40 CFR Part 158 — Data Requirements for Pesticides

PART 158—DATA REQUIREMENTS FOR PESTICIDES Authority: 7 U.S.C. 136-136y; 21 U.S.C. 346a. Source: 72 FR 60957, Oct. 26, 2007, unless otherwise noted. Subpart A—General Provisions § 158.1 Purpose and scope. (a) Purpose. (b) Scope. (2) This part establishes general policies and procedures associated with the submission of data in support of a pesticide regulatory action. (3) This part does not include study protocols, methodology, or standards for conducting or reporting test results; nor does this part describe how the Agency uses or evaluates the data and information in its risk assessment and risk management decisions, or the regulatory determinations that may be based upon the data. (c) Scope of individual subparts. Conventional pesticides. (2) Biochemical pesticides. (3) Microbial pesticides. (4) Antimicrobial pesticides. [72 FR 60957, Oct. 26, 2007, as amended at 78 FR 26978, May 8, 2013; 87 FR 22474, Apr. 15, 2022] § 158.3 Definitions. All terms defined in sec. 2 of the Federal Insecticide, Fungicide, and Rodenticide Act apply to this part and are used with the meaning given in the Act. Applicable terms from the Federal Food, Drug, and Cosmetic Act also apply to this part. Individual subparts may contain definitions that pertain solely to that subpart. The following additional terms apply to this part: Applicant (1) An application for registration or amended registration of a pesticide product under FIFRA sec. 3 or 24. (2) A submission of data required in conjunction with reregistration of a currently registered product under FIFRA sec. 4. (3) An application for an experimental use permit under FIFRA sec. 5. (4) A submission of data in response to a notice issued by EPA under FIFRA sec. 3(c)(2)(B). (5) A petition to establish or modify a tolerance or an exemption from the requirement of a tolerance for a pesticide chemical residue under FFDCA sec. 408. Registration § 158.5 Applicability. (a) The requirements of this part apply to the following submissions: (1) An application for new or amended registration under FIFRA sec. 3 or 24. (2) An application for experimental use permit under FIFRA sec. 5. (3) A submission of data or information to support the continuation of a registration under FIFRA sec. 3, 4, or 24. (4) A petition to establish, modify or revoke a tolerance or exemption from a tolerance under FFDCA sec. 408. (b) The information specified in this part must be furnished with each submission described in paragraph (a) of this section if it has not been submitted previously, or if any previous submission is not accurate or complete. § 158.30 Flexibility. (a) FIFRA provides EPA flexibility to require, or not require, data and information for the purposes of making regulatory judgments for pesticide products. EPA has the authority to establish or modify data needs for individual pesticide chemicals. The actual data required may be modified on an individual basis to fully characterize the use and properties, characteristics, or effects of specific pesticide products under review. The Agency encourages each applicant to consult with EPA to discuss the data requirements particular to its product prior to and during the registration process. (b) The Agency cautions applicants that the data routinely required in this part may not be sufficient to permit EPA to evaluate the potential of the product to cause unreasonable adverse effects to man or the environment. EPA may require the submission of additional data or information beyond that specified in this part if such data or information are needed to appropriately evaluate a pesticide product. (c) This part will be updated as needed to reflect evolving program needs and advances in science. § 158.32 Format of data submissions. (a) General. (2) The requirements of this section do not apply to administrative materials accompanying a data submission, including forms, labeling, and correspondence. (b) Transmittal document. (1) Identity of the submitter. (2) The transmittal date. (3) Identification of the regulatory action with which the submission is associated, e.g., the registration or petition number. (4) A list of the individual documents included in the submission. (c) Individual documents. (1) A title page including the following information: (i) The title of the study, including identification of the substance(s) tested and the test name or data requirement addressed. (ii) The author(s) of the study. (iii) The date the study was completed. (iv) If the study was performed in a laboratory, the name and address of the laboratory, project numbers or other identifying codes. (v) If the study is a commentary on or supplement to another previously submitted study, full identification of the other study with which it should be associated in review. (vi) If the study is a reprint of a published document, all relevant facts of publication, such as the journal title, volume, issue, inclusive page numbers, and date of publication. (2) The appropriate statement(s) regarding any data confidentiality claims as described in § 158.33. (3) A statement of compliance or non-compliance with respect to Good Laboratory Practice Standards as required by 40 CFR 160.12, if applicable. (4) A complete and accurate English translation must be included for any information that is not in English. (5) A flagging statement as prescribed by § 158.34, if applicable. § 158.33 Confidential data. (a) Definitions. (1) Registered or previously registered pesticide (2) Safety and efficacy information (b) Applicability. (2) FFDCA sec. 408(i) protects confidential information submitted in connection with an application for a tolerance or exemption to the same extent as FIFRA sec. 10. References in this section to FIFRA sec. 10 are deemed to apply equally to information submitted pursuant to FFDCA sec. 408, pursuant to the authority in sec. 408(i). (c) Method of asserting business confidentiality claims Claim required. (2) Statement required. (i) No claim of confidentiality. No claim of confidentiality, on any basis whatsoever, is made for any information contained in this document. I acknowledge that information not designated as within the scope of FIFRA sec. 10(d)(1)(A), (B), or (C) and which pertains to a registered or previously registered pesticide is not entitled to confidential treatment and may be released to the public, subject to the provisions regarding disclosure to multinational entities under FIFRA sec. 10(g). (ii) Claim of confidentiality. Information claimed as confidential has been removed to a confidential attachment. (3) Confidential attachment. (ii) All information in the confidential attachment that consists of (or whose disclosure would in turn disclose) manufacturing or quality control processes must be individually identified in the confidential attachment as a claim for information within the scope of FIFRA sec. 10(d)(1)(A). (iii) All information in the confidential attachment that consists of (or whose disclosure would in turn disclose) the details of any methods for testing, detecting, or measuring the quantity of any deliberately added inert ingredient of a pesticide, must be individually identified in the confidential attachment as a claim for information within the scope of FIFRA sec. 10(d)(1)(B). (iv) All information in the confidential attachment that consists of (or whose disclosure would in turn disclose) the identity or percentage quantity of any deliberately added inert ingredient of a pesticide must be individually identified in the confidential attachment as a claim for information within the scope of FIFRA sec. 10(d)(1)(C). (v) Information in the confidential attachment that is designated in accordance with paragraphs (c)(3)(ii) - (iv) of this section must be on a separate page from information that is not so designated. (4) Voluntary release of information to States and foreign governments. I authorize the Environmental Protection Agency to release any information contained in this document to State or foreign governments, without relinquishing proprietary rights or any confidentiality claims asserted above. (ii) Information designated as releasable to state or foreign governments in accordance with this section may be released to such a government without further notice to the submitter. EPA will inform the State or foreign government of any of the confidentiality claims associated with the information. (d) Release of information. (2) Information that is not entitled to be protected as confidential in accordance with FIFRA sec. 10(b), this section and with EPA confidentiality regulations at 40 CFR part 2, subpart B, may be released to the public without the affirmation of non-multinational status provided under FIFRA sec. 10(g), provided that the information does not contain or consist of any complete unpublished report submitted to EPA, or excerpts or restatements of any such report which reveal the full methodology and complete results of the study, test, or experiment, and all explanatory information necessary to understand the methodology or interpret the results. § 158.34 Flagging of studies for potential adverse effects. (a) Any applicant who submits a study of a type listed in paragraph (b) of this section must submit with the study a statement in accordance with paragraph (c) of this section. (b) The following table indicates the study types and the criteria to be applied to each. Column 1 lists the study types by name. Column 2 lists the associated Pesticide Assessment Guideline number. Column 3 lists the criteria applicable to each type of study. Column 4 lists the reporting code to be included in the statement specified in paragraph (c) of this section when any criterion is met or exceeded. Table—Flagging Criteria Study Type(s) Guideline No. Criteria: Treated animals show any of the following: Criteria No. Carcinogenicity or combined carcinogenicity/chronic feeding study 870.4200 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 870.3700 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 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 870.4100 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 (c) Identification of studies. (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. (a) The data requirements specified in this part as applicable to a category of products will not always be appropriate for every product in that category. Some products may have unusual physical, chemical, or biological properties or atypical use patterns which would make particular data requirements inappropriate, either because it would not be possible to generate the required data or because the data would not be useful in the Agency's evaluation of the risks or benefits of the product. The Agency will waive data requirements it finds are inappropriate, but will ensure that sufficient data are available to make the determinations required by the applicable statutory standards. (b)(1) Applicants are encouraged to discuss a data waiver request with the Agency before developing and submitting supporting data, information, or other materials. (2) All waiver requests must be submitted to the Agency in writing. The request must clearly identify the data requirement(s) for which a waiver is sought along with an explanation and supporting rationale why the applicant believes the data requirement should be waived. In addition, the applicant must describe any unsuccessful attempts to generate the required data, furnish any other information which the applicant(s) believe(s) would support the request, and when appropriate, suggest alternative means of obtaining data to address the concern which underlies the data requirement. (c) The Agency will review each waiver request and subsequently inform the applicant in writing of its decision. If the decision could apply to more than the requested product, the Agency, in its discretion, may choose to send a notice to all registrants or publish a notice in the Federal Register § 158.60 Minor use data policies. FIFRA sec. 2(ll) defines the term “minor use”and FIFRA provides a number of statutory provisions concerning minor uses. In addition, EPA has established policies with respect to minor uses of pesticides, including, but not limited to, the following: (a) A new data requirement pertinent to both an unregistered minor use and a registered major use will not be applied to a minor use applicant until it is applied to the major use registration. (b) EPA will accept appropriate and adequate extrapolations and regional data to support establishment of individual minor use tolerances. § 158.70 Satisfying data requirements. (a) General policy. (1) The provisions in this part 158 should be read in conjunction with the provisions in § 152.85 to claim eligibility for the formulators' exemption. (2) [Reserved] (b) Good laboratory practices. (c) Agency guidelines. www.epa.gov/pesticides. (d) Study protocols General. (2) Organization for Economic Co-Operation and Development (OECD) protocols. (e) Combining studies. § 158.75 Requirements for additional data. The data routinely required by this part may not be sufficient to permit EPA to evaluate every pesticide product. If the information required under this part is not sufficient to evaluate the potential of the product to cause unreasonable adverse effects on man or the environment, additional data requirements will be imposed. However, EPA expects that the information required by this part will be adequate in most cases for an assessment of the properties and effects of the pesticide. § 158.80 Use of other data. (a) Data developed in foreign countries. (b) Data generated for other purposes. Subpart B—How To Use Data Tables § 158.100 Pesticide use patterns. (a) General use patterns for conventional, biochemical, and microbial pesticides. (1) Terrestrial food crop use. (2) Terrestrial feed crop use. (3) Terrestrial nonfood crop use. (4) Aquatic food crop use. (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 for conventional, biochemical, and microbial pesticides. http://www.epa.gov/pesticides. (c) Antimicrobial pesticide use patterns. (d) Pesticide use site index for antimicrobial pesticides. http://www.epa.gov/pesticides. (e) Determination of use pattern. [72 FR 60957, Oct. 26, 2007, as amended at 78 FR 26978, May 8, 2013] § 158.110 Required and conditionally required data. The tables in this part use the descriptors R (required), CR (conditionally required), and NR (not required) as a general indication of the applicability of a data requirement. In all cases, the test notes referred to in the table must be consulted to determine the actual applicability of the data requirement. (a) EPA requires data designated as “required”(R) for products with a given use pattern in order to evaluate the risks or benefits of a product having that use pattern under any conditions established by the test notes. (b) Data designated as “conditionally required” (CR) for products with a given use pattern are required by EPA to evaluate the risks or benefits of a product having that use pattern if the product meets the conditions specified in the notes accompanying the requirement. The determination of whether the data must be submitted is based on the product's use pattern, physical or chemical properties, expected exposure of nontarget organisms, and/or results of previous testing (for example, tier testing). Applicants must evaluate each applicable test note for the conditions and criteria to be considered in determining whether conditionally required data must be submitted. (c) Data not required for the Agency's assessment of the risks and benefits of a particular use pattern are designated “not required” (NR) in data tables. § 158.120 Determining data requirements. As with current practice, the actual data and studies required may be modified on an individual basis to fully characterize the use and properties of specific pesticide products under review. While EPA is attempting to assist the applicant in this subpart, it is important to emphasize that it is the applicant's obligation under FIFRA to demonstrate that an individual product meets the standard under FIFRA and/or FFDCA. Accordingly, applicants are encouraged to consult with the Agency on the appropriate data requirements as set forth here as they relate to their specific product prior to and during the registration process. (a) Finding the appropriate data table. (2) Key to table notations. R = required data; CR = conditionally required data; NR = Not required; MP = manufacturing-use product; EP = end-use product; TEP = typical end-use product; TGAI = technical grade of the active ingredient; PAI = pure active ingredient; PAIRA = pure active ingredient, radiolabeled; Choice = choice of several test substances depending on studies required. (b) Identifying required studies. (1) Refer to the applicable subpart(s) of this part. These subparts describe the data requirements including data tables for each subject area. (2) Select the general use pattern(s) that best cover the use pattern(s) specified on the pesticide product label as explained in § 158.100. All applicable use patterns must be included. (3) Proceed down the appropriate general use pattern column in the table and note which tests are required (R), conditionally required (CR), or not required (NR). Required and conditionally required studies are described in § 158.110. (4) Review the notes for each requirement to determine its applicability to the specific product proposed for registration. (5)(i) Proceed down the Test substance columns and determine the appropriate test substance needed for that study. If the data are intended to support a manufacturing-use product, use the MP column. If the data are intended to support an end-use product, use the EP column. (ii) The test substances columns specify which substance is to be used for testing. Applicants should note that the substance that must be used when performing the study may or may not be the product itself. For example, the data from a certain study may be required to support the registration of an end-use product, but the test substance column may state that the particular test shall be performed using the technical grade of the active ingredient(s) in the end-use product. (iii) Manufacturing-use products (MP) and end-use products (EP) containing a single active ingredient and no intentionally added inert ingredients are considered identical in composition to each other, and to the technical grade of the active ingredient (TGAI) from which they were derived. Therefore, the data from a test conducted using any one of these as the test substance is also suitable to meet the requirement (if any) for the same test to be conducted using either of the other substances. (6) Refer to the Pesticide Assessment Guideline reference number for each study located in the first column. See § 158.70(c) for information pertaining to the guidelines and how to obtain copies. § 158.130 Purposes of the registration data requirements. (a) General. (b) Product chemistry Product composition. (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. (3) Physical and chemical characteristics. (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. (d) Toxicology-humans and domestic animals. (1) Acute studies. (2) Subchronic studies. (3) Chronic studies. (4) Developmental toxicity and reproduction studies. (5) Mutagenicity studies. (i) To detect, with sensitive assay methods, the capacity of a chemical to alter genetic material in cells. (ii) To determine the relevance of these mutagenic changes to mammals. (iii) When mutagenic potential is demonstrated, to incorporate these findings in the assessment of heritable effects, carcinogenicity, and, possibly, other health effects. (6) Metabolism studies. (e) Hazards to nontarget organisms General. (2) Short-term studies. (3) Long-term and field studies. i.e. (f) Applicator and post-application exposure. (g) Pesticide spray drift evaluation. (h) Environmental fate General. (2) Degradation studies. (3) Metabolism studies. (4) Mobility studies. (5) Dissipation studies. (i) Residue chemistry. (2) Information on the chemical identity and composition of the pesticide product, the amounts, frequency and time of the pesticide application, and results of tests on the amount of residues remaining on or in the treated food or feed, are needed to support a finding as to the magnitude and identity of residues which result in food or animal feed as a consequence of a proposed pesticide usage. (3) Residue chemistry data are also needed to support the adequacy of one or more methods for the enforcement of the tolerance, and to support practicable methods for removing residues that exceed any proposed tolerance. (4) Accumulation studies. Subpart C—Experimental Use Permits § 158.200 Experimental use permit data requirements tables. Sections 158.200 through 158.270 describe how to use these tables to determine the experimental use permit data requirements for a particular pesticide product. Notes that apply to an individual test and include specific conditions, qualifications, or exceptions to the designated test are listed at the end of each table. Refer to 40 CFR part 172 for further information on experimental use permits. § 158.210 Experimental use permit data requirements for product chemistry. 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. All product performance data, as described in paragraph (c) of this section, must be submitted to support a request for an experimental use permit. (a) Use patterns. (2) Data are also required for forestry and residential outdoor uses. (b) Key. (c) Table. Table—Experimental Use Permit 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. 1. The Agency has waived the requirement to submit efficacy data unless the pesticide product bears a claim to control pest microorganisms that pose a threat to human health and whose presence cannot readily be observed by the user including, but not limited to, microorganisms infectious to man in any area of the inanimate environment, or a claim to control vertebrates (such as rodents, birds, bats, canids, and skunks) that may directly or indirectly transmit diseases to humans. However each registrant must ensure through testing that his product is efficacious when used in accordance with label directions and commonly accepted pest control practices. The Agency reserves the right to require, on a case-by-case basis, submission of efficacy data for any pesticide product registered or proposed for registration. 2. [Reserved] [72 FR 60957, Oct. 26, 2007, as amended at 73 FR 75596, Dec. 12, 2008] § 158.230 Experimental use permit data requirements for toxicology. 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. (2) Nonfood use patterns include products classified under the general use patterns of terrestrial nonfood crop use, aquatic nonfood crop use, aquatic nonfood outdoor use, greenhouse nonfood crop use, forestry use, residential outdoor use, indoor nonfood use, and indoor residential use. (b) Key. (c) Table. Table—Experimental Use Permit Toxicity Data Requirements Guideline Number Data Requirement Use Pattern Test substance to support Test Note No. Food Nonfood MP EP Acute Testing 870.1100 Acute oral toxicity - rat R R MP and TGAI TGAI, EP 1 870.1200 Acute dermal toxicity R R MP and TGAI TGAI, EP 1, 2 870.1300 Acute inhalation toxicity - rat R R MP and TGAI TGAI and EP 3 870.2400 Primary eye irritation - rabbit R R MP TGAI and EP 2 870.2500 Primary dermal irritation R R MP TGAI and EP 1, 2 870.2600 Dermal sensitization R R MP TGAI and EP 2, 4 870.6100 Delayed neurotoxicity (acute) - hen CR CR TGAI TGAI 5 Subchronic Testing 870.3100 90-day Oral - rodent R NR TGAI TGAI — 870.3150 90-day Oral - non-rodent R NR TGAI TGAI — Chronic Testing 870.4100 Chronic oral - rodent R NR TGAI TGAI 6 Developmental Toxicity and Reproduction 870.3700 Prenatal Developmental toxicity - rat and rabbit, preferred R NR TGAI TGAI 7, 8 870.3800 Reproduction R NR TGAI TGAI 6 Mutagenicity Testing 870.5100 Bacterial reverse mutation assay R NR TGAI TGAI 9 870.5300 In vitro R NR TGAI TGAI 9, 10 870.5385 In vivo R NR TGAI TGAI 9, 11 (d) Test notes. 1. Not required if test material is a gas or a highly volatile liquid. 2. Not required if test material is corrosive to skin or has a pH of less than 2 or greater than 11.5. 3. Required if the product consists of, or under conditions of use will result in, a respirable material (e.g., gas, vapor, aerosol, or particulate). 4. Required if repeated dermal exposure is likely to occur under conditions of use. 5. Required if the test material is an organophosphorus substance, which includes uncharged organophosphorus esters, thioesters, or anhydrides of organophosphoric, organophosphonic, or organophosphoramidic acids, or of related phosphorothioic, phosponothioic, or phosphorothioamidic acids, or is structurally related to other substances that may cause the delayed neurotoxicity sometimes seen in this class of chemicals. 6. These studies are seldom required to support EUPs. They may be required if the dietary exposure for these EUPs occupies a large part, e.g., greater than 50%, of the reference dose. 7. The oral route, by oral intubation, is preferred unless the chemical or physical properties of the test substance or the pattern of exposure suggests a more appropriate route of exposure. 8. May be combined with the 2-generation reproduction study in rodents by utilizing a second mating of the parental animals in either generation. 9. At a minimum, an initial battery of mutagenicity tests with possible confirmatory testing is required. Other relevant mutagenicity tests that may have been performed, plus a complete reference list must also be submitted. 10. Choice of assay using either: i. Mouse lymphoma L5178Y cells, thymidine kinase (tk) gene locus, maximizing assay conditions for small colony expression or detection; ii. Chinese hamster ovary (CHO) or Chinese hamster lung fibroblast (V79) cells, hypoxanthine-guanine phosphoribosyl transferase (hgprt) gene locus, accompanied by an appropriate in vitro 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. [72 FR 60957, Oct. 26, 2007, as amended at 73 FR 75596, Dec. 12, 2008] § 158.240 Experimental use permit data requirements for ecological effects. All data for terrestrial nontarget organisms and aquatic nontarget organisms as described in § 158.243 must be submitted to support a request for an experimental use permit. No data for nontarget plant protection must be submitted to support a request for an experimental use permit. § 158.243 Experimental use permit data requirements for terrestrial and aquatic nontarget organisms. All terrestrial and aquatic nontarget organism data, as described in paragraph (c) of this section, must be submitted to support a request for an experimental use permit. (a) Use patterns. (2) Data are also required for the general use patterns of forestry and residential outdoor use. (b) Key. (c) Table. Table—Experimental Use Permit Terrestrial and Aquatic Nontarget Organism 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. 