EPA Requirements and Guidelines
under 40 CFR 158, Subpart V
TABLE B-1 Microbial Pesticides Product Analysis Data Requirements Test Substance
Guideline Number | Data Requirement | All Use Patterns | Test Substance | Test Notesa | |
MP | EP | ||||
Product Chemistry and Composition | |||||
885.1100 | rtodua Identity | R | MP | HP | — |
885.1200 | Manufacturing process | R | TGAI and MP | TGAI andEP | — |
Deposition of a sample in a nationally recognized culture collection | R | TGAI | TGAI | — | |
885.1300 | Discussion of formation of uaorsanoml inEedients | R | TGAI and MP | TGAI andEP | — |
Analysis and Certified Limits | |||||
885.1400 | Analysis of samples | R | TGAI and MP | TGAI andEP | 1 |
885.1500 | Certification of limits | R | MP | EP | — |
Physical and Chemical Characteristics | |||||
830.6302 | Color | R | TGAI | TGAI | — |
830.6303 | Physical state | R | TGAI | TGAI | — |
830.6304 | Odor | R | TGAI | TGAI | — |
830.6313 | Stability to normal and elevated temperatures, metals and metal ions | R | TGAI | TGAI | — |
830.6317 | Storage stability | R | TGAI and MP | TGAI andEP | — |
830.6319 | Miscibility | R | MP | EP | 2 |
830.6320 | Corrosion Characteristics | R | MP | EP | 3 |
830.7000 | pH | R | TGAI | TGAI | — |
Guideline Number | Data Requirement | All Use Patterns | Test Substance | Test Notesa | |
MP | EP | ||||
Physical and Chemical Characteristics | |||||
830.7100 | Viscosity | R | MP | EP | 4 |
830.7300 | Density/relative density/bulk density (specific gravity) | R | TGAI | TGAI | — |
Abbreviations: EP, end-use product; MP. manufacturing-use product; R, required; TGAI. technical grade of the active ingredient.
aTest notes. The following test notes are applicable to the data requirements for microbial pesticides product analysis as referenced m the last column of the table contained in paragraph (c) of this section.
1. Required to support registration of each manufacturing-use product and end-use product. This analysis must be conducted at the point in the production process after which there would be no potential for microbial contamination or microbial regrowth. For full registration, generally an analysis of samples is a compilation of batches, over a period of time, depending on the frequency of manufacturing.
2. Only required for emulsifiable liquid forms of microbial pesticides.
3. Required when microbial pesticides are packaged in metal, plastic, or paper containers.
4. Only required for liquid forms of microbial pesticides. Source: CFR 40 Part 158 Subpart V.
TABLE B-2 Microbial Pesticides Residue Data Requirements
Guideline Number | Data Requirement | All Use Patterns | Test Substance Data to Support MP or EP | Test Notesa |
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 |
Abbreviations: CR, conditionally required: EP, end-use product; TGAI, technical grade of the active ingredient.
aTest notes. The following test note is applicable to the data requirements for microbial pesticides residue as referenced in the last column of the table contained in paragraph (c) of this section.
1. Required when the results of testing:
i. Indicate the potential to cause adverse human health effects or the product characterization indicates the microbial pesticide has a significant potential to produce a mammalian toxin; and
ii. The use pattern is such that residues may be present in or on food or feed crops.
Source: CFR 40 Part 158 Subpart V.
