Spiromesifen

                 Proposed Interim Registration Review Decision
                              Case Number 124871

                                   March 2021

                                                                   Approved by:

Mary Elissa Reaves, Ph.D.

Director

Pesticide Re-evaluation Division
                                                                          Date:
      03/31/2021

                               Table of Contents
I.	INTRODUCTION	3
A.	Summary of Spiromesifen Registration Review	4
B.	Summary of Public Comments on the Draft Risk Assessments and Agency Responses	5
II.	USE AND USAGE	12
III.	SCIENTIFIC ASSESSMENTS	13
A.	Human Health Risks	13
1.	Risk Summary and Characterization	13
2.	Human Incidents and Epidemiology	17
3.	Tolerances	18
4.	Human Health Data Needs	18
B.	Ecological Risks	18
1.	Risk Summary and Characterization	19
2.	Ecological Incidents	24
3.	Ecological and Environmental Fate Data Needs	24
C.	Benefits Assessment	24
IV.	PROPOSED INTERIM REGISTRATION REVIEW DECISION	25
A.	Proposed Risk Mitigation and Regulatory Rationale	25
1.	Proposed Application Rate Reductions	26
2.	Proposed Label Mitigation: Personal Protective Equipment	28
3.	Proposed Label Mitigation: Engineering Controls	28
4.	Proposed Label Mitigation: Prohibition of Certain Application Equipment	28
5.	Proposed Label Mitigation: Re-entry Prohibitions	29
6.	Proposed Label Mitigation: Resistance Management	30
7.	Proposed Label Mitigation: Spray Drift Management	31
8.	Proposed Label Mitigation: Pollinator Advisory Language	32
9.	Proposed Label Mitigation: Surface Water Advisory Language	33
10.	Proposed Label Mitigation: Ground Water Advisory Language	33
 B.	Tolerance Actions	33
C.	Proposed Interim Registration Review Decision	34
V. NEXT STEPS AND TIMELINE	35
A.	Proposed Interim Registration Review Decision	35
B.	Implementation of Mitigation Measures	35
Appendix A: Summary of Proposed Actions for Spiromesifen	36
Appendix B: Proposed Labeling Changes for Spiromesifen Products	37
Appendix C: Listed-Species Assessment	45

 INTRODUCTION

This document is the Environmental Protection Agency's (EPA or the Agency) Proposed Interim Registration Review Decision (PID) for spiromesifen (case 7442, PC Code 024875). In a registration review decision under the Federal Insecticide, Fungicide, Rodenticide Act (FIFRA), the Agency determines whether a pesticide continues to meet FIFRA's registration standard. Where appropriate, the Agency may issue an interim registration review decision before completing a registration review. Among other things, the interim registration review decision may determine that new risk mitigation measures are necessary, lay out interim risk mitigation measures, identify data or information required to complete the review, and include schedules for submitting the required data, conducting the new risk assessment and completing the registration review. For more information on spiromesifen, see EPA's public docket (EPA-HQ-OPP-2014-0263) at www.regulations.gov.

FIFRA mandates the continuous review of existing pesticides. All pesticides distributed or sold in the United States must be registered by EPA based on scientific data showing that they will not cause unreasonable risks to human health or to the environment when used as directed on product labeling. In 2006, the Agency began implementing the registration review program. EPA will review each registered pesticide every 15 years. Through the registration review program, the Agency intends to verify that all registered pesticides continue to meet the registration standard as the ability to assess and reduce risk evolves and as policies and practices change. By periodically re-evaluating pesticides as science, public policy, and pesticide-use practices change, the Agency ensures that the public can continue to use products in the marketplace that do not present unreasonable adverse effects. For more information on the registration review program, see http://www.epa.gov/pesticide-reevaluation.

The Agency is issuing a PID for spiromesifen so that it can (1) move forward with aspects of the registration review that are complete and (2) implement interim risk mitigation (see Appendices A and B). EPA is currently working with the U.S. Fish and Wildlife Service and the National Marine Fisheries Service (the Services) to improve the consultation process for national threatened and endangered (listed) species for pesticides under the Endangered Species Act (ESA). The Agency has not yet fully evaluated spiromesifen's risks to federally listed species. However, EPA will complete its listed-species assessment and any necessary consultation with the Services before completing the spiromesifen registration review. Before completing registration review, EPA will also complete endocrine screening for spiromesifen under the Federal Food, Drug, and Cosmetic Act (FFDCA). For more information on the listed-species assessment and the endocrine screening for the spiromesifen registration review, see Appendices C and D.

Spiromesifen is a tetronic and tetramic acid selective, locally systemic insecticide/acaricide with residual and contact activity. Spiromesifen is registered for use on agricultural crops including corn, cotton, leafy Brassica greens and leafy greens, fruiting vegetables (including cucurbits), tuberous and corm vegetables, and low growing berries. Spiromesifen is also registered for use on mint/peppermint/spearmint in Washington under a FIFRA section 24(c) Special Local Needs registration. In addition to these agricultural uses, spiromesifen is registered for use on ornamental plants (for professional application only) on residential ornamentals and in the commercial production of ornamentals. Spiromesifen products are formulated as suspension or flowable concentrates.  Spiromesifen is applied via ground (e.g., ground boom and hand-held equipment) or aerial equipment.

This document is organized in five sections: Introduction, which includes this summary and a summary of public comments and EPA's responses; Use and Usage, which describes how and why spiromesifen is used and summarizes data on its use; Scientific Assessments, which summarizes EPA's risk and benefits assessments, updates or revisions to previous risk assessments, and provides broader context with a discussion of risk characterization; the Proposed Interim Registration Review Decision, which describes the mitigation measures proposed to address risks of concern and the regulatory rationale; and, lastly, the Next Steps and Timeline for completion of this registration review.

 Summary of Spiromesifen Registration Review

Pursuant to 40 CFR § 155.50, EPA formally initiated registration review for spiromesifen with the opening of the registration review docket for the case. The following summary highlights the docket opening and other significant milestones that have occurred thus far during the registration review of spiromesifen.

 March 2015- EPA posted the Spiromesifen Preliminary Work Plan (PWP), Spiromesifen Human Health Assessment Scoping Document in Support of Registration Review, the Registration Review Problem Formulation for Spiromesifen, and other supporting documents to the docket for a 60-day public comment period.
 September 2015- EPA posted the Final Work Plan (FWP) for spiromesifen to the public docket. Three groups submitted comments on the PWP. The comments did not result in changes to the data needs, anticipated risk assessments, or the registration review timeline presented in the FWP.
 May 2016- The Agency issued a Generic Data Call-In Notice (GDCI-024875-1535) for spiromesifen for data needed to conduct the registration review risk assessments. Several data requirements have not been satisfied. The registrant submitted ECM/ILV data but they were deficient and new data are needed. New data are also needed for chronic larval honey bee toxicity study because the submitted data did not provide a definitive endpoint. Some higher tier pollinator data are still in review; it appears that additional higher tier data may be needed; the Agency will confirm once the review of the submitted data is complete.
       May 2020- The Agency published the Spiromesifen: Draft Human Health Draft Risk Assessment for Registration Review, Spiromesifen: Draft Ecological Risk Assessment for Registration Review, and several other supporting documents in the docket for a 60-day public comment period. Bayer CropScience (Bayer), the technical registrant, and the U.S. Department of Agriculture (USDA) submitted comments on the risk assessments. These comments and the Agency's responses are summarized below.
 March 2021- The Agency is now completing the Proposed Interim Registration Review Decision (PID) for spiromesifen, in preparation for issuance in the docket for a 60-day public comment period. Along with the spiromesifen PID, the following documents are also available in the spiromesifen registration review docket EPA-HQ-OPP-2014-0263:
          Response to Public Comments on the Draft Environmental Fate and Ecological Risk Assessment for Spiromesifen (December 16, 2020)
          Addendum to the Drinking Water Exposure Assessment (DWA) for Registration Review of Spiromesifen (March 19, 2021)
          Spiromesifen.  Response to comments from Bayer Crop Science and USDA regarding HED's most recent Draft Human Health Risk Assessment in Support of Registration (March 29, 2021)
          Assessment of the Use, Usage, and Benefits of Spiromesifen (PC# 024875) and Impacts of Potential Mitigation Measures in Agricultural and Non-agricultural Use Sites (March 30, 2021)

 Summary of Public Comments on the Draft Risk Assessments and Agency Responses

During the 60-day public comment period for the spiromesifen draft risk assessments, which opened on May 4, 2020 and closed on July 4, 2020, the Agency received public comments from five sources. Comments were submitted by Bayer CropScience, (the technical registrant), the United States Department of Agriculture (USDA), the Arizona Farm Bureau, the Arizona Pest Management Center, and the Washington State Potato Commission. All public comments that are substantive are summarized below, along with the Agency's responses. The Agency thanks all commenters for their comments and has considered them in developing this PID.

Comments Submitted by Bayer CropScience (EPA-HQ-OPP-2014-0263-0029)

Comment:  Bayer noted various errors and omissions in the draft human health and ecological risk assessments. Bayer suggested the need for refinements to the drinking water and residential post-application risk assessments through the use of formation-decline modeling and an alternate Dislodgeable Foliar Residue (DFR) study, respectively. Bayer also offered several risk management proposals, including shifting away from seasonal or "per crop cycle" to "per year" application rates, some additional application rate reductions, prohibiting the use of mechanically pressurized handguns, and implementing re-entry restrictions.

Comments on the Human Health Risk Assessment

According to Bayer, the Total Residue method used by the Agency to estimate the amount of spiromesifen in drinking water is a very conservative modeling approach that does not appropriately describe transformation and degradation processes in water or the different fate properties of the parent and degradates. Formation-decline modeling accounts for those factors, providing a more realistic estimate of overall exposure. Bayer proposed the use of the formation-decline approach to generate exposure estimates for drinking water assessment using the Pesticide in Water Calculator (PWC).