1. Data using the TGAI are required to support all outdoor end-use product uses including, but not limited to, turf. Data are generally not required to support end-use products in the form of a gas, a highly volatile liquid, a highly reactive solid, or a highly corrosive material. 2. For greenhouse and indoor end-use products, data using the TGAI are required to support manufacturing-use products to be reformulated into these same end-use products or to support end-use products when there is no registered manufacturing-use product. Avian acute oral data are not required for liquid formulations for greenhouse and indoor uses. The study is not required if there is no potential for environmental exposure. 3. Data are required on one passerine species and either one waterfowl species or one upland game bird species for terrestrial, aquatic, forestry, and residential outdoor uses. Data are preferred on waterfowl or upland game bird species for indoor and greenhouse uses. 4. Data are required on waterfowl and upland game bird species. 5. Data are required on one coldwater fish and one warmwater fish for terrestrial, aquatic, forestry, and residential outdoor uses. For indoor and greenhouse uses, testing with only one of either fish species is required. 6. EP or TEP testing is required for any product which meets any of the following conditions: i. The end-use pesticide will be introduced directly into an aquatic environment (e.g., aquatic herbicides and mosquito larvicides) when used as directed. ii. The maximum expected environmental concentration (MEEC) or the estimated environmental concentration (EEC) in the aquatic environment is ≥one-half the LC 50 50 iii. An ingredient in the end-use formulation other than the active ingredient is expected to enhance the toxicity of the active ingredient or to cause toxicity to aquatic organisms. 7. Data are required on one freshwater aquatic invertebrate species. 8. Data are generally not required for outdoor residential uses, other than turf, unless data indicate that pesticide residues from the proposed use(s) can potentially enter waterways. 9. Data are required on one freshwater fish species. If the test species is different from the two species used for the freshwater fish acute toxicity tests, a 96 hour LC 50 10. Not required when: i. The octanol/water partition coefficients of the pesticide and its major degradates are <1,000; or ii. There are no potential exposures to fish and other nontarget aquatic organisms; or iii. The hydrolytic half-life is <5 days at pH 5, 7 and 9. 11. The freshwater fish test species for the TEP testing is the most sensitive of the species tested with the TGAI. A freshwater invertebrate must also be tested with the EP or TEP using the same species tested with the TGAI. [72 FR 60957, Oct. 26, 2007, as amended at 73 FR 75596, Dec. 12, 2008] § 158.250 Experimental use permit data requirements for human exposure. No data for applicator exposure and post-application exposure must be submitted to support a request for an experimental use permit. § 158.260 Experimental use permit data requirements for environmental fate. 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. (2) Data are also required for the general use patterns of forestry use and residential outdoor use. (b) Key. (c) Table. Table—Experimental Use Permit 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 Leaching and adsorption/desorption R NR NR NR R NR TGAI or PAIRA 3 (d) Test notes. 1. Study is required for indoor uses in cases where environmental exposure is likely to occur. Such sites include, but are not limited to, agricultural premises, in or around farm buildings, barnyards, and beehives. 2. Required for aquatic uses for aquatic sites that are intermittently dry. Such sites include, but are not limited to cranberry bogs and rice paddies. 3. Adsorption and desorption using a batch equilibrium method is preferred. However, in some cases, for example, where the pesticide degrades rapidly, soil column leaching with unaged or aged columns may be more appropriate to fully characterize the potential mobility of the parent compound and major transformation products. [72 FR 60957, Oct. 26, 2007, as amended at 73 FR 75596, Dec. 12, 2008] § 158.270 Experimental use permit data requirements for residue chemistry. All residue chemistry data, as described in § 158.1410, are required for an experimental use permit for which a temporary tolerance under FFDCA section 408(r) is sought. Residue chemistry data are not required for an experimental use permit issued on a crop-destruct basis. §§ 158.280-158.290 [Reserved] Subpart D—Product Chemistry § 158.300 Definitions. The following terms are defined for the purposes of this subpart: Active ingredient End-use product (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 (1) The process of mixing, blending, or dilution of one or more active ingredients with one or more other active or inert ingredients, without an intended chemical reaction, to obtain a manufacturing-use product or an end-use product, or (2) The repackaging of any registered product. Impurity Impurity associated with an active ingredient (1) Any impurity present in the technical grade of active ingredient; and (2) Any impurity which forms in the pesticide product through reactions between the active ingredient and any other component of the product or packaging of the product. Inert ingredient Integrated system (1) Contains any active ingredient derived from a source that is not an EPA-registered product; or (2) Contains any active ingredient that was produced or acquired in a manner that does not permit its inspection by the Agency under FIFRA sec. 9(a) prior to its use in the process. Manufacturing-use product Nominal concentration Starting material Technical grade of 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). § 158.310 Product chemistry data requirements table. (a) General. (b) Use patterns. (c) Test substance. (d) Key. (e) Table. 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 Partition coefficient (n-octanol/water) R TGAI or PAI TGAI or PAI 24 830.7840 Water solubility R TGAI or PAI TGAI or PAI 9 830.7950 Vapor pressure R TGAI or PAI TGAI or PAI 9, 25 (f) Test notes. 1. Data must be provided in accordance with § 158.320. 2. Data must be provided in accordance with § 158.325. 3. Data must be provided in accordance with § 158.330. 4. Data must be provided in accordance with § 158.335. 5. Data must be provided in accordance with § 158.340. 6. Data must be provided in accordance with § 158.345. 7. Data must be provided in accordance with § 158.350. 8. Data must be provided in accordance with § 158.355. 9. If the TGAI cannot be isolated, data are required on the practical equivalent of the TGAI. 10. Data are required if the product is produced by an integrated system. 11. Basic manufacturers are required to provide the Agency with a sample of each TGAI used to formulate a product produced by an integrated system when the new TGAI is first used as a formulating ingredient in products registered under FIFRA. A sample of the active ingredient (PAI) suitable for use as an analytical standard is also required at this time. Samples of end-use products produced by an integrated system must be submitted on a case-by-case basis. 12. Data on the stability to metals and metal ions are required only if the TGAI is expected to come into contact with either material. 13. Required when the product contains an oxidizing or reducing agent. 14. Required when the product contains combustible liquids. 15. Required when the product is potentially explosive. 16. Required when the product is an emulsifiable liquid and is to be diluted with petroleum solvent. 17. Required when the EP is a liquid and is to be used around electrical equipment. 18. Required when the test substance is soluble or dispersible in water. 19. Required when the product is a liquid. 20. Required when the TGAI is solid at room temperature. 21. Required when the TGAI is liquid at room temperature. 22. Required when the test substance contains an acid or base functionality (organic or inorganic) or an alcoholic functionality (organic). 23. Required for water insoluble test substances (>10 −6 24. Required if technical chemical is organic and non-polar. 25. Not required for salts. 26. Data on stability of the MP and TGAI to storage at normal temperatures are required. Data on the stability of the TGAI to high temperatures are required if the TGAI is expected to be subjected to temperatures >50 °C (122 °F) during production or storage. § 158.320 Product identity and composition. Information on the composition of the pesticide product must be furnished. The information required by paragraphs (a), (b), and (f) of this section must be provided for each product. In addition, if the product is produced by an integrated system, the information on impurities required by paragraphs (c) and (d) of this section must be provided. (a) Active ingredient. (1) If the source of any active ingredient in the product is an EPA-registered product: (i) The chemical and common name (if any) of the active ingredient, as listed on the source product. (ii) The nominal concentration of the active ingredient in the product, based upon the nominal concentration of active ingredient in the source product. (iii) Upper and lower certified limits of the active ingredient in the product, in accordance with § 158.350. (2) If the source of any active ingredient in the product is not an EPA-registered product: (i) The chemical name according to Chemical Abstracts Society (CAS) nomenclature, the CAS Registry Number, and any common names. (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. (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. (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. (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. (f) Ingredients that cannot be characterized. § 158.325 Description of materials used to produce the product. The following information must be submitted on the materials used to produce the product: (a) Products not produced by an integrated system. (i) The name of the EPA-registered product. (ii) The EPA registration number of that product. (2) For each inert ingredient: (i) Each brand name, trade name, common name, or other commercial designation of the ingredient. (ii) All information that the applicant knows (or that is reasonably available to him) concerning the composition (and, if requested by the Agency, chemical and physical properties) of the ingredient, including a copy of technical specifications, data sheets, or other documents describing the ingredient. (iii) If requested by the Agency, the name and address of the producer of the ingredient or, if that information is not known to the applicant, the name and address of the supplier of the ingredient. (b) Products produced by an integrated system. (2) The following information concerning each active ingredient that is not derived from an EPA-registered product: (i) The name and address of the producer of the ingredient (if different from the applicant). (ii) Information about each starting material used to produce the active ingredient, as follows: (A) Each brand name, trade name, or other commercial designation of the starting material. (B) The name and address of the person who produces the starting material or, if that information is not known to the applicant, the name and address of each person who supplies the starting material. (C) All information that the applicant knows (or that is reasonably available to him), concerning the composition (and if requested by the Agency, chemical or physical properties) of the starting material, including a copy of all technical specifications, data sheets, or other documents describing it. (3) The information required by paragraph (a)(2) of this section concerning each inert ingredient. (c) Additional information. § 158.330 Description of production process. If the product is produced by an integrated system, the applicant must submit information on the production (reaction) processes used to produce the active ingredients in the product. The applicant must also submit information about the formulation process, in accordance with § 158.335. (a) Information must be submitted for the current production process for each active ingredient that is not derived from an EPA-registered product. If the production process is not continuous (a single reaction process from starting materials to active ingredient), but is accomplished in stages or by different producers, the information must be provided for each such production process. (b) The following information must be provided for each process resulting in a separately isolated substance: (1) The name and address of the producer who uses the process, if not the same as the applicant. (2) A general characterization of the process (e.g., whether it is a batch or continuous process). (3) A flow chart of the chemical equations of each intended reaction occurring at each step of the process, and of the duration of each step and of the entire process. (4) The identity of the materials used to produce the product, their relative amounts, and the order in which they are added. (5) A description of the equipment used that may influence the composition of the substance produced. (6) A description of the conditions (e.g., temperature, pressure, pH, humidity) that are controlled during each step of the process to affect the composition of the substance produced, and the limits that are maintained. (7) A description of any purification procedures (including procedures to recover or recycle starting materials, intermediates or the substance produced). (8) A description of the procedures used to assure consistent composition of the substance produced, e.g., calibration of equipment, sampling regimens, analytical methods, and other quality control methods. § 158.335 Description of formulation process. The applicant must provide information on the formulation process of the product (unless the product consists solely of a technical grade of active ingredient) as required by the following sections: (a) Section 158.330(b)(2), pertaining to characterization of the process. (b) Section 158.330(b)(4), pertaining to ingredients used in the process. (c) Section 158.330(b)(5), pertaining to process equipment. (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. The applicant must provide a discussion of the impurities that may be present in the product, and why they may be present. The discussion should be based on established chemical theory and on what the applicant knows about the starting materials, technical grade of active ingredient, inert ingredients, and production or formulation process. If the applicant has reason to believe that an impurity that EPA would consider toxicologically significant may be present, the discussion must include an expanded discussion of the possible formation of the impurity and the amounts at which it might be present. The impurities which must also be discussed are the following, as applicable: (a) Technical grade active ingredients and products produced by an integrated system. (2) Each other impurity which the registrant or applicant has reason to believe may be present in his product at any time before use at a level ≥0.1 percent (1,000 ppm) by weight of the technical grade of the active ingredient, based on what he knows about the following: (i) The composition (or composition range) of each starting material used to produce his product. (ii) The impurities which the applicant knows are present (or believes are likely to be present) in the starting materials, and the known or presumed level (or range of levels) of these impurities. (iii) The intended reactions and side reactions which may occur in the production of the product, and the relative amounts of byproduct impurities produced by such reactions. (iv) The possible degradation of the ingredients in the product after its production but prior to its use. (v) Post-production reactions between the ingredients in the product. (vi) The possible migration of components of packaging materials into the pesticide. (vii) The possible carryover of contaminants from use of production equipment previously used to produce other products or substances. (viii) The process control, purification and quality control measures used to produce the product. (b) Products not produced by an integrated system. (1) The possible carryover of impurities present in any registered product which serves as the source of any of the product's active ingredients. The identity and level of impurities in the registered source need not be discussed or quantified unless known to the formulator. (2) The possible carryover of impurities present in the inert ingredients in the product. (3) Possible reactions occurring during the formulation of the product between any of its active ingredients, between the active ingredients and inert ingredients, or between the active ingredient and the production equipment. (4) Post-production reactions between any of the product's active ingredients and any other component of the product or its packaging. (5) Possible migration of packaging materials into the product. (6) Possible contaminants resulting from earlier use of equipment to produce other products. (c) Expanded discussion. (1) From other possible chemical reactions. (2) Involving other ingredients. (3) At additional points in the production or formulation process. § 158.345 Preliminary analysis. (a) If the product is produced by an integrated system, the applicant must provide a preliminary analysis of each technical grade of active ingredient contained in the product to identify all impurities present at 0. 1 percent or greater of the technical grade of the active ingredient. The preliminary analysis should be conducted at the point in the production process after which no further chemical reactions designed to produce or purify the substances are intended. (b) Based on the preliminary analysis, a statement of the composition of the technical grade of the active ingredient must be provided. If the technical grade of the active ingredient cannot be isolated, a statement of the composition of the practical equivalent of the technical grade of the active ingredient must be submitted. § 158.350 Certified limits. 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. (1) An upper and lower limit for each active ingredient. (2) An upper and lower limit for each inert ingredient. (3) If the product is a technical grade of active ingredient or is produced by an integrated system, an upper limit for each impurity of toxicological significance associated with the active ingredient and found to be present in any sample of the product. (4) On a case-by-case basis, certified limits for other ingredients or impurities as specified by EPA. (b) EPA determination of standard certified limits for active and inert ingredients. (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. (2) If certified limits are required for impurities, the applicants must propose a certified limit. The standard certified limits may not be used for such substances. (3) Certified limits should: (i) Be based on a consideration of the variability of the concentration of the ingredient in the product when good manufacturing practices and normal quality control procedures are used. (ii) Allow for all sources of variability likely to be encountered in the production process. (iii) Take into account the stability of the ingredient in the product and the possible formation of impurities between production and sale or distribution. (4) The applicant may include an explanation of the basis of his proposed certified limits, including how the certified limits were arrived at (e.g., sample analysis, quantitative estimate based on production process), and its accuracy and precision. This will be particularly useful if the range of the certified limit for an active or inert ingredient is greater than the standard certified limits. (d) Special cases. (1) More precise limits. (2) More thorough explanation of how the certified limits were determined. (3) A narrower range between the upper and lower certified limits than that proposed. (e) Certification statement. I hereby certify that, for purposes of FIFRA sec. 12(a)(1)(C), the description of the composition of [ insert product name insert registration number § 158.355 Enforcement analytical method. 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 for Products Claiming Effectiveness Against Vertebrate Pests, Products With Prion-Related Claims, and Products for Control of Organisms Producing Mycotoxins § 158.400 Product performance data requirements table. (a) General. (b) Use patterns. (c) Key. (d) Table. 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 810.2700 Products with prion-related claims NR NR NR NR NR NR NR NR R 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 (e) Test notes. 1. The Agency has waived the requirement to submit product performance data unless the pesticide product bears a claim to control pest microorganisms that pose a threat to human health and whose presence cannot readily be observed by the user including, but not limited to, microorganisms infectious to man in any area of the inanimate environment, or a claim to control vertebrates (such as rodents, birds, bats, canids, and skunks) that may directly or indirectly transmit diseases to humans. However each registrant must ensure through testing that his product is efficacious when used in accordance with label directions and commonly accepted pest control practices. The Agency reserves the right to require, on a case-by-case basis, submission of product performance data for any pesticide product registered or proposed for registration. 2. [Reserved] [72 FR 60957, Oct. 26, 2007, as amended at 78 FR 13507, Feb. 28, 2013; 78 FR 26978, May 8, 2013] Subpart F—Toxicology § 158.500 Toxicology data requirements table. (a) General. (b) Use patterns. (2) Nonfood use patterns include products classified under the general use patterns of terrestrial nonfood crop use, aquatic nonfood use, greenhouse nonfood crop use, forestry use, residential outdoor use, and indoor nonfood use. (c) Key. (d) Table. 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, 3 870.2600 Dermal sensitization R R TGAI and MP TGAI and EP 3, 5 870.6100 Delayed neurotoxicity (acute) - hen CR CR TGAI TGAI 6 870.6200 Acute neurotoxicity - rat R R TGAI TGAI 7 Subchronic Testing 870.3100 90-day Oral - rodent R CR TGAI TGAI 8, 9 870.3150 90-day Oral - non-rodent R CR TGAI TGAI 36 870.3200 21/28-day Dermal R NR TGAI TGAI and EP 10, 11 870.3250 90-day Dermal CR R TGAI TGAI and EP 11, 12 870.3465 90-day Inhalation - rat CR CR TGAI TGAI 13, 14 870.6100 28-day Delayed neurotoxicity-hen CR CR TGAI TGAI 6, 15 870.6200 90-day Neurotoxicity - rat R R TGAI TGAI 7, 16 Chronic Testing 870.4100 Chronic oral - rodent R CR TGAI TGAI 17, 18, 19 870.4200 Carcinogenicity - two rodent species - rat and mouse preferred R CR TGAI TGAI 9, 17, 18, 19, 20, 21 Developmental Toxicity and Reproduction 870.3700 Prenatal Developmental toxicity - rat and rabbit, preferred R R TGAI TGAI 22, 23, 24, 25, 26 870.3800 Reproduction and fertility effects R R TGAI TGAI 26, 27, 29 870.6300 Developmental neurotoxicity CR CR TGAI TGAI 27, 28, 29 Mutagenicity Testing 870.5100 Bacterial reverse mutation assay R R TGAI TGAI 30 870.5300 In vitro R R TGAI TGAI 30, 31 870.5385 In vivo 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. 1. Not required if test material is a gas or a highly volatile liquid. 2. Diluted EP testing is required to support the end product registration if results using the EP meet the criteria for restricted use classification under § 152.170(b) or special review consideration under § 154.7(a)(1). 3. Not required if the test material is corrosive to skin or has a pH of less than 2 or greater than 11.5. 4. Required if the product consists of, or under conditions of use will result in, a respirable material (e.g., gas, vapor, aerosol, or particulate). 5. Required if repeated dermal exposure is likely to occur under conditions of use. 6. Required if the test material is an organophosphorus substance, which includes uncharged organophosphorus esters; thioesters or anhydrides of organophosphoric, organophosphonic, or organophosphoramidic acids; or of related phosphorothioic, phosponothioic, or phosphorothioamidic acids; or is structurally related to other substances that may cause the delayed neurotoxicity sometimes seen in this class of chemicals. 7. As determined by the Agency, additional measurements may also be required, such as cholinesterase activity for certain pesticides, e.g., organophosphates and some carbamates. The route of exposure must correspond with the primary route of exposure. 8. Required for nonfood use pesticides if oral exposure could occur. 9. The 90-day study is required in the rat for hazard characterization (possibly endpoint selection) and dose-setting for the chronic/carcinogenicity study. It is not required in the mouse, but the Agency would strongly encourage the registrant to conduct a 90-day range finding for the purposes of dose selection for the mouse carcinogenicity study to achieve adequate dosing and an acceptable study. The registrant is also encouraged to consult with the Agency on the results of the 90-day mouse study prior to conducting the carcinogenicity study. 10. Required for agricultural uses or if repeated human dermal exposure may occur. Not required if an acceptable 90-day dermal toxicity study is performed and submitted. 11. EP testing is required if the product, or any component of it, may increase dermal absorption of the active ingredient(s) as determined by testing using the TGAI, or increase toxic or pharmacologic effects. 12. Required for food uses if either of the following criteria is met: (i) The use pattern is such that the dermal route would be the primary route of exposure; or (ii) The active ingredient is known or expected to be metabolized differently by the dermal route of exposure than by the oral route, and a metabolite is the toxic moiety. 13. Required if there is the likelihood of significant repeated inhalation exposure to the pesticide as a gas, vapor, or aerosol. 14. Based on estimates of the magnitude and duration of human exposure, studies of shorter duration, e.g., 21- or 28-days, may be sufficient to satisfy this requirement. Registrants should consult with the Agency to determine whether studies of shorter duration would meet this requirement. 