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 ingre dients, without an intended chemical reaction, to obtain a manufacturing-use product or an end-use product, or (2) The repackaging of any registered product.
I mpurity 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 degradatio n products.
I mpurity 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 o f the product or p ackaging of the product.
I nert 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.
I ntegrated 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.
M

anufacturing-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.
N

ominal 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 p roduct 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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10/17/2008 12:07 PM 16 of 62§ 158.310 Product chemistry data requirements table.
top (a) General . Sections 158.100 through 158.130 describe how to use this table to determine the product chemistry data requirements for a particular p esticide 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 adde d. (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 sec tion. Product Chemistry Data Requirements

Guideline Number Data Requirement Use Pattern Test substance to support Test Note No. All MP EP 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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10/17/2008 12:07 PM 17 of 62830.7950 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 sect ion: 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 a n 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 a s 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 m aterial. 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 functionalit y (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 h igh 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.
top 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 p aragraphs (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 ingredie nt in the source p roduct. (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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10/17/2008 12:07 PM 18 of 62(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 t o identify its source and qualitative composition.
§ 158.325 Description of materials used to produce the product.
top 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 requ ested by the Agency, chemical and physical properties) of the ingredient, including a copy of technical specifications, data sheets, or other docume nts 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 t o the applicant, the 

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10/17/2008 12:07 PM 19 of 62name 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 reque sted 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 p roduct.
§ 158.330 Description of production process.
top If the product is produced by an integrated system, the applicant must submit information on the production (reaction) processe s 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 ac complished 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 pro cess 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 p roduced). (8) A description of the procedures used to assure consistent composition of the substance produced, e.g., calibration of equip ment, sampling regimens, analytical methods, and other quality control methods.
§ 158.335 Description of formulation process.
top The applicant must provide information on the formulation process of the product (unless the product consists solely of a techn ical 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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10/17/2008 12:07 PM 20 of 62(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.
top 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 in gredient, inert ingredients, and production or formulation process. If the applicant has reason to believe that an impurity that EPA would cons ider toxicologically significant may be present, the discussion must include an expanded discussion of the possible formation of the impurity and th e 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 p ercent (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 b yproduct impurities p roduced 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 a ctive 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 activ e 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 pac kaging. (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.
top (a) If the product is produced by an integrated system, the applicant must provide a preliminary analysis of each technical gra de of active ingredient 