Bayer noted that in response to the recommendations of OPP's Hazard and Science Policy Council (HASPOC; discussed in more detail in Section III), it had suggested refinements to the human health risk assessment and offered specific risk mitigation proposals. Bayer concluded that based on those refinements and risk mitigation measures, the risks associated with the use of spiromesifen would meet Agency standards even with retention of the uncertainty factor related to the lack of comparative thyroid assay with spiromesifen. Bayer indicated that it had chosen not to undertake additional data development to address the absence of the thyroid data.

Comments on the Ecological Risk Assessment

The registrant recommended using a different value for the anaerobic aquatic half-life and suggested a correction to the average organic-carbon normalized soil-water distribution coefficient (KOC). Bayer observed that the Agency used a pollinator contact toxicity endpoint for calculating risks from oral exposures, did not utilize a recent pollinator larval chronic data submission, and cited studies from the open literature on bumble bee microcolony effects that were not supported with analytical data.

EPA Response: The Agency acknowledges Bayer's observations about the risk assessments, which are discussed in detail in the Response to Public Comments on the Draft Environmental Fate and Ecological Risk Assessment for Spiromesifen and Spiromesifen. Response to comments from Bayer Crop Science and USDA regarding HED's most recent Draft Human Health Risk Assessment in Support of Registration Review.

The Agency also notes that the risk assessments already reflect both the current "per crop cycle" and the proposed "per year" application rates and is appreciative of Bayer's commitment to implementing protections for occupational handlers and post-application workers.

Response to Comments on the Human Health Risk Assessment

The Agency has conducted formation-decline refinements as suggested by Bayer and the results for drinking water are described in the Addendum to the Drinking Water Exposure Assessment (DWA) for Registration Review of Spiromesifen and reflected in the Response to Public Comments on the Draft Human Health Risk Assessment for Spiromesifen, both of which available on the public docket. The updated dietary risk assessment resulting from these refinements is summarized below.

As noted above, Bayer's comments on the Agency's risk assessments suggested the use of formation-decline modeling to generate drinking water concentrations for use in the dietary risk assessment. The Agency has now refined the dietary risk assessment with the use of formation-decline modeling for drinking water and with use parameter changes suggested by Bayer.

The use of formation-decline modeling resulted in overall reductions in estimated concentrations of spiromesifen in the drinking water. The Agency's drinking water risk assessments are typically based on the use site associated with the greatest potential contribution to residues in drinking water. In the case of spiromesifen, prior to consideration of application rate and crop cycle reductions and the use of formation-decline modeling, ornamentals was the greatest contributor. Based on the proposed changes to spiromesifen use parameters and formation-decline refinements, the greatest potential contributor to drinking water is now associated with the use of spiromesifen on corn, with a chronic Estimated Drinking Water Concentration (EDWC) of 60.6 ug/L (or 60.6 ppb). Using this chronic EDWC along with estimated dietary (food-only) exposures results in a chronic dietary risk estimate of 44% of the chronic Population-Adjusted Dose (cPAD) for the general population and for the most highly exposed subgroup (infants less than one year old), 95% of the cPAD. A cPAD of 100% or greater represents a chronic dietary risk of concern. Thus, based on the proposed changes to use parameters and formation-decline modeling, the potential dietary risks associated with the use of spiromesifen are not of concern.

Because the drinking water assessment has changed, the Agency needed to re-evaluate aggregate risk, which in this case is an assessment of combined exposures from diet (including drinking water) and residential post-application exposures. Bayer recently proposed reduced maximum single application rates for residential ornamentals -- 0.0125 lb active ingredient/acre (ai/A) for trees and indoor plants, and 0.0625 lb ai/A for ornamental gardens. Bayer also suggested in its comments on the human health risk assessment that the Agency use a study in Easter lilies to determine a more appropriate factor for describing the amount of pesticide residue that can potentially dislodge from leaves of treated plants to come into contact with people in the treated area after application. Based on data from this Easter lily DFR study (MRID 51219301), the Agency has estimated potential post-application exposures to adults and children. A detailed description of the assessment is found in Response to Public Comments on the Draft Human Health Risk Assessment for Spiromesifen; the results are summarized in Table 1.

Table 1. Residential Post-Application Risk Estimates for Spiromesifen Assuming Modifications to Ornamentals Application Rates (LOC = 1000)
                                   Lifestage
                                   Use Site
                          Application Rate (lb ai/A)
                           Margin of Exposure (MOE)
                                     Adult
                                   Gardens
                                    0.0625
                                     2,600

                                    Trees
                                     0.125
                                    14,000

                                 Indoor Plants
                                     0.125
                                    110,000
                            Child 6 to <11 years
                                    Gardens
                                    0.0625
                                     3,800

                                    Trees
                                     0.125
                                    21,000

                                 Indoor Plants
                                     0.125
                                    160,000

Based on the use of the Easter lily DFR study and the proposed rate reductions, the Agency has concluded that if these changes are made the residential post-application risks are not of concern for either adults or children.

Potential risks from aggregate exposure are summarized below. Short-term aggregate exposure for children is the sum of the most sensitive dietary exposure among children (for infants less than one year old) and post-application exposure for children 6 to <11 years old.

Table 2. Short-Term Aggregate Risk Estimates for Spiromesifen Assuming Modifications to Ornamentals Application Rates (LOC = 1000)
                                  Population
                      Average Dietary Exposure mg/kg/day
                        Residential Exposure mg/kg/day
                           Total Exposure mg/kg/day
                 Aggregate MOE (food, water, and residential)
Adults
                                   0.001623
                                     0.001
                                   0.002623
                                     1400
Children
                                   0.001612
                                     0.001
                                   0.002612
                                     1500

Thus, based on the refinements discussed above and the proposed rate changes, the Agency has determined that aggregate risks will not be of concern if the proposed mitigation is implemented on product labels.

In reference to Bayer's comments on the HASPOC memo conclusions, EPA notes that the database uncertainty factor (10X) will continue to be applied to the risk assessment for spiromesifen until labels are amended in response to the registration review interim decision. If mitigation proposed in this PID is reflected in amended labels, the Agency's aggregate risk estimates will be considered protective of the thyroid effects that may occur at sensitive lifestages.

Response to Comments on the Ecological Risk Assessment

EPA agrees that the correct organic carbon-normalized soil-partition coefficient (KOC) value for modeling should have been 69,445 mL/g; however, the current PWC is not sensitive to small changes in KOC. Even if the value recommended by Bayer was used in modeling, it would not have impacted the estimated drinking water concentrations or estimated environmental concentrations.

Bayer's comments on discrepancies in the hazard characterization for bees are constructive, but, as explained in detail in the response to comments document, the endpoint selections for acute and contact effects in this case do not alter the Agency's risk conclusions. The new larval honey bee (Apis mellifera) chronic toxicity study (MRID 51391701) will be reviewed and risk conclusions adjusted as necessary in future assessments.

The Agency appreciates Bayer's concerns about the bumble bee (Bombus terrestris) microcolony studies. As indicated in the ecological risk assessment, it is not possible to directly compare exposure levels from these studies since neither study analytically verified treatment levels. Because EPA does not have a process for estimating risk to bumble bees, the risk assessment should not have referred to the Besard et al. 2020 study as indicative of possible risks. Consistent with the EPA processes, the risk assessment noted that risk estimates for honey bees would be protective for bumbles bees.

Comments Submitted by USDA (EPA-HQ-OPP-2014-00263-0027)

Comment:  USDA provided comments on the use and benefits of spiromesifen, its overall risk profile relative to other pest management options, and how mandates on droplet size for spiromesifen might impact usage. USDA commented extensively on the risk assessments.

Comments on the Human Health Risk Assessment

USDA remarked that surface water exposure was not of concern and that drinking water levels of concern were only exceeded for groundwater, where the modeling approach for ascertaining pesticide concentrations is conservative. USDA further commented that outdoor ornamentals are unlikely to be treated at the maximum use rate for three applications per crop cycle outdoors and three crop cycles.

USDA went on to discuss risk estimates based on the uses sites other than ornamentals, assessed at typical application rates. USDA also suggested that in vegetable production, where crop rotation is routine, it is unlikely that repeated perennial use of any single active ingredient for control of mites, psyllids, or whiteflies would be common, particularly considering grower attention to resistance management. USDA stressed the need for characterization around upper-bound groundwater exposure estimates. USDA encouraged EPA to consider regulatory options such as well setbacks for vulnerable soils, and asked EPA to consider sub-surface degradation of spiromesifen, which could considerably refine ground water exposure estimates.

USDA also noted that the use of mechanically-pressurized handguns in field crops is limited and requested that the Agency reconsider the default daily handling assumption of 1,000 gallons for estimation of exposures to handlers using such equipment.

For occupational post-application scenarios, USDA requested that EPA consider the use of average application rates and more realistic measures of the length of time during a workday that is devoted to specific post-application activities. USDA further suggested that DFR data from cotton may overestimate exposures in vegetable crops and recommended that the Agency consider the practical implications of extended restricted-entry intervals (REIs) for growers.

USDA's comments supported EPA's consideration of opportunities for tolerance harmonization, including cases where Codex has established MRLs that are higher than U.S. tolerances, or where Codex has established MRLs and there is no U.S. tolerance. USDA noted other opportunities for harmonization in cucumber, eggplant, eggs, meat, melons (except watermelon), dried chili peppers, poultry fat/meat/offal, tomato, tomato paste, and dried tomato.

Comments on the Ecological Risk Assessment

USDA appreciated EPA's discussion of typical application rates in characterizing chronic risks for freshwater invertebrates in the water column. USDA suggested that the two-fold difference between the LOAEC and the NOAEC, considered in combination with typical application rates and conservative assumptions in quantifying aquatic exposures, indicates that these risks may not be of concern.