TABLE B-3 Microbial Pesticides Toxicology Data Requirements
Guideline | All Use | Test | Test | |||
Number | Data Requirement | Patterns | Substance | Notesc | ||
Tire I | ||||||
885.3050 | Acute oral toxicity/pathogenicity | R | TGAI | 1 | ||
885.3150 | Acute pulmonary toxicity pathogenicity | R | TGAI | — | ||
885.3200 | Acute injection toxicity/pathogenicity/Cintravenous) Acute injection toxicity/pathogenicity/(intraperitoneal) | R | TGAI | 2 | ||
885.3400 | Hypersensitivity incidents | R | All | 3 | ||
885.3500 | Cell culture | R | TGAI | 4 | ||
870.1100 | Acute oral toxicity | R | MP, EP | 1,5 | ||
870.1200 | Acute dermal toxicity | R | MP. EP | 5 | ||
870.1300 | Acute inhalation toxicity | R | MP.EP | 5,6 | ||
870.2400 | Acute eye irritation | R | MP. EP | 5 | ||
870.2500 | Primary dermal irritation | R | MP, EP | 5 | ||
Tire II | ||||||
885.3550 | Acute toxicology | CR | TGAI | 7 | ||
885.3600 | Subchronic toxicity/pathogenicity | CR | TGAI | 8 | ||
Tire 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 | ||
Abbreviations: CR, conditionally required: EP. end-use product; MP. manufacturing-use product: R. required; TGAI. teclmical grade of the active ingredient
aTest notes. The following test notes are applicable to the data requirements for microbial pesticides toxicology as referenced in the last column of the table contained in paragraph (c) of this section:
1. The acute oral toxicity/pathogenicity study is required to support the TGAI. However, it can be combined with the unit dose portion of the acute oral toxicity study, with an EP or MP test material to fulfill the requirement for the TGAI and the MP or EP in a single study, if the new protocol is designed to address the endpoints of concern.
2. Data not required for products whose active ingredient is a virus. For test materials whose size or consistency may prevent use of an intravenous injection, the intraperitoneal injection procedure may be employed.
3. Hypersensitivity incidents, including immediate type and delayed-type reactions of humans or domestic animals, occur during the testing or production of the TGAI, MP, or EP, or are otherwise known to the applicant must be reported if they occur.
4. Data must be submitted only for products whose active ingredient is a virus.
5. The 870 series studies for the MP and EP are intended to provide data on the acute toxicity of the product. Waivers for any or all of these studies may be granted when the applicant can demonstrate that the combination of inert ingredients is not likely to pose any significant human health risks. Where appropriate, the limit dose approach to testing is recommended.
6. Required when the product consists of, or under conditions of use would result in, an inhalable material (e.g., gas, volatile substances, or aerosol particulate).
7. Data required when significant toxicity, in the absence of pathogenicity and significant infectivity, is observed in acute oral, injection, or pulmonary studies (Tier I). Route(s) of exposure correspond to route(s) where toxicity was observed in Tier I studies. The toxic component of the TGAI is to be tested.
8. Data required when significant infectivity and/or unusual persistence is observed in the absence of pathogenicity or toxicity in Tier I studies. Routes of exposure (oral and/or pulmonary) correspond to routes in Tier I studies where adverse effects were noted. Data may also be required to evaluate adverse effects due to microbial contaminants or to toxic byproducts.
9. Data are required when one or more of the following criteria are met:
i. Significant infectivity of the microbial pest control agent (MPCA) was observed in test animals in the Tier II subchronic study and in which no significant signs of toxicity or pathogenicity were observed.
ii. The microbial pesticide is a virus which can persist or replicate in mammalian cell culture lines.
iii. The microbial pesticide is not amenable to thorough taxonomic classification, and is related to organisms known to be parasitic for mammalian cells.
iv. The microbial pesticide preparation is not well purified, and may contain contaminants which are parasitic for mammals.
10. Data may be required for products known to contain or suspected to contain carcinogenic viruses or for microbial components that are identified as having significant toxicity in Tier II testing.
11. Data may be required for products known to contain or suspected to contain viruses that can interact in an adverse manner with components of the mammalian immune system.
12. An analysis of human infectivity/pathogenicity potential using scientific literature, genomic analysis, and/or actual specific cell culture/animal data may be required for products known to contain or suspected of containing intracellular parasites of mammalian cells for products that exhibit pathogenic characteristics in Tier I and/or Tier II, for products which are closely related to known human pathogens based on the product analysis data, or for known human pathogens that have been “disarmed” or rendered nonpathogenic 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.