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10/17/2008 12:07 PM 21 of 62contained in the product to identify all impurities present at 0. 1 percent or greater of the technical grade of the active ing redient. The preliminary analysis should be conducted at the point in the production process after which no further chemical reactions designed to produ ce 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 p rovided. 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.
top 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 im purity 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 p aragraph (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 paragrap h (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 limi ts 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 manufacturin g 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 product ion 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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10/17/2008 12:07 PM 22 of 62(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 t hat: (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 fo r 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 specifie d, that all quantities of such ingredient will be obtained from the source specified in the Statement of Formula.
§ 158.355 Enforcement analytical method.
top 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.
top (a) General . Sections 158.100 through 158.130 describe how to use this table to determine the product performance data requirements for a p articular pesticide product. Notes that apply to an individual test, including specific conditions, qualifications, or exceptio ns 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 nonfo od 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 p roduct. (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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10/17/2008 12:07 PM 23 of 6293–16 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 contr ol 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 practi ces. 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.
top (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, qualif ications, 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 fe ed 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 no nfood 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 severa l 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 Test Note No. Food Nonfood MP EP 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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10/17/2008 12:07 PM 24 of 62870.2600 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 restric ted 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, aer osol, 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; o r 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 pesti cides, 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 c hronic/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 select ion 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 requir ed 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) a s 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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10/17/2008 12:07 PM 25 of 6213. Required if there is the likelihood of significant repeated inhalation exposure to the pesticide as a gas, vapor, or aeroso l. 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 availa ble 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 neurotoxicit y 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 9 0–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 toxicit y 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 sp an 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) cau ses 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 a fter 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 potentia l 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 scientif ic 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., S AR 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 additi on 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 mutag enicity 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 d etection; (ii) Chinese hamster ovary (CHO) or Chinese hamster lung fibroblast (V79) cells, hypoxanthine-guanine phosphoribosyl transferas e (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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10/17/2008 12:07 PM 26 of 62further elucidated by metabolism studies. 34. May be required if the product's use will result in exposure to domestic animals thro ugh, 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 i s 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.
top 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 specif ic 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.
top (a) General . Sections 158.100 through 158.130 describe how to use this table to determine the terrestrial and aquatic nontarget data requi rements for a particular pesticide product. Notes that apply to an individual test including specific conditions, qualifications, or ex ceptions 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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10/17/2008 12:07 PM 27 of 62crop, 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 greenho use 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 LD 50 , two avian dietary LC 50 , two avian reproduction studies, two freshwater fish LC 50 , one freshwater invertebrate EC 50 , one honeybee acute contact LD 50 , one freshwater fish early-life stage, one freshwater invertebrate life cycle, and three estuarine acute LC 50 /EC 50 studies -- 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 p roduct; 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 Note No. Terrestrial Aquatic Forestry 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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10/17/2008 12:07 PM 28 of 62850.3040 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 ge nerally 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 ref ormulated 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 liqu id 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 u se 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 l aboratory toxicity endpoints and refined exposure assessments. 7. Environmental chemistry methods used to generate data associated with this study must include results of a successful confir matory method trial by an independent laboratory. Test standards and procedures for independent laboratory validation are available as addenda to the guideline for this test requirem ent. 8. Data are required on one coldwater fish and one warmwater fish for terrestrial, aquatic, forestry, and residential outdoor u ses. 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 larvici des) 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 LC 50 or EC 50 of 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 activ e 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 freshw ater fish acute toxicity tests, a 96–hour LC 50 on 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 LC 50 or EC 50<1 milligram/liter (mg/l). iv. If the estimated environmental concentration (EEC) in water is ≥ 0.01 of the acute EC 50 or LC 50 or 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 u se pattern, and environmental fate characteristics that 

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10/17/2008 12:07 PM 29 of 62indicate 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 LC 50 /EC 50values 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 es tuarine 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 o f its expected use or mobility pattern. 24. Data are required only when the formulation contains one or more active ingredients having an acute LD 50 of<11 micrograms per bee as determined in the honey bee acute contact study and the use pattern(s) indicate(s) that honey bees may be exposed to the pesticide. 25. Required if any of the following conditions are met: i. Data from other sources (Experimental Use Permit program, university research, registrant submittals, etc.) indicate potenti al 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 behavior al 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.
top (a) General . Sections 158.100 through158.130 describe how to use this table to determine the nontarget plant data requirements for a particular p esticide 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 p roduct. (d) Table . The following table shows the nontarget plant protection data requirements. The table notes are shown in paragraph (e) of thi s section. Table—Nontarget Plant Protection Data Requirements

Guideline Number Data Requirement Use Pattern Test substance Test Note No. Terrestrial Aquatic 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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10/17/2008 12:07 PM 30 of 62850.4400 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 re ceived 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.
top (a) If EPA determines that industrial standards, such as the workplace standards set by the Occupational Safety and Health Admi nistration (OSHA), p rovide 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 req uirements and contain adequate replicates of acceptable quality data to reflect the specific use prescribed on the label and the applicator a ctivity of concern, including formulation type, application methods and rates, type of activity, and other pertinent information. The Agency will c onsider using such surrogate data for evaluating human exposure on a case-by-case basis.
§ 158.1010 Applicator exposure—criteria for testing.
top Applicator exposure data described in paragraph (d) of this section are required based on toxicity and exposure criteria. Data are required if a p roduct 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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10/17/2008 12:07 PM 31 of 62(2) Scientifically sound epidemiological or poisoning incident data indicate that adverse health effects may have resulted from handling of the p esticide. (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.
top (a) General . Sections 158.100 through 158.130 describe how to use this table to determine the applicator exposure data requirements for a p articular pesticide product. Notes that apply to an individual test and include specific conditions, qualifications, or excepti ons 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, terrestria l feed crop, terrestrial nonfood crop, aquatic food, aquatic nonfood use, forestry, greenhouse food, greenhouse nonfood, indoor food u se, and indoor nonfood use. Occupational use patterns also include commercial (“for hire”) applications to residential outdoor and indoor site s. (2) Residential use patterns include residential outdoor use and residential indoor use. These use patterns are limited to nono ccupational, 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 no tes are shown in paragraph (e) of this section. Table—Applicator Exposure Data Requirements