USDA referred to conservative assumptions in the assessment of chronic risks to mammals, particularly the selection of an endpoint based on marginal weight reductions. While USDA acknowledged the potential for risks to bees, it also suggested that the limited systemicity of spiromesifen reduces potential exposure through ingestion of pollen, and that bees primarily would be exposed via contact during spiromesifen application. USDA noted that growers may respond to mite outbreaks by spraying spiromesifen while crops are blooming but requested that EPA consider risk management within the context of comparative risks associated with the most likely alternatives. Given these and other considerations, USDA suggested that bloom restrictions on spiromesifen are not warranted.

EPA Response: The Agency is always open to receiving input on pesticide benefits, such as that provided by USDA in its comments, and makes use of it whenever possible. The Agency appreciates USDA's perspective on the management of risks associated with the use of spiromesifen, but notes that consideration of relative risk from alternative pesticides is not considered in risk assessment itself, although it was a factor in the development of the risk management proposal.

Response to Comments on the Human Health Risk Assessment

Per the discussion above, refinements and use parameter proposals have combined to yield drinking water risk estimates that are not of concern (if the proposals are implemented). The reduced application rate and annual maximum number of applications for production ornamentals, as well as the elimination of multiple crop cycle labeling, have made the characterization of typical application rates and the impact of crop rotation as suggested by USDA moot.

To address potential handler risks of concern posed by the use of mechanically pressurized handguns, the registrant has agreed that spiromesifen labels will prohibit the use of this application equipment. Relative to USDA's comments about occupational risks posed by certain post-application activities, the Agency agrees that the use of average, rather than maximum, application rates would reduce the amount of time after application estimated for potential risks of concern. The Agency must account for potential post-application exposures based on maximum application rates but has determined that other factors mandated by current labeling and use practices provide adequate justification for its decisions on these re-entry concerns.

For hand set irrigation, the registrant consulted with personnel in the field and advised EPA that hand set irrigation is not a typical practice for the carrots, mint/peppermint/spearmint, ornamentals, potatoes, or tuberous and corm vegetables, and so the Agency has not considered the characterization suggested by USDA. For cotton, spiromesifen labels prohibit use for 30 days prior to harvest, so prohibiting re-entry for the purpose of harvesting for 8 days after application will not present an impediment to harvest. For the harvest of Brassica species, including cauliflower, the registrant has indicated that the last application of spiromesifen occurs one month before harvest, so prohibiting re-entry for harvest activities for 14 days after application also is not problematic. According to the registrant, hand-tying and training of cauliflower occurs about two weeks before harvest, and with the last application of spiromesifen one month before harvest, a re-entry prohibition of 14 days after application for the purpose of hand-tying and training fits within that interval. The Agency is specifically soliciting comment from growers on the impacts associated with the proposed re-entry prohibitions.

USDA's comments on tolerances will be taken into consideration when the Agency proposes tolerance revisions for spiromesifen. EPA attempts to harmonize existing U.S. tolerances with Codex MRLs whenever feasible, but harmonization is not possible in some cases due to a difference in tolerance expression, a difference in commodity definition, or a difference in use pattern. In addition, EPA does not routinely harmonize tolerances in/on livestock feed commodities with Codex MRLs.

Response to Comments on the Ecological Risk Assessment

While USDA suggested that use of the LOAEC rather than the NOAEC in assessing risks to aquatic invertebrates might offset conservative assumptions, EPA notes that the LOAEC in this case was associated with a 31% reduction in the number of offspring per female, which suggests lower doses could also elicit adverse effects.

The Agency maintains that the weight reduction observed in mammals exposed to spiromesifen cannot be dismissed as an endpoint because such reductions can diminish the ability of the animals to thrive under actual field conditions where multiple stressors are present. With respect to risk to bees, the translocation of spiromesifen residues into pollen and nectar is accounted for in the risk assessment by refinements based on measured residues, which indicate that risks to honey bee larvae remain a concern. The Agency is not proposing bloom restrictions for spiromesifen.

Comments Submitted by Washington State Potato Commission (EPA-HQ-OPP2014-00263-0025, Arizona Farm Bureau Federation (EPA-HQ-OPP2014-00263-0026) and Arizona Pest Management Center, University of Arizona (EPA-HQ-OPP-2014-00263-0028)

Comment: The Washington State Potato Commission noted the importance of spiromesifen in the control of spider mite, whitefly, and potato psyllid, all of which are major pests of potatoes in Washington and the latter of which serves as a vector for zebra chip disease in potatoes.  The commenter further remarked that given the method of irrigation in Washington potatoes and limited rainfall, off-site movement of spiromesifen is limited.

The Arizona Farm Bureau Federation's comments discussed the importance of controlling mites and whitefly on corn, cotton, and melons, and detailed the economic value of those crops in the state. Additionally, the comments noted that spiromesifen is an important to Integrated Pest Management, especially given its role in combating resistance. The commenter touted the additional benefit of spiromesifen's selective chemistry, credited with controlling target pests while leaving non-target insects unharmed.

The Arizona Pest Management Center submitted comments that reinforced the information provided by the Arizona Farm Bureau on the benefits of spiromesifen. The Pest Management Center advised that growers in Arizona are mindful of the interests of beekeepers and it is common practice to spray at night or early in the morning before bees are active in the field. The commenter explained the value of spiromesifen against multiple pests simultaneously and emphasized that spiromesifen is frequently applied at less than the maximum application rate.

EPA Response: EPA appreciates the information provided by these three entities and considered it in the development of this decision.

For a detailed response to these public comments, see the Response to Public Comments on the Draft Environmental Fate and Ecological Risk Assessment for Spiromesifen, the Addendum to the Drinking Water Exposure Assessment (DWA) for Registration Review of Spiromesifen; Spiromesifen. Response to comments from Bayer Crop Science and USDA regarding HED's most recent Draft Human Health Risk Assessment in Support of Registration Review, and the Assessment of the Use, Usage, and Benefits of Spiromesifen (PC# 024875) and Impacts of Potential Mitigation Measures in Agricultural and Non-agricultural Use Sites.

 USE AND USAGE

Spiromesifen is registered for use on agricultural crops including corn, cotton, leafy Brassica greens and leafy greens, fruiting vegetables (including cucurbits), tuberous and corm vegetables, and low growing berries. Spiromesifen is also registered for use on mint/peppermint/spearmint in Washington under a FIFRA section 24(c) Special Local Needs registration. In addition to these agricultural uses, spiromesifen is registered for use on ornamental plants (for professional application only) on residential ornamentals and in the commercial production of ornamentals. Spiromesifen products are formulated as suspension or flowable concentrates. Spiromesifen is applied via ground (e.g., ground boom and hand-held equipment) or aerial equipment.

The largest crop uses, in terms of acres treated, are on corn, potatoes and cotton. In terms of percent of crop treated, the greatest usage of spiromesifen in agriculture is on strawberry, cantaloupe, and peppers. From 2015 to 2019, about 20% of strawberry, 15% of cantaloupe and 10% of peppers acres were treated with spiromesifen in the United States annually.

Data on spiromesifen use in ornamental plant production indicate some use in major ornamental production areas, including California and Florida. California Department of Pesticide Regulation data indicate that approximately 150 lbs of spiromesifen were applied to ornamental plants in California from 2014 to 2018 (reflecting the most recent publicly available data). Although California is a top producer of ornamentals, spiromesifen usage in California may not be indicative of national level usage on ornamental plants. Depending on how spiromesifen is used (e.g., on greenhouse plants in small containers), the number of plants treated with spiromesifen within the industry could potentially be substantial.

For additional information on the usage and usage of spiromesifen, and for citations of information provided in this section, see the Assessment of the Use, Usage, and Benefits of Spiromesifen (PC# 024875) and Impacts of Potential Mitigation Measures in Agricultural and Non-agricultural Use Sites, posted to the public docket.
 SCIENTIFIC ASSESSMENTS
Human Health Risks

The Agency has summarized the spiromesifen human health risk assessment below. The Agency used the most current science policies and risk assessment methodologies to prepare this risk assessment in support of the registration review of spiromesifen. For additional details on the March 2020, human health risk assessment, see the Spiromesifen Draft Human Health Risk Assessment for Registration Review, in EPA's public docket (EPA-HQ-OPP-2014-0263).

OPP's Hazard and Science Policy Council (HASPOC) determined in 2020 that due to the lack of data on potential developmental susceptibility to thyroid function disruption, a database uncertainty factor of 10X is applied to dietary, residential, and occupational scenarios. The HASPOC recommended a comparative metabolism with dogs, rats, and humans to help
explain the basis for the species differences in target organ toxicity, because the dog appears to be more sensitive to thyroid effects than the usual test species, the rat. Such a study would also facilitate understanding of potential thyroid effects in humans. For more detail about that determination, please see Spiromesifen: Summary of Hazard and Science Policy Council (HASPOC) Meeting on January 23, 2020: Recommendations on the Need for a Comparative
Thyroid Assay, available on the public docket.

The endpoint and point of departure for spiromesifen, for all human health risk scenarios, is derived from a two-generation reproduction study in the rat, with a No-Observed Adverse-Effect Level (NOAEL) of 3.8 mg/kg/day based on decreased pup body weight. The NOAEL is the lowest dose in a study at which adverse effects are not observed. The risk assessment assumed equivalent toxicity for metabolites of spiromesifen and the Agency used a total residue approach for assessing human health risks.

Risk Summary and Characterization

Dietary (Food + Water) Risks

An acute dietary risk assessment was not needed because no endpoint attributable to a single exposure was observed for spiromesifen and, as a result, potential acute risks are not expected.

A chronic dietary risk assessment was conducted. The 2018 human health risk assessment found that there were chronic dietary risks of concern for combined exposures from food and water. The Agency determined that groundwater was the major contributor to dietary exposure.