15. Required if results of acute neurotoxicity study indicate significant statistical or biological effects, or if other available data indicate the potential for this type of delayed neurotoxicity, as determined by the Agency. 16. All 90-day subchronic studies in rats can be designed to simultaneously fulfill the requirements of the 90-day neurotoxicity study using separate groups of animals for testing. Although the subchronic guidelines include the measurement of neurological endpoints, they do not meet the requirement of the 90-day neurotoxicity study. 17. Required if either of the following are met: (i) The use of the pesticide is likely to result in repeated human exposure over a considerable portion of the human lifespan, as determined by the Agency; (ii) The use requires a tolerance or an exemption from the requirement of a tolerance. 18. Based on the results of the acute and subchronic neurotoxicity studies, or other available data, a combined chronic toxicity and neurotoxicity study may be required. 19. Studies which are designed to simultaneously fulfill the requirements of both the chronic oral and carcinogenicity studies ( i.e. (i) Chronic rodent feeding study (food use) - 24 months. (ii) Chronic rodent feeding study (nonfood use) - 12 months. (iii) Mouse carcinogenicity study - 18 months. (iv) Rat carcinogenicity study - 24 months. 20. Required if any of the following, as determined by the Agency, are met: (i) The use of the pesticide is likely to result in significant human exposure over a considerable portion of the human life span which is significant in terms of either frequency, duration, or magnitude of exposure; (ii) The use requires a tolerance or an exemption from the requirement of a tolerance; or (iii) The active ingredient, metabolite, degradate, or impurity (a) is structurally related to a recognized carcinogen, (b) causes mutagenic effects as demonstrated by in vitro in vivo 21. If this study is modified or waived, a subchronic 90-day oral study conducted in the same species may be required. 22. Testing in two species is required for all uses. 23. The oral route, by oral intubation, is preferred unless the chemical or physical properties of the test substance or the pattern of exposure suggests a more appropriate route of exposure. 24. Additional testing by other routes may be required if the pesticide is determined to be a prenatal developmental toxicant after oral dosing. 25. May be combined with the 2-generation reproduction study in rodents by utilizing a second mating of the parental animals in either generation. 26. Required to support products intended for food uses and to support products intended for nonfood uses if use of the product is likely to result in significant human exposure over a portion of the human life span in terms of frequency, magnitude or duration of exposure. 27. An information-based approach to testing is preferred, which utilizes the best available knowledge on the chemical (hazard, pharmacokinetic, or mechanistic data) to determine whether a standard guideline study, an enhanced guideline study, or an alternative study should be conducted to assess potential hazard to the developing animal, or in some cases to support a waiver for such testing. Registrants should submit any alternative proposed testing protocols and supporting scientific rationale to the Agency prior to study initiation. 28. Study required using a weight-of-evidence approach considering: (i) The pesticide causes treatment-related neurological effects in adult animal studies ( i.e. (ii) The pesticide causes treatment-related neurological effects in developing animals, following pre- and postnatal exposure ( i.e. (iii) The pesticide elicits a causative association between exposures and adverse neurological effects in human epidemiological studies. (iv) The pesticide evokes a mechanism that is associated with adverse effects on the development of the nervous system (e.g., SAR relationship to known neurotoxicants, altered neuroreceptor or neurotransmitter responses). 29. The use of a combined study that utilizes the 2-generation reproduction study in rodents as a basic protocol for the addition of other endpoints or functional assessments in the immature animal is encouraged. 30. At a minimum, an initial battery of mutagenicity tests with possible confirmatory testing is required. Other relevant mutagenicity tests that may have been performed, plus a complete reference list must also be submitted. 31. Choice of assay using either: (i) Mouse lymphoma L5178Y cells, thymidine kinase (tk) gene locus, maximizing assay conditions for small colony expression or detection; (ii) Chinese hamster ovary (CHO) or Chinese hamster lung fibroblast (V79) cells, hypoxanthine-guanine phosphoribosyl transferase (hgprt) gene locus, accompanied by an appropriate in vitro (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 further elucidated by metabolism studies. 34. May be required if the product's use will result in exposure to domestic animals through, but not limited to, direct application. 35. A risk assessment assuming that dermal absorption is equal to oral absorption must be performed to determine if the study is required, and to identify the doses and duration of exposure for which dermal absorption is to be quantified. 36. A 1-year non-rodent study ( i.e. § 158.510 Tiered testing options for nonfood pesticides. For nonfood use pesticides only, applicants have two options for generating and submitting required toxicology (§ 158.500) and human exposure (§§ 158.1020, 158.1070, and 158.1410) studies. Applicants are to select one of the following: (a) Acute, subchronic, chronic, and other toxicological studies on the active ingredient must be submitted together. The specific makeup of the set of toxicology study requirements is based on the anticipated exposure to the pesticide as determined by the Agency. If hazards are identified based upon review of these studies, specific exposure data will be required to evaluate risk. (b) Certain toxicological and exposure studies must be submitted simultaneously with the toxicology data submitted in a tiered system. Exposure data must be submitted along with first tier toxicology data. The requirement for additional second and third level toxicology testing will be determined by the Agency based on the results of the first tiered studies. (1) The required first-tier toxicology studies consist of: (i) Battery of acute studies. (ii) A subchronic 90-day dermal study or a subchronic 90-day inhalation study. (iii) An acute and subchronic neurotoxicity screening battery in the rat. (iv) Prenatal developmental toxicity studies in both the rat and rabbit. (v) Reproduction and fertility studies in rats. (vi) Battery of mutagenicity studies. (vii) Immunotoxicity study. (2) The conditionally required second-tier studies include: (i) Subchronic 90-day feeding studies in both the rodent and nonrodent. (ii) Dermal penetration study. (3) The conditionally required third-tier studies include: (i) Chronic feeding studies in the rodent. (ii) Carcinogenicity. (iii) Metabolism study. (iv) Additional mutagenicity testing. Subpart G— Ecological Effects § 158.630 Terrestrial and aquatic nontarget organisms data requirements table. (a) General. (b) Use patterns. (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 50 50 50 50 50 50 i.e. (c) Key. i.e. (d) Table. 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 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 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 24 850.3040 Field testing for pollinators CR CR CR CR NR NR TEP 25 (e) Test notes. 1. Data using the TGAI are required to support all outdoor end-use product uses including, but not limited to turf. Data are generally not required to support end-use products in the form of a gas, a highly volatile liquid, a highly reactive solid, or a highly corrosive material. 2. For greenhouse and indoor end-use products, data using the TGAI are required to support manufacturing-use products to be reformulated into these same end-use products or to support end-use products when there is no registered manufacturing-use product. Avian acute oral data are not required for liquid formulations for greenhouse and indoor uses. The study is not required if there is no potential for environmental exposure. 3. Data are required on one passerine species and either one waterfowl species or one upland game bird species for terrestrial, aquatic, forestry, and residential outdoor uses. Data are preferred on waterfowl or upland game bird species for indoor and greenhouse uses. 4. Data are required on waterfowl and upland game bird species. 5. Tests are required based on the results of lower tier toxicology studies, such as the acute and subacute testing, intended use pattern, and environmental fate characteristics that indicate potential exposure. 6. Higher tier testing may be required for a specific use pattern when a refined risk assessment indicates a concern based on laboratory toxicity endpoints and refined exposure assessments. 7. Environmental chemistry methods used to generate data associated with this study must include results of a successful confirmatory method trial by an independent laboratory. Test standards and procedures for independent laboratory validation are available as addenda to the guideline for this test requirement. 8. Data are required on one coldwater fish and one warmwater fish for terrestrial, aquatic, forestry, and residential outdoor uses. For indoor and greenhouse uses, testing with only one of either fish species is required. 9. EP or TEP testing is required for any product which meets any of the following conditions: i. The end-use pesticide will be introduced directly into an aquatic environment (e.g., aquatic herbicides and mosquito larvicides) when used as directed. ii. The maximum expected environmental concentration (MEEC) or the estimated environmental concentration (EEC) in the aquatic environment is ≥one-half the LC 50 50 iii. An ingredient in the end-use formulation other than the active ingredient is expected to enhance the toxicity of the active ingredient or to cause toxicity to aquatic organisms. 10. Data are required on one freshwater aquatic invertebrate species. 11. Data are required on one estuarine/marine mollusk, one estuarine/marine invertebrate and one estuarine/marine fish species. 12. Data are generally not required for outdoor residential uses, other than turf, unless data indicate that pesticide residues from the proposed use(s) can potentially enter waterways. 13. Data are required on one freshwater fish species. If the test species is different from the two species used for the freshwater fish acute toxicity tests, a 96-hour LC 50 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 50 iv. If the estimated environmental concentration (EEC) in water is ≥0.01 of the acute EC 50 50 A. Studies of other organisms indicate the reproductive physiology of fish and/or invertebrates may be affected. B. Physicochemical properties indicate bioaccumulation of the pesticide. C. The pesticide is persistent in water (e.g., half-life in water >4 days). 16. Data are required on one estuarine/marine fish species. 17. Data are required on estuarine/marine species if the product is intended for direct application to the estuarine or marine environment, or the product is expected to enter this environment in significant concentrations because of its expected use or mobility patterns. 18. Data are required on freshwater species if the end-use product is intended to be applied directly to water, or is expected to be transported to water from the intended use site, and when any of the following conditions apply: i. If the estimated environmental concentration (EEC) is ≥0.1 of the no-observed-effect level in the fish early-life stage or invertebrate life cycle test; ii. If studies of other organisms indicate that the reproductive physiology of fish may be affected. 19. Not required when: i. The octanol/water partition coefficients of the pesticide and its major degradates are <1,000; or ii. There are no potential exposures to fish and other nontarget aquatic organisms; or iii. The hydrolytic half-life is <5 days at pH 5, 7 and 9. 20. Data are required based on the results of lower tier studies such as acute and chronic aquatic organism testing, intended use pattern, and environmental fate characteristics that indicate significant potential exposure. 21. Data are required if: i. The half-life of the pesticide in the sediment is ≤10 days in either the aerobic soil or aquatic metabolism studies and if any of the following conditions exist: A. The soil partition coefficient (Kd) is ≥50. B. The log Kow is ≥3. C. The Koc ≥1,000. ii. Registrants must consult with the Agency on appropriate test protocols prior to designing the study. 22. Data are required if: i. The estimated environmental concentration (EEC) in sediment is >0.1 of the acute LC 50 50 ii. The half-life of the pesticide in the sediment is >10 days in either the aerobic soil or aquatic metabolism studies and if any of the following conditions exist: A. The soil partition coefficient (Kd) is ≥50. B. The log Kow is ≥3. C. The Koc ≥1,000. iii. Registrants must consult with the Agency on appropriate test protocols prior to designing the study. 23. Sediment testing with estuarine/marine test species is required if the product is intended for direct application to the estuarine or marine environment or the product is expected to enter this environment in concentrations which the Agency believes to be significant, either by runoff or erosion, because of its expected use or mobility pattern. 24. Data are required only when the formulation contains one or more active ingredients having an acute LD 50 25. Required if any of the following conditions are met: i. Data from other sources (Experimental Use Permit program, university research, registrant submittals, etc.) indicate potential adverse effects on colonies, especially effects other than acute mortality (reproductive, behavioral, etc.); ii. Data from residual toxicity studies indicate extended residual toxicity. iii. Data derived from studies with terrestrial arthropods other than bees indicate potential chronic, reproductive or behavioral effects. 26. The freshwater fish test species for the TEP testing is the most sensitive of the species tested with the TGAI. Freshwater invertebrate and acute estuarine and marine organisms must also be tested with the EP or TEP using the same species tested with the TGAI. § 158.660 Nontarget plant protection data requirements table. (a) General. (b) Use patterns. (2) Data are also required for the general use patterns of forestry use and residential outdoor use. (c) Key. (d) Table. 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 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, 7 850.4400 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. 1. Not required for contained pesticide treatments such as bait boxes and pheromone traps unless adverse effects reports are received by the Agency. 2. Not required for known phytotoxicants. 3. Generally not required for granular formulations. May be requested on a case-by-case basis. 4. Required for known phytotoxicants such as herbicides, desiccants and defoliants. 5. Required if a tested terrestrial species exhibits a 25 percent or greater detrimental effect in the Tier I study. When Tier II testing is required, the test species should be the species that showed detrimental effects in the Tier I testing. 6. Required if the tested aquatic species exhibits a 50 percent or greater detrimental effect in the Tier I study. When Tier II testing is required, the test species should be the species that showed detrimental effects in the tier I testing. 7. Not required for aquatic residential uses. 8. Environmental chemistry methods used to generate data must include the results of a successful confirmatory method trial by an independent laboratory. 9. Tests are required on a case-by-case basis based on the results of lower tier phytotoxicity studies, adverse incident reports, intended use pattern, and environmental fate characteristics that indicate potential exposure. 10. Registrants must consult with the Agency on appropriate test protocols prior to designing the study. Subparts H-J [Reserved] §§ 158.700-158.900 [Reserved] Subpart K—Human Exposure § 158.1000 Applicator exposure—general requirements. (a) If EPA determines that industrial standards, such as the workplace standards set by the Occupational Safety and Health Administration (OSHA), provide adequate protection from risk under FIFRA for a particular pesticide use pattern, exposure data may not be required for that use pattern. Applicants should consult with the Agency on appropriate testing prior to the initiation of studies. (b) The Agency may accept surrogate exposure data estimations from other sources to satisfy applicator exposure data requirements if the data meet the basic quality assurance, quality control, good laboratory practice, and other scientific requirements set by EPA. In order to be acceptable, the Agency must find that the surrogate exposure data estimations have adequate information to address applicator exposure data requirements and contain adequate replicates of acceptable quality data to reflect the specific use prescribed on the label and the applicator activity of concern, including formulation type, application methods and rates, type of activity, and other pertinent information. The Agency will consider using such surrogate data for evaluating human exposure on a case-by-case basis. § 158.1010 Applicator exposure—criteria for testing. Applicator exposure data described in paragraph (d) of this section are required based on toxicity and exposure criteria. Data are required if a product meets, as determined by the Agency, at least one of the toxicity criteria in paragraph (a) of this section and either or both of the exposure criteria in paragraph (b) of this section. (a) Toxicity criteria. (2) Scientifically sound epidemiological or poisoning incident data indicate that adverse health effects may have resulted from handling of the pesticide. (b) Exposure criteria. (2) Respiratory exposure may occur during the prescribed use. § 158.1020 Applicator exposure data requirements table. (a) General. (b) Use patterns. (2) Residential use patterns include residential outdoor use and residential indoor use. These use patterns are limited to nonoccupational, i.e. (c) Key. (d) Table. 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. 1. Protocols must be submitted for approval prior to the initiation of the study. Details for developing protocols are available from the Agency. 2. Biological monitoring data may be submitted in addition to, or in lieu of, dermal and inhalation exposure data, provided the human pharmacokinetics of the pesticide and/or metabolite/analog compounds ( i.e. 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. (a) If EPA determines that industrial standards, such as the workplace standards set by the Occupational Safety and Health Administration, provide adequate protection for a particular pesticide use pattern, post-application exposure data may not be required for that use pattern. Applicants should consult with the Agency on appropriate testing before the initiation of studies. (b) The Agency may accept surrogate exposure data from other sources to satisfy post-application exposure data requirements if the data meet the basic quality assurance, quality control, good laboratory practice, and other scientific needs of EPA. In order to be acceptable, among other things, the Agency must find that the surrogate exposure data have adequate information to address post-application exposure data requirements and contain adequate replicates of acceptable quality data to reflect the specific use prescribed on the label and the post-application activity of concern, including formulation type, application methods and rates, type of activity, and other pertinent information. The Agency will consider using such surrogate data for evaluating human exposure on a case-by-case basis. § 158.1060 Post-application exposure—criteria for testing. Exposure data described in § 158.1070(d) are required based upon toxicity and exposure criteria. Data are required if a product meets, as determined by the Agency, either or both of the toxicity criteria in paragraph (a) of this section and either or both of the exposure criteria in paragraph (b) of this section. (a) Toxicity criteria. (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. (1) For outdoor uses. (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. (ii) Residential human post-application exposure to pesticide residues could occur following the application of the pesticide to indoor spaces or surfaces at residential sites, such as, but not limited to homes, daycare centers, hospitals, schools, and other public buildings. § 158.1070 Post-application exposure data requirements table. (a) General. (b) Use patterns. (2) Residential use patterns include residential outdoor use and indoor residential use. These use patterns are limited to nonoccupational, i.e. (c) Key. (d) Table. 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. 1. Protocols must be submitted for approval prior to the initiation of the study. Details for developing protocols are available from the Agency. 2. Bridging applicable residue dissipation data to dermal exposure data is required. 3. Turf grass transferable residue dissipation data are required when pesticides are applied to turf grass. Dislodgeable foliar residue dissipation data are required when pesticides are applied to the foliage of plants other than turf grass. 4. Data are required for occupational sites if (i) there are uses on turf grass or other plant foliage, and (ii) the human activity data indicate that workers are likely to have post-application dermal contact with treated foliage while participating in typical activities. 5. Data are required for residential sites if there are uses on turf grass or other plant foliage. 6. Data are required for occupational sites, if (i) there are outdoor or greenhouse uses to or around soil or other planting media, and (ii) the human activity data indicate that workers are likely to have post-application dermal contact with treated soil or planting media while participating in typical activities. 7. Data are required for residential sites if the pesticide is applied to or around soil or other planting media both outdoors and indoors, e.g., residential greenhouse or houseplant uses. 8. Data are required for occupational sites if the pesticide is applied to or around on non-plant surfaces, e.g., flooring or countertops, and if the human activity data indicate that workers are likely to have post-application dermal contact with treated indoor surfaces while participating in typical activities. 9. Data are required for residential sites if the pesticide is applied to or around non-plant surfaces, e.g., flooring and countertops. 10. Data are required for occupational sites if the human activity data indicate that workers are likely to have post-application exposures while participating in typical activities. 11. Data are required for residential sites if post-application exposures are likely. 12. Biological monitoring data may be submitted in addition to, or in lieu of, dermal and inhalation exposure data provided the human pharmocokinetics of the pesticide and/or metabolite/analog compounds ( i.e. 13. Data are required when passive dosimetry techniques are not applicable for a particular exposure scenario, such as a swimmer exposure to pesticides. 14. Data reporting and calculations are required when any post-application exposure monitoring data are submitted. 15. The selection of a sampling method will depend on the nondietary pathway(s) of interest. Data must be generated to consider all potential pathways of nondietary ingestion exposure that are applicable (e.g., soil ingestion, hand-to-mouth transfer, and object-to-mouth transfer of surface residues). Subpart L—Spray Drift § 158.1100 Spray drift data requirements table. (a) General. (b) Use patterns. (c) Key. (d) Table. 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. 1. This study is required when aerial applications (rotary and fixed winged) and mist blower or other methods of ground application are proposed and it is estimated that the detrimental effect level of those nontarget organisms expected to be present would be exceeded. The nontarget organisms include humans, domestic animals, fish and wildlife, and nontarget plants. 2. [Reserved] Subpart M [Reserved] §§ 158.1200-158.1299 [Reserved] Subpart N—Environmental Fate § 158.1300 Environmental fate data requirements table. (a) General. (b) Use patterns. (2) Data are also required for the general use patterns of forestry use and residential outdoor use. (c) Key. (d) Table. 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 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 Ground Water Monitoring 835.7100 Ground water monitoring CR NR NR NR CR CR TEP 7, 9, 11 (e) Test notes. 1. Study is required for indoor uses in cases where environmental exposure is likely to occur. Such sites include, but are not limited to, agricultural premises, in or around farm buildings, barnyards, and beehives. 2. Not required when the electronic absorption spectra, measured at pHs 5, 7, and 9, of the chemical and its hydrolytic products, if any, show no absorption or tailing between 290 and 800 nm. 3. Not required when the chemical is to be applied only by soil injection or is incorporated in the soil. 4. Requirement based on use patterns and other pertinent factors including, but not limited to, the Henry's Law Constant of the chemical. In view of methodological difficulties with the study of photodegradation in air, prior consultation with the Agency regarding the protocol is recommended before the test is performed. 5. Required for aquatic food and nonfood crop uses for aquatic sites that are intermittently dry. Such sites include, but are not limited to, cranberry bogs and rice paddies. 6. Adsorption and desorption using a batch equilibrium method is preferred. However in some cases, for example, where the pesticide degrades rapidly, soil column leaching with unaged or aged columns may be more appropriate to fully characterize the potential mobility of the parent compound and major transformation products. 7. Environmental chemistry methods used to generate data associated with this study must include results of a successful confirmatory method trial by an independent laboratory. Test standards and procedures for independent laboratory validation are available as addenda to the guideline for this test requirement. 