Guideline Number Data requirement Use pattern Test substance Test Note No. Occupational Residential 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 availabl e from the Agency. 2. Biological monitoring data may be submitted in addition to, or in lieu of, dermal and inhalation exposure data, provided thehuman 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.
top (a) If EPA determines that industrial standards, such as the workplace standards set by the Occupational Safety and Health Admi nistration, 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 requi rements 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 c onsider 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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10/17/2008 12:07 PM 32 of 62top 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 crit eria 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 c ommodities, 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 t o indoor spaces or surfaces at residential sites, such as, but not limited to homes, daycare centers, hospitals, schools, and other public buildin gs.
§ 158.1070 Post-application exposure data requirements table.
top (a) General . Sections 158.100 through 158.130 describe how to use this table to determine the post-application data requirements for a par ticular p esticide 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, terrestria l 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 nono ccupational, 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 Test Substance Test Note No. Occupational Residential 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 availabl e from the Agency. 

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10/17/2008 12:07 PM 33 of 622. 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 foliarresidue 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 acti vity 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 me dia, 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 activitie s. 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 c ountertops, 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 activiti es. 9. Data are required for residential sites if the pesticide is applied to or around non-plant surfaces, e.g., flooring and coun tertops. 10. Data are required for occupational sites if the human activity data indicate that workers are likely to have post-applicati on 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 thehuman 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 swimme r 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 considerall 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.
top (a) General . Sections 158.100 through 158.130 describe how to use this table to determine the spray drift data requirements for a particul ar p esticide product. Notes that apply to an individual test, including specific conditions, qualifications, or exceptions to the designated test are listed in p aragraph (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 nonfo od 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 th is 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 includehumans, domestic animals, fish and wildlife, and nontarget plants. 2. [Reserved] 

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10/17/2008 12:07 PM 34 of 62Subpart 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.
top (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 nonf ood. 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 sec tion. Table—Environmental Fate Data Requirements

Guideline Number Data Requirement Use Pattern Test substance Test Note No. Terrestrial Aquatic Greenhouse Indoor Forestry 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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10/17/2008 12:07 PM 35 of 62Ground 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 n ot 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 pesti cide 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 tr ansformation 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 requirem ent. 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 m ay 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 con sult 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, t aking 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 requi red.
Subpart O—Residue Chemistry
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§ 158.1400 Definitions.
top The following terms are defined for the purposes of this subpart:
L ivestock , for the purposes of this section, includes all domestic animals that are bred for human consumption, including, but not limit ed to, cattle, swine, sheep, and poultry.
P lant or animal metabolite means a pesticide chemical residue that is the result of biological breakdown of the parent pesticide within the plant or animal.
R esidue 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.
top (a) General . Sections 158.100 through 158.130 describe how to use this table to determine the residue chemistry data requirements for a particular p esticide 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, ter restrial 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 p urposes even though tolerances may not be necessary in all cases. 