Risk estimates above 100% of the chronic population-adjusted dose (cPAD) represent potential risks of concern. Assessments typically are estimated based on maximum application rates for the uses of the pesticide. For children 1-2 years of age, the most highly exposed population subgroup, the risk estimate from food alone was 31% of the cPAD. The combined food and water risk estimate, for the mist highly exposed population in this case, infants less than one year old, was 637% of the cPAD. The risk estimate for the general U.S. population was 254% of the cPAD.

Having identified ground water as the biggest contributor to dietary risk and ornamentals as the biggest contributor to ground water, the Agency also estimated dietary risks based on possible changes to labeled use patterns.
 Risk estimates for food and water combined, at maximum application rates for all use sites except for ornamentals at (1/2) the current rate applied three times/year, were 92% of the cPAD for the general population and for the most highly exposed subgroup, infants less than one year old, was 218% of the cPAD.
 Estimates for other scenarios are detailed in the risk assessment. Of these alternate scenarios, risk estimates fell below the cPAD for infants less than one year in age (97% of the cPAD) and all other population subgroups only for 1) agricultural use sites at average (rather than maximum) application rates and 2) no ornamental use.

The Agency subsequently conducted a refined drinking water exposure assessment by using a formation-decline modeling approach in conjunction with proposed new application rates. In the refined assessment, corn (rather than commercial ornamentals at the proposed lower rate of 0.125 lbs ai/A) yielded the highest EDWC (see Addendum to the Drinking Water Exposure Assessment (DWA) for Registration Review of Spiromesifen). A chronic EDWC of 60.6 ug/L was used in a revised human health dietary risk assessment (as detailed in Spiromesifen. Response to comments from Bayer Crop Science and USDA regarding HED's most recent Draft Human Health Risk Assessment in Support of Registration Review). When using this EDWC with the food exposures used in the DRA, dietary food + water risk was 44% of the cPAD for the general population and for the most highly exposed subgroup, infants less than one year old, was 95% of the cPAD.

 Residential Handler Risks

Residential handler exposure was not assessed because all labels require the use of PPE and products are not intended for application by homeowners.

Residential Post-Application Risks

Commercial applicators only may apply spiromesifen to residential ornamentals. Residential post-application exposures were previously assessed and updated to incorporate the 2012 Residential Standard Operating Procedures (SOPs). More recently, Bayer has agreed to lower the maximum single application rate for production ornamentals to 0.125 lb ai/A. Bayer also has agreed to a maximum single application rate for residential garden ornamentals of 0.0625 lb ai/A and, for residential trees and indoor plants, 0.125 lb ai/A. (personal communication from Jill Bloom, March 17, 2021). EPA has revised the residential post-application risk estimates for spiromesifen using these proposed maximum single application rate reductions and Easter lily DFR data.

For residential post-application exposures from liquid applications to gardens, dermal MOEs for ornamental gardens are 2,600 for adults and 3,800 for children 6 to <11 years old based on the proposed rate reductions. The Level of Concern (LOC) is 1000; MOEs lower than the LOC represent risks of concern. Residential post-application risks are not of concern with the proposed rate changes.

Non-occupational Spray Drift Risks

Off-target movement of pesticides can occur via many types of pathways and it is governed by a variety of factors. Sprays that are released and do not deposit in the application area end up off-target and can lead to exposures to those it may directly contact.  They can also deposit on surfaces where contact with residues can eventually lead to indirect exposures (e.g., children playing on lawns where residues have deposited next to treated fields).

A quantitative non-occupational spray drift assessment was conducted for the registered uses of spiromesifen to evaluate potential exposure to people who live adjacent to treated fields.  Adult dermal and children's (1 to < 2-year-old) dermal and incidental oral risk estimates from indirect exposure related to spray drift are not of concern (MOEs >=1000) at the edge of the field. Therefore, there are no non-occupational spray drift risks of concern.

 Aggregate Risks

In an aggregate assessment, EPA considers the combined pesticide exposures and risks from three major sources: food, drinking water, and residential exposures. The Agency sums the exposures from these sources and compares the aggregate risk to quantitative estimates of hazard. Aggregate short-/intermediate-term (food + water + residential) and chronic (food + water) risk assessments were conducted.

A short-term aggregate risk assessment was performed for adults and children. In the revised aggregate risk assessment incorporating proposed rate changes, the residential scenario with the highest risks of concern are for post-application exposures in ornamental gardens treated with liquid formulations at the maximum application rate of 0.0625 lb ai/A, with MOEs of 1,400 for adults and 1,500 for children between the ages of 6 and 11. All short-term aggregate MOEs are above the LOC of 1000 and are not of concern with the proposed rate changes.

 Cumulative Risks

The Agency has not made a common mechanism of toxicity to humans for spiromesifen and any other substance. Spiromesifen does not appear to produce a toxic metabolite produced by other substances. Therefore, the Agency has premised this PID and the underlying risk assessments on the belief that spiromesifen does not have a common mechanism of toxicity with other substances for registration review.

 Occupational Handler Risks

Occupational handlers are individuals involved in the pesticide application process (including mixers, loaders, and applicators). All handlers are assessed with the assumption that they are wearing baseline attire (long-sleeved shirt, long pants, socks, and shoes). Aerial applicators are assumed to be in enclosed cabs. Spiromesifen poses potential risks of concern to some occupational handlers based on combined dermal and inhalation exposures. For handlers with potential risks of concern at baseline, risks also are estimated for increasing levels of PPE. MOEs below the LOC of 1000 for both the dermal and inhalation exposures are considered to represent risks of concern. Only the scenarios that resulted in potential risks of concern are summarized below. The first MOE represents handlers wearing baseline attire. The second MOE represents the baseline attire plus the lowest level of PPE that yields an MOE > 1000.

Mixer/Loaders (M/L) supporting aerial applications to "typical" field crops:
 MOE = 440 at baseline
 MOE = 2200 with gloves

M/L supporting aerial applications to high-acreage field crops
 MOE=130 at baseline.
 MOE=2600 with engineering controls (EC).

M/L supporting chemigation in typical field crops and high acreage field crops
 MOE=440 at baseline
 MOE=2200 with the addition of gloves

M/L supporting groundboom broadcast applications to high acreage field crops
 MOE=770 at baseline
 MOE =2200 with the addition of gloves.

Applicators using air blast equipment for application to nursery crops (ornamentals, vegetables, trees, container stock)
 MOE=930 at baseline
 MOE=1100 with the addition of gloves.

Mixer/Loader/Applicators (M/L/A) using mechanically pressurized handguns for broadcast foliar and ground-directed applications to typical field crops
 MOE=55 baseline
 There is no combination of PPE that yields an MOE greater than the LOC, and the use of ECs is not feasible.

 Occupational Post-Application Risks

A quantitative non-cancer occupational post-application inhalation exposure assessment was not performed for the agricultural uses of spiromesifen. If new policies or procedures are put into place, then the Agency may revisit the need for a quantitative occupational post-application inhalation exposure assessment for spiromesifen.

Based on the currently registered uses of spiromesifen, occupational post-application exposures are expected, and there are some dermal risks of concern. Potential occupational post-application activities resulting in dermal risk estimates of concern (LOC > 1000) on the day of application of spiromesifen products were identified in the DRA. Occupational post-application MOEs range from 460 to 170,000 on the day of application, and do not reach acceptable MOEs until anywhere from 12 hours after application up to 14 days after application.

Table 3. Occupational Post-Application Activities Resulting in Dermal Risk Estimates > LOC on the Day of Application
                                   Activity
                                     Crop
                          Application Rate (lb ai/A)
                                # of Days Until
                                 MOEs > LOC
Moving hand set irrigation equipment
Carrot
                                     0.25
                                      11
Moving hand set irrigation equipment
Mint, Peppermint, Spearmint
                                     0.25
                                      11
Moving hand set irrigation equipment
Ornamentals
                                     0.125
                                       0
Moving hand set irrigation equipment
Potatoes, white & Irish
                                     0.25
                                      11
Moving hand set irrigation equipment
Tuberous & corm vegetables
                                     0.25
                                      11
Harvesting
Cotton
                                     0.168
                                       4
Hand tying and training (for blanching)
Cauliflower
                                     0.25
                                      14
Harvesting
Cauliflower
                                     0.133
                                      14
Harvesting
Leafy Brassica greens
                                     0.133
                                      14

The original occupational post-application risk assessment for ornamentals was based on a maximum single application rate of 0.25 lb ai/A, and the Agency estimated that it would take 11 days after application to achieve an LOC at or above the LOC for moving hand-set irrigation equipment. At the new, lower proposed maximum single application rate of 0.125 lb ai/A, there are no risks of concern for re-entry workers on the day of application.

For cotton, the labeled Pre-Harvest Interval (PHI), which is minimum interval allowed between the last application of the pesticide and harvest, is 30 days, so harvest would not take place within the interval shown in the table above. Therefore, there are no post-application risks of concern for harvesting cotton.

Human Incidents and Epidemiology

The last spiromesifen human incidents search was conducted on July 23, 2019.  Both the Incident Data System (IDS) and National Institute of Occupational Safety and Health (NIOSH) Sentinel Event Notification System for Occupational Risk (SENSOR)-Pesticides databases were searched.

For the Main IDS analysis covering the timeframe from January 1, 2014 to July 23, 2019, there were two incidents involving a single active ingredient.  Of the two incidents, one involved the single active ingredient spiromesifen (only) which was classified as moderate severity.  The second spiromesifen incident reported involving multiple active ingredients which was reported to Main IDS. There were five spiromesifen incidents reported to Aggregate IDS for the five years from January 1, 2014 to July 23, 2019. Four incidents were classified as minor severity and on incident had no or unknown effects. A query of SENSOR-Pesticides 1998-2015 identified one case involving spiromesifen.