8. Requirement for terrestrial uses is based on potential for aquatic exposure and if pesticide residues have the potential for persistence, mobility, nontarget aquatic toxicity or bioaccumulation. Not required for aquatic residential uses. Field testing under the terrestrial field dissipation requirement may be more appropriate for some aquatic food crops, such as rice and cranberry uses, that are managed to have a dry-land period for production. The registrant is encouraged to consult with the Agency on protocols. 9. Agency approval of a protocol is necessary prior to initiation of the study. 10. This study may be triggered if there is specific evidence that the presence of one pesticide can affect the dissipation characteristics of another pesticide when applied simultaneously or serially. 11. Required if the weight-of-evidence indicates that the pesticide and/or its degradates is likely to leach to ground water, taking into account other factors such as the toxicity of the chemicals(s), available monitoring data, and the vulnerability of ground water resources in the pesticide use area. 12. If the terrestrial dissipation study cannot assess all of the major routes of dissipation, the forestry study will be required. Subpart O—Residue Chemistry § 158.1400 Definitions. The following terms are defined for the purposes of this subpart: Livestock Plant or animal metabolite Residue of concern Tolerance § 158.1410 Residue chemistry data requirements table. (a) General. (b) Use patterns. (2) Data may be required for nonfood uses if pesticide residues may occur in food or feed as a result of the use. Data requirements for these nonfood uses will be determined on a case-by-case basis. For example, most products used in or near kitchens require residue data for risk assessment purposes even though tolerances may not be necessary in all cases. (c) Key. (d) Table. 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. 1. Required if indoor use could result in pesticide residues in or on food or feed. 2. Material safety data sheets must accompany standards as specified by OSHA in 29 CFR 1910.1200. 3. Required for residential outdoor uses on food crops if the corresponding agricultural use is not approved or the residential use is expected to produce higher residues based on the label directions. 4. Required for indoor uses where the pesticide is applied directly to food, in order to determine metabolites and/or degradates. Not required when only indirect contact with food would occur (e.g., crack and crevice treatments). 5. Data for fish are required for all pesticides applied directly to water inhabited, or which will be inhabited, by fish that may be caught or harvested for human consumption. 6. Required when a pesticide is to be applied directly to livestock, to livestock premises, to livestock drinking water, or to crops used for livestock feed. If results from the plant metabolism study show differing metabolites in plants from those found in animals, an additional livestock metabolism study involving dosing with the plant metabolite(s) may also be required. 7. Required when the Agency determines that it is reasonably foreseeable that a food or feed crop could be subsequently planted on the site of pesticide application after harvest or failure of the treated crop. Typically not required for pesticide uses in permanent food crops (e.g., various tree crops, vines) or semi-permanent crops (e.g., asparagus, pineapples). 8. A residue analytical method suitable for enforcement purposes is required whenever a numeric tolerance (including temporary and time-limited tolerances) is proposed. 9. New analytical methods to be used for enforcement purposes must include results from an independent laboratory validation. 10. A residue method, storage stability data, and crop field trials are required for the nonfood crop tobacco (green, freshly harvested). Depending on the level of residues found on the green tobacco, additional data may be required on cured/dried tobacco and pyrolysis products. 11. Data are required to determine whether FDA/USDA multiresidue methodology would detect and identify the pesticides and any metabolites. 12. Data are required for any magnitude of the residue study unless analytical samples are stored frozen for 30 days or less, and the active ingredient is not known to be volatile or labile. 13. Studies using single serving samples of a raw agricultural commodity may be needed for acutely toxic pesticides and/or their metabolites. These residue studies must be conducted using a statistical design accepted by the Agency. 14. Required for indoor uses which are direct postharvest treatments of raw agricultural commodities (e.g., fungicidal waxes or stored grain fumigants). 15. Data on the nature and level of residues in processed food/feed are required if residues could potentially concentrate on processing thus requiring the establishment of a separate tolerance higher than that of the raw agricultural commodity. 16. Required when the pesticide use is a direct application to livestock. 17. Data are required if pesticide residues are present in or on livestock feed items or intentionally added to drinking water. These studies, however, may not be required in cases where the livestock metabolism studies indicate negligible transfer of the pesticide's residues of concern to tissues, milk, and eggs at the maximum expected exposure level for the animals. 18. If results from the plant metabolism study show differing metabolites in plants from those found in animals, an additional livestock feeding study involving dosing with the plant metabolite(s) may also be required. 19. Data are required whenever a pesticide may be applied directly to water, unless it can be demonstrated that the treated water would not be available for human or livestock consumption. 20. Data are required when a pesticide is to be applied directly to water that could be used for irrigation or to irrigation facilities such as irrigation ditches. 21. Data are required whenever a pesticide may be used in a food handling or feed handling establishment. 22. Required when residues at the tolerance level may result in a risk of concern. These data may include washing, cooking, processing or degradation studies as well as market basket surveys for a more precise residue determination. 23. Typically required if pesticide residues of concern greater than 0.01 ppm are found in crops at the appropriate plant back intervals (taking into account plant back restrictions on product labels) in the confined rotational crop study. If residues of concern in the confined study are greater than 0.01 ppm but less than the limit of quantitation of the analytical method to be used on field trial samples, the Agency will consider not requiring, on a case-by-case basis, the limited field trials. If there are particular toxicological concerns with the parent pesticide or any metabolites, limited field studies may be needed if such residues are identified at levels below 0.01 ppm in the confined study. 24. Crop field trials are required to establish tolerances on rotational crops when quantifiable residues of concern are observed in the field rotational crops study. 25. Not required for an exemption from a tolerance provided that dietary exposure estimates are not needed due to low toxicity or that theoretical estimates of exposure are adequate to assess dietary risk. 26. Not required for an exemption from a tolerance. Subparts P-Q [Reserved] §§ 158.1500-158.1699 [Reserved] Subpart R—Product Performance for Products Claiming Effectiveness Against Invertebrate Pests Source: 87 FR 22475, Apr. 15, 2022, unless otherwise noted. § 158.1700 General requirements. (a) General. (1) Test substance. (2) Test organism. (3) Testing. (4) Data requirements. (b) Product performance data submission. § 158.1701 Definitions. Definitions. Complete protection time (CPT) Introduction Invasive species Performance standard Pest group labeling claim Pest-specific labeling claim Pest sub-group labeling claim Skin-applied insect repellent Species Wood-destroying Vector § 158.1703 Application categories. The following terms are defined for purposes of this subpart. Bait treatment Soil-applied termiticides i.e., i.e., Spatial repellents Structural protection Wood protectants and other non-structural protection § 158.1704 Performance standards for data acceptability. (a) General. (b) Skin-applied insect repellent labeling claims. (2) Any testing required under this part which involves any human subjects must comply with all applicable requirements under 40 CFR part 26. For example, 40 CFR part 26 requirements are pertinent to the part 158 testing requirement if the testing involves intentional exposure of human subjects. Protocols for such testing must be submitted to EPA for review prior to study initiation. Those protocols determined by EPA to involve intentional exposure of human subjects also require review by EPA's Human Studies Review Board (HSRB)) prior to study initiation. If you are uncertain about the applicability of the 40 CFR part 26 requirements to this 40 CFR part 158 testing requirement or uncertain about the nature of your planned testing (such as, for example, whether the testing would involve intentional exposure of human subjects or whether the testing would be an observational study), you should contact the Agency prior to initiating the testing. (c) Labeling claims for products other than skin-applied insect repellents. § 158.1705 Test guidelines. EPA has published the Harmonized Test Guidelines, which set forth the recommended approach to generate the data required in this subpart. The Product Performance Guidelines (Series 810, Group C—Invertebrate Control Agent Test Guidelines) are available on the Agency's website. These guidelines cover some, but not all, of the tests that would be used to generate data under this subpart. In instances where there is a conflict between one of the Harmonized Test Guidelines and the provisions of this subpart, this subpart will control. § 158.1707 Data requirement modifications. The data requirements (including the performance standards associated with the data requirements) specified in this subpart as applicable to a category of products will not always be appropriate for every product in that category. Data requirements may, on a case-by-case basis, be modified by EPA in response to requests for novel technologies or products that have unusual physical, chemical, or biological properties or atypical use patterns which would make a particular data requirement, or data performance standard, inappropriate. Requests for such data requirement modifications must be submitted in the same manner as waiver requests submitted under 40 CFR 158.45. EPA will respond in writing to those requests. The Agency may grant the request if it finds such modifications are appropriate for the pesticide in question, and will ensure that sufficient data are available to make the determinations required by the applicable statutory standards. § 158.1708 Invasive species claims. (a) General. (b) Specific. Agrilus planipennis, Anoplophora glabripennis, § 158.1709 Invertebrate disease vector claims. If an application for registration or amended registration requests a labeling claim specific to a disease vector (such as repels mosquitoes that may carry West Nile virus), then submission of test data conducted with the species specific to the disease vector claim and meeting the specific performance standard for that species is required even if the disease vector species is not the test species required in §§ 158.1712 through 158.1786. § 158.1710 Structural and wood-destroying pest claims. If an application for registration or amended registration requests a labeling claim specific to a structural or wood-destroying pest not identified in §§ 158.1782 through 158.1786, EPA may require submission of product performance data, with testing on that specific pest and subject to specific performance standards, to support those claims for effectiveness. § 158.1712 Mites (excluding chiggers). (a) General. (b) Test species. Table 1 to Paragraph (b) [Excluding chiggers] Labeling claim Required test species Dog Follicle Mite Dog follicle mite ( Demodex canis Dust Mite Testing on one of the following species is required: Dermatophagoides farinae Dermatophagoides pteronyssinus Human Itch or Scabies Mite Human itch mite ( Sarcoptes scabiei (c) Performance standards. (2) For the human itch or scabies mite, the performance standard is 100 percent. § 158.1714 Chiggers. If the pesticide product labeling makes a claim against chiggers, then testing is required using the following test species: Chigger ( Trombicula alfreddugesi § 158.1718 Ticks. (a) General. (b) Test species. Table 1 to Paragraph (b) Labeling claim Required test species Ticks Testing on a total of three hard tick species is required: Ixodes scapularis Amblyomma americanum AND One of the following three species: Dermacentor variabilis Rhipicephalus sanguineus Dermacentor andersoni Cattle Ticks Testing on one of the following species is required: Rhipicephalus microplus Rhipicephalus annulatus Soft Ticks Soft tick ( Ornithodoros hermsi (c) Specific parameters. 1. For products applied to dogs, testing is required on three species: Blacklegged tick ( Ixodes scapularis Dermacentor variabilis Rhipicephalus sanguineus 2. For products applied to cats, testing is required on three species: Blacklegged tick ( Ixodes scapularis Amblyomma americanum Dermacentor variabilis § 158.1722 Scorpions. If the pesticide product labeling makes a claim against scorpions, then testing is required using one of the following test species: Striped bark scorpion ( Centruroides vittatus Centrurioides sculpturatus § 158.1726 Spiders. (a) General. (b) Test species. Table 1 to Paragraph (b) Labeling claim Required test species Pest Group Claim Spiders Testing on two species is required: Loxosceles reclusa AND One of the following species is required: Latrodectus variolus Latrodectus mactans Latrodectus hesperus Pest Sub-Group Claims Black Widow Spiders Testing on one of the following species is required: Latrodectus variolus Latrodectus mactans Latrodectus hesperus Pest-Specific Claims Brown recluse spider Brown recluse spider ( Loxosceles reclusa Brown widow spider Brown widow spider ( Latrodectus geometricus Northern black widow spider Northern black widow spider ( Latrodectus variolus Southern black widow spider Southern black widow spider ( Latrodectus mactans Western black widow spider Western black widow spider ( Latrodectus hesperus § 158.1732 Centipedes. (a) General. (b) Test species. Table 1 to Paragraph (b) Labeling claim Required test species Centipedes Testing on one of the following species is required: Scutigera coleoptrata Hemiscolopendra marginata Scolopendra § 158.1736 Lice. (a) General. (b) Test species. Table 1 to Paragraph (b) Labeling claim Required test species Lice Testing on one of the following species is required: Pediculus humanus capitis Pediculus humanus humanus (c) Performance standards. § 158.1740 Fleas. (a) General. (b) Test species. Table 1 to Paragraph (b) Labeling claim Required test species Pest Group Claim Fleas Testing on the following species is required: Ctenocephalides felis Pest-Specific Claims Cat flea Cat flea ( Ctenocephalides felis Chigoe flea Chigoe flea ( Tunga penetrans Dog flea Dog Flea ( Ctenocephalides canis Hen flea Hen flea ( Ceratophyllus gallinae Human flea Human flea ( Pulex irritans Oriental rat flea Oriental rat flea ( Xenopsylla cheopis § 158.1744 Cockroaches. (a) General. (b) Test species. Table 1 to Paragraph (b) Labeling claim Required test species Pest Group Claims Cockroaches Testing on two species is required: Periplaneta americana Blattella germanica Pest-Specific Claims American cockroach American cockroach ( Periplaneta americana Australian cockroach Australian cockroach ( Periplaneta australasiae Brown cockroach Brown cockroach ( Periplaneta brunnea Brownbanded cockroach Brownbanded cockroach ( Supella longipalpa German cockroach German cockroach ( Blattella germanica Oriental cockroach Oriental cockroach ( Blatta orientalis Smokybrown cockroach Smokybrown cockroach ( Periplaneta fuliginosa Turkestan cockroach Turkestan cockroach ( Blatta lateralis § 158.1748 Keds, screwworms, and bot flies. (a) General. (b) Test species. Table 1 to Paragraph (b) Labeling claim Required test species Bot Flies (excluding Human bot fly) Testing is required on one of the following species: Gasterophilus intestinalis Gasterophilus nasalis Gasterophilus haemorrhoidalis Human bot fly Human bot fly ( Dermatobia hominis Keds Testing is required on the following species: Melophagus ovinus Screwworms Testing is required on one of the following species: Cochliomyia hominivorax Cochliomyia macellaria § 158.1752 Flies. (a) General. (b) Test species. Table 1 to Paragraph (b) Labeling claim Required test species Pest Group Claim Flies Testing of five species is required: Musca domestica Sarcophaga Wohlfahrtia Phaenicia Calliphora Stomoxys calcitrans Culicoides Simulium Prosimulium Leptoconops Tabanus atratus Chrysops Tabanus lineola Pest Sub-Group Claims Filth Flies Testing on two species is required: Musca domestica AND One of the following species is required: Sarcophaga Wohlfahrtia genera Phaenicia Calliphora genera Biting flies (excluding Sand flies) Testing is required on three species: Stomoxys calcitrans AND one of the large biting fly species: Tabanus atratus Chrysops Tabanus lineola AND one of the small biting fly species: Culicoides Simulium Prosimulium Leptoconops Large Biting Flies Testing is required on two species: Stomoxys calcitrans AND one of the following species: Tabanus atratus Chrysops Tabanus lineola Small Biting Flies (excluding Sand flies) Testing is required on one of the following species: Culicoides Simulium Prosimulium Leptoconops Pest-Specific Claims Blow fly Blow fly ( Phaenicia Calliphora genera Cluster fly Cluster fly ( Pollenia rudis Face fly Face fly ( Musca autumnalis Flesh fly Flesh fly ( Sarcophaga Wohlfahrtia genera House fly House fly ( Musca domestica Little house fly Little house fly ( Fannia canicularis Biting midges (punkie, granny nipper, no-see-um) Biting midge (punkie, granny nipper, no-see-um) ( Culicoides Black flies Testing on one of the following species is required: Simulium Prosimulium Black gnats Black gnat ( Leptoconops Deer flies Deer fly ( Chrysops Greenhead Greenhead ( Tabanus nigrovittatus Horn fly Horn fly ( Haematobia irritans Horse flies Testing on one of the following species is required: Tabanus atratus Tabanus lineola Sand flies Testing on one of the following species is required: Lutzomyia Phlebotomus Stable fly Stable fly ( Stomoxys calcitrans § 158.1756 Mosquitoes. (a) General. (b) Test species. Table 1 to Paragraph (b) Labeling claim Required test species Mosquitoes Testing in three genera ( Culex, Aedes, Anopheles One of the following Culex Culex pipiens Culex quinquefasciatus Culex tarsalis AND one of the following Aedes Aedes aegypti Aedes albopictus AND one of the following Anopheles Anopheles albimanus Anopheles freeborni Anopheles gambiae Anopheles hermsi Anopheles punctipennis Anopheles quadrimaculatus Anopheles stephensi § 158.1768 Bed bugs. (a) General. (b) Test species. Table 1 to Paragraph (b) Labeling claim Required test species Pest Group Claim Bed bugs Common bed bug ( Cimex lectularius Pest-Specific Claims Common bed bug Common bed bug ( Cimex lectularius Tropical bed bug Tropical bed bug ( Cimex hemipterus § 158.1772 Conenose bugs and kissing bugs. (a) General. (b) Test species. Table 1 to Paragraph (b) Labeling claim Required test species Conenose bug Conenose bug ( Triatoma sanguisuga Kissing bug Kissing bug ( Triatoma protracta § 158.1776 Ants (excluding carpenter ants). (a) General. (b) Test species. Table 1 to Paragraph (b) [Excluding carpenter ants] Labeling claim Required test species Pest Group Claim Ants (excluding carpenter ants) Testing is required on the following two species: Monomorium pharaonis Solenopsis invicta Pest Sub-Group Claim Fire and Harvester Testing is required on the following species: Solenopsis invicta Fire ants Testing is required on the following species: Solenopsis invicta Pest-Specific Claims European fire ant European fire ant ( Myrmica rubra Harvester ant Harvester ant ( Pogonomyrmex Pharaoh ant Pharaoh ant ( Monomorium pharaonis Red imported fire ant Red imported fire ant ( Solenopsis invicta Southern fire ant Southern fire ant ( Solenopsis xyloni Tropical fire ant Tropical fire ant ( Solenopsis geminata Black imported fire ant Black imported fire ant ( Solenopsis richteri (c) Colony Claims. S. invicta, S. richteri, (d) Bait products or claims involving outdoor use. § 158.1780 Bees, wasps, yellowjackets, and hornets. (a) General. (b) Test species. Table 1 to Paragraph (b) Labeling claim Required test species Pest Group Claims Bees, Wasps, Yellowjackets, and Hornets Testing on three species is required: Vespula Dolichovespula maculata Polistes Pest-Specific Claims Bald-faced hornet Bald-faced hornet ( Dolichovespula maculata Mud dauber wasp Mud dauber wasp ( Sphecidae Paper wasp Paper wasp ( Polistes Yellowjackets Yellowjacket ( Vespula (c) Colony claims. Vespula Vespula Vespula § 158.1782 Carpenter ants. (a) General. (b) Test species. Table 1 to Paragraph (b) Labeling claim Required test species Carpenter ants Testing on one of the following carpenter ant species is required: Camponotus pennsylvanicus Camponotus floridanus Camponotus modoc (c) Performance standards. Table 2 to Paragraph (c) Claim category Performance standard Non-Structural Protection: Wood Preservative Treatment 100% prevention of damage to wood for ≥2 years. Structural Protection, except Baits 95% prevention of damage to wood ≥5 years. Structural Protection: Bait Treatment 95% prevention of damage to wood ≥3 years. (d) Colony Claims. (e) Bait products or claims involving outdoor use. § 158.1784 Wood-destroying beetles. (a) General. (b) Test species. Table 1 to Paragraph (b) Labeling claim Required test species True powderpost beetles Testing on one species from the Lyctinae subfamily is required. Wood-destroying or wood-boring beetles Testing on three species is required: Anobiidae Bostrichidae Hylotrupes bajulus (c) Performance standards. Table 2 to Paragraph (c) Claim category Performance standard Non-Structural Protection: Wood Preservative Treatment 100% prevention of damage to wood for ≥2 years. Structural Protection, except Baits 95% prevention of damage to wood ≥5 years. Structural Protection: Bait Treatment 95% prevention of damage to wood ≥3 years. § 158.1786 Termites. (a) General. (b) Test species. Table 1 to Paragraph (b) Labeling claim Required test species Pest Group Claim Termites Testing on species from four genera of termites is required: Coptotermes Coptotermes formosanus Reticulitermes Reticulitermes flavipes Reticulitermes hesperus Reticulitermes virginicus Nasutitermes corniger Cryptotermes brevis Cryptotermes cavifrons Incisitermes minor Incisitermes snyderi Pest Sub-Group Claim Arboreal Termites Testing of one arboreal termite species is required: Nasutitermes corniger. Dampwood Termites Testing of the following dampwood termite is required: Zootermopsis Drywood Termites Testing of one of the following drywood termites is required: Cryptotermes brevis Cryptotermes cavifrons Incisitermes minor Incisitermes snyderi. Subterranean Termites, including Formosan Subterranean Termites Testing in two genera of termites is required: Testing on the following Coptotermes Coptotermes formosanus Reticulitermes Reticulitermes flavipes Reticulitermes hesperus Reticulitermes virginicus. (c) Performance standards. Table 2 to Paragraph (c) Claim category Performance standard Non-Structural Protection: Wood Preservative Treatment 100% prevention of damage to wood for ≥2 years. Structural Protection, except Baits 95% prevention of damage to wood ≥5 years. Structural Protection: Bait Treatment 95% prevention of damage to wood ≥3 years. Subparts S—T §§ 158.1800-158.1900 [Reserved] Subpart U—Biochemical Pesticides Source: 72 FR 61002, Oct. 26, 2007, unless otherwise noted. § 158.2000 Biochemical pesticides definition and applicability. This subpart applies to all biochemical pesticides as defined in paragraphs (a), (b), and (c) of this section. (a) Definitions. (1) A biochemical pesticide (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 pesticides, is equivalent to a naturally-occurring substance that has such a history; and (iii) Has a non-toxic mode of action to the target pest(s). (2) A Pheromone (i) An Arthropod Pheromone (ii) A Lepidopteran Pheromone (iii) A Straight Chain Lepidopteran Pheromone (b) Examples. (1) Semiochemicals (insect pheromones and kairomones), (2) Natural plant and insect regulators, (3) Naturally-occurring repellents and attractants, and (4) Enzymes. (c) Applicability. § 158.2010 Biochemical pesticides data requirements. (a) Sections 158.2030 through 158.2070 identify the data requirements that are required to support registration of biochemical pesticides. Sections 158.2080 through 158.2084 identify the data requirements that are required to support Experimental Use Permits (EUPs). Variations in the test conditions are identified within the test notes. Definitions that apply to all biochemical data requirements can be found in § 158.2000. (b) Each data table includes “use patterns” under which the individual data are required, with variations including food and nonfood uses for terrestrial and aquatic applications, greenhouse, indoor, forestry, and residential outdoor applications under certain circumstances. (c) The categories for each data requirement are “R”, which stands for required, and “CR” which stands for conditionally required. Generally, “R” indicates that the data are more likely required than for those data requirements with “CR.” However, in each case, the regulatory text preceding the data table and the test notes following the data table must be used to determine whether the data requirement must be satisfied. (d) Each table identifies the test substance that is required to be tested to satisfy the data requirement. Test substances may include: technical grade active ingredient (TGAI), manufacturing-use product (MP), end-use product (EP), typical end-use product (TEP), residue of concern, and pure active ingredient (PAI) or all of the above (All). Commas between the test substances ( i.e. (e) The data requirements are organized into a tier-testing system with specified additional studies at higher tiers being required if warranted by adverse effects observed in lower tier studies. The lower tier studies are a subset of those required for conventional pesticides, and the studies overall are generally selected from those required for conventional pesticides. (f) Two sets of guideline numbers are provided for some of the environmental fate data requirements. For ease of understanding, the current guidelines will be used as an interim measure until the new guidelines (in parentheses) are finalized. § 158.2030 Biochemical pesticides product chemistry data requirements table. (a) General. (2) Definitions in § 158.300 apply to data requirements in this section. (b) Use patterns. (c) Key. (d) Table. 