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10/17/2008 12:07 PM 36 of 62(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 parag raph (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 degradate s. 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 inv olving 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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10/17/2008 12:07 PM 37 of 628. 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 h arvested). 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 m etabolites. 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 thei r 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., f ungicidal 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 p rocessing 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, an d 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 wat er 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 fa cilities 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, pro cessing 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 b ut 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 observ ed 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.
top 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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10/17/2008 12:07 PM 38 of 62p esticides, 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 o f 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 b ackbone. (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 pesticidesto determine whether to review the pesticide under this subpart U.
§ 158.2010 Biochemical pesticides data requirements.
top (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). Variatio ns in the test conditions are identified within the test notes. Definitions that apply to all biochemical data requirements can be found in §1 58.2000. (b) Each data table includes “use patterns” under which the individual data are required, with variations including food and no nfood uses for terrestrial and aquatic applications, greenhouse, indoor, forestry, and residential outdoor applications under certain circumst ances. (c) The categories for each data requirement are “R”, which stands for required, and “CR” which stands for conditionally requir ed. Generally, “R” indicates that the data are more likely required than for those data requirements with “CR.” However, in each case, the regulat ory 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 mayinclude: technical grade active ingredient (TGAI), manufacturing-use product (MP), end-use product (EP), typical end-use product (TEP), residue of conce rn, 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 pesticid es, 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.
top (a) General . (1) Sections 158.100 through 158.130 describe how to use this table to determine the product chemistry data requirements for a p articular pesticide product. Notes that apply to an individual test and include specific conditions, qualifications, or excepti ons 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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10/17/2008 12:07 PM 39 of 62p roduct; 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 Test Notes MP EP 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 referen ced 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 T GAI. 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 wi th §158.345. Also, required to support the re gistration 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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10/17/2008 12:07 PM 40 of 6214. 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 wit h 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.
top (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 pest icides, i.e. , naturally occurring insect repellents and attractants, semiochemicals (e.g., insect pheromones), natural and plant growth regulators. Not es 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, ter restrial 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. Da ta 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 d ata 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, d egradates, 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 p aragraph (e) of this section. Table—Biochemical Residue Data Requirements for Specific Uses 

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10/17/2008 12:07 PM 41 of 62Guideline Number Data Requirement Use Patterns
Test Substance Test Notes Terrestrial Aquatic Greenhouse Food Indoor Food Food/Feed 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 req uired, 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 emphasi s on impurities. 3. Required information includes crops to be treated, rate of application, number and timing of applications, preharvest interv als, 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 degradate s. 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 l ivestock 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 tempo rary 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 m etabolites. 12. Data are required whenever a pesticide may be applied directly to water, unless it can be demonstrated that the treated wat er 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 m ay 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 fa cilities 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 conc entrate 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, proce ssing, or degradation studies as well as market basket surveys for a more precise residue determination. 

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10/17/2008 12:07 PM 42 of 6218. 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.
top (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; t errestrial 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 no nfood 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 p roduct; 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 p aragraph (e) of this section. Table—Biochemical Pesticides Human Health Assessment Data Requirements

Guideline Number Data Requirement Use Patterns Test Substance Test Notes Food Nonfood MP EP 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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10/17/2008 12:07 PM 43 of 62875.1300 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 refere nced 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 hu man 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 r oute 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, oraerosol. 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 differe nt 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 c ompounds containing a known mutagen. Additional mutagenicity tests that may have been performed plus a complete reference list must also be submitted. Subsequent testing may b e 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 de tection; 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 t o 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 potent ial 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 prot ocol 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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10/17/2008 12:07 PM 44 of 62i. 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 studi es 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 respo nse 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 stu dies 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 aberrati on to occur. 20. May be required if the product's use will result in exposure to domestic animals thro ugh, but not limited to, direct application or consumption of treated feed.
§ 158.2060 Biochemical pesticides nontarget organisms and environmental fate data requirements table.
top (a) General . (1) Sections 158.100 through 158.130 describe how to use this table to determine the terrestrial and aquatic nontarget organi sms 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 e nd-use products including turf, the following studies are required: one avian acute oral, one avian dietary, one acute freshwater fish, one acute freshwa ter invertebrate study, p lant 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 ac tive 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 p atterns 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 p roduct; 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 te st 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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10/17/2008 12:07 PM 45 of 62880.4350 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 environme ntal 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 t o 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 m 3 /mol). 