The Agricultural Health Study (AHS) is a federally funded study that evaluates associations between pesticide exposures and cancer and other health outcomes and represents a collaborative effort between the U.S. National Cancer Institute (NCI), National Institute of Environmental Health Sciences (NIEHS), Centers for Disease Control and Prevention's (CDC's) NIOSH, and EPA. Spiromesifen is not included in the AHS, and therefore this study does not provide information for this report.

Based on the continued low frequency and severity of spiromesifen incidents reported to both IDS and SENSOR-Pesticides, there does not appear to be a concern at this time. The Agency will continue to monitor the incident information. Additional analyses will be conducted if ongoing human incident monitoring indicates a concern.

Tolerances

Tolerances for spiromesifen are established under 40 CFR §180.607. The current plant and livestock methods are adequate for tolerance enforcement. The tolerance expressions are up-to-date. During the risk assessment process, EPA determined that changes to some tolerances are needed to cover residues in or on food from uses of spiromesifen. For more information, see Section IV.B, below.

Human Health Data Needs

The human health database for spiromesifen is mostly complete. A comparative metabolism study in rats, dogs, and humans is needed to help elucidate the basis for the species differences in target organ toxicity. Until such data are available, a database uncertainty factor of 10X has been retained for all exposure scenarios being assessed for spiromesifen.

Ecological Risks

A summary of the Agency's ecological risk assessment is presented below. The Agency used the most current science policies and risk assessment methodologies to prepare a risk assessment in support of the registration review of spiromesifen. For additional details on the ecological assessment for spiromesifen, see Spiromesifen: Draft Ecological Risk Assessment for Registration Review  in EPA's public docket (EPA-HQ-OPP-2014-0263).

Ecological risks are estimated as Risk Quotients (RQs), which show the relationship of measures of toxicity to environmental exposures. The Agency typically calculates risk estimates based on the No Observed Adverse Effects Level or Concentration (NOAEL/NOAEC), which would be the highest dose or concentration in the selected toxicity study that does not produce statistically significant adverse effects relative to untreated controls. The acute risk LOC for all non-listed animal taxa except bees is 0.5; for bees, it is 0.4. The chronic risk LOC for animals is 1.0. The LOCs for risk to plant species are not categorized as either acute or chronic; the LOC is 1.0. An RQ that is greater than the LOC represents a potential risk of concern.

 Risk Summary and Characterization

 Terrestrial Risks

The Agency selected endpoints for assessing chronic mammalian risks from a 2-generation reproduction study in which 14% reduction in pup weight and a 10% reduction in female body weight prior to mating were observed at the lowest adverse effect level (LOAEL) or concentration (LOAEC).

For terrestrial vertebrate wildlife, the Agency relies foremost on the "Kenaga nomogram" to quantify residues in different terrestrial food items like grass, fruits, and arthropods contaminated with pesticide residues as a result of applications on the field or originating from off-site movement of the pesticide. The Kenaga nomogram provides exposure estimates for three size ranges of birds and mammals (for dose-based RQs; there are no size distinctions for dietary-based RQs). The Agency usually starts with "upper-bound" Kenaga values, maximum application rates, and the NOAEL/NOAEC. The Agency also may do alternative calculations based on "mean" Kenaga values, reduced application rates, or the LOAEL/LOAEC, which is the lowest dose in the selected toxicity study where statistically significant adverse effects were observed relative to untreated controls. It is expected that exposure will be higher than the mean Kenaga Estimated Environmental Concentrations (EECs) in some fields. The Agency has a different approach for assessing risks to bees, as explained in detail in the ecological risk assessment.

There were no acute or chronic risks of concern identified for birds, reptiles, and terrestrial-phase amphibians for any of the uses of spiromesifen evaluated. For mammals, there were no acute risks of concern identified. For both mammals and birds, the highest doses tested in the acute toxicity studies were greater than the EECs.

Mammals

The ecological risk assessment identified the potential for chronic risk to mammals. The Agency selected endpoints for assessing chronic mammalian risks from a 2-generation reproduction study in which 14% reduction in pup weight and a 10% reduction in female body weight prior to mating were observed.

On-Field Risks

Based on upper-bound Kenaga exposure estimates for maximum application rates and the NOAEL/NOAEC, chronic dose-based RQs exceeding the LOC range from 1.1 to 23. RQs exceed the LOC for most combinations of mammal size, food source, and target crop. Chronic dietary RQs ranged up to 6.6, and potential risks of concern were identified for most crop and food type combinations.

The Agency also evaluated alternate scenarios to characterize risks relative to these high-end estimates. Combinations of maximum application rates with different Kenaga values and measures of toxicity yielded lower RQs. Overall:
    For the NOAEL/NOAEC and mean Kenaga values, RQs are reduced by about 65%.
    For the LOAEL/LOAEC and upper-bound Kenaga values, RQs are reduced by about 74%.
    For the LOAEL/LOAEC and mean Kenaga values, RQs are reduced by about 90% and fall below the chronic risk LOC across all-sized mammals and forage categories.

The Agency also calculated risk estimates based on average, rather than maximum, application rates. Chronic dose-based RQs above the LOC and based on upper-bound Kenaga and the NOAEL/NOAEC ranged from 1.1 to 12. Dietary-based RQs were as high as 3.6. For uses with more than one application/year, or for single applications with rates greater than 0.124 lb ai/A, dietary-based RQs exceed the chronic risk LOC for mammals foraging on short grass for all use sites except corn, broccoli, and cantaloupe. When risk estimates are based on average rates, the LOAEL/LOAEC, and mean Kenaga exposure values, RQs are reduced by 91% relative and fall below the chronic risk LOC across all-sized mammals and forage categories.

EPA also looked at the percentage of the mammalian diet that would need to come from a treated field to result in potential chronic risks of concern. Due to large differences in application rates for different use sites, what food sources are utilized by different animals, and animal size, these percentages cover a large range of values. The percent of diet needed for exceedance of the LOC for mammals was calculated to be as low as 3% and as high as 114%; the latter value indicates that even if this mammal got all of its diet from treated fields, the chronic risk LOC would not be exceeded.

Off-Field Risks

Mammals also forage in habitats adjacent to treated fields where residues of spiromesifen are present due to spray drift. Residues from spray drift differ based on application rate, the method of application (higher for aerial vs. ground applications), and the size of droplets in the spray; for spiromesifen, residues may increase over time when there are multiple applications over the course of crop development. For aerial applications with medium to coarse droplet sizes, there is a chronic risk of concern to mammals up to 125 feet from the edge of the treated field. For ground applications with the same parameters, this "effects distance" can be as high 59 feet.

Residues of spiromesifen can accumulate in the food chain over time, and mammals and birds that prey on aquatic organisms can be exposed to those residues through their diets. Risks for mammals that feed on aquatic organism are estimated differently than described above (the ecological risk assessment details the methodology), although dietary exposures differ based on application rate and number of applications. For residues attributable to the use of spiromesifen on ornamentals in California, EPA has calculated chronic dose-based RQs up to 1.87.

Overall, the Agency has determined that spiromesifen may result in chronic risks of concern to mammals from consumption of both terrestrial and aquatic dietary items.

 Terrestrial Invertebrates (Pollinators)

The chronic toxicity endpoint for spiromesifen in larval bees cannot be definitively determined with available data; chronic endpoints for the metabolite spiromesifen-enol include 36% larval mortality. For adult bees, the chronic endpoint was 57% mortality for both spiromesifen and for spiromesifen-enol.

On-Field Risks

The Agency uses pollinators to represent terrestrial invertebrates. All the registered use sites for spiromesifen are attractive to pollinators. In EPA's risk assessments, pollinators are represented primarily by honey bees, although there is some discussion of other bee species. Experimental toxicity data from contact or oral exposure of different durations and for different castes of honey bee are used to estimate potential risks. Higher tier data may also be available for residues in honey bee food sources (pollen and nectar) and from field studies.

The highest dose in the acute contact toxicity test for adult honey bees did not produce any adverse effects and the Agency has determined that there are no acute risks of concern to adult bees from contact exposure. RQs for acute oral risk to adult bees are well below the LOC.

The ecological risk assessment identified potential acute oral risks of concern for larval worker bees from exposure to both parent spiromesifen (RQs up to 0.67 for average application rates and to  1.19 for maximum application rates) and the metabolite spiromesifen-enol (RQs ranging from 13 to 26 for maximum application rates and 9 to 23 for average rates), with an LOC of 0.4.

The Agency also assessed risks for chronic exposure of bees to spiromesifen and spiromesifen-enol. For adult bees, RQs for the parent compound are below the chronic risk LOC based on average and maximum application rates for all assessed uses. Chronic RQs for the metabolite are above the LOC of 1.0 for all uses, with RQs from 36 to 71 for maximum rates; for average rates, RQs are 24 to 64. For larval bees exposed at the maximum rate, RQs for the degradate spiromesifen-enol range from 30 to 60 while at average rates, RQs range from 20 to 54.

In refinements to these risk assessments, the Agency compared available data on residues of spiromesifen and spiromesifen-enol in pollen and nectar to the appropriate measures of toxicity. Although risk estimates were calculated for both adult foragers and adult nurse bees, acute estimates are not specific to task. For chronic risks, estimates for nurse bees are (1/2) to (2/3) those for foragers and only estimates for foragers are presented here. Chronic toxicity data for larval bees could not be used quantitatively. The risks, based on maximum application rates for all use sites that the Agency assessed can be summarized as follows:

Table 4.  Summary of Honey Bee Risk Estimates (RQs above the LOC) for Residues in Pollen and Nectar Based on Maximum Application Rates
                                   Bee Caste
                                 Spiromesifen
                               Spiromesifen-enol

                                     Acute
                                    Chronic
                                     Acute
                                    Chronic
                                Adult Forager/
                                   Nurse Bee
                                 Below the LOC
                                 Below the LOC
                                Not calculated
                               6.8 (cotton only)
                               Larval Worker Bee
                              0.49 (cotton only)
                                Not calculated
                               2.4 (cotton only)
                               5.6 (cotton only)

The Agency also evaluated several honey bee field studies including semi-field colony-level enclosure studies and greenhouse residue studies. The Agency has concluded that, overall, these studies show that there are adverse on larval and adult bee survival, foraging activity, brood index, and hive weight at application rates as low as 0.13-0.16 lb ai/A. The results of studies with bumble bees were mixed but adverse effects were observed. The Agency concluded that risk estimates for honey bees endpoints are likely protective of risks to bumble bees.