Source: CFR 40 Part 158 Subpart V.
TABLE B-4 Microbial Pesticides Nontarget Organisms and Environmental Fate Data Requirements
Guideline Number | Data Requirement | Use Patterns | Test Substance | Test Notesa | |||||||
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 orTEP | 1,2,5 |
885.4240 | Freshwater invertebrate toxicity/pathogenicity | R | R | R | R | CR | CR | CR | CR | TGAI orTEP | 1,2,5 |
885.4280 | Estuarine Marine fish testing Estuarine and marine invertebrate testing | CR | CR | CR | CR | CR | NR | NR | CR | TGAI | 1,6 |
885.4300 | Nontarget plant testing | CR | CR | CR | R | CR | NR | CR | CR | TEP | 1,7 |
885.4340 | Nontarget insect testing | R | R | R | R | R | CR | NR | CR | TGAI | 1,8 |
885.43S0 | 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 orTEP | 9 |
885.5300 | Freshwater environmental expression tests | CR | CR | CR | CR | CR | NR | NR | CR | TGAI orTEP | 10 |
885.5400 | Marine or estiiarine environmental expression tests | CR | CR | CR | CR | CR | NR | NR | CR | TGAI orTEP | 11,12 |
TierIII | |||||||||||
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 | |||||||||||
350.2500 350.1950 | Field testing for terrestrial wildlife and Field testing for aquatic organisms | CR | CR | CR | CR | CR | NR | NR | CR | TGAI orTEP | 11,16 |
350.2500 | Simulated or actual field tests (birds, mammals) | CR | CR | CR | CR | CR | NR | NR | CR | TEP | 16,17, 20 |
Guideline Number | Data Requirement | Use Patterns | Test Substance | Test Notesa | |||||||
Aquatic | Terrestrial | ||||||||||
Food/Feed | Nonfood | Food/Feed/Nonfood | Forestry | Residential | Greenhouse | Indoor | Industrial | ||||
Outdoor | Food/Nonfood | Food/Nonfood | |||||||||
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 |
350.4300 | Simulated or actual field tests (plants) | CR | CR | CR | CR | CR | NR | NR | CR | TEP | 16, 18, 19,20 |
Abbreviations: CR, conditionally required; NR, not required; R, required; TEP. typical end-use product; TGAI, technical grade of the active ingredient
aTest notes. The following test notes are applicable to the data requirements for microbial pesticides nontarget organism and environmental fate as referenced m the last column of the table contained in paragraph (d) of this section.
1. Tests for pesticides intended solely for indoor application would be required on a case-by-case basis, depending on use pattern, production volume, and other pertinent factors.
2. The preferred species for the avian oral study is either the upland game or waterfowl. The preferred species for the avian inhalation toxicity/pathogenicity study and the avian chronic toxicity/pathogenicity study is the upland game. There is also the option to test the passerine if there is a concern. The coldwater fish is preferred for freshwater fish testing. However, two species(coldwater and warmwater fish species are the preferred species) must be tested for uses involving direct freshwater exposure. Freshwater invertebrate testing is also required.
3. Data required when the nature of the microbial pesticide and/or its toxins indicates potential pathogenicity to birds.
4. Required on a case-by-case basis if results of tests required by §158.2140 are inadequate or inappropriate for assessment of hazards to wild mammals.
5. Required when there will be significant exposure to aquatic organisms (fish and invertebrates).
6. Required if the product is intended for direct application into the estuarine or marine environment or expected to enter this environment in significant concentrations because of expected use or mobility pattern.
7. Required if the microbial pesticide is taxonomically related to a known plant pathogen.
8. Data are not required unless an active microbial ingredient controls the target insect pest by a mechanism of infectivity; i.e., may create an epizootic condition in nontarget insects.