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 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. 1. Data must be provided in accordance with § 158.320. 2. If the MP and EP are produced by an integrated formulation system (non-registered source), these data are also required on TGAI. 3. Data must be provided in accordance with §§ 158.325, 158.330, and § 158.335. 4. Data must be provided in accordance with § 158.340. 5. Data must be provided in accordance with § 158.345. Also, required to support the registration of each manufacturing-use product (including registered TGAIs) and end-use products produced by an integrated formulation system. Data on other end-use products would be required on a case-by-case basis. 6. Data must be provided in accordance with § 158.350. 7. Data must be provided in accordance with § 158.355. 8. If the TGAI cannot be isolated, data are required on the practical equivalent of the TGAI. EP testing may also be appropriate. 9. Required if the product contains combustible liquids. 10. Required if the product is an emulsifiable liquid and is to be diluted with petroleum solvents. 11. Required if the test substance is soluble or dispersible in water. 12. Required if the product is a liquid. 13. Required when the technical chemical is a solid at room temperature. 14. Required when the technical chemical is a liquid at room temperature. 15. Required for water insoluble test substances (>10 −6 16. Required for organic chemicals unless they dissociate in water or are partially or completely soluble in water. 17. Data on the stability to metals and metal ions is required only if the active ingredient is expected to come in contact with either material during storage. 18. True density or specific density are required for all test substances. Data on bulk density is required for MPs or EPs that are solid at room temperature. 19. Not required for salts. § 158.2040 Biochemical pesticides residue data requirements table. (a) General. i.e. (b) Use patterns. (2) Data are conditionally required for nonfood uses if pesticide residues may occur in food or feed as a result of the use. Data requirements for these nonfood uses would be determined on a case-by-case basis. For example, most products used in or near kitchens require residue data for risk assessment purposes even though tolerances may not be necessary in all cases. (c) Key. (d) Data requirements table. Table—Biochemical Residue Data Requirements for Specific Uses 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 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. 1. Residue chemistry data requirements apply to biochemical pesticide products when Tier II or Tier III toxicology data are required, as specified for biochemical agents in the biochemical human health assessment data requirements, § 158.2050. 2. The same chemical identity data are required for biochemical product chemistry data requirements, § 158.2030, with an emphasis on impurities. 3. Required information includes crops to be treated, rate of application, number and timing of applications, preharvest intervals, and relevant restrictions. 4. Required for residential outdoor uses on food crops if the corresponding agricultural use is not approved or the residential use is expected to produce higher residues based on the label directions. 5. Required unless it is an arthropod pheromone applied at a rate less than or equal to 150 grams active ingredient per acre. 6. Required for indoor uses where the pesticide is applied directly to food, in order to determine metabolites and/or degradates. Not required when only indirect contact with food would occur (e.g., crack and crevice treatments). 7. Required when a pesticide is to be applied directly to livestock, to livestock premises, to livestock drinking water, or to crops used for livestock feed. 8. If results from the plant metabolism study show differing metabolites in plants from those found in animals, an additional livestock metabolism study involving dosing with the plant metabolite(s) may also be required. 9. A residue analytical method suitable for enforcement of tolerances is required whenever a numeric tolerance (including temporary and time-limited tolerances) is proposed. 10. Required if indoor use could result in pesticide residues in or on food or feed. 11. Data are required to determine whether FDA/USDA multiresidue methodology would detect and identify the pesticides and any metabolites. 12. Data are required whenever a pesticide may be applied directly to water, unless it can be demonstrated that the treated water would not be available for human or livestock consumption. 13. Data on fish are required for all pesticides applied directly to water inhabited, or which will be inhabited by fish that may be caught or harvested for human consumption. 14. Data are required when a pesticide is to be applied directly to water that could be used for irrigation or to irrigation facilities such as irrigation ditches. 15. Data are required whenever a pesticide may be used in food/feed handling establishments. 16. Data on the nature and level of residue in processed food/feed are required when detectible residues could potentially concentrate on processing thus requiring the establishment of a separate tolerance higher than that of the raw agricultural commodity. 17. Required when residues at the tolerance level may result in risk of concern. These data may include washing, cooking, processing, or degradation studies as well as market basket surveys for a more precise residue determination. 18. The proposed tolerance must reflect the maximum residue likely to occur in crops, in meat, milk, poultry, or eggs. 19. Required when a residue analytical method is required. § 158.2050 Biochemical pesticides human health assessment data requirements table. (a) General. (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. (2) Nonfood use patterns include products classified under the general use patterns of terrestrial nonfood crop use; aquatic nonfood residential use; aquatic nonfood outdoor use; aquatic nonfood industrial use; greenhouse nonfood crop use; forestry use; residential outdoor use; residential indoor use; indoor food use; indoor nonfood use; indoor medical use. (c) Key. (d) Table. 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 In vitro R CR TGAI TGAI 10, 11 Tier II Mutagenicity Testing ( In vivo 870.5385 In vivo 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 15 875.1300 Inhalation outdoor exposure CR CR TGAI TGAI 15 875.1400 Inhalation indoor exposure CR CR TGAI TGAI 15 875.1500 Biological monitoring CR CR TGAI TGAI 15 Tier III Chronic Testing/Special Testing 880.3800 Immune response CR CR TGAI TGAI 14 870.3800 Reproduction and fertility effects CR CR TGAI TGAI 16 870.4100 Chronic oral - rodent and nonrodent CR CR TGAI TGAI 17 870.4200 Carcinogenicity - two species - rat and mouse preferred CR CR TGAI TGAI 18 870.5380 Mammalian spermatogonial chromosome aberration test CR CR TGAI TGAI 19 Special Testing 870.7200 Companion animal safety CR CR NR TGAI or EP 20 (e) Test notes. 1. Required unless the test material is a gas or highly volatile (vapor pressure >10 −4 2. Required unless the test material is corrosive to skin or has pH <2 or >11.5. 3. Required when the pesticide, under conditions of use, would result in respirable material (e.g., gas, volatile substance or aerosol/particulate), unless it is a straight chain lepidopteran pheromone. 4. Required if repeated contact with human skin is likely to occur under conditions of use. 5. Hypersensitivity incidents must be reported as adverse effects data. 6. Required for non-food uses that are likely to result in repeated oral exposure to humans. 7. Required to support uses involving purposeful application to the human skin or which would result in comparable prolonged human exposure to the product (e.g., insect repellents) and if any of the following criteria are met: i. Data from a 90-day oral study are not required. ii. The active ingredient is known or expected to be metabolized differently by the dermal route of exposure than by the oral route and the metabolite is of toxicological concern. iii. The use pattern is such that the dermal route would be the primary route of exposure. 8. Required if there is a likelihood of significant levels of repeated inhalation exposure to the pesticide as a gas, vapor, or aerosol. 9. Required if the use of the product under widespread and commonly recognized practice may reasonably be expected to result in significant exposure to female humans (e.g., occupational exposure or repeated application of insect repellents directly to the skin). Tier II data is required on a different test species from Tier I data when developmental effects are observed in the first study and information on species-to-species extrapolation is needed. 10. Required to support nonfood uses if either: i. The use is likely to result in significant human exposure; or ii. The active ingredient (or its metabolites) is structurally related to a known mutagen or belongs to any chemical class of compounds containing a known mutagen. Additional mutagenicity tests that may have been performed plus a complete reference list must also be submitted. Subsequent testing may be required based on the available evidence. 11. Choice of assay using either: i. Mouse lymphoma L5178Y cells, thymidine kinase (tk) gene locus, maximizing assay conditions for small colony expression or detection; ii. Chinese hamster ovary (CHO) or Chinese hamster lung fibroblast (V79) cells, hypoxanthine-guanine phosphoribosyl transferase (hgprt) gene locus, accompanied by an appropriate in vitro iii. CHO cells strains AS52, xanthine-guanine phosphoribosyl transferase (xprt) gene locus. 12. Required if there are effects on hematology, clinical chemistry, lymphoid organ weights, and histopathology are observed in the 90-day studies. 13. The micronucleus rodent bone marrow assay is preferred; however, rodent bone marrow assays using metaphase analysis (aberrations) are acceptable. 14. Required if adverse effects are observed in the Tier II immunotoxicity study. The protocol for evaluating adverse effects to the immune response should be developed after evaluating the effects noted in the immunotoxicity study. 15. These data are required when the data used for the human health assessment indicates that the biochemical may pose a potential hazard to the applicator/user. 16. Required if there is evidence of: i. Endocrinological effects from the subchronic toxicity studies. ii. Developmental effects in the prenatal developmental toxicity study(s), or iii. Genotoxicity to mammals based on results from the mutagenicity tests. The use of a combined study that utilizes the two-generation reproduction study in rodents (guideline 870.3800) as a basic protocol for the addition of other endpoints or functional assessments in the immature animal is encouraged. 17. Required if the potential for adverse chronic effects is indicated based on any of the following: i. The subchronic effect level established in the following Tier I studies: 90-day oral toxicity study, 90-day dermal toxicity study, or 90-day inhalation toxicity study. ii. The pesticide use pattern (e.g., rate, frequency, and site of application). iii. The frequency and level of repeated human exposure that is expected. 18. Required if the product meets either of the following criteria: i. The active ingredient (or any of its metabolites, degradation products, or impurities) produce(s) in Tier I subchronic studies a morphologic effect (e.g., hyperplasia or metaplasia) in any organ that potentially could lead to neoplastic change. ii. Adverse cellular effects suggesting carcinogenic potential are observed in Tier II immunotoxicity and Tier III immune response study or in Tier II mammalian mutagenicity assays. In addition, a 90-day range finding study in both rats and mice is required to determine the dose levels if carcinogenicity studies are required. If the mouse carcinogenicity study is not required, the 90-day mouse subchronic study is likewise not required. 19. Required if results from lower tiered mutation or reproductive studies indicate there is potential for chromosomal aberration to occur. 20. May be required if the product's use will result in exposure to domestic animals through, but not limited to, direct application or consumption of treated feed. § 158.2060 Biochemical pesticides nontarget organisms and environmental fate data requirements table. (a) General. (2) The data in this section are not required for arthropod pheromones when applied at up to a maximum use rate of 150 grams active ingredient/acre/year except when the product is expected to be available to avian species ( i.e. (b) Use patterns. (c) Key. (d) Table. 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 880.4350 Nontarget Insect Testing R R R R NR TGAI 14 Tier II Environmental Fate Testing 163-1 (835.1230) Sediment and soil adsorption/desorption for parent and degradates CR CR CR CR NR TGAI 6 163-1 (835.1240) Soil column leaching CR CR CR CR NR TGAI 6 163-2 (835.1410) Laboratory volatilization from soil CR NR CR CR NR TEP 7 161-1 (835.2120) Hydrolysis CR CR CR CR NR TGAI 6 161-1 (835.4100) Aerobic soil metabolism CR NR CR CR NR TGAI 6 161-2 (835.2240) Photodegradation in water CR CR CR CR NR TGAI 6 161-3 (835.2410) Photodegradation on soil CR NR CR CR NR TGAI 6 162-2 (835.4200) Anaerobic soil metabolism CR NR NR NR NR TGAI 6 162-4 (835.4300) Aerobic aquatic metabolism CR CR CR CR NR TGAI 6 162-3 (835.4400) Anaerobic aquatic metabolism CR CR NR NR NR TGAI 6 880.4425 Dispenser - water leaching CR NR CR CR NR EP 8 Nontarget Plant 850.4225 Seedling emergence R R NR R NR TGAI 9 850.4250 Vegetative vigor R R NR R NR TGAI 9 Tier III Aquatic Fauna Chronic, Life Cycle, and Field Studies 850.1300 Freshwater fish/invertebrate testing CR CR NR CR NR TGAI 10 850.1025 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 Nontarget plant CR CR NR CR NR TGAI 13 (e) Test notes. 1. Required for the EP when any end-use formulation may contain other ingredients that may be toxic to nontarget organisms or to support arthropod pheromones that would be available to avian wildlife, (e.g., a granular product). 2. Tests for pesticides intended solely for indoor application would be required on a case-by-case basis, depending on use pattern, physical/chemical properties, production volume, and other pertinent factors. 3. Not required for any use groups if the pesticide is highly volatile (estimated volatility >5 × 10 −5 3 4. Preferred test species are Upland game, waterfowl, or passerine for avian acute oral toxicity studies; Upland game and waterfowl for avian dietary studies; and coldwater fish species for acute freshwater fish studies. 5. Required for the EP when the end-use formulation may contain other ingredients that may be toxic to nontarget organisms. 6. Required on a case-by-case basis when results from Tier I studies indicate adverse effects. 7. Required when results of any one or more of the nontarget organism studies in Tier I indicate potential adverse effects on nontarget organisms and the pesticide is to be applied on land. In view of methdological difficulties with the study of photodegradation in air, prior consultation with the Agency regarding the protocol is recommended before the test is performed. 8. Required when results of any one or more of the nontarget organism studies in Tier I indicate potential adverse effects on nontarget organisms and the pesticide is to be applied in a passive dispenser. 9. Required to support registration of known phytotoxicants, i.e. 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 50 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 50 ii. The pesticide or any of its metabolites or degradation products are stable in the environment to the extent that potentially toxic amounts may persist in the avian or mammalian feed. 12. Required when results of Tier I nontarget organism studies indicate potential adverse effects on nontarget insects and results of Tier II tests indicate exposure of nontarget insects. Additional insect species may have to be tested if necessary to address issues raised by use patterns and potential exposure of important nontarget insect species, (e.g., threatened or endangered species). 13. Required if the product is expected to be transported from the site of application by air, soil, or water. The extent of movement would be determined by the results of the Tier II environmental fate studies. 14. Required depending on pesticide mode of action, method and timing of application, and results of any available efficacy data. Typically the honeybee acute toxicity guideline (guideline 850.3020) satisfies this requirement, however, additional nontarget insect species may have to be tested if necessary to address issues raised by use patterns and potential exposure of important nontarget insect species, (e.g., endangered species.) § 158.2070 Biochemical pesticides product performance data requirements. (a) General. (b) Product performance data for each product that bears a claim against an invertebrate pest that is covered by subpart R of this part. (c) Product performance data for each product that bears a public health pest claim, excluding those covered under paragraph (b). [87 FR 22484, Apr. 15, 2022] § 158.2080 Experimental use permit data requirements—biochemical pesticides. (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. (a) General. (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. (c) Key. (d) Table. 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 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. 1. Data must be provided in accordance with § 158.320. 2. If the MP and EP are produced by an integrated formulation system (non-registered source), these data are also required on TGAI. 3. Data must be provided in accordance with § 158.325, § 158.330, and § 158.335. 4. Data must be provided in accordance with § 158.340. 5. Data must be provided in accordance with § 158.345. Also, required to support the registration of each manufacturing-use product (including registered TGAIs) and end-use products produced by an integrated formulation system. Data on other end-use products would be required on a case-by-case basis. For pesticides in the production stage, a preliminary product analytical method and data would suffice to support an experimental use permit. 6. Data must be provided in accordance with § 158.350. 7. Data must be provided in accordance with § 158.355. 8. If the TGAI cannot be isolated, data are required on the practical equivalent of the TGAI. EP testing may also be appropriate. 9. Required if the product contains combustible liquids. 10. Required if the product is an emulsifiable liquid and is to be diluted with petroleum solvents. 11. Required if the test substance is soluble or dispersible in water. 12. Required if the product is a liquid. 13. Required when the technical chemical is a solid at room temperature. 14. Required when the technical chemical is a liquid at room temperature. 15. Required for water insoluble test substances (>10 −6 16. Required for organic chemicals unless they dissociate in water or are partially or completely soluble in water. 17. Data on the stability to metals and metal ions is required only if the active ingredient is expected to come in contact with either material during storage. 18. True density or specific density are required for all test substances. Data on bulk density is required for MPs or EPs that are solid at room temperature. 19. Not required for salts. § 158.2082 Experimental use permit biochemical pesticides residue data requirements table. (a) General. i.e. (b) Use patterns. (2) Data are conditionally required for nonfood uses if pesticide residues may occur in food or feed as a result of the use. Data requirements for these nonfood uses would be determined on a case-by-case basis. For example, most products used in or near kitchens require residue data for risk assessment purposes even though tolerances may not be necessary in all cases. (c) Key. (d) Data table. 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. 1. Residue chemistry data requirements apply to biochemical pesticide products when Tier II or Tier III toxicology data are required, as specified for biochemical agents in the biochemical human health assessment data requirements, § 158.2050. 2. The same chemical identity data are required for biochemical product chemistry data requirements,§ 158.2030 with an emphasis on impurities. 3. Required information includes crops to be treated, rate of application, number and timing of applications, preharvest intervals, and relevant restrictions. 4. Required for residential outdoor uses on food crops if the corresponding agricultural use is not approved or the residential use is expected to produce higher residues based on the label directions. 5. Required unless it is an arthropod pheromone applied at a rate less than or equal to 150 grams active ingredient per acre. 6. Required for indoor uses where the pesticide is applied directly to food, in order to determine metabolites and/or degradates. Not required when only indirect contact with food would occur (e.g., crack and crevice treatments). 7. Required when a pesticide is to be applied directly to livestock, to livestock premises, to livestock drinking water, or to crops used for livestock feed. If results from the plant metabolism study show differing metabolites in plants form those found in animals, an additional livestock metabolism study involving dosing with the plant metabolite(s) may also be required. 8. Livestock feeding studies are required whenever a pesticide residue is present in livestock feed or when direct application to livestock uses occurs. 9. Required if indoor use could result in pesticide residues in or on food or feed. 10. Data are required to determine whether FDA/USDA multiresidue methodology would detect and identify the pesticides and any metabolites. 11. Data are required whenever a pesticide may be applied directly to water, unless it can be demonstrated that the treated water would not be available for human or livestock consumption. 12. Data on fish are required for all pesticides applied directly to water inhabited, or which will be inhabited, by fish that may be caught or harvested for human consumption. 13. Data are required when a pesticide is to be applied directly to water that could be used for irrigation or to irrigation facilities such as irrigation ditches. 14. Data are required whenever a pesticide may be used in food/feed handling establishments. 15. Data on the nature and level of residue in processed food/feed are required when detectible residues could potentially concentrate on processing thus requiring the establishment of a separate tolerance higher than that of the raw agricultural commodity. 16 Anticipated residue data are required when the assumption of tolerance level residues would result in predicted exposure at an unsafe level of exposure. Data, using single serving samples of a raw agricultural commodity, on the level or residue in food as consumed would be used to obtain a more precise estimate of potential dietary exposure. These data may also include washing, cooking, processing or degradation studies as well as market basket surveys for a more precise residue determination. 17. The proposed tolerance must reflect the maximum residue likely to occur in crops, in meat, milk, poultry, or eggs. 18. Required when a residue analytical method is required. § 158.2083 Experimental use permit biochemical pesticides human health assessment data requirements table. (a) General. (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. (2) Nonfood use patterns include products classified under the general use patterns of terrestrial nonfood crop use; aquatic nonfood residential use; aquatic nonfood outdoor use; aquatic nonfood industrial use; greenhouse nonfood crop use; forestry use; residential outdoor use; residential indoor use; indoor food use; indoor nonfood use; indoor medical use. (c) Key. (d) Table. 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 Acute Testing 870.1100 Acute oral toxicity - rat R R TGAI and MP TGAI and EP 1 870.1200 Acute dermal toxicity R R TGAI and MP TGAI and EP 1, 2 870.1300 Acute inhalation toxicity - rat R R TGAI and MP TGAI and EP 3 870.2400 Primary eye irritation - rabbit R R TGAI and MP TGAI and EP 2 870.2500 Primary dermal irritation R R TGAI and MP TGAI and EP 1, 2 none Hypersensitivity incidents R R All All 4 Subchronic Testing 870.3100 90-day oral (one species) R NR TGAI TGAI — Developmental Toxicity 870.3700 Prenatal developmental - rat preferably R CR TGAI TGAI 5 Mutagenicity Testing 870.5100 Bacterial reverse mutation test R CR TGAI TGAI 6 870.5300 In vivo R CR TGAI TGAI 6, 7 Tier II Developmental Toxicity 870.3700 Prenatal developmental CR CR TGAI TGAI 5 (e) Test notes. 1. Required unless the test material is a gas or highly volatile (vapor pressure >10 −4 2. Required unless the test material is corrosive to skin or has pH <2 or >11.5. 3. Required when the pesticide, under conditions of use, would result in respirable material (e.g., gas, volatile substance or aerosol/particulate), unless it is a straight chain lepidopteran pheromone. 4. Hypersensitivity incidents must be reported as adverse effects data. 5. Required if the use of the product under widespread and commonly recognized practice may reasonably be expected to result in significant exposure to female humans (e.g., occupational exposure or repeated application of insect repellents directly to the skin). Tier II data is required on a different test species from Tier I data when developmental effects are observed in the first study and information on species-to-species extrapolation is needed. 6. Required to support nonfood uses if either: i. The use is likely to result in significant human exposure; or ii. The active ingredient (or its metabolites) is structurally related to a known mutagen or belongs to any chemical class of compounds containing a known mutagen. Additional mutagenicity tests that may have been performed plus a complete reference list must also be submitted. Subsequent testing may be required based on the available evidence. 