Off-field Risks

The Agency used the AgDrift model to estimate the distance outside of a treated field that honey bees could be exposed to residues from drift without potential risks of concern (the effects distance). For spiromesifen, there are acute LOC exceedances only for larval honey bees. Larval honey bees can be exposed to pesticide residues via the consumption of food stores within hives that are harvested by adult forager bees and are not likely to be exposed directly to spray drift.

For aerial applications with spiromesifen at medium and coarser droplet sizes, the Agency estimated that a single application rate of 0.088 lb ai/A would result in an effects distance of about 10 feet. For ground applications with the same parameters and at a high boom height, the effects distance is about 3 feet.

 Terrestrial Plants

The endpoints for terrestrial plants are based on effects from seedling emergence and vegetative vigor laboratory studies. Based on these endpoints, the Agency identified potential risks of concern to some non-target terrestrial plants from the use of spiromesifen. Risks were estimated for aerial and ground sprays, maximum and average single application rates, for dry and semi-aquatic areas, for monocotyledonous (monocot) and dicotyledonous (dicot) terrestrial plants, and for drift and drift and run-off combined. Potential risks of concern (i.e., RQs above the LOC of 1.0) were identified for both aerial and ground applications at the maximum rate for use sites with higher application rates (i.e., >=0.25 lb ai/A) for monocots in semi-aquatic areas, as a result of spray drift and run-off combined. The highest RQ was calculated as 1.66, for monocots in semi-aquatic areas as a result of aerial applications to corn. When average application rates were assessed for the same parameters, only the use on strawberries resulted in potential risks of concern, with the highest RQ at 1.5. Risks to monocots are perhaps not unexpected; spiromesifen is structurally similar to bicyclic tetramic acid compounds that originally were developed as herbicides targeting monocots. The assessment did not report effects distances.

Incident data show eight reports of adverse effects in a variety of field-grown and greenhouse plants with a relatively high confidence that the damage resulted from the use of spiromesifen. Effects included stunting, defoliation, chlorosis, distortion of growing tips, and plant death, and the affected plants included ornamentals (especially croton) and broccoli.

Overall, the Agency concluded that there are potential risks of concern to monocots and, based on the dissonance between risk estimates from empirical data and the reported incidents, risks to dicots are uncertain.

 Aquatic Risks

Although the Agency did not recalculate ecological risk estimates based on formation-decline modeling (as it did for human health risks associated with drinking water), the use of formation-decline modeling would likely yield reduced concentrations in aquatic habitat and reduce risk estimates for aquatic species.

 Freshwater Fish and Aquatic-Phase Amphibians; Estuarine/Marine Fish; Estuarine/Marine Invertebrates; Aquatic Plants (Vascular and Non-vascular)

The Agency determined that there are no potential acute or chronic risks of concern for the aquatic animal taxa exposed to spiromesifen. In most cases, these conclusions were based on RQs that did not exceed the LOCs. In other cases, the available toxicity studies did not provide definitive endpoints -- the highest doses tested, which did not result in adverse effects, were well above the EECs.

For aquatic plants, the highest doses tested did not elicit adverse effects, but they were below the EEC. These high doses were approximately (1/2) the EEC. Because the Agency cannot identify a dose at which adverse effects were observed, risks to aquatic plants are uncertain.

 Freshwater Invertebrates

 In acute toxicity studies for daphnids, representing freshwater invertebrates, no adverse lethal or sublethal effects were recorded. The highest dose tested was well above the water column and sediment EECs. There are no acute risks of concern for freshwater invertebrates.

 In the study selected by EPA for the risk assessment, chronic exposure produced a 31% reduction in the number of offspring per adult female at the LOAEC, based on concentrations of parent spiromesifen in the water column. EPA identified only two scenarios where RQs exceed the chronic risk LOC of 1. RQs exceed the LOC for aerial applications to corn (RQ= 1.04) based on two applications at 0.266 lb ai/A, and for ground-based applications to ornamentals (RQ = 1.38), when based on three crop cycles and three applications/crop cycle at 0.25 lb ai/A. For the ornamental use, the RQ based on only a single crop cycle per year (0.67) falls below the chronic risk LOC. For the corn use, the RQ (0.32) based on EECs calculated with the average use rate (1x @ 0.12 lb ai/A) also falls below the chronic risk LOC.

Based on its environmental fate properties, spiromesifen is considered likely to partition to benthic sediments in aquatic systems. In several such studies, an endpoint could not be identified, and in another study, adverse effects were reported but concentrations of spiromesifen were not analytically verified. Collectively, data from the two sub-chronic spiked sediment studies indicate little transformation of parent spiromesifen to -enol in the sediment, and only minimal partitioning of parent spiromesifen in the sediment to the pore water, where it then transforms to varying extents into spiromesifen-enol. Based on the available data there are no chronic risks of concern for benthic aquatic invertebrates from spiromesifen uses when exposed via contact with sediment or pore water residues of parent spiromesifen.

Ecological Incidents

A search of the Incident Data System (IDS) for spiromesifen was conducted in support of risk assessment for reports between the time spiromesifen was first registered until September 2019.  In addition to the eight incident reports for terrestrial plants (discussed above), one honey bee incident was reported in the Main IDS, but was classified as "unlikely" because dimethoate, an insecticide, was also implicated. All incidents in the Main IDS are detailed in the ecological risk assessment. The aggregate incident database for spiromesifen contains four other incidents (all of which involved "minor" non-target injury to plants), but no additional information is available for those incidents.

The Agency will continue to monitor ecological incident information as it is reported to the Agency. A detailed analysis of these incidents will be conducted if reported information monitoring indicates concerns for risks to nontarget organisms.

Ecological and Environmental Fate Data Needs

The Agency issued a Generic Data Call-In (GDCI-024875-1535) in June 2016. The ecological effects and environmental fate database for spiromesifen is considered complete, except for:
 ECM/ILV data for soil and water have been submitted but, due to study deficiencies, new data are needed.
 Chronic larval toxicity data for spiromesifen in the honey bee have been submitted, but because a definitive endpoint could not be identified, new data are needed.
 Some higher tier pollinator data submitted in response to the DCI are still in review. It is likely that additional higher tier data may be needed; the Agency will confirm once the review of the submitted data is complete.

Although not required by the DCI, the Agency has determined that a bioconcentration study would be useful. The Agency will consider issuing a DCI for bioconcentration data in the future.

Benefits Assessment

Spiromesifen is a selective insecticide/acaricide with contact and systemic activity. It works by inhibiting acetyl-CoA carboxylase (Mode of Action, or MoA, Group 23). Spiromesifen is efficacious against all mite life stages and certain immature insects. Most commonly, spiromesifen is used for the control of mites, particularly spider mites, but it also used for the control of invasive and/or disease vectoring whiteflies and psyllids. Spiromesifen is one of three active ingredients with this MoA registered for use in the U.S., where it is used on many agronomic and ornamental plant use sites.

Spiromesifen may provide benefits to Integrated Pest Management (IPM) as an early season insecticide/acaricide as it is reported to have attributes such as a relatively low toxicity against many non-target, biological control agents such as parasitoids, lacewings, predatory bugs relative to several alternative pesticide chemistries. Additionally, spiromesifen may provide value to growers managing insecticide/acaricide resistance.

In agriculture, spiromesifen provides benefits to growers of strawberries, cantaloupes, and peppers; extension recommendations highlight the importance of spider mites and whiteflies as economically important and yield-limiting pests. The value of spiromesifen to growers of strawberries, cantaloupes, and peppers for the control of spider mites and whiteflies is reflected in the percent of strawberries, cantaloupes, and peppers treated with spiromesifen. Additionally, spiromesifen may provide regional benefits to growers producing corn in arid climates and to potato growers managing sporadic outbreaks of the highly damaging potato psyllid. Across other agricultural use sites, spiromesifen is likely to provide minimal benefits outside of considerations related to IPM and resistance management of spider mites, whiteflies, and psyllids.

In ornamental plant production, spiromesifen is a useful tool for managing spider mites and whiteflies. Spiromesifen may provide benefits as a potential pesticide rotational partner for resistance management in the production and maintenance of ornamentals in greenhouses, nurseries, or landscapes as there are no reported cases of insects or mites currently resistant to spiromesifen in the U.S. However, the development of resistance by pests can occur quickly, particularly in greenhouse production systems, and instances of resistance may be underreported.

 PROPOSED INTERIM REGISTRATION REVIEW DECISION

       Proposed Risk Mitigation and Regulatory Rationale

The Agency has reviewed the risks and benefits associated with the registered uses of spiromesifen in developing this Proposed Interim Registration Review Decision. The Agency has determined that there are potential human health and ecological risks of concern associated with the uses of spiromesifen, as currently registered. The Agency concluded that there are potential human health risks of concern in these areas: dietary, residential post-application, aggregate, occupational handler, and occupational post-application exposures. The Agency has re-evaluated these potential risks of concern based on proposed risk mitigation measures, as detailed earlier in this document. The Agency has concluded that there are potential ecological risks of concern in these taxa: mammals, pollinators, terrestrial plants (monocots), and freshwater aquatic invertebrates.

The Agency is proposing a number of mitigation measures to address these risks, including application rate reductions, PPE and ECs, prohibition of certain application equipment, re-entry prohibitions for some crops and post-application activities, spray drift management labeling, and new or updated advisory statements related to aquatic resources and pollinator protection.