9. Required if toxic or pathogenic effects are observed in one or more of the following tests for microbial pesticides:
i. Avian acute oral or avian inhalation studies.
ii. Wild mammal studies.
iii. Nontarget plant studies(terrestrial).
iv. Honey bee studies.
v. Nontarget insect studies.
10. Required when toxic or pathogenic effects are observed in any of the following TierI 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 TierI 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 TierI 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 TierI 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.
Source: CFR 40 Part 158 Subpart V.
TABLE B-5 Series 885—Microbial Pesticide Test Guidelines as of January 2010
OPPTS Guideline Number | Guideline Names | Other Reference Numbers | EPA Pub Number | Dare Issued | ||
OPPT | OPP | OECD | ||||
Final 885 Test Guidelines | ||||||
885.0001 | Overview for Microbial Pest Control Agents | none | 150A | none | 712-C-96-280 | Feb-96 |
Group A-Product Analysis Test Guidelines | ||||||
885.1100 | Product Identity | none | 151A-10 | none | 712-C-96-273 | Feb-96 |
885.1200 | Manufacturing Process | none | 151A-11 | none | 712-C-96-293 | Feb-96 |
885.1300 | Discussion of Formation of Unintentional Ingredients | none | 151A-01 | none | 712-C-96-294 | Feb-96 |
885.1400 | Analysis of Samples | none | 151A-13 | none | 712-C-96-295 | Feb-96 |
885.1500 | Certification of Limits | none | 151A-15 | none | 712-C-96-296 | Feb-96 |
Group B-Residues Test Guidelines | ||||||
885.2000 | Background for Residue Analysis of Microbial Pest Control Agents | none | 153A-1 | none | 712-C-96-299 | Feb-96 |
885.2100 | Chemical Identity | none | 153A-4 | none | 712-C-96-300 | Feb-96 |
885.2200 | Nature of the Residue in Plants | none | 153A-6 | none | 712-C-96-302 | Feb-96 |
885.2250 | Nature of the Residue in Animals | none | 153A-7 | none | 712-C-96-303 | Feb-96 |
885.2300 | Analytical Methods-Plants | none | 153A-8a | none | 712-C-96-304 | Feb-96 |
885.2350 | Analytical Methods-Animals | none | 153A-8b | none | 712-C-96-305a | Feb-96 |
885.2400 | Storage Stability | none | 153A-9 | none | 712-C-96-306 | Feb-96 |
885.2500 | Magnitude of Residues in Plants | none | 153 A-10 | none | 712-C-96-307 | Feb-96 |
885.2550 | Magnitude of Residues in Meat, Milk. Poultry. Eggs | none | 153 A-11 | none | 712-C-96-308 | Feb-96 |
885.2600 | Magnitude of Residues in Potable Water. Fish, and Irrigated Crops | none | 153A-01 | none | 712-C-96-309 | Feb-96 |
OPPTS Guideline Number | Guideline Names | Other Reference Numbers | EPA Pub Number | Dare Issued | ||
OPPT | OPP | OECD | ||||
Group C-Toxicology Test Guidelines | ||||||
885.3000 | Background-Mammalian Toxicity/Pa tho genie itylnfectivity | none | 152A-1 | none | 712-C-96-314 | Feb-96 |
885.3050 | Acute Oral Toxicity Pathogenicity | none | 152A-10 | none | 712-C-96-315 | Feb-96 |
885.3100 | Acute Dermal Toxicity/Pathology | none | 152A-11 | none | 712-C-96-316 | Feb-96 |
885.3150 | Acute Pulmonary Toxicity/Pathogenicity | none | 152A-12 | none | 712-C-96-317b | Feb-96 |
885.3200 | Acute Injection Toxicity Pathogenicity | none | 152A-13 | none | 712-C-96-318 | Feb-96 |