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10/17/2008 12:07 PM 46 of 624. Preferred test species are Upland game, waterfowl, or passerine for avian acute oral toxicity studies; Upland game and water fowl 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 n ontarget 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 regar ding 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 n ontarget 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 EC 50 or LC 50 determined 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 LC 50 or equal to>0.20 the avian oral single dose LD 50 (converted to ppm). ii. The pesticide or any of its metabolites or degradation products are stable in the environment to the extent that potentiall y 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 resu lts 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 mo vement would be determined by the results of the Tier II environmental fate studies. 14. Required depending on pesticid e 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 necessar y 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.
top 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 infec tious 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, eachregistrant 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.
top (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.
top (a) General . (1) Sections 158.100 through 158.130 describe how to use this table to determine the product chemistry data requirements for a p articular 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 p roduct; 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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10/17/2008 12:07 PM 47 of 62(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 Test Notes MP EP 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 c hemistry 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 T GAI. 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 wi th §158.345. Also, required to support the re gistration 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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10/17/2008 12:07 PM 48 of 6214. 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 wit h 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.
top (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 pest icides, i.e. , naturally occurring insect repellents and attractants, semiochemicals (e.g., insect pheromones), natural and plant growth regulators. Not es 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, ter restrial 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. Da ta 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 d ata 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, d egradates,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 Food/Feed 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 referen ced 

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10/17/2008 12:07 PM 49 of 62referenced 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 req uired, 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 interv als, 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 degradate s. 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 inv olving 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 m etabolites. 11. Data are required whenever a pesticide may be applied directly to water, unless it can be demonstrated that the treated wat er 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 fa cilities 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 conc entrate 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 pre cise 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 r esidue 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.
top (a) General . (1) Sections 158.100 through 158.130 describe how to use this table to determine the human health assessment data requirement s for a p articular 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; t errestrial 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 no nfood 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 p roduct; 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. T he 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 Test Notes Food Nonfood MP EP Tier I 

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10/17/2008 12:07 PM 50 of 62Acute 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 hea lth 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 differe nt 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 c ompounds containing a known mutagen. Additional mutagenicity tests that may have been performed plus a complete reference list must also be submitted. Subsequent te sting 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 de tection; 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.
top (a) General . (1) Sections 158.100 through 158.130 describe how to use this table to determine the terrestrial and aquatic nontarget organi sms 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 e nd-use products including turf, the following studies are required: one avian acute oral, one avian dietary, one acute freshwater fish, and one acute fre shwater 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 ac tive 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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10/17/2008 12:07 PM 51 of 62p roduct; 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 t o 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 m 3 /mol). 3. Preferred test species are: upland game, waterfowl, or passerine for avian acute oral toxicity studies; upland game or water fowl 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
top
Source: 72 FR 61002, Oct. 26, 2007, unless otherwise noted.
§ 158.2100 Microbial pesticides definition and applicab ility.
top (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 p lant 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 re gistered microbial p esticide 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 b asis depending on the p articular 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 F IFRA as authorized by section 25(b) of FIFRA and specified in §152.20 (a) of this chapter. 

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10/17/2008 12:07 PM 52 of 62§ 158.2110 Microbial pesticides data requirements.
top (a) For all microbial pesticides. (1) The following §158.2120 through §158.2150 identify the data requirements that are require d 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 mayinclude: technical grade active ingredient (TGAI), manufacturing-use product (MP), end-use product (EP), typical end-use product (TEP), residue of conce rn, 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 conta ining solely the technical grade of the active ingredient and manufacturing-use products to which other ingredients have been intentionally adde d. 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 ingred ient that is expected to enhance the toxicity of the product. (b) Additional data requirements for genetically modified microbial pesticides. Additional requirements for genetically modifie d 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” trai ts or characteristics that are intended to be expressed; tests to evaluate genetic stability and exchange; and selected Tier II environmental express ion and toxicology tests.
§ 158.2120 Microbial pesticides product analysis data requirements table.
top (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 ar e 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 p roduct; TGAI=Technical grade of the active ingredient; All=All of the above. Specific conditions, qualifications, or exceptionsto 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 Test Notes MP EP 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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10/17/2008 12:07 PM 53 of 62830.6320 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 t he 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 sample s 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.
top (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 designat ed 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 p roduct; TGAI=Technical grade of the active ingredient; All=All of the above. Specific conditions, qualifications, or exceptionsto 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) o f 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 col umn 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 pestici de 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.
top (a) General . Sections 158.100 through 158.130 describe how to use this table to determine the toxicology data requirements for a particular p esticide 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 p roduct; TGAI=Technical grade of the active ingredient; All=All of the above. Specific conditions, qualifications, or exceptionsto the designated 