Once implemented, the proposed risk mitigation measures and updates proposed by the Agency will allow spiromesifen to meet the standard for registration. In developing the proposed risk mitigation, the Agency has considered both the risks and benefits associated with the use of spiromesifen. At this time, the sole registrant of spiromesifen products, Bayer, has expressly agreed to all the proposed mitigation measures except for specific elements of the spray drift management labeling. Potential user impacts for each of the proposed measures are discussed below, except for proposed advisory statements, which are not considered by the Agency to result in such impacts.

 Proposed Label Mitigation: Application Rate Reductions

The Agency has identified potential risks of concern related to dietary, residential, and aggregate exposures, and is proposing risk mitigation measures to address those risks. The proposed measures will also reduce exposures to wildlife.

The Agency is proposing that all end-use product labels eliminate phrasing that refers to application rates crop cycles and seasons and replace it with "annual" or "per/year" statements. At the same time, the Agency is proposing that the number of applications per year allowed on product labels will be equivalent to the current number of applications allowed for one crop cycle or season. As an example, EPA is proposing that a product label with Directions for Use that include:

   Maximum amount allowed per crop season: x per acre; maximum crop season per year: 3; maximum number of applications per crop season: 3

Would be revised to read:

   Maximum amount allowed per year: x per acre; maximum number of applications per year: 3

In addition, the Agency is proposing that some maximum application rates be reduced, through changes to the single maximum application rate; all maximum annual application rates will be limited to no more than 0.35 lb ai/A. Based on the proposals in this PID, the new use parameters would appear on spiromesifen labels as shown in the table below. The single application rates that are proposed to change are marked with an asterisk (*).

Table 5. Proposed Application Parameters for Spiromesifen
Use Site
Maximum single application rate in lb ai/A (proposed rates marked with *)
Proposed maximum annual application rate in lb ai/A
Carrot
                                     0.25
                                     0.35
Corn, Field, Pop & Sweet
                                     0.27
                                     0.35
Cotton
                                    0.168*
                                     0.35
Cucurbits
                                     0.133
                                     0.35
Fruiting vegetables
                                     0.133
                                     0.35
Leafy greens
                                     0.133
                                     0.35
Low growing berries, inc. strawberry, lowbush blueberry, cranberry
                                     0.25
                                     0.35
Mint, Peppermint, Spearmint
                                     0.25
                                     0.35
Ornamentals
(Commercial Production)
                                    0.125*
                                     0.35
Ornamentals
(Residential garden)
                                    0.0625*
                                     0.188
Ornamentals
(Residential trees & indoors)
                                    0.125*
                                     0.35
Potatoes, White & Irish
                                     0.25
                                     0.35
Tuberous & corm vegetables
                                     0.25
                                     0.35

Users must not apply more than 0.35 lb ai of spiromesifen per acre per year from any source.

These changes, once implemented, will result in dietary, residential post-application, and aggregate risks that are not of concern. They also will help reduce occupational post-application risks.

For field crops such as corn, cotton, and potato that are planted once per year, the maximum annual application rate change has limited effect on users. The single application rate reduction to cotton would impact some cotton growers; nearly 30% of cotton acres treated with spiromesifen, or 5,500 acres annually, are currently treated above this rate. The lower rate is unlikely to provide control of target pests and growers would have to use alternative forms of control. However, less than one percent of cotton acreage is treated with spiromesifen on average, so the aggregate impact may be small. Target pests may rarely cause substantial damage and/or cost-effective alternatives are likely to be available.

Strawberry and some vegetable crops may be planted two or more times per year, so the application rate restrictions may cause growers to turn to alternative chemistries. Strawberry growers are likely to be most impacted. About 15 percent of the strawberry acreage treated with spiromesifen is treated at annual rates over the proposed maximum 0.35 lb ai/A per year, based on grower surveys. Strawberry growers have access to other chemistries that, like spiromesifen, will target mites, but those alternative treatments may come at an increased cost.

In general, the impacts of reductions in application rates and the number of applications of spiromesifen on ornamental plants are expected to be low because alternatives are available if rates do not provide adequate performance or if more applications are needed over the course of the year. Spiromesifen use in ornamental plant settings is most likely based on principles of IPM and resistance managment considerations for utilizing rotation of pesticides with different modes of action.

Proposed Label Mitigation: Personal Protective Equipment

The Agency identified potential risks of concern for handlers of spiromesifen products, and is proposing that spiromesifen product labels require the use of chemical-resistant gloves for the following:
 Mixer/Loaders (M/Ls) supporting the application of spiromesifen via aerial equipment to field crops, typical acreage
 M/Ls supporting application via chemigation to field crops, typical acreage and field crops, high acreage
 M/Ls supporting application via ground boom to field crops, high acreage
 Applicators using ground boom and airblast equipment to treat ornamentals, vegetables, trees, and container stock in nurseries

The use of gloves will mitigate potential risks of concern for these handlers. In addition, the Agency is proposing that spiromesifen product labels that already include glove requirements be updated to current standards. Impacts on users are expected to be minimal because gloves are inexpensive and readily available.

Proposed Label Mitigation: Engineering Controls

The Agency has identified potential risks of concern for certain mixer/loaders supporting aerial applications of spiromesifen. To address these potential risks, the Agency is proposing that spiromesifen labels allowing application via aerial application require that mixer/loaders supporting these applications to high acreage field crops use closed mixing/loading systems. The use of these systems will mitigate potential risks of concern for these handlers.

Aerial applicators are likely to already have appropriate equipment and the impact of requiring engineering controls for aerial applications will unlikely impede the use of spiromesifen on high acreage field crops such as field corn or cotton.

Proposed Label Mitigation: Prohibition of Certain Application Equipment

The Agency has identified risks of concern for mixer/loader/applicators using specific hand-held equipment to apply spiromesifen. To address those risks, the Agency is proposing that spiromesifen labels prohibit the use of mechanically pressurized hand gun equipment.

Due to the small acreage of commercial ornamental and nursery production and the limited amount of spiromesifen that would be used on residential ornamentals by commercial applicators, it is likely that spiromesifen is applied with handheld equipment. Handheld equipment is a practical application method for ornamentals grown on difficult terrain that may be inaccessible or unrealistic to treat with other application equipment. The use of handheld equipment on ornamental use sites may reduce costs associated with materials, equipment, and labor. The prohibition of mechanically pressurized hand guns for ornamental plant uses could potentially be more impactful than the prohibition on agricultural use sites. However, ornamental applicators would also have access to other handheld equipment or could choose an alternative insecticide/acaricide that allows for applications with a mechanically pressurized hand gun.

In crop production, the impact of prohibiting mechanically pressurized hand gun application equipment is expected to be low. The prohibition of mechanically pressurized hand guns may reduce application method flexibility, particularly for growers who use mechanically pressurized hand guns that are mounted on boom sprayers, which allow growers to easily treat areas that would otherwise be unreachable with the boom due to obstacles or variations in terrain. However, applicators could still apply spiromesifen with manually pressurized handheld equipment such as compressed air or backpack sprayers. If the use of a compressed air or backpack sprayers is not feasible or if a grower does not have such sprayer, the use of alternative insecticide/acaricides that allow for applications with mechanically pressurized hand guns is likely.

Proposed Label Mitigation: Re-entry Prohibitions

The Agency has identified potential risks of concern for workers entering certain areas to which spiromesifen has been applied in order to perform certain post-application activities. The Agency is proposing that spiromesifen product labels restrict worker entry for specified intervals after the application of spiromesifen for certain specific post-application activities. The affected use sites and activities, along with the amount of time the Agency proposes to restrict entry after applications of spiromesifen are:

 Moving hand-set irrigation equipment in carrots, mint/peppermint/spearmint, potatoes, and tuberous and corm vegetables -- entry prohibited for 11 days after spiromesifen application.
 Hand tying and training cauliflower -- entry prohibited for 14 days after spiromesifen application.
 Harvesting leafy Brassica greens and cauliflower -- entry prohibited for 14 days after spiromesifen application.

The Agency has determined that, while the original occupational risk assessment indicated that there are potential risks of concern for workers entering nurseries to which spiromesifen has been applied in order to move hand-set irrigation equipment, at the proposed reduced application rate for these uses, exposure will not result in risks of concern. In addition, as explained previously, the PHI in cotton is protective of worker re-entry for the purpose of harvesting cotton after application of spiromesifen.

An 11-day prohibition for re-entry to move hand-set equipment after spiromesifen application is potentially infeasible for some growers. Such growers would probably use an alternative insecticide/acaricide rather than try to schedule irrigation activities around spiromesifen applications. The number of growers who may be affected is likely to be small. According to the USDA's 2017 Census of Agriculture; full citation available in Assessment of the Use, Usage, and Benefits of Spiromesifen (PC# 024875) and Impacts of Potential Mitigation Measures in Agricultural and Non-agricultural Use Sites, available on the public docket), hand-set irrigation was used on less than 400,000 acres in 2017. However, slightly more than 80% of the acres reported to use hand-set irrigation equipment occur in the Pacific Northwest (Idaho, Montana, Oregon, Washington, Wyoming) and California, which are major production areas for potatoes, carrots, mint, and ornamentals, although the use of hand-set irrigation equipment in potatoes has reportedly declined considerably in recent years.

Overall, the impact of a 14-day entry prohibition for hand tying and training in cauliflower is expected to be low because spiromesifen is most likely to be applied earlier in the growing season, prior to tying activities, when targets pests such as whiteflies are at an immature life stage susceptible to spiromesifen. As noted above, the registrant has indicated that hand tying and training of cauliflower occurs about two weeks before harvest, and the last application of spiromesifen would be about one month before harvest; a re-entry prohibition of 14 days after application for the purpose of hand tying and training fits within that interval. Later in the season, growers could use alternative insecticides, such as spirotetramat, with REIs and pre-harvest intervals (PHI) of one day.

