Microbial pesticides-Product analysis data requirements.

§ 158.740 Microbial pesticides—Product analysis data requirements.

(a) Microbial pesticides product analysis data requirements—(1) Table. Sections 158.50 and 158.100 through 158.102 describe how to use this table to determine the microbial pesticides—product analysis data requirements and the substance to be tested.

Kind of data required (2) Notes General use patterns Terrestrial Food crop Nonfood Aquatic Food crop Nonfood Greenhouse Food crop Nonfood Forestry Domestic outdoor Indoor Test substance Data to support MP Data to support EP Guidelines reference No. Product identity manufacturing process [R] [R] [R] [R] [R] [R] [R] [R] [R] MP EP* 151-20 (i) [R] [R] [R] [R] [R] [R] [R] [R] [R] MP and TGAI EP* and TGAI 151-21 Discussion of formation of unintentional ingredients (ii) [R] [R] [R] [R] [R] [R] [R] [R] [R] MP and TGAI EP* and TGAI 151-22 Analysis of samples (iii) [CR] [CR] [CR] [CR] [CR] [CR] [CR] [CR] [CR] MP and TGAI EP* and TGAI 151-23 Certification of limits [R] R [R] R [R] R R R R MP EP* 151-25 Analytical methods R R R R R R R R R MP EP* 151-25 Physical and chemical properties [R] [R] [R] [R] [R] [R] [R] [R] [R] MP and TGAI EP* and TGAI 151-26 Submittal of samples (iv) [CR] [CR] [CR] [CR] [CR] [CR] [CR] [CR] [CR] MP and TGAI, PAI EP* TGAI and PAI 151-27 Key: R=Required; CR=Conditionally required; MP=Manufacturing-use product: EP*=End-use product (asterisk identifies those data requirements that end-use applicants (i.e., “formulators”) must satisfy, provided that their active ingredient(s) is (are) purchased from a registered source); TGAI=Technical grade of the active ingredient;[]=Brackets (i.e., [R], [CR]) indicate data requirements that apply when an experimental use permit is being sought. (2) Notes. The following notes are referenced in column two of the table contained in paragraph (a)(1) of this section. (i) If an experimental use permit is being sought, a schematic diagram and/or description of the manufacturing process will suffice if the pesticide is not already under scale production. (ii) If the product is not already under full scale production and an experimental use permit is being sought, a discussion of unintentional ingredients shall be submitted to the extent this information is available. (iii) Required to support registration of each manufacturing-use product and end use products produced by an integrated formulation system. Data on other end use products will be required on a case-by-case basis. For pesticide in the production stage, a rudimentary product analytical method and data will suffice to support an experimental use permit. AAA(iv) Routinely required for products produced by an integrated formulation system. Required on a case-by-case basis for other products or materials.

(b) Microbial pesticides-residue data requirements—(1) Table. Sections 158.50 and 158.100 through 158.102 describe how to use this table to determine the microbial pesticides-residue data requirements and the substances to be tested.

(c) Microbial pesticides-toxicology data requirements—(1) Table. Sections 158.50 and 158.100 through 158.102 describe how to use this table to determine the microbial pesticides-toxicology data requirements and the substances to be tested.

