Arthur Putt, Research Director, presented the webinar, “
Environmental Risk Assessment of Microbial Crop Protection Products.” Read below for responses to the questions asked during the audience Q&A.
Q: What testing is needed on the AI vs the formulations?
A: For US registration of a microbial pesticide, most studies are conducted with the Technical Grade Active Ingredient (TGAI). Testing with formulation or Typical End-Use Product (TEP) is required for miscibility, corrosion characteristics, and viscosity. Testing with TGAI and formulation is required for sample analysis and storage stability. All non-target organism testing is done with TGAI except if non-target plant testing is required on the formulation. Options exist for freshwater fish and invertebrates to be done with either TGAI or TEP.
Q: How are non-target species selected?
A: In addition to selecting species from two of the following groups (parasitic dipterans, predaceous hemipterans, predaceous coleopterans, predaceous mites, predaceous neuropterans, parasitic hymenopterans), it is important to select insect species that can be dosed with Microbial Pest Control Agents (MPCA) product via a relevant route (contact or dietary exposure), provide sufficient exposure duration to assess infectivity/pathogenicity based on product mode of action, and provide reliable laboratory performance.
Q: Is the single dose based on the GAP table and use of the microbial a.s. highest rate or a standard dose like 1x10(to the sixth) cfu/l? How are issues of turbidity resolved to reach an acceptable LC50?
A: Yes, the single limit dose for testing is based on 1 x 106 CFU/mL or 100 to 1000x the EEC, whichever highest concentration is feasible or practical, for aquatic studies (some variation is 10x to 100x EEC for terrestrial studies). Turbidity of solution in aquatic studies would need to be assessed in a trial, prior to definitive test, to ensure that 1) turbidity did not cause physical effects to the test organisms, 2) the exposure system was able to provide a consistent suspension and exposure to the MPCA product and 3) the turbidity did not impact the ability to observe organism for mortality during the exposure. If any of these were to occur, lower dose level(s) would need to be considered.
Q: How is dose verification accomplished for aquatic tests? How is homogeneity assessed? What if test material is not water soluble?
A: MPCA products are not soluble in water/diets by definition as they are microorganisms. Dose verification is accomplished by measuring newly prepared and aged exposure solutions during the exposure. As with conventional pesticides that are at or above water solubility, sampling technique and approach is important. Many times, larger sample volume or multiple samples from the same solution is necessary due to inherent variability. Higher variability in dose verification is expected with MPCA products compared to most conventional pesticides.
Q: Why does EPA consider that Non-Target Insect (NTA) testing run under IOBC Guidelines does not cover oral exposure?
A: If the testing under IOBC guidelines meet the criteria of EPA guidance under Non-target Insect, Tier I (OCSPP 885.4340), then it would be expected that the study(ies) would be acceptable for US registration. One would have to look at route of exposure (diet versus contact) and study duration to see if it meets requirements of OCSPP guidance. To be confident, the acceptance of OECD studies should be confirmed in a pre-submission meeting.
Q: For the trout testing under OCSPP, for the dietary route of exposure, is the test substance (microbe) amended to the trout diet or just available within the water column following traditional addition directly to the water?
A: Yes, for the trout study under OCSPP, the dietary route of exposure is included at 100x EEC along with aqueous exposure of trout in the water column.
Q: Is there guidance on the temperature to test at (i.e. chemical guidelines can adjust to best temp for non-target organism, but is the best temperature for the test compound more appropriate)?
A: Yes, guidance exists from EPA and OECD to test temperatures best suited for microbes and to provide justification if you deviate from the test organism fixed temperature range. One would need to ensure that the change in temperature, to optimize microbe growth, will not impact performance of the organisms in the test.
Q: Is EPA's pesticide in water calculator compatible/useable for microbial product environmental fate modelling?
A: Not to our knowledge. These models (EPA pesticide concentration calculator) are designed for conventional pesticide products, not microbial pesticides.
Q: What is your experience with EPA accepting studies that meet OECD but not necessarily all details of OPPTS guidelines? Do they seem to be amenable to guideline bridging?
A: The primary challenge with acceptance of OECD studies for microbial pesticides by EPA is seen as study duration. Most OECD acute studies have durations that are too short to assess infectivity and pathogenicity. I believe an OECD study, modified or conducted in sufficient duration (> 4-day duration) would be acceptable to meet data requirements for EPA registration. An example of what would not be suitable would be the use of OECD 213/214 honeybee tests (2-4 days duration) to fulfill the EPA Tier I honeybee testing requirement which would be looking at a longer duration honeybee study.
Q: You had mentioned most environmental fate related studies are waived. Are there any that are not waived (or tend to not be waived)?
A: Not to our knowledge for naturally occurring/derived microbes. A genetically engineered microbe would fall into a different group and would require data on fate of the microbe in the environment.
Q: I think one of the biggest issues is reliable evaluation of infectivity/pathogenicity. What are your thoughts on evaluation of infectivity?
A: Yes, evaluation of infectivity and pathogenicity can be difficult to assess in some cases. Tests need to include appropriate control groups, and additional research and guidance on methodologies would be useful in this area.
Q: In case waiver won't be sufficient anymore, do you think the actual test guidance for environmental fate are adequate to microbial PPP? Or they should be adjusted? Or new guidelines must be published?
A: If environmental fate data were to be required and could not be waived, development and execution of a study would be challenging, especially for a naturally occurring microbes. Updated guidance or testing guidelines might be needed in this case.
Q: While the environmental expression tests at Tier II are environmental fate in nature (persistence), there appear to be no classical environmental fate lab or field tests as required for biochemical pesticides. Please confirm these are the relevant data requirements for US EPA for microbial pesticides.
A: For US microbial pesticide registration, the Tier II data requirements are 885.5200, 885.5300 and 885.5400 and correct; there are no classical environmental fate lab or field tests for microbial pesticides.
Q: Is there “boilerplate” language that leads to a successful waiving of the Tier II environmental expression data requirements or is it a case-by-case process?
A: In most cases of US registration, Tier II data is not required as almost all microbial products do not elicit toxicity sufficient to trigger Tier II data requirements. Most times, if some toxicity does occur, mitigation measures are used to reduce concern versus moving to Tier II testing.
Q: What exactly are the “Environmental Toxicology” requirements referenced in the webinar?
A: The typical data requirements for environmental toxicology for a microbial pesticide for US registration are: Freshwater fish, tier I (OCSPP 885.4200), Freshwater Aquatic Invertebrate, tier I (OCSPP 885.4240), Non-target Insect, Tier I (OCSPP 885.4340), Honey bee Testing, Tier I (OCSPP 885.4380) and Avian Oral, Tier I (OCSPP 885.4050).
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