Abbreviations: EP, end-use product; MP. manufacturing-use product; R, required; TGAI. technical grade of the active ingredient.

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.

Abbreviations: CR, conditionally required; NR, not required; R, required; TEP. typical end-use product; TGAI, technical grade of the active ingredient

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.

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.

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