7. Choice of assay using either: i. Mouse lymphoma L5178Y cells, thymidine kinase (tk) gene locus, maximizing assay conditions for small colony expression or detection; ii. Chinese hamster ovary (CHO) or Chinese hamster lung fibroblast (V79) cells, hypoxanthine-guanine phosphoribosyl transferase (hgprt) gene locus, accompanied by an appropriate in vivo 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. (a) General. (2) The data in this section are not required for arthropod pheromones when applied at up to a maximum use rate of 150 grams active ingredient/acre/year except when the product is expected to be available to avian species ( i.e. (b) Use patterns. (c) Key. (d) Table. 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. 1. Required for the EP when any end-use formulation may contain other ingredients that may be toxic to nontarget organisms or to support arthropod pheromones that would be available to avian wildlife, (e.g., a granular product). 2. Not required for any use groups if the pesticide is highly volatile (estimated volatility >5 × 10 −5 3 3. Preferred test species are: upland game, waterfowl, or passerine for avian acute oral toxicity studies; upland game or waterfowl for avian dietary studies; and coldwater fish for acute freshwater fish studies. 4. Required for the EP when the end-use formulation may contain other ingredients that may be toxic to nontarget organisms. Subpart V—Microbial Pesticides Source: 72 FR 61002, Oct. 26, 2007, unless otherwise noted. § 158.2100 Microbial pesticides definition and applicability. (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 (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. (2) Each new isolate of a microbial pesticide is a new active ingredient and must be registered independently of any similarly designated and already registered microbial pesticide active ingredient. Each new isolate for which registration is sought must have a unique identifier following the taxonomic name of the microorganism, and the registration application must be supported by data required in this subpart. This does not preclude the possibility of using data from another isolate, provided sufficient similarity is established, to support registration. (3) Genetically modified microbial pesticides may be subject to additional data or information requirements on a case-by-case basis depending on the particular microbial agent and/or its parental strains, the proposed pesticide use pattern, and the manner and extent to which the organism has been genetically modified. (4) Pest control organisms such as insect predators, nematodes, and macroscopic parasites are exempt from the requirements of FIFRA as authorized by section 25(b) of FIFRA and specified in § 152.20 (a) of this chapter. [72 FR 61002, Oct. 26, 2007, as amended at 77 FR 52612, Aug. 30, 2012] § 158.2110 Microbial pesticides data requirements. (a) For all microbial pesticides. (2) Each data table includes “use patterns” under which the individual data are required, with variations including all use patterns, food and nonfood uses for terrestrial and aquatic applications, greenhouse, indoor, forestry, and residential outdoor applications under certain circumstances. (3) The categories for each data requirement are “R,” which stands for required, and “CR” which stands for conditionally required. If a bracket appears around the “R” or “CR,” the data are required for both the registration and experimental use permit requests. Generally, “R” indicates that the data are more likely required than for those data requirements with “CR.” However, in each case, the regulatory text preceding the data table and the test notes following the data table must be used to determine whether the data requirement must be satisfied. (4) Each table identifies the test substance that is required to be tested to satisfy the data requirement. Test substances may include: technical grade active ingredient (TGAI), manufacturing-use product (MP), end-use product (EP), typical end-use product (TEP), residue of concern, and pure active ingredient (PAI) or all of the above (All). Commas between the test substances ( i.e. i.e. (b) Additional data requirements for genetically modified microbial pesticides. § 158.2120 Microbial pesticides product analysis data requirements table. (a) General. (b) Key. (c) Table. Table—Microbial Pesticides Product Analysis Data Requirements Test guideline No. Data requirement All use 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 885.1250 Deposition of a sample in a nationally recognized culture collection R TGAI TGAI 1 885.1300 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 2 885.1500 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 3 830.6320 Corrosion characteristics R MP EP 4 830.7000 pH R TGAI TGAI 830.7100 Viscosity R MP EP 5 830.7300 Density/relative density/bulk density (specific gravity) R TGAI TGAI (d) Test notes. 1. Required for each isolate of a microbial pesticide. Isolates must be deposited with an agreement to ensure that the sample will be maintained and will not be discarded for the duration of the associated registration(s). 2. Required to support registration of each manufacturing-use product and end-use product. This analysis must be conducted at the point in the production process after which there would be no potential for microbial contamination or microbial regrowth. For full registration, generally an analysis of samples is a compilation of batches, over a period of time, depending on the frequency of manufacturing. 3. Only required for emulsifiable liquid forms of microbial pesticides. 4. Required when microbial pesticides are packaged in metal, plastic, or paper containers. 5. Only required for liquid forms of microbial pesticides. [72 FR 61002, Oct. 26, 2007, as amended at 77 FR 52612, Aug. 30, 2012] § 158.2130 Microbial pesticides residue data requirements table. (a) General. (b) Key. (c) Table. 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. 1. Required when the results of testing: i. Indicate the potential to cause adverse human health effects or the product characterization indicates the microbial pesticide has a significant potential to produce a mammalian toxin; and ii. The use pattern is such that residues may be present in or on food or feed crops. § 158.2140 Microbial pesticides toxicology data requirements table. (a) General. (b) Key. (c) Table. 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) 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. 1. The acute oral toxicity/pathogenicity study is required to support the TGAI. However, it can be combined with the unit dose portion of the acute oral toxicity study, with an EP or MP test material to fulfill the requirement for the TGAI and the MP or EP in a single study, if the new protocol is designed to address the endpoints of concern. 2. Data not required for products whose active ingredient is a virus. For test materials whose size or consistency may prevent use of an intravenous injection, the intraperitoneal injection procedure may be employed. 3. Hypersensitivity incidents, including immediate type and delayed-type reactions of humans or domestic animals, occur during the testing or production of the TGAI, MP, or EP, or are otherwise known to the applicant must be reported if they occur. 4. Data must be submitted only for products whose active ingredient is a virus. 5. The 870 series studies for the MP and EP are intended to provide data on the acute toxicity of the product. Waivers for any or all of these studies may be granted when the applicant can demonstrate that the combination of inert ingredients is not likely to pose any significant human health risks. Where appropriate, the limit dose approach to testing is recommended. 6. Required when the product consists of, or under conditions of use would result in, an inhalable material (e.g., gas, volatile substances, or aerosol particulate). 7. Data required when significant toxicity, in the absence of pathogenicity and significant infectivity, is observed in acute oral, injection, or pulmonary studies (Tier I). Route(s) of exposure correspond to route(s) where toxicity was observed in Tier I studies. The toxic component of the TGAI is to be tested. 8. Data required when significant infectivity and/or unusual persistence is observed in the absence of pathogenicity or toxicity in Tier I studies. Routes of exposure (oral and/or pulmonary) correspond to routes in Tier I studies where adverse effects were noted. Data may also be required to evaluate adverse effects due to microbial contaminants or to toxic byproducts. 9. Data are required when one or more of the following criteria are met: i. Significant infectivity of the microbial pest control agent (MPCA) was observed in test animals in the Tier II subchronic study and in which no significant signs of toxicity or pathogenicity were observed. ii. The microbial pesticide is a virus which can persist or replicate in mammalian cell culture lines. iii. The microbial pesticide is not amenable to thorough taxonomic classification, and is related to organisms known to be parasitic for mammalian cells. iv. The microbial pesticide preparation is not well purified, and may contain contaminants which are parasitic for mammals. 10. Data may be required for products known to contain or suspected to contain carcinogenic viruses or for microbial components that are identified as having significant toxicity in Tier II testing. 11. Data may be required for products known to contain or suspected to contain viruses that can interact in an adverse manner with components of the mammalian immune system. 12. An analysis of human infectivity/pathogenicity potential using scientific literature, genomic analysis, and/or actual specific cell culture/animal data may be required for products known to contain or suspected of containing intracellular parasites of mammalian cells for products that exhibit pathogenic characteristics in Tier I and/or Tier II, for products which are closely related to known human pathogens based on the product analysis data, or for known human pathogens that have been “disarmed” or rendered non-pathogenic for humans. 13. Test standards may have to be modified depending on the characteristics of the microorganism. Requirements may vary for these studies depending on the active ingredient being tested. Consultation with the Agency is advised before performing these Tier III studies. § 158.2150 Microbial pesticides nontarget organisms and environmental fate data requirements table. (a) General. (b) Use patterns. (c) Key. (d) Table. 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 CR CR CR CR CR NR NR CR TGAI 1, 6 885.4300 Nontarget plant 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, 13 885.4650 Aquatic invertebrate range testing CR CR CR CR CR NR NR CR TGAI 12, 14 885.4700 Fish life cycle studies CR CR CR CR CR NR NR CR TGAI 12, 14 885.4750 Aquatic ecosystem test CR CR CR CR CR NR NR CR TGAI 15 Tier IV 850.2500 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. 1. Tests for pesticides intended solely for indoor application would be required on a case-by-case basis, depending on use pattern, production volume, and other pertinent factors. 2. The preferred species for the avian oral study is either the upland game or waterfowl. The preferred species for the avian inhalation toxicity/pathogenicity study and the avian chronic toxicity/pathogenicity study is the upland game. There is also the option to test the passerine if there is a concern. The coldwater fish is preferred for freshwater fish testing. However, two species (coldwater and warmwater fish species are the preferred species) must be tested for uses involving direct freshwater exposure. Freshwater invertebrate testing is also required. 3. Data required when the nature of the microbial pesticide and/or its toxins indicates potential pathogenicity to birds. 4. Required on a case-by-case basis if results of tests required by § 158.2140 are inadequate or inappropriate for assessment of hazards to wild mammals. 5. Required when there will be significant exposure to aquatic organisms (fish and invertebrates). 6. Required if the product is intended for direct application into the estuarine or marine environment or expected to enter this environment in significant concentrations because of expected use or mobility pattern. 7. Required if the microbial pesticide is taxonomically related to a known plant pathogen. 8. Data are not required unless an active microbial ingredient controls the target insect pest by a mechanism of infectivity; i.e. 9. Required if toxic or pathogenic effects are observed in one or more of the following tests for microbial pesticides: i. Avian acute oral or avian inhalation studies. ii. Wild mammal studies. iii. Nontarget plant studies (terrestrial). iv. Honey bee studies. v. Nontarget insect studies. 10. Required when toxic or pathogenic effects are observed in any of the following Tier I tests for microbial pest control agents: i. Freshwater fish studies. ii. Freshwater invertebrate studies. iii. Nontarget plant studies (aquatic). 11. Required if product is applied on land or in fresh water or marine/estuarine environments and toxic or pathogenic effects are observed in any of the following Tier I tests for microbial pesticides: i. Estuarine and marine animal toxicity and pathogenicity. ii. Plant studies - estuarine or marine species. 12. An appropriate dose-response toxicity test is required when toxic effects on nontarget terrestrial wildlife or aquatic organisms (including plants) are reported in one or more Tier I tests and results of Tier II tests indicate exposure of the microbial agent to the affected nontarget terrestrial wildlife or aquatic organisms. The protocols for these tests may have to be modified in accordance with results from the nontarget organism and environmental expression studies. 13. Required when one or more of the following are present: i. Pathogenic effects are observed in Tier I avian studies. ii. Tier II environmental expression testing indicate that long-term exposure of terrestrial animals is likely. 14. Required when product is intended for use in water or expected to be transported to water from the intended use site, and when pathogenicity or infectivity was observed in Tier I aquatic studies. 15. Required if, after an analysis of the microbial pesticide's ability to survive and multiply in the environment and what ecological habitat it would occupy, the intended use patterns, and the results of previous nontarget organisms and environmental expression tests, it is determined that use of the microbial agent may result in adverse effects on the nontarget organisms in aquatic environments. Testing is to determine if applications of the microbial pest control would be expected to disrupt the balance of populations in the target ecosystem. 16. Tier IV studies may be conducted as a condition of registration as post-registration monitoring if the potential for unreasonable adverse effects appears to be minimal during that period of use due to implementation of mitigation measures. 17. Required when both of the following conditions occur: i. Pathogenic effects observed at actual or expected field residue exposure levels are reported in Tier III; and ii. The Agency determines that quarantine methods would not prevent the microbial pesticide from contaminating areas adjacent to the test area. 18. Short term simulated or actual field studies are required when it is determined that the product is likely to cause adverse short-term or acute effects, based on consideration of available laboratory data, use patterns, and exposure rates. 19. Data from a long-term simulated field test (e.g., where reproduction and growth of confined populations are observed) and/or an actual field test (e.g., where reproduction and growth of natural populations are observed) are required if laboratory data indicate that adverse long-term, cumulative, or life-cycle effects may result from intended use. 20. Since test standards would be developed on a case-by-case basis, consultation with the Agency and development of a protocol is advised before performing these Tier IV studies. § 158.2160 Microbial pesticides product performance data requirements. (a) General. (b) Product performance data for each product that bears a claim against an invertebrate pest that is covered by subpart R of this part. (c) Product performance data for each product that bears a public health pest claim, excluding those covered under paragraph (b). [87 FR 22484, Apr. 15, 2022] § 158.2170 Experimental use permit data requirements—microbial pesticides. (a) For all microbial pesticides. (2) For general information on the data requirement tables, see § 158.2110(a)(2)-(4). (b) Additional data requirements for genetically modified microbial pesticides. § 158.2171 Experimental use permit microbial pesticides product analysis data requirements table. (a) General. (b) Key. (c) Table. Table—EUP Microbial Pesticides Product Analysis Data Requirements Test guideline No. 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, 2 885.1250 Deposition of a sample in a nationally recognized culture collection R TGAI TGAI 3 885.1300 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, 4 885.1500 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 5 830.6320 Corrosion characteristics R MP EP 6 830.7000 pH R TGAI TGAI 830.7100 Viscosity R MP EP 7 830.7300 Density/relative density/bulk density (specific gravity) R TGAI TGAI (d) Test notes. 1. If an experimental use permit is being sought, and if the pesticide is not already under full-scale production, a schematic diagram and/or description of the manufacturing process suffices. 2. If an experimental use permit is being sought, and if the product is not already under full-scale production, a discussion of unintentional ingredients is required to be submitted to the extent this information is available. 3. Required for each isolate of a microbial pesticide. Isolates must be deposited with an agreement to ensure that the sample will be maintained and will not be discarded for the duration of the associated experimental use permit(s). 4. Required to support registration of each manufacturing-use product and end-use product. This analysis must be conducted at the point in the production process after which there would be no potential for microbial contamination or microbial regrowth. For pesticides in the production stage, a preliminary product analytical method and data would suffice to support an experimental use permit. For full registration, generally an analysis of samples is a compilation of batches, over a period of time, depending on the frequency of manufacturing. 5. Only required for emulsifiable liquid forms of microbial pesticides. 6. Required when microbial pesticides are packaged in metal, plastic, or paper containers. 7. Only required for liquid forms of microbial pesticides. [72 FR 61002, Oct. 26, 2007, as amended at 77 FR 52613, Aug. 30, 2012] § 158.2172 Experimental use permit microbial pesticides residue data requirements table. (a) General. (b) Key. (c) Table. Table—EUP 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. 1. Required when the results of testing: i. Indicate the potential to cause adverse human health effects or the product characterization indicates the microbial pesticide has a significant potential to produce a mammalian toxin; and ii. The use pattern is such that residues may be present in or on food or feed crops. § 158.2173 Experimental use permit microbial pesticides toxicology data requirements table. (a) General. (b) Key. (c) Table. 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) 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. 1. The acute oral toxicity/pathogenicity study is required to support the TGAI. However, it can be combined with the unit dose portion of the acute oral toxicity study, with an EP or MP test material to fulfill the requirement for the TGAI and the MP or EP in a single study, if the new protocol is designed to address the endpoints of concern. 2. Data not required for products whose active ingredient is a virus. For test materials whose size or consistency may prevent use of an intravenous injection, the intraperitoneal injection procedure may be employed. 3. Hypersensitivity incidents, including immediate type and delayed type reactions of humans or domestic animals occur during the testing or production of the TGAI, MP, or EP, or are otherwise known to the applicant must be reported if they occur. 4. Data must be submitted only for products whose active ingredient is a virus. 5. The 870 series studies for the MP and EP are intended to provide data on the acute toxicity of the product. Waivers for any or all of these studies may be granted when the applicant can demonstrate that the combination of inert ingredients is not likely to pose any significant human health risks. Where appropriate, the limit dose approach to testing is recommended. 6. Required when the product consists of, or under conditions of use that would result in an inhalable material (e.g., gas, volatile substances, or aerosol particulate). § 158.2174 Experimental use permit microbial pesticides nontarget organisms and environmental fate data requirements table. (a) General. (b) Use patterns. (c) Key. (d) Table. 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 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 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. 1. Tests for pesticides intended solely for indoor application would be required on a case-by-case basis, depending on use pattern, production volume, and other pertinent factors. Tests to support EUP's are based on the application timing and acreage. 2. The preferred species for the avian oral study is either the upland game or waterfowl. The preferred species for the avian inhalation toxicity/pathogenicity study and the avian chronic toxicity/pathogenicity study is the upland game. There is also the option to test a passerine species if there is a concern. The coldwater fish is preferred for freshwater fish testing. However, two species (coldwater and warmwater fish are the preferred species) must be tested for uses involving direct freshwater exposure. Freshwater invertebrates are preferred for invertebrate testing. 3. Required when there will be significant exposure to aquatic organisms (fish and invertebrates). 4. Required if the microbial pesticide is taxonomically related to a known plant pathogen. 5. Data are not required unless an active microbial ingredient controls the target insect pest by a mechanism of infectivity; i.e. Subpart W—Antimicrobial Pesticide Data Requirements Source: 78 FR 26978, May 8, 2013, unless otherwise noted. § 158.2200 Applicability. Part 158, subpart W establishes data requirements for any pesticide product that is: (a) A pesticide that is intended for use as an “antimicrobial pesticide” within the meaning of FIFRA sec. 2(mm)(1)(A), regardless of whether it also meets the criterion of FIFRA sec. 2(mm)(1)(B). That criterion excludes from the definition any antimicrobial product that is intended for a food-use requiring a tolerance or exemption under FFDCA sec. 408 or a food additive regulation or clearance under FFDCA sec. 409. EPA will apply this subpart to all products intended for an antimicrobial use, purpose or function; the exclusion in FIFRA sec. 2(mm)(1)(B) does not exclude products from the data requirements of this subpart. (b) A product that bears both antimicrobial and non-antimicrobial uses or claims is subject to the data requirements for pesticides in subparts C through O, R, and U or V of this part with respect to its non-antimicrobial uses and claims, and to the requirements of this subpart with respect to its antimicrobial uses and claims. (c) A wood preservative, including a product that is intended to prevent wood degradation problems due to fungal rot or decay, sapstain, or molds. (d) An antifoulant, including a product that is intended to kill or repel organisms that can attach to underwater surfaces, such as boat bottoms. [78 FR 26978, May 8, 2013, as amended at 87 FR 22484, Apr. 15, 2022] § 158.2201 Antimicrobial use patterns. (a) Antimicrobial use patterns. (1) Agricultural premises and equipment. (2) Food-handling/storage establishments, premises and equipment. (3) Commercial, institutional and industrial premises and equipment. (4) Residential and public access premises. (5) Medical premises and equipment. (6) Human drinking water systems. (7) Materials preservatives. (8) Industrial processes and water systems. (9) Antifoulant paints and coatings. (10) Wood preservatives. (11) Swimming pools. (12) Aquatic areas. (b) Use site index. http://www.epa.gov/pesticides. § 158.2203 Definitions. The following terms are defined for the purposes of this subpart: Disinfectant Fungicide Microbiological water purifier Sanitizer Sterilant Tuberculocide Virucide § 158.2204 Public health and nonpublic health claims. (a) Public health claim. (1) A claim is made for control of specific microorganisms that are directly or indirectly infectious or pathogenic to man (or both man and animals). Examples of specific microorganisms include, but are not limited to: Mycobacterium tuberculosis, Pseudomonas aeruginosa, Escherichia coli (E. coli), human immunodeficiency virus (HIV), Streptococcus, and Staphylococcus aureus. (2) A claim is made for the pesticide product as a sterilant, disinfectant, virucide, sanitizer, or tuberculocide against microorganisms that are infectious or pathogenic to man. (3) A claim is made for the pesticide product as a fungicide against fungi infectious or pathogenic to man, or the product does not clearly state that it is intended for use only against nonpublic health fungi. (4) A claim is made for the pesticide product as a microbiological water purifier or microbial purification system. (5) A non-specific claim is made that the pesticide product will beneficially impact or affect public health at the site of use or in the environment in which it is applied, and: (i) The pesticide product contains one or more ingredients that, under the criteria in 40 CFR 153.125(a), is an active ingredient with respect to a public health microorganism and there is no other functional purpose for the ingredient in the product; or (ii) The pesticide product is similar in composition to a registered pesticide product that makes antimicrobial public health claims. (b) Nonpublic health claim. § 158.2210 Product chemistry. The product chemistry data requirements of subpart D of this part apply to antimicrobial products covered by this subpart. § 158.2220 Product performance. (a) General Product performance requirement for all antimicrobial pesticides. (2) Product performance data for each product that bears a public health claim. (3) Product performance data for each product that bears a nonpublic health claim. (4) Determination of data requirements. (b) Key. (c) Antimicrobial product performance data requirements table. Table—Antimicrobial Product Performance Data Requirements Guideline No. Data requirement All use patterns Test substance 810.2100 Sterilants—Efficacy Data Recommendations R EP 810.2200 Disinfectants for Use on Hard Surfaces—Efficacy Data Recommendations R EP 810.2300 Sanitizers for Use on Hard Surfaces—Efficacy Data Recommendations R EP 810.2400 Disinfectants and Sanitizers for Use on Fabrics and Textiles—Efficacy Data Recommendations R EP 810.2500 Air Sanitizers—Efficacy Data Recommendations R EP 810.2600 Disinfectants for Use in Water—Efficacy Data Recommendations R EP § 158.2230 Toxicology. (a) General. (b) Uses. (c) Tiering of data requirements. (d) 200 parts per billion (ppb). (e) Use of OSHA standards. (f) Key. (g) Antimicrobial toxicology data requirements table. Table—Antimicrobial Toxicology Data Requirements Guideline Data Food uses Nonfood uses Test substance Test note No. Direct food uses Indirect food uses (>200 ppb) Indirect food uses (≤200 ppb) Swimming pools, All other nonfood uses MP EP Acute Testing 870.1100 Acute oral toxicity—rat R R R R R MP and TGAI EP and TGAI 1, 2 870.1200 Acute dermal toxicity R R R R R MP and TGAI EP and TGAI 1, 2, 3 870.1300 Acute inhalation toxicity—rat R R R R R MP and TGAI EP and TGAI 2, 4 870.2400 Primary eye irritation—rabbit R R R R R MP and TGAI EP and TGAI 1, 2, 3 870.2500 Primary dermal irritation R R R R R MP and TGAI EP and TGAI 1, 2, 3 870.2600 Dermal sensitization R R R R R MP and TGAI EP and TGAI 1, 2, 3, 5 870.2600 Acute neurotoxicity—rat R R CR R CR TGAI TGAI 6, 11 Subchronic Testing 870.3100 90-Day oral toxicity—rodent R R R R CR TGAI TGAI 8, 9, 15, 38 870.3150 90-Day oral toxicity—nonrodent R R CR R CR TGAI TGAI 10, 15 870.3200 21/28-Day dermal toxicity CR CR CR CR CR TGAI EP and TGAI 12, 13 870.3250 90-Day dermal toxicity CR CR CR CR CR TGAI EP and TGAI 7, 13, 14, 15 870.3465 90-Day inhalation toxicity—rat CR CR CR CR CR TGAI TGAI 7, 15, 16, 17 870.6200 90-Day neurotoxicity—rat R R CR R CR TGAI TGAI 6, 8 Chronic Testing 870.4100 Chronic oral toxicity—rodent R R CR R CR TGAI TGAI 18, 19, 20 870.4200 Carcinogenicity—two rodent species—rat and mouse preferred R R CR R CR TGAI TGAI 19, 21, 22 Developmental Toxicity and Reproduction 870.3700 Prenatal developmental toxicity—rat and rabbit preferred R R R R R TGAI TGAI 23, 24, 25, 26 870.3800 Reproduction and fertility effects R R R R R TGAI TGAI 26, 27, 28, 29 870.6300 Developmental neurotoxicity CR CR CR CR CR TGAI TGAI 28, 29, 30 Mutagenicity 870.5100 Reverse mutation assay R R R R R TGAI TGAI 31, 32 870.5300 In vitro R R R R R TGAI TGAI 31, 33 870.5385 In vivo R R R R R TGAI TGAI 31, 34 Special Testing 870.7485 Metabolism and pharmacokinetics R R CR R CR PAI or PAIRA PAI or PAIRA 35, 39 870.7200 Companion animal safety CR CR CR CR CR NR Choice 36 870.7600 Dermal penetration CR CR CR CR CR Choice Choice 3, 37 870.7800 Immunotoxicity R R R R R TGAI TGAI 8 (h) Test notes. 