Kind of data required (2) Notes General use patterns Terrestrial Food crop Nonfood Aquatic Food crop Nonfood Greenhouse Food crop Nonfood Forestry Domestic outdoor Indoor use Test substance Data to support MP Data to support EP Guidelines reference No. Tier I: Acute oral [R] [R] [R] [R] [R] [R] [R] [R] [R] MP and TGAI EP* or EP* dilution and TGAI 152-30 Acute dermal [R] [R] [R] [R] [R] [R] [R] [R] [R] MP and TGAI EP* or EP dilution and TGAI 152-31 Acute inhalation (i) [R] [R] [R] [R] [R] [R] [R] [R] [R] MP and TGAI EP* or EP Dilution* and TGAI 152-32 I.V., I.C., I.P. injection (ii) [R] [R] [R] [R] [R] [R] [R] [R] [R] TGAI TGAI 152-33 Primary dermal [R] [R] [R] [R] [R] [R] [R] [R] [R] MP EP* 152-34 Primary eye [R] [R] [R] [R] [R] [R] [R] [R] [R] MP EP* 152-35 Hypersensitivity study (iii) R R R R R R R R R MP EP* 152-36 Hypersensitivity incidents (iv) CR CR CR CR CR CR CR CR CR 152-37 Immune response [R] R [R] R [R] R R R R TGAI TGAI 152-38 Tissue culture (v) [R] R [R] R [R] R R R R TGAI TGAI 152-39 Tier II: Acute oral (vi) CR CR CR CR CR CR CR CR CR MP EP* 152-40 Acute inhalation (vii) CR CR CR CR CR CR CR CR CR MP EP* 152-41 Subchronic oral (viii) CR CR CR CR CR CR CR CR CR TGAI TGAI 152-42 Acute I.P., I.C. (ix) CR CR CR CR CR CR CR CR CR TGAI TGAI 152-43 Primary dermal (x) CR CR CR CR CR CR CR CR CR EP* 152-44 Primary eye (xi) CR CR CR CR CR CR CR CR CR EP* 152-45 Immune response (xii) CR CR CR CR CR CR CR CR CR TGAI TGAI 152-46 Teratogenicity (xiii) CR CR CR CR CR CR CR CR CR TGAI TGAI 152-47 Virulence enhancement (xiv) CR CR CR CR CR CR CR CR CR TGAI TGAI 152-48 Mammalian mutagenicity (xv) CR CR CR CR CR CR CR CR CR TGAI TGAI 152-49 Tier III: Chronic feeding (xvi) CR CR CR CR TGAI TGAI 152-50 Oncogenicity (xvii) CR CR CR CR TGAI TGAI 151-51 Mutagenicity (xviii) CR CR CR CR CR CR CR CR CR TGAI TGAI 152-52 Teratogenicity (xix) CR CR CR CR CR CR CR CR CR TGAI TGAI 152-53 Key: R=Required; CR=Conditionally required; MP=Manufacturing-use product; EP*=End use product (asterisk identifies those data requirements that end-use applicants (i.e., “formulators”) must satisfy, provided that their active ingredient(s) is (are) purchased from a registered source); TGAI=Technical Grade of the Active Ingredient; []=Brackets (i.e., [R], [CR]) indicate data requirements that apply when an experimental use permit is being sought. (2) Notes. The following notes are referenced in column two of the table contained in paragraph (c)(1) of this section. (i) Required if 20 percent or more of the aerodynamic equivalent of the product (as registered or under conditions of use) is composed of particulates less than 10 microns in diameter. (ii) Data required for products as follows: (A) Intravenous (“IV”) infectivity study for bacterial, and viral agents; (B) Intracerebral (“IC”) infectivity study for viral and protozoan agents; and (C) Intraperitoneal (“IP”) infectivity study for fungal and protozoan agents. (iii) Required if commonly recognized use practices will result in repeated human contact by inhalation or dermal routes. (iv) Hypersensitivity incidents must be reported, if they occur. (v) Data required for products whose active ingredient is a virus. (vi) Required if survival, replication, infectivity, toxicity, or persistence of the microbial agent (virus or protozoa) is observed in the test animals treated in the Tier I acute oral infectivity tests or the intraperitoneal or intracerebral injection test for protozoa. (vii) Required if survival, replication, infectivity, toxicity, or persistence of the microbial agent (virus or protozoa) is observed in the test animals treated in the comparable Tier I acute inhalation tests. (viii) Required if there is evidence of survival, replication, infectivity, or persistence of the protozoan agent in the Tier I oral infectivity test. (ix) Required if in Tier I acute oral infectivity testing, Tier I dermal toxicity/infectivity testing, or Tier I intraperitoneal or intracerebral injection testing, the test microorganism (bacteria, fungi, or protozoa) survived for more than 2 weeks, caused toxic effects, or caused a severe illness response in an experimental animal as evidenced by irreversible gross pathology, severe weight loss, toxemia, or death. (x) Required if infectivity or if marked edema or broad erythema was observed in the Tier I dermal irritation study. (xi) Required if infectivity or if severe ocular lesions are observed in the Tier I primary eye irritation study. (xii) Required if results of the Tier I immune response test indicate abnormalities. (xiii) Required when Tier I tests on viral agents show replication of the virus in mammalian hosts and significant damage to mammalian cells. (xiv) Required when Tier I infectivity tests on bacteria or fungi indicate prolonged survival (including presence of viable microbial agents in test animal excreta) and/or multiplication (infectivity) of the bacteria or fungal agent, respectively. (xv) Required if any of the following criteria are met: (A) Acute infectivity tests are positive in Tier I studies. (B) Adverse effects are observed in immune response studies. (C) Positive results are obtained in tissue culture tests with viral agents. (xvi) Required when the potential for chronic adverse effects (e.g., replication or persistence of viral or subviral constituents, protozoans, fungi, or bacteria) are demonstrated by any of the Tier II tests (except primary dermal, primary ocular, and mammalian mutagenicity tests). (xvii) Required when the potential for oncogenic effects is indicated (e.g., adverse cellular effects due to presence, replication, or persistence of viral or subviral constituents, or bacteria, fungi or protozoans; or mutagenic effects) by any of the Tier II tests except the primary dermal and primary ocular studies. (xviii) Required when the potential for mutagenic effects is indicated (e.g., adverse cellular effects due to presence, replication, or persistence of viral or subviral constituents, bacteria, fungi or protozoa) by any of the Tier II tests except primary dermal or primary ocular studies. (xix) Required when the potential for teratogenic effects is expected based on the presence of persistence of fungi, bacteria, viruses, or protozoa in mammalian species as a result of testing performed in Tier II, except primary dermal and primary ocular studies.