The 14-day prohibition on hand harvesting leafy Brassica greens and cauliflower following an application of spiromesifen is also expected to have a limited impact. Spiromesifen use in leafy Brassica greens and cauliflower is most likely to occur early in the season, so most growers would not have to alter their usual practices. The registrant has affirmed this timing in its comments on the risk assessments (also noted above).

EPA encourages comments on any potential impacts to growers from these re-entry restrictions.

 Proposed Label Mitigation: Resistance Management

The Agency proposes adding resistance-management language to spiromesifen labels to address pesticide resistance. Consistent with EPA's Pesticide Registration Notice (PRN) on general pesticide resistance management, EPA is proposing the addition of language addressing pesticide resistance to the labels of currently registered pesticides (during registration review) and for new registrations and new uses for currently registered pesticides (at the time of registration). To combat pesticide resistance, resistance management experts recommend using pesticides with different chemical modes (or mechanisms) of action against the same target pest population as part of integrated pest management (IPM) programs. This approach may prevent or delay target pest populations from developing resistance to a particular mode (or mechanism) of action without necessitating increased rates and frequency of applications, possibly prolonging the useful life of pesticides.

Adding this language will provide pesticide users with easy access to important information on maintaining the effectiveness of pesticides -- including spiromesifen--thereby preserving the benefits of spiromesifen and other pesticides. Resistance-management labeling has already been implemented on some subject pesticide labels; mitigation will be most effective when all product labels for the active ingredient consistently reflect resistance-management best practices.

Proposed Label Mitigation: Spray Drift Management

The Agency has identified potential risks of concern for mammals, pollinators, terrestrial plants, and freshwater aquatic invertebrates associated with off-target movement of spiromesifen via spray drift. The Agency is proposing that consistent and appropriate spray drift management language be included on spiromesifen product labels. Such labeling is designed to reduce off-target spray drift and establish a baseline level of protection against spray drift.

The proposed spray drift management language includes mandatory, enforceable statements that will supersede any conflicting language already present on product labels (either advisory or mandatory) covering the same topics. The Agency is also proposing that the spiromesifen registrant standardize all spray drift management advisory language on its product labels, and that the registrant ensure that any existing advisory language left on labels does not contradict or modify the new advisory spray drift statements proposed in this PID. The proposed label language is detailed in Appendix B and includes the following elements:

 Applicators must not spray during temperature inversions.
 For aerial and ground boom applications, select nozzle and pressure that deliver medium or coarser droplets in accordance with American Society of Agricultural & Biological Engineers Standard 572 (ASABE S572).
 Do not apply when wind speeds exceed 15 miles per hour at the application site.
 For aerial applications, if the windspeed is 10 miles per hour or less, applicators must use (1/2) swath displacement upwind at the downwind edge of the field. When the windspeed is between 11-15 miles per hour, applicators must use (3/4) swath displacement upwind at the downwind edge of the field.
 Also for aerial applications, if the windspeed is greater than 10 mph, the boom length must be 65% or less of the wingspan for fixed wing aircraft and 75% or less of the rotor diameter for helicopters. Otherwise, the boom length must be 75% or less of the wingspan for fixed-wing aircraft and 90% or less of the rotor diameter for helicopters.
 For ground boom applications, only apply with the release height recommended by the manufacturer, but no more than 4 feet above the ground surface.

The Agency is proposing a restriction on droplet size because coarser droplets have been demonstrated to decrease spray drift, and therefore, reduce potential risks to non-target species.
In addition to including the spray drift management language on spiromesifen labels, the Agency is proposing that all references to volumetric mean diameter (VMD) information for spray droplets be removed from all spiromesifen labels where such information currently appears. The proposed language above, which cites ASABE S572, eliminates the need for VMD information.

Reducing spray drift will reduce the extent of environmental exposure and risk to non-target plants and animals. Although the Agency is not making a complete endangered species finding at this time, these label changes are expected to reduce the extent of exposure and may reduce risk to listed species whose range and/or critical habitat co-occur with the use of spiromesifen.

Regarding the anticipated impact of the mandatory droplet size range, spiromesifen is locally systemic and primarily works via residual activity from contacting the target pest. Thorough coverage of the plant's foliage is necessary for effective control. University extension publications commonly recommend fine-to-medium sized droplets for contact insecticides and acaricides. Larger droplets may provide less control over pests, such as spider mites, which commonly reside on the underside of leaves and produce webbing that offers protection from pesticides on foliage. Reduced control, in turn, could lead to reduced yields and/or increased selection pressure for the evolution of insecticide resistance. Growers could compensate by increasing application rate or making more insecticide applications (if allowed by the label), or use alternative products, potentially increasing production costs. Mandatory droplet sizes may also complicate growers' ability to tank mix multiple pesticides in a single application.

The impacts of a required swath displacement could include yield loss if a field edge does not receive adequate coverage. These field edges could also serve as a refuge for insects that could subsequently re-infest the field. Aerial applicators should be able to achieve adequate coverage while accounting for swath displacement, but it may complicate treatment by resulting in longer application times and higher costs to the grower.

EPA encourages comments on any potential impacts to growers from specifying a mandatory minimum droplet size on product labels.

Proposed Label Mitigation: Pollinator Advisory Language

The Agency has identified potential risks of concern for pollinators exposed to residues of spiromesifen on treated crops or from plants that are exposed to spiromesifen through residues in drift. The potential for risk is supported by higher tier pollinator data, including information on residues in pollinator food sources, and field and greenhouse studies. Additionally, spiromesifen is registered for use on crops that are attractive to honey bees and other pollinators.

The Agency is proposing that spiromesifen product labels include information that alerts users to the potential for adverse effects to pollinators associated with the use of spiromesifen, and provides information on best management practices aimed at reducing risk to pollinators. The proposed advisory language also provides contact information for reporting bee kills suspected of being associated with exposure to pesticides.

Proposed Label Mitigation: Surface Water Advisory Language

The Agency has identified potential risks of concern to freshwater aquatic invertebrates associated with the use of spiromesifen. To address these potential risks, the Agency is proposing that spiromesifen product labels include a consistent, updated surface water advisory. The proposed advisory statement alerts users to the potential for spiromesifen to affect surface water and the habitat of aquatic organisms, and provides practical information on ways to reduce the contamination of surface waters with spiromesifen.

Proposed Label Mitigation: Ground Water Advisory Language

The Agency has identified potential human health risks of concern associated with residues of spiromesifen in drinking water, including drinking water sourced from ground water. Furthermore, spiromesifen has environmental fate properties associated with chemicals found in groundwater. The Agency is proposing that spiromesifen product labels include a ground water advisory that alerts the user to the potential for ground water contamination with spiromesifen.

 Tolerance Actions

The Agency plans to exercise its FFDCA authority to modify the tolerances for spiromesifen as summarized in Table 4, below.

Table 6.  Anticipated Changes to Tolerances for Spiromesifen
                                   Commodity
                          Established Tolerance (ppm)
                          Anticipated Tolerance (ppm)
                                   Comments
                                 180.607(a)(1)
Bean, edible podded [1]
                                     0.80
                                       1
Harmonization with Codex MRL
Bean, succulent shelled[1]
                                      --
                                      0.1
Update commodity definition and corrected values to be consistent with OECD Rounding Class Practice.
Berry and small fruit, low growing berry, subgroup 13-07G
                                      2.0
                                       3
Harmonization with Codex MRL
      Brassica, head and stem, subgroup 5A
                                      2.0
Remove; crop group 5-16, 4-16, and kohlrabi tolerances are recommended
      Brassica, leafy greens, subgroup 5B
                                      12
Remove; crop group 4-16 tolerances are recommended
Celtuce
                                      --
                                       6
Updating crop group definitions
Coffee, green bean[2]
                                     0.20
                                      0.2
Corrected values to be consistent with OECD Rounding Class Practice.

Corn, field, forage
                                      5.0
                                       5

Corn, field, stover
                                      8.0
                                       8

Corn, pop, stover
                                      4.0
                                       4

Cotton, undelinted seed
                                     0.50
                                      0.7
Harmonization with Codex MRL
Fennel, Florence, fresh leaves and stalk
                                      --
                                       6
Updating to current crop group definitions

Kohlrabi
                                      --
                                       6

Leaf petiole subgroup 22B
                                      --
                                       6

      Leaf petiole subgroup 4B
                                      6.0
Remove; crop group 4-16, 22B, celtuce, and fennel Florence tolerances are recommended
      Leafy greens subgroup 4A
                                      12
Remove; crop group 4-16 tolerance is recommended
Pea, dry, seed
                                     0.20
                                      0.2
Corrected values to be consistent with OECD Rounding Class Practice.
Peppermint, fresh leaves
                                      --
                                      50
Commodity definition revision and corrected values to be consistent with OECD Rounding Class Practice.
      Peppermint, tops
                                      45
Remove
Spearmint, fresh leaves
                                      --
                                      50
Commodity definition revision and corrected values to be consistent with OECD Rounding Class Practice.
      Spearmint, tops
                                      45
Remove
Tea, dried[2]
                                      --
                                      70
Commodity definition revision, harmonization with Codex MRL
      Tea, dry[2]
                                      40
Remove

Tomato, paste
                                     0.80
                                      0.8
Corrected values to be consistent with OECD Rounding Class Practice.
Vegetable, cucurbit, group 9
                                     0.10
                                      0.1

      Vegetable, fruiting, group 8
                                     0.45
Remove; crop group 8-10 tolerance is recommended
Vegetable, fruiting, group 8-10
                                      --
                                      0.5
Update to current group definition and harmonization with Codex pepper MRL
Vegetable, Brassica head and stem group 5-16
                                      --
                                       3
Harmonization with Codex MRL
Vegetable, leafy group 4