1. Not required if test material is a gas or highly volatile liquid. 2. The six end-use product (EP) acute toxicity studies are required using the product as formulated for sale and distribution. In addition, if the EP label has directions for diluting the product, then, the applicant may also need to conduct certain of the acute toxicity studies using the highest concentration labeled for dilution ( i.e. 3. Not required if test material is corrosive to skin or has pH less than 2 or greater than 11.5. 4. Data are required when the product consists of, or under conditions of use will result in, a respirable material (e.g., gas, vapor, aerosol or particulates). 5. Data are required if repeated dermal exposure is likely to occur under conditions of use. 6. For indirect food uses ≤200 ppb, and all other nonfood uses, data are required if the neurotoxicity screen in the 90-day oral rodent study or other data indicate neurotoxicity. 7. The 90-day dermal toxicity study and/or 90-day inhalation toxicity study are required if the Agency determines that dermal and/or inhalation exposure is the primary route of exposure. 8. All 90-day subchronic studies in the rodent can be designed to simultaneously fulfill the requirements of the 90-day neurotoxicity and/or immunotoxicity studies by adding separate groups of animals for testing of neurotoxicity and/or immunotoxicity parameters. 9. The 90-day study is required in the rodent for hazard characterization (possibly endpoint selection) and dose-setting for the chronic/carcinogenicity study. It is not required in the mouse, but the Agency would encourage the applicant to conduct a 90-day range finding study for the purposes of dose selection for the mouse carcinogenicity study to achieve adequate dosing and an acceptable study. 10. A 1-year non-rodent study ( i.e. 11. Although the subchronic toxicity testing guidelines include measurement of neurological endpoints, such screens do not meet the requirement of the 90-day neurotoxicity study. For nonfood uses, if the 90-day study does not include a neurotoxicity screen, then the acute neurotoxicity study will be required. 12. Data are required if all of the following criteria are met: i. The intended use of the antimicrobial pesticide product is expected to result in repeated dermal human exposure to the product. ii. Data from a 90-day dermal toxicity study are not available. iii. The 90-day dermal toxicity study has not been triggered. 13. EP testing is required if the product or any component of the product may increase dermal absorption of the active ingredient(s) or increases its toxic or pharmacologic effects, as determined by testing using the TGAI or based on available information about the toxic effects of the product or its components. 14. Data are required if the active ingredient in the product is known or expected to be metabolized differently by the dermal route of exposure than by the oral route, and a metabolite of the active ingredient is the toxic moiety. 15. A 90-day oral toxicity test is not required for heating, ventilation, air conditioning, and refrigeration systems (collectively referred to as HVAC&R). Instead, two 90-day toxicity tests, one by the dermal route and one by the inhalation route are required. 16. Data are required if there is the likelihood of significant repeated inhalation exposure to the pesticide as a gas, vapor, or aerosol. 17. 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. The prime consideration in determining the appropriateness of a shorter duration study is the likely period of time for which humans will be exposed. 18. Based on the positive results of the acute or 90-day neurotoxicity studies, or on other data indicating neurotoxicity, a chronic neurotoxicity study ( i.e. 19. Studies which are designed to simultaneously fulfill the requirements of both the chronic oral and carcinogenicity studies ( i.e. 20. For indirect food uses ≤200 ppb, and all other nonfood uses, data are required if either of the following criteria are met: i. The use of the pesticide is likely to result in repeated human exposure over a considerable portion of the human lifespan; or ii. The use requires that a tolerance, tolerance exemption, or food additive regulation or clearance be established. 21. For indirect food uses ≤200 ppb, and all other nonfood uses, data are required if any of the following criteria, are met: i. The use of the pesticide is likely to result in significant human exposure over a considerable portion of the human life span which is significant in terms of frequency, time, duration, and/or magnitude of exposure. ii. The use requires that a tolerance, tolerance exemption, or food additive regulation or clearance be established. iii. The active ingredient, metabolite, degradate, or impurity: A. Is structurally related to a recognized carcinogen; B. Causes mutagenic effects as demonstrated by in vitro in vivo C. Produces a morphologic effect in any organ (e.g., hyperplasia, metaplasia) in subchronic studies that may lead to a neoplastic change. 22. If the requirement for a carcinogenicity study in any species is modified or waived for any reason, then a subchronic 90-day oral study in the same species may be required. 23. Testing in two species is required for all uses. 24. The oral route, by oral intubation, is preferred, unless the chemical or physical properties of the test substance, or the pattern of human exposure, suggest a more appropriate route of exposure. 25. Additional testing by other routes of exposure may be required if the pesticide is determined to be a prenatal developmental toxicant after oral dosing. 26. The developmental toxicity study in rodents may be combined with the two-generation reproduction study in rodents by using a second mating of the parental animals in either generation. Protocols must be approved by the Agency prior to the initiation of the study. 27. A two-generation reproduction study is required. 28. An information-based approach to testing is preferred, which utilizes the best available knowledge on the chemical (hazard, pharmacokinetic, or mechanistic data) to determine whether a standard guideline study, an enhanced guideline study, or an alternative study should be conducted to assess potential hazard to the developing animal. Applicants must submit any alternative proposed testing protocols and supporting scientific rationale to the Agency. Protocols must be approved by the Agency prior to the initiation of the study. 29. The use of a combined two-generation reproduction/developmental neurotoxicity study that utilizes the two-generation reproduction study in rodents as a basic protocol for the addition of other endpoints or functional assessments in the immature animal is encouraged. 30. A DNT study is required using a weight-of-evidence approach when: i. The pesticide causes treatment-related neurological effects in adult animal studies ( i.e. ii. The pesticide causes treatment-related neurological effects in developing animals, following pre- or post-natal exposure ( i.e. 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 ( i.e. 31. To facilitate the weight-of-evidence determination for the pesticide's mutagenicity, in addition to those specifically listed in this table, the Agency requires submission of other mutagenicity test results that may have been performed. A reference list of all studies and papers known to the applicant concerning the mutagenicity of the test chemical must be submitted with the required studies. 32. Due to the nature of antimicrobials, if testing with bacterial strains has not been conducted, then testing using a mammalian cell assay such as the mouse lymphoma TK ±assay is preferred. If reverse mutation assay testing with bacterial strains has already been conducted, and the testing was conducted at levels that did not cause toxicity to the bacterial strains tested, then the applicant may submit the study to fulfill this data requirement. 33. For the in vitro in vitro 34. There is a choice of assays, but the micronucleus rodent bone marrow assay is preferred; the rodent bone marrow assays using metaphase analysis (aberrations) are acceptable. 35. Data are required when chronic toxicity or carcinogenicity studies are also required. 36. Data is required if the product label directs that it be applied to domestic animals, such as cats, dogs, cattle, pigs, and horses. 37. In the absence of dermal absorption data or a repeated dose dermal toxicity study, the assumption of 100 percent dermal absorption would be used in a risk assessment to determine if a dermal penetration study is required, and to identify the doses and duration of exposure for which dermal absorption is to be quantified. 38. Required for nonfood uses, if oral exposure could occur. 39. Data may be required if significant adverse effects are seen in available toxicology studies and these effects can be further elucidated by metabolism and pharmacokinetics studies. [78 FR 26978, May 8, 2013, as amended at 84 FR 18996, May 3, 2019] § 158.2240 Nontarget organisms. (a) General. (1) Terrestrial and aquatic nontarget organism data are required to support the registration of most end-use and manufacturing-use antimicrobial products. (2) Data are generally not required to support end-use products of a gas, highly volatile liquid, highly reactive solid, or a highly corrosive material. (3) Data on transformation/degradation products or leachate residues of the parent compound are also required to support registration, if the transformation/degradation/degradation products or leachate residues meet one of the following criteria: (i) More toxic, persistent, or bioaccumulative than the parent; (ii) Have been shown to cause adverse effects in mammalian or aquatic reproductive studies; or (iii) The moiety of concern ( i.e. (4) If an antimicrobial may be applied to a field crop, horticultural crop, or turf, then the data requirements in § 158.630 apply. (5) For the purpose of determining data requirements, the all other use patterns category includes the following use patterns: (i) Agricultural premises and equipment. (ii) Food-handling/storage establishments, premises, and equipment. (iii) Commercial, institutional and industrial premises and equipment. (iv) Residential and public access premises. (v) Medical premises and equipment. (vi) Human drinking water systems. (vii) Materials preservatives. (viii) Swimming pools. (b) Key. (c) Antimicrobial nontarget organism data requirements table. Table—Antimicrobial Nontarget Organism Data Requirements Guideline No. Data Use pattern Test substance Test note No. Industrial Antifoulant coatings and paints Wood Aquatic areas All other use patterns MP EP Tier One Testing 850.2100 Acute avian oral toxicity R R R R R TGAI TGAI 1 850.1010 Acute freshwater invertebrates toxicity R R R R R TGAI TGAI 2 850.1075 Acute freshwater fish toxicity R R R R R TGAI TGAI 3 Higher Tier Testing Avian Testing 850.2200 Avian dietary toxicity CR CR CR CR CR TGAI TGAI 4 850.2300 Avian reproduction CR CR CR CR CR TGAI TGAI 1, 6 Aquatic Organisms Testing 850.1010 Acute freshwater invertebrates toxicity CR CR CR CR CR TEP 2, 5, 7 850.1075 Acute freshwater fish toxicity CR CR CR CR CR TEP 3, 5, 7 850.1025 Acute estuarine and marine organisms toxicity CR R CR CR CR TGAI TGAI 8, 9 850.1035 850.1045 850.1055 Acute estuarine and marine organisms toxicity CR CR CR CR CR TEP 5, 7, 8 850.1075 850.1400 Fish early-life stage R R R R R TGAI TGAI 10 850.1300 Aquatic invertebrate life-cycle R R R R R TGAI TGAI 10 850.1350 850.1500 Fish life-cycle CR CR CR CR CR TGAI TGAI 11, 12 850.1710 Aquatic organisms, bioavailability, biomagnification, toxicity tests CR CR CR CR CR TGAI, PAI, degradate TGAI, PAI, degradate 13 850.1730 850.1850 850.1950 Simulated or actual field testing for aquatic organisms CR CR CR CR CR TEP TEP 14, 15, 16 Sediment Testing 850.1735 Whole sediment; acute freshwater invertebrates CR CR CR CR CR TGAI TGAI 15, 17 850.1740 Whole sediment; acute marine invertebrates CR CR CR CR CR TGAI TGAI 15, 17, 19 None Whole sediment; chronic invertebrates fresh-water and marine CR CR CR CR CR TGAI TGAI 15, 18, 19 Insect Pollinator Testing 850.3020 Honeybee acute contact NR NR R NR CR TGAI TGAI 20 850.3030 Toxicity of residues to honeybees NR NR R NR CR TGAI TEP or treated wood 20, 21 (d) Test notes. 1. For industrial processes and water systems, antifoulant paints and coatings, wood preservatives, and aquatic areas, data are required for two avian species: one waterfowl species and one upland game bird species. For the all other use patterns category (as specified in § 158.2240(a)(5)), data are required for one avian species. 2. Data are required on one freshwater aquatic invertebrate species. 3. For the industrial processes and water systems, antifoulant paints and coatings, wood preservatives, and aquatic use pattern areas, data are required on two species of fish, one cold water species and one warm water species. For the all other use patterns category (as specified in § 158.2240(a)(5)), data are required on one species of fish, either one cold water species or one warm water species. Testing on a second species is required if the active ingredient or principal transformation products are stable in the environment and the LC 50 4. Data are required on one avian species, either one waterfowl species or one upland game bird species, if the avian acute oral LD 50 50 5. If TEP testing cannot be conducted due to the physical characteristics of the test substance (for example, a paint), then the applicant should request a waiver. 6. Data are required if one or more of the following criteria are met: i. Birds may be subjected to repeated or continued exposure to the pesticide or any of its transformation products, especially preceding or during the breeding season. ii. The pesticide or any of its major metabolites or degradation products are stable in the environment to the extent that a potentially toxic amount may persist in avian feed. iii. The pesticide or any of its major metabolites or degradation products are stored or accumulated in plant or animal tissues, as indicated by the octanol/water partition coefficient (K ow iv. Any other information, such as that derived from mammalian reproduction studies, indicates that reproduction in terrestrial vertebrates may be adversely affected by the anticipated use of the pesticide product. 7. TEP testing is required for any product which meets one or more of the following conditions: i. When based on deterministic modeling results: If the Estimated Environmental Concentration (EEC) in the aquatic environment is equal to or greater than one-half the LC 50 50 ii. When based on probabilistic modeling results: If the estimated 10th percentile 7Q10 Surface Water Concentration exceeds the acute concentration of concern ( i.e. 50 50 iii. If an ingredient in the end-use product other than the active ingredient is expected to enhance the toxicity of the active ingredient or to cause toxicity to aquatic organisms. iv. The end-use antimicrobial product will be applied directly into an aquatic environment. 8. Data are required on one estuarine/marine mollusk, one other estuarine/marine invertebrate, and one estuarine/marine fish species. 9. For the all other use patterns category (as specified in § 158.2240(a)(5)), industrial processes and water systems, wood preservatives, and aquatic areas, data are required if the pesticide residues from the parent compound and/or transformation products are likely to enter the estuarine/marine environment. 10. Testing must be conducted with the most sensitive organism (either freshwater or estuarine/marine vertebrates, or freshwater or estuarine/marine invertebrates), as determined from the results of the acute toxicity tests (acute EC 50 50 50 50 11. 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. 12. 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 one or more of the following conditions apply: i. When based on deterministic modeling results: If the Estimated Environmental Concentration (EEC) in water is equal to or greater than 0.1 of the no-observed-adverse-effect concentration or no-observed-adverse-effect level (NOAEC/NOAEL) in the fish early-life stage or invertebrate life cycle tests. ii. When based on probabilistic modeling results: If the estimated 10th percentile 7Q10 Surface Water Concentration based on probabilistic modeling exceeds for 20 days or more the chronic concentration of concern ( i.e. iii. If studies of other organisms indicate that the reproductive physiology of fish may be affected. 13. Not required when: i. The octanol/water partition coefficients of the pesticide and its major degradates are less than 1,000; ii. There are no potential exposures to fish and other nontarget aquatic organisms; or iii. The hydrolytic half-life is less than 5 days at pH 5, 7, and 9. 14. Environmental chemistry methods used to generate data associated with this study must include results of a successful confirmatory method trial by an independent laboratory. Test standards and procedures for independent laboratory validation are available as addenda to the guideline for this test requirement. 15. Protocols must be approved by the Agency prior to the initiation of the study. 16. Data are required if the intended use pattern, and the physical/chemical properties and environmental fate characteristics of the antimicrobial indicate significant potential exposure, and, based on the results of the acute and chronic aquatic organism testing, significant impairment of nontarget aquatic organisms could result. 17. Data are required if the half-life of the pesticide in the sediment is equal to or less than 10 days in either the aerobic soil or aquatic metabolism studies, and if one or more of the following conditions are met: i. The soil partition coefficient (K d ii. The log K ow iii. The K oc 18. Data are required if the EEC in sediment is greater than 0.1 of the acute LC 50/ 50 i. The soil partition coefficient (K d ii. The log K ow iii. The K oc 19. Sediment testing with estuarine/marine test species is required if the product is intended for direct application to the estuarine or marine environment or the product is expected to enter this environment in significant concentrations either by runoff or erosion, because of its expected use or mobility pattern. 20. For the all other use patterns category (as specified in § 158.2240(a)(5)), data are required only for beehive applications when the beehive (empty or occupied) may be treated. 21. A study similar to “Honey Bee Toxicity of Residues on Foliage” is required using treated wood instead of the foliage. Protocols must be approved by the Agency prior to the initiation of the study. § 158.2250 Nontarget plant protection. (a) Subpart B of this part and § 158.2201 describe how to use the table in paragraph (f) of this section to determine the nontarget plant protection data requirements for a particular antimicrobial pesticide product. Notes that apply to an individual test including specific conditions, qualifications, or exceptions are listed in paragraph (g) of this section. (b) Data on transformation/degradation products or leachate residues of the parent compound are also required to support registration, if the transformation/degradation products or leachate residues meet one of the following criteria: (1) More toxic, persistent, or bioaccumulative than the parent; (2) Have been shown to cause adverse effects in mammalian or aquatic reproductive studies; or (3) The moiety of concern ( i.e. (c) For the purpose of determining data requirements, the all other use patterns category includes the following use patterns: (1) Agricultural premises and equipment. (2) Food-handling/storage establishments, premises, and equipment. (3) Commercial, institutional and industrial premises and equipment. (4) Residential and public access premises. (5) Medical premises and equipment. (6) Human drinking water systems. (7) Materials preservatives. (8) Swimming pools. (d) If an antimicrobial may be applied to a field crop, horticultural crop, or turf, then the data requirements in § 158.660 apply. (e) Key. (f) Nontarget plant protection data requirements table. Table—Nontarget Plant Protection Data Requirements Guideline No. Data Use pattern Test substance Test note No. Industrial processes and water systems Antifoulant coatings and paints Wood preservatives Aquatic areas All other use patterns MP EP 850.4225 Seedling emergence, Tier II—dose response CR CR CR CR CR TEP TEP 1, 2 850.4250 Vegetative vigor, Tier II—dose response CR NR CR CR CR TEP TEP 1, 3 850.4400 Aquatic plant growth (aquatic vascular plant) Tier II—dose response R R R R CR TGAI, TEP TGAI, TEP 4, 10 850.5400 Aquatic plant growth (algal) Tier II (dose response) R R R R R TGAI, TEP TGAI, TEP 4, 5, 6 850.4300 Terrestrial field CR CR CR CR CR TEP TEP 7, 8, 9 850.4450 Aquatic field CR CR CR CR CR TEP TEP 7, 8, 9 (g) Test notes. 1. Data on only one plant species (rice, Oryza sativa 2. Data are required if the risk quotient from any aquatic plant growth Tier II study exceeds a level of concern for aquatic plants. 3. Not required when: i. There are no potential exposures to plants; ii. The hydrolytic half-life is less than 5 days at pH 5, 7, and 9; or iii. The results of a biodegradation study indicate that the active ingredient or principal degradation products are not biodegradable in 28 days, i.e. 4. For TEP testing, data are required for the applicant's end-use product if an ingredient in the end-use product, other than the active ingredient, is expected to enhance the toxicity of the active ingredient. 5. One Tier II (dose response) study, conducted with Selenastrum capricornutum, 50 Anabaena flos-aquae, Navicula pelliculosa, and Skeletonema costatum). 6. For industrial processes and water systems, antifoulant coatings and paints, wood preservatives, and aquatic areas, Tier II (dose response) studies are required on four species ( Anabaena flos-aquae, Navicula pelliculosa, Skeletonema costatum, Selenastrum capricornutum 7. Environmental chemistry methods used to generate data must include the results of a successful confirmatory method trial by an independent laboratory. 8. Tests are required on a case-by-case basis based on the results of lower tier plant protection studies, adverse incident reports, intended use pattern, and environmental fate characteristics that indicate potential exposure. 9. Protocols must be approved by the Agency prior to the initiation of the study. 10. For the all other use patterns category (as specified in § 158.2250(c)), data are required if the aquatic (algal) plant growth Tier II study demonstrates detrimental effects at less than 1.0 ppm or mg/L. § 158.2260 Applicator exposure. (a) General. (1) The Agency may accept surrogate exposure data estimations and/or modeling estimations from other sources to satisfy exposure data requirements. The surrogate data must meet the basic quality assurance, quality control, good laboratory practice, and other scientific requirements set by EPA. To be acceptable, the Agency must find that the surrogate exposure data estimations have adequate information to address the applicable exposure data requirements and contain adequate monitoring events of acceptable quality. The data must reflect the specific use prescribed on the label and the activity of concern, including formulation type, application methods and rates, type of activity, and other pertinent information. (2) Occupational uses include not only handlers, mixers, loaders, and applicators, but also commercial applications to residential sites. Residential uses are limited to non-occupational, i.e. (b) Criteria for testing. (1) Toxicity criteria. (ii) Scientifically sound epidemiological or poisoning incident data with a clear cause-effect relationship indicating that adverse health effects may have resulted from exposure to the pesticide. (2) Exposure criteria. (ii) Respiratory exposure may occur during product use. (c) Key. (d) Antimicrobial applicator exposure data requirements table. Table—Antimicrobial Applicator Exposure Data Requirements Guideline No. Data requirements Use sites Test Test note No. Occupational Residential 875.1100 Dermal exposure R R TEP 1, 2, 3, 4 875.1200 875.1300 Inhalation exposure R R TEP 1, 2, 3, 4 875.1400 875.1500 Biological monitoring CR CR TEP 1, 2, 3 875.1600 Data reporting and calculations R R TEP 5 875.1700 Product use information R R TEP (e) Test notes. 