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10/17/2008 12:07 PM 54 of 62test 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. W here 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, volatil e substances, or aerosol particulate). 7. Data required when significant toxicity, in the absence of pathogenicity and significant infectivity, is observed in acute o ral, 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 toxicit y 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 adver se 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 st udy 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 para sitic 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 w ith components of the mammalian immune system. 12. An analysis of human infectivity/pathogenicity potential using scientific literature, genomic analysis, and/or actual speci fic 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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10/17/2008 12:07 PM 55 of 62are 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 the se 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.
top (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: Foo d, Feed, N on-Food, Forestry, Residential outdoor, greenhouse (food and food), Indoor (food an d 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 p roduct; TGAI=Technical grade of the active ingredient; All=All of the above. Specific conditions, qualifications, or exceptionsto 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 testnotes 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 Industrial Outdoor Food/Nonfood Food/Nonfood 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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10/17/2008 12:07 PM 56 of 62885.4650 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 environmenta l 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 i nhalation 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 thi s 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 agen ts: 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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10/17/2008 12:07 PM 57 of 62i. 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 w hen 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 eco logical 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 exp ected 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 unreas onable 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 t o 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/o r 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 lif e-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.
top Product performance data must be developed for all microbial pesticides. However, the Agency has waived all requirements to sub mit efficacy data unless the pesticide product bears a claim to control public health pests, such as pest microorganisms infectious to man in anyarea of the inanimate environment or a claim to control vertebrates (including but not limited to: rodents, birds, bats, canids, and skunks) or inver tebrates (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 prac tices. The Agency reserves the right to require, on a case-by-case basis, submission of efficacy data for any pesticide product registered or pro posed for registration.
§ 158.2170 Experimental use permit data requirements—microbial pesticides.
top (a) For all microbial pesticides. (1) The following §158.2171 through §158.2174 identify the data requirements that are require d 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 modifie d 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” trai ts or characteristics that are intended to be expressed; tests to evaluate genetic stability and exchange; and selected Tier II environmental express ion and toxicology tests.
§ 158.2171 Experimental use permit microbial pesticides product analysis data requirements table.
top (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 ar e 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 p roduct; TGAI=Technical grade of the active ingredient; All=All of the above. Specific conditions, qualifications, or exceptionsto the designated 

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10/17/2008 12:07 PM 58 of 62test 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 n otes are shown in paragraph (d) of this section. Table—EUP Microbial Product Analysis Data Requirements

Guideline Number Data Requirement All Use Patterns Test Substance Test Notes MP EP 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 ana lysis 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 o f 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 t he 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 aperiod 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.
top (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 designat ed 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 p roduct; TGAI=Technical grade of the active ingredient; All=All of the above. Specific conditions, qualifications, or exceptionsto 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 p aragraph (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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10/17/2008 12:07 PM 59 of 62Number 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 re ferenced 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 pestici de 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.
top (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 p roduct; TGAI=Technical grade of the active ingredient; All=All of the above. Specific conditions, qualifications, or exceptionsto 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 t he 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. W here appropriate, the limit dose approach to testing is 

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10/17/2008 12:07 PM 60 of 62recommended. 6. Required when the product consists of, or under conditions of use that would result in an inhalable material (e.g., gas, vol atile substances, or aerosol particulate).
§ 158.2174 Experimental use permit microbial pesticides nontarget organisms and environmental fate data requirements table.
top (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: Foo d, Feed, N on-Food, Forestry, Residential outdoor, greenhouse (food and food), Indoor (food an d 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 p roduct; TGAI=Technical grade of the active ingredient; All=All of the above. Specific conditions, qualifications, or exceptionsto 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 envi ronmental 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 Industrial Outdoor Food/Nonfood Food/Nonfood 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 environmenta l 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 i nhalation 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 con cern. 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]
top
Subparts X–Z [Reserved] 

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10/17/2008 12:07 PM 61 of 62top
§§ 158.2300-158.2500 [Reserved]
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