(d) Microbial pesticides non-target organism and environmental expression data requirements—(1) Table. Sections 158.50 and 158.100 through 158.102 describe how to use this table to determine the microbial pesticides non-target organism and environmental expression data requirements and substances to be tested.

Kind of data required (2) Notes General use patterns Terrestrial Food crop Nonfood Aquatic Food crop Nonfood Greenhouse Food crop Nonfood Forestry Domestic outdoor Indoor use Test substance Data to support MP Data to support EP Guidelines reference No. Tier I: Avian oral (i), (ii), (iii) [R] [R] [R] [R] CR CR [R] [R] CR TGAI TGAI 154-16 Avian injection test (i), (ii), (iii) [R] [R] [R] [R] CR CR [R] [R] CR TGAI TGAI 154-17 Wild mammal testing (iv) CR CR CR CR CR CR TGAI TGAI 154-18 Freshwater fish testing (i) [R] [R] [R] [R] CR CR [R] CR CR TGAI TGAI 154-19 Freshwater aquatic invertebrate testing (i) [R] [R] [R] [R] CR CR [R] CR CR TGAI TGAI 154-20 Estuarine and marine animal testing (v) CR CR CR CR CR CR TGAI TGAI 154-2 Nontarget plant studies [R] [R] [R] [R] [R] [R] CR TEP TEP 154-2 Nontarget insect testing [R] [R] [R] [R] CR CR [R] [R] TGAI TGAI 154-23 Honey bee testing [R] [R] [R] [R] CR CR [R] [R] TGAI TGAI 154-24 Tier II: Terrestrial environmental testing (vi) CR CR CR CR CR CR TGAI or TEP TGAI or TEP 155-18 Freshwater environmental expression tests (vii) CR CR CR CR CR CR TGAI or TEP TGAI or TEP 155-19 Marine or estuarine environmental expression tests (xiii), (ix) CR CR CR CR CR CR TGAI or TEP TGAI or TEP 155-20 Tier III: Terrestrial wildlife and aquatic organism testing (x) CR CR CR CR CR CR TGAI or TEP TGAI or TEP 154-25 Avian pathogenicity/reproduction test (xi) CR CR CR CR CR CR TGAI TGAI 154-26 Definitive aquatic animal tests (xii) CR CR CR CR CR CR TGAI TGAI 154-27 Aquatic embryo larvae and life cycle studies (xiii) CR CR CR CR CR CR TGAI TGAI 154-28 Aquatic ecosystem test (xiv) CR CR CR CR CR CR TGAI TGAI 154-29 Special aquatic tests (reserved) 154-30 Nontarget plant studies (xv) CR CR CR CR CR CR TGAI TEP 154-31 Tier IV: (xvi) Simulated and actual field tests (birds, mammals) (xiii) CR CR CR CR CR CR TEP TEP 154-33 Simulated and actual field tests (aquatic organisms) (xvii), (xviii) CR CR CR CR CR CR TEP TEP 154-34 Simulated and actual field tests (insect predators, parasites) (reserved) 154-35 Simulated and actual field tests (insect pollinators) (reserved) 154-36 AAAKey: R=Required; CR=Conditionally required; []=Brackets (i.e., [R], [CR]) indicates data requirements that apply to products for which an experimental use permit is being sought; MP=Manufacturing-use Product; TEP=Typical end-use product; TGAI=Technical grade of the active ingredient; EP=End-use product; PAI=“Pure” active ingredient. AAA(2) Notes. The following notes are referenced in column two of the table contained in paragraph (d)(1) of this section. AAA(i) Tests for pesticides intended solely for indoor application will be required on a case-by-case basis, depending on use pattern, production volume, and other pertinent factors. AAA(ii) Preferable test species are: bobwhite quail or mallard for avian acute oral and avian dietary studies; rainbow trout for freshwater fish studies. AAA(iii) Data from either the avian acute oral or the avian injection study are required to support an experimental use permit. AAA(iv) Required on a case-by-case basis if results of tests required by paragraph (c)(1) of this section are inadequate or inappropriate for assessment of hazards to wild animals. AAA(v) Required when 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. AAA(vi) Required when toxic or pathogenic effects are observed in any of the following Tier I tests for microbial pest control agents: AAA(A) Avian single dose oral toxicity