885.3400 | Hypersensitivity Incidents | none | 152A-15 | none | 712-C-96-320 | Feb-96 |
885.3500 | Cell Culture | none | 152A-16 | none | 712-C-96-321 | Feb-96 |
885.3550 | Acute Toxicology, Tier II | none | 152A-20 | none | 712-C-96-322 | Feb-96 |
885.3600 | Subclironic Toxicity/Pathogenicity | none | 152A-21 | none | 712-C-96-323c | Feb-96 |
885.3650 | Reproductive/Fertility Effects | none | 152A-30 | none | 712-C-96-324 | Feb-96 |
Group D-Nontarget Organism and Environmental Expression Test Guidelines | ||||||
885.4000 | Background for Nontarget Organism Testing of Microbial Pest Control Agents | none | 154A-1, 154A-2, 154A-3, 154A-4, 154A-5 | none | 712-C-96-328 | Feb-96 |
885.4050 | Avian Oral, Tier I | none | 154A-16 | none | 712-C-96-329 | Feb-96 |
885.4100 | Avian Inhalation Test, Tier I | none | 154A-17 | none | 712-C-96-330 | Feb-96 |
885.4150 | Wild Mammal Testing. Tier I | none | 154A-18 | none | 712-C-96-331 | Feb-96 |
885.4200 | Freshwater Fish Testing, Tier I | none | 154A-19 | none | 712-C-96-332 | Feb-96 |
885.4240 | Freshwater Aquatic Invertebrate Testing, Tier I | none | 154A-20 | none | 712-C-96-333 | Feb-96 |
885.4280 | Estuarine and Marine Animal Testing, Tier I | none | 154A-21 | none | 712-C-96-334 | Feb-96 |
885.4300 | Nontarget Plant Studies. Tier I | none | 154A-22 | none | 712-C-96-335 | Feb-96 |
885.4340 | Nontarget Insect Testing, Tier I | none | 154A-23 | none | 712-C-96-336 | Feb-96 |
885.4380 | Honey Bee Testing. Tier I | none | 154A-24 | none | 712-C-96-337 | Feb-96 |
885.4600 | Avian Chronic Pathogenicity and Reproduction Test, Tier m | none | 154A-26 | none | 712-C-96-342 | Feb-96 |
885.4650 | Aquatic Invertebrate Range Testing, Tier III | none | 154A-27 | none | 712-C-96-343 | Feb-96 |
885.4700 | Fish Life Cycle Studies. Tier m | none | 154A-28 | none | 712-C-96-344 | Feb-96 |
885.4750 | Aquatic Ecosystem Test | none | 154A-29 | none | 712-C-96-345 | Feb-96 |
Group E-Environmental Expression Test Guidelines | ||||||
885.5000 | Background for Microbial Pesticides Testing | none | 155A-1.2 | none | 712-C-96-056 | Feb-96 |
885.5200 | Expression in a Terrestrial Environment | none | 155A-10 | none | 712-C-96-338 | Feb-96 |
885.5300 | Expression in a Freshwater Environment | none | 155A-11 | none | 712-C-96-339 | Feb-96 |
885.5400 | Expression in a Marine or Estuarine Environment | none | 155A-12 | none | 712-C-96-312 | Feb-96 |
DRAFT 885 Test Guidelines | ||||||
Please note those guidelines labeled as “’Public Draft” are not yet available in final form. Although you may consult these guidelines, please check with the appropriate office before you use a draft guideline to generate data for submission to EPA under FIFRA. FFDCA or TSCA. | ||||||
Reserved: We use the phrase “[Reserved]” in the title column as a placeholder whenever the number has been assigned, but the FINAL Guideline has not yet been issued.
aDocument incorrectly says publication Number ends in “-304”.
bDocument incorrectly says publication Number ends in “-318”.
cDocument incorrectly says publication Number ends in “-232”.
Source: CFR40 Part 158 Subpart V.