1. Prior to initiation of the study, protocols involving intentional exposure of human subjects must be submitted for review by EPA and then the Human Studies Review Board (HSRB) according to 40 CFR 26.1125. Examples of proposed human study research can be found in various reviews provided by the Human Studies Review Board ( http://www.epa.gov/osa/hsrb/index.htm 2. Biological monitoring data may be submitted in addition to, or in lieu of, dermal and inhalation passive dosimetry exposure data, provided the human pharmacokinetics of the pesticide or metabolite/analog compounds ( i.e., 3. For products with both indoor and outdoor uses, and similar conditions of use, data are generally required for the indoor applications only. However, data for outdoor uses are required if the Agency expects outdoor uses to result in greater exposure than indoor uses (e.g., higher use rates and application frequency, or longer exposure duration, or application methods/equipment create potential for increased dermal or inhalation exposure in outdoor versus indoor use sites). In certain cases, when a pesticide may be used both indoors and outdoors under dissimilar conditions of use, the Agency may require submission of applicator exposure data for both use patterns. 4. EPA will consider waiving this data requirement for antimicrobials applied via closed loading systems if the antimicrobial has a low vapor pressure. 5. Data reporting and calculations are required only if handler exposure data are required. § 158.2270 Post-application exposure. (a) General. (1) Post-application exposure data are required when certain toxicity criteria are met and the human activities associated with the pesticide's use pattern can lead to potential adverse exposures. (2) The Agency may accept surrogate exposure data estimations and/or modeling estimations from other sources to satisfy exposure data requirements. The surrogate data must meet the basic quality assurance, quality control, good laboratory practice, and other scientific requirements set by EPA. To be acceptable, the Agency must find that the surrogate exposure data estimations have adequate information to address the applicable exposure data requirements and contain adequate monitoring events of acceptable quality. The data must reflect the specific use prescribed on the label and the activity of concern, including formulation type, application methods and rates, type of activity, and other pertinent information. (b) Criteria for testing. (1) Toxicity criteria. (ii) Scientifically sound epidemiological or poisoning incident data with a clear cause-effect relationship indicating that adverse health effects may have resulted from exposure to the pesticide. (2) Exposure criteria Outdoor uses. (B) Residential human post-application or bystander exposure to residues of antimicrobial pesticides could occur following the application of antimicrobial pesticides to outdoor areas and spaces at residential sites, such as, but not limited to homes, daycare centers, and other public buildings. (ii) Indoor uses. (B) Residential human post-application or bystander exposure to pesticide residues could occur following the application of the antimicrobial pesticide to indoor spaces or surfaces at residential sites, such as, but not limited to homes, daycare centers, hospitals, schools, and other public buildings. (c) Key. (d) Antimicrobial post-application exposure data requirements table. Table—Antimicrobial Post-Application Exposure Data Requirements Guideline No. Data requirement Use sites Test Test note No. Occupational Residential 875.2200 Soil residue dissipation CR CR TEP 2, 3 875.2300 Indoor surface residue dissipation CR R TEP 3, 4, 5, 6 875.2400 Dermal exposure CR CR TEP 1, 7, 8 875.2500 Inhalation exposure CR CR TEP 1,7, 8, 9 875.2600 Biological monitoring CR CR TEP 1, 8 875.2700 Product use information R R TEP 875.2800 Description of human activity R R TEP 875.2900 Data reporting and calculations R R TEP 10 (e) Test notes. 1. Prior to initiation of the study, protocols involving intentional exposure of human subjects must be submitted for review by EPA and then the Human Studies Review Board (HSRB) according to 40 CFR 26.1125. Examples of proposed human study research can be found in various reviews provided by the Human Studies Review Board (HSRB) ( http://www.epa.gov/osa/hsrb/index.htm). 2. For residential wood preservative uses, data may be required if soil has the potential to be an important exposure pathway, and soil is in contact with or adjacent to treated wood, including but not limited to decks, play sets, and gazebos, 3. Protocols must be approved by the Agency prior to the initiation of the study. 4. For wood preservatives, data are required for treated wood surfaces where post-application contact with treated wood is anticipated. 5. For occupational uses, data are required if the pesticide may be applied to or around surfaces, and if the human activity data indicate that workers are likely to have post-application dermal contact with treated surfaces while participating in typical activities. 6. Data are required for residential use sites, schools, and daycare institutions. This includes but is not limited to the following: Residential and public access premises; material preservatives (including those used in residential products, including but not limited to clothing and plastic toys) and wood preservatives (when contact with treated wood is likely to occur). 7. Data are required for occupational and residential uses if the human activity data indicate the potential for post-application dermal and/or inhalation exposures while participating in typical activities and no acceptable modeling options are available. 8. Biological monitoring data may be submitted in addition to, or in lieu of, dermal and inhalation passive dosimetry exposure data provided the human pharmacokinetics of the pesticide or metabolite/analog compounds ( i.e., 9. Data are required for occupational and residential uses if there is the potential for bystander exposure and the pesticide use could result in respirable and/or inhalable material (e.g., gas, vapor, aerosol, or particulates). 10. Data reporting and calculations are required only if post-application exposure data are required. § 158.2280 Environmental fate. (a) General. (1) Environmental fate data are required to support the registrations of all end-use and manufacturing-use antimicrobial products. (2) Data on transformation/degradation products or leachate residues of the parent compound are also required to support registration, if the transformation/degradation products or leachate residues meet one of the following criteria: (i) More toxic, persistent, or bioaccumulative than the parent; (ii) Have been shown to cause adverse effects in mammalian or aquatic reproductive studies; or (iii) The moiety of concern ( i.e. (3) For the purpose of determining data requirements, the all other use patterns category includes the following use patterns: (i) Agricultural premises and equipment. (ii) Food-handling/storage establishments, premises, and equipment. (iii) Commercial, institutional and industrial premises and equipment. (iv) Residential and public access premises. (v) Medical premises and equipment. (vi) Human drinking water systems. (vii) Materials preservatives. (viii) Swimming pools. (b) Key. (c) Antimicrobial environmental fate data requirements table. Table—Antimicrobial Environmental Fate Data Requirements Guideline No. Data Use pattern Test substance Test note No. Industrial Antifoulant coatings and paints Wood Aquatic areas All other use patterns MP EP Degradation Studies—Laboratory 835.2120 Hydrolysis R R R R R TGAI or PAIRA TGAI or PAIRA 1 835.2240 Photodegradation in water R R R R R TGAI or PAIRA TGAI or PAIRA 2 835.2410 Photodegradation in soil NR NR R NR NR TGAI or PAIRA TGAI or PAIRA 10 Toxicity and Fate in Wastewater Systems 850.6800 Activated Sludge, Respiration Inhibition Test R R R NR R TGAI TGAI 21 OECD 209 835.1110 Activated Sludge Sorption Isotherm CR CR CR NR CR TGAI TGAI 19, 20 835.3110 Ready Biodegradability CR CR CR NR CR TGAI TGAI 3, 4, 18 835.3220 Porous Pot Study CR CR CR NR CR TGAI TGAI 3, 18 835.3280 Simulation Tests to Assess the Biodegradability of Chemicals Discharged in Wastewater CR CR CR NR CR TGAI TGAI 3, 18 835.3240 Simulation Test—Aerobic Sewage Treatment: A. Activated Sludge Units CR CR CR NR CR TGAI TGAI 3, 18 Mobility Studies 835.1230 Leaching and adsorption/de-sorption R R R R CR TGAI or PAIRA TGAI or PAIRA 5, 6 835.1240 Metabolism Studies—Laboratory 835.4100 Aerobic soil metabolism CR NR R CR CR TGAI or PAIRA TGAI or PAIRA 7, 8, 9 835.4200 Anaerobic soil metabolism NR NR R NR CR TGAI or PAIRA TGAI or PAIRA 5, 8 835.4300 Aerobic aquatic metabolism R R R R CR TGAI or PAIRA TGAI or PAIRA 5, 8 835.4400 Anaerobic aquatic metabolism R R R R CR TGAI or PAIRA TGAI or PAIRA 5, 8 Dissipation Studies—Field 835.6200 Aquatic (sediment) CR R CR R CR TEP TEP 11, 12, 13 Ground and Surface Water Monitoring None Monitoring of representative U.S. waters CR CR CR CR CR ROC ROC 11, 14, 17 Special Studies None Special leaching NR R R NR NR TGAI TEP 15, 16 (d) Test notes. 1. For testing antifoulant paints and coatings, testing is to be performed separately with both sterile buffered distilled water and sterile synthetic seawater at pHs 5, 7, and 9. 2. Not required if: i. 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, inclusive; or ii. The results of the hydrolysis study at all three pHs (5, 7, and 9) demonstrates a half-life of less than 30 days. 3. The results of the activated sludge, respiration inhibition (ASRI) test determine which of the following tests are required: Ready biodegradability, porous pot, the biodegradation in activated sludge study as described in the “Simulation Tests to Assess the Biodegradability of Chemicals Discharged in Wastewater,” or simulation test—aerobic sewage treatment: A. activated sludge units. i. If the ASRI test EC 50 A. Conduct the biodegradation in activated sludge study as described in the “Simulation Tests to Assess the Biodegradability of Chemicals Discharged in Wastewater”; B. Conduct the porous pot test; or C. Conduct the simulation test—aerobic sewage treatment: A. activated sludge units. ii. If the ASRI test EC 50 A. Conduct a ready biodegradability study; or B. Conduct one of the following studies: The biodegradation in activated sludge study as described in the “Simulation Tests to Assess the Biodegradability of Chemicals Discharged in Wastewater,” the porous pot test, or the simulation test—aerobic sewage treatment: A. activated sludge units. 4. Pass criteria for the ready biodegradability study are: 70 percent removal of dissolved organic carbon (DOC) and 60 percent removal of theoretical oxygen demand (ThOD) or theoretical carbon dioxide (ThCO 2 5. For the all other use patterns category (as specified in § 158.2280(a)(3)), data are required based on a weight-of-evidence evaluation of the results of the hydrolysis, photodegradation in water, activated sludge sorption isotherm, biodegradability, and activated sludge, respiration inhibition tests. 6. Adsorption and desorption using a batch equilibrium method is preferred. In some cases, as when the antimicrobial pesticide degrades rapidly, soil column leaching with unaged or aged columns may be more appropriate to fully characterize the potential mobility of the parent compound and major transformation products. 7. For industrial processes and water systems, aquatic areas, and the all other use patterns category (as specified in § 158.2280(a)(3)), data are required based on a weight-of-evidence evaluation of the results of the hydrolysis, photodegradation in water, activated sludge sorption isotherm, biodegradability, and activated sludge, respiration inhibition tests. 8. The environmental media (soil, water, hydrosoil, and biota) to be utilized in these studies must be collected from areas representative of potential use sites. 9. For industrial processes and water systems, and aquatic areas, data are required for use sites that are intermittently dry. 10. Data are not required if the antimicrobial is an inorganic substance or a metal salt; or if the standardized soil profiles demonstrate that the antimicrobial is likely to readily degrade either microbially or via redox reactions (chemically) and no transformation/degradate/leachate products of concern (as described under § 158.2280(a)(2)) are produced. 11. Analytical methods used to generate data associated with this study must include results of a successful confirmatory method trial by an independent laboratory. 12. Protocols must be approved by the Agency prior to the initiation of the study. 13. For industrial processes and water systems, wood preservatives, and the all other use patterns category (as specified in § 158.2280(a)(3)), data are required based on the potential for aquatic exposure and if the weight-of-evidence indicates that the active ingredient or principal transformation products are likely to have the potential for persistence, mobility, nontarget aquatic toxicity, or bioaccumulation. 14. Data are required if the weight-of-evidence indicates that the active ingredient or principal transformation products are likely to occur in nontarget freshwater, estuarine, or marine waters such that human or environmental exposures are likely to occur. In making that determination, the Agency takes into account other factors such as the toxicity of the chemical(s), available monitoring data and the vulnerability of the freshwater, estuarine, or marine water resources in the antimicrobial use area. 15. For wood preservatives, an aquatic leaching study is required. A soil leaching study is required if human or environmental exposures are likely to occur from leachates that contain the active ingredient or principal transformation products from wood treated with a preservative product. Protocols must be approved by the Agency prior to the initiation of the study. 16. For antifoulant paints and coatings, a leaching study is required. Protocols must be approved by the Agency prior to the initiation of the study. 17. Protocols, which include the residues of concern (such as parent, degradate/transformation product, and/or leachate residues) that would be monitored, must be approved by the Agency prior to the initiation of the study. 18. A biodegradation study is not required if the antimicrobial meets one or more of the following criteria: i. Classified as a metal, ii. Relatively volatile, but not hydrophobic, iii. Highly reactive, iv. Both the parent and all transformation/degradate products (as described under § 158.2280(a)(2)) have half-lives of less than 3 hours, v. None of the registered or proposed product uses would result in transport of the parent and its transformation/degradate products (as described under § 158.2280(a)(2)) to a wastewater treatment plant. 19. The activated sludge sorption isotherm test is not required if the antimicrobial is: i. Relatively volatile, but not hydrophobic; ii. Highly reactive; or iii. The log K ow 20. If the criteria of test note 19 of this paragraph are not met, then the activated sludge sorption isotherm test is required if one or more of the following criteria are also met: i. The antimicrobial is a metal, ii. The log K ow iii. The antimicrobial is positively charged or polycationic, iv. The EC 50 v. The EC 50 21. The activated sludge respiration inhibition study is not required if none of the registered or proposed product uses would result in transport of the parent and its transformation/degradate products (as described under § 158.2280(a)(2)) to a wastewater treatment plant. § 158.2290 Residue chemistry. (a) General. (b) Residue chemistry data are required for: (1) Antimicrobial end-use products with uses that may result in residues in or on food, including but not limited to: (i) Products that require a tolerance, tolerance exemption, or food additive regulation or clearance. (ii) Products that may be used to treat livestock or poultry drinking water, for food egg washing, or for fruit and vegetable rinses. (iii) Products that may be applied to a surface or incorporated into a material that may contact food or feed. Data are required regardless of whether the antimicrobial is applied or impregnated for the purpose of imparting antimicrobial protection to external surfaces of the substance or article, or for the purpose of protecting the substance or article itself. (iv) Products that may be applied to water that have the potential to result in residues in potable water, or in water used for livestock and poultry drinking water, irrigation of crops, or water containing fish that may be used for human food. (v) Wood preservative or antifoulant products intended for treating submerged materials that may result in food contact (e.g., lobster pots, fish cages on fish farms). (2) Each manufacturing-use product bearing directions for formulation into an end-use product bearing uses described in paragraph (b)(1) of this section. (c) Residue chemistry data are not required under paragraph (b) of this section if no adverse effects (no toxicity endpoints) are associated with dietary exposure to the active ingredient or if theoretical (high-end) dietary exposure estimates combined with the applicable toxicity endpoint result in acute and chronic dietary risks that are below the Agency levels of concern. (d) For purposes of this section, Magnitude of the Residue Studies include the following: Food-handling, migration studies, potable water, fish, irrigated crops, meat/milk/poultry/eggs, crop field trails, processed food or feed, and anticipated residues. (e) If the antimicrobial chemical may be applied to a field crop, then the residue chemistry data requirements of § 158.1410 apply. (f) The following term is defined for the purposes of this section: Residue of concern (g) Key. (h) Antimicrobial residue chemistry data requirements table. Table—Antimicrobial Residue Chemistry Data Requirements Guideline No. Data requirement Uses Test Test note No. Agricultural Indirect food Direct food Aquatic Supporting Information 860.1100 Chemical identity R R R R TGAI 860.1200 Directions for use R R R R 860.1550 Proposed tolerance/tolerance exemption R R R R 1 860.1560 Reasonable grounds in support of petition R R R R 1 860.1650 Submittal of analytical reference standards R R R R PAI/ROC 2 Food-Contact Surfaces or Impregnated Materials 860.1460 Food-handling CR CR CR CR TEP 3 None Nature of residue on surfaces CR CR CR CR PAIRA or TGAI 4 None Migration studies CR CR CR CR TEP 5 860.1340 Residue analytical method for data collection CR CR CR CR ROC 6 860.1380 Storage stability R R R R TEP or ROC 7 Higher tiered 860.1300 Nature of the residue in plants CR CR CR CR PAIRA 8 860.1300 Nature of the residue in livestock CR CR CR CR PAIRA 9 860.1340 Residue analytical methods for tolerance/tolerance exemption enforcement CR CR CR CR ROC 10 860.1360 Multiresidue method testing CR CR CR CR ROC 11 860.1400 Potable water CR CR CR CR TEP 12 860.1400 Fish CR CR CR CR TEP 13 860.1400 Irrigated crops CR CR CR CR TEP 14 860.1480 Meat/milk/poultry/eggs CR CR CR CR TGAI or ROC 15 860.1500 Crop field trials CR CR CR CR TEP 16 860.1520 Processed food or feed CR CR CR CR TEP 17 None Anticipated residues CR CR CR CR ROC 18 (i) Test notes. 1. A petition proposing a numerical tolerance or a tolerance exemption is required for any food or feed use subject to section 408 of FFDCA if the use is not covered by an existing tolerance or tolerance exemption. If the use is subject to FFDCA section 409, the applicant must identify to EPA an applicable section 409 food additive regulation or clearance, or submit a copy of a petition to FDA requesting a section 409 food additive regulation or clearance for the food or feed use. 2. An analytical reference standard is required for any food or feed use requiring a numeric tolerance or exemption. Material safety data sheets as specified by the Occupational Safety and Health Administration in 29 CFR 1910.1200 must accompany analytical standards. 3. Data are required if a pesticide may be used in a food-handling establishment unless data including, but not limited to, theoretical (high-end) estimates, radiolabeled laboratory data, or the nature of the residue on surfaces study show that residues will not occur in food or feed. 4. If an antimicrobial pesticide may be applied to a food-contact surface or impregnated into a food-contact material and if theoretical (high-end) estimates of exposure exceed EPA's risk level of concern, then the nature of the residue on surfaces study is required. Protocols must be approved by the Agency prior to the initiation of the study. 5. Based on the results of the nature of the residue on surfaces study, if residues of concern are identified, then the migration study will be required. Protocols must be approved by the Agency prior to the initiation of the study. 6. If a magnitude of the residue study, as specified in § 158.2290(d), is required, then a residue analytical method suitable for collecting data is also required. The method must be capable of determining all residues of concern, to permit calculation of dietary risk or to establish a tolerance or tolerance exemption. 7. If a magnitude of the residue study, as specified in § 158.2290(d), is required, then storage stability data are also required, unless analytical samples are stored for 30 days or less. If, during hazard characterization, a residue has been identified as “of concern” and is known to be volatile or labile, then storage stability data are required regardless of sample storage time. 8. If crop plants or metabolically active raw agricultural commodities of food crops may be directly or indirectly exposed to an antimicrobial, plant metabolism studies are required to determine the transformation products that may enter the human diet. Such exposure could include, but is not limited to: i. Treatment of storage or shipping containers, ii. Postharvest fruit and vegetable treatment prior to shipping or storage, iii. Use of antimicrobial-treated water for irrigation, and iv. Any direct food contact use. 9. If livestock may be exposed to an antimicrobial, then hen and ruminant metabolism studies are required to determine the identities of residues of concern that may enter the human diet from consumption of livestock commodities. Livestock may be exposed via the oral, dermal, or inhalation route following treatment or contamination of sites including, but not limited to, livestock premises, feed, and drinking water. Shell eggs and other metabolically active livestock products may also be treated. If livestock may be exposed to one or more residues of concern differing from those found in animals, then one or more additional livestock metabolism studies involving dosing with these residues may be required. 10. If there is a numerical tolerance or tolerance exemption level to enforce, then a residue analytical method suitable for enforcement purposes is required. The method must be supported by an independent laboratory validation. 11. If there is a numerical tolerance or tolerance exemption level to enforce, then testing is required to determine whether the Food and Drug Administration/United States Department of Agriculture multiresidue methodology would detect and identify the antimicrobial and its residues of concern, as part of programs to monitor pesticides in the U.S. food supply. 12. Data are required if an antimicrobial may be applied directly to water or if there is the potential that the antimicrobial-treated water could be used directly for drinking water purposes by humans or animals or that contaminated water could run-off, leach, or be discharged from treated sites or materials and make its way into potable water. 13. Data are required if an antimicrobial may be applied directly to water inhabited by fish or that will be inhabited by fish or if contaminated water could run-off, leach, or be discharged from treated sites or materials and make its way into bodies of water containing fish that may be used for human consumption. 14. Data are required if an antimicrobial may be applied directly to water used for irrigation of food crops or such that contaminated water could run-off, leach, or be discharged from treated sites or materials to make its way into water used for irrigation of food crops. 15. If the antimicrobial may be applied directly to livestock, metabolically-active livestock commodities (e.g., eggs), livestock feed or drinking water, or livestock premises, or a livestock metabolism study indicates that residues of the antimicrobial may result in livestock commodities, studies are required to determine the magnitude of the residues of concern in fat, meat, meat by-products, milk, poultry, and eggs that may be consumed by humans. These studies, however, may not be required in cases where the livestock metabolism studies indicate that transfer of pesticide residues of concern to tissues, milk, and eggs is not expected to occur at the maximum expected exposure level for the animals. 16. If food crops or raw agricultural commodities of food crops may be exposed to an antimicrobial, then residue studies are required to determine the magnitude of the residues of concern that may enter the human diet. Such exposures include, but are not limited to, postharvest fruit and vegetable treatments and application of antimicrobial chemicals to field crops, mushroom houses, empty or occupied beehives, or wood used to construct beehives. 17. Data on the nature and magnitude of residues in processed food or feed are required if antimicrobial residues could potentially concentrate on processing. If so, the establishment of a separate tolerance higher than that in the raw agricultural commodity may be required. 18. Data are required when dietary exposure values at the tolerance level or screening-level (high-end) result in estimates of dietary or aggregate risk that meet or exceed the Agency's level of concern. These data may include, but are not limited to, washing, cooking, processing, or degradation studies as well as market basket surveys for a more realistic residue determination. Protocols must be approved by the Agency prior to the initiation of the study. Subparts X-Z [Reserved] §§ 158.2300-158.2500 [Reserved]

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