and pathogenicity tests. AAA(B) Avian injection pathogenicity tests. AAA(C) Wild mammals toxicity and pathogenicity test. AAA(D) Plant studies—terrestrial. AAA(E) Honey bee toxicity/pathogenicity test. AAA(F) Testing for toxicity/pathogenicity to insect predators and parasites. AAA(vii) Required when toxic or pathogenic effects are observed in any of the following Tier I test for microbial pest control agents: AAA(A) Freshwater fish toxicity and pathogenicity testing. AAA(B) Freshwater aquatic invertebrate toxicity and pathogenicity test. AAA(C) Plant studies—aquatic. AAA(viii) Required if product is applied on land or in fresh water and toxic or pathogenic effects are observed in any of the following Tier I tests for microbial pest control agents: AAA(A) Estuarine and marine animal toxicity and pathogenicity test. AAA(B) Plant studies—estuarine or marine. AAA(ix) Required if product is applied in marine or estuarine environments and toxic or pathogenic effects are observed in any of the following Tier I tests: AAA(A) Avian single dose oral toxicity and pathogenicity test. AAA(B) Avian injection pathogenicity test. AAA(C) Estuarine and marine animal toxicity and pathogenicity test. AAA(x) Required when toxic effects on nontarget terrestrial wildlife or aquatic organisms are reported in one or more Tier I tests and results of Tier II tests indicate exposure of the mocrobial agent to the affected nontarget terrestrial wildlife or aquatic organisms. AAA(xi) Required when: AAA(A) Pathogenic effects are observed in Tier I avian tests at a level equal to the adjusted host equivalent amount. AAA(B) Chronic, carcinogenic, or teratogenic effects are reported in tests required by paragraph (c)(1) of this section for evaluating hazard to humans and domestic animals. AAA(C) Tier II Environmental expression testing indicates that exposure of terrestrial animals to the microbial agent is likely. AAA(xii) 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 tests. AAA(xiii) Required when both of the following conditions are met: AAA(A) Pathogenic effects at actual or expected field residue exposure levels are reported in Tier III. AAA(B) The agency determines that quarantine methods will prevent the microbial pest control agent from contaminating areas adjacent to the test area. AAA(xiv) Required if, after an analysis of the microbial agent's properties, the individual use patterns, and the results of previous nontarget organism 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, including those of the water column and bottom sediments. When a microbial pest control agent is used in or is expected to transport to water from the intended use site, major considerations for requiring these infectivity tests include, but are not limited to: AAA(A) Infectivity or pathogenicity demonstrated in previous testing. AAA(B) Viability of the microorganism in natural waters as demonstrated in Tier II tests. AAA(xv) Required if the product is transported from the site of application by air, soil, or water or transmission by other animals. The extent of movement will be determined by the environmental expression tests in Tier II. AAA(xvi) The Agency expects that Tier IV requirements would be imposed retrospectively—after product registration as post registration monitoring, since it is unlikely a registrant would pursue registration of a microbial agent posing potential hazards such that testing beyond Tier III is required. AAA(xvii) 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. AAA(xviii) 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 adverse long-term, cumulative, or life-cycle effects may result from intended use. [49 FR 42881, Oct. 24, 1984. Redesignated at 53 FR 15993, May 4, 1988, and amended at 58 FR 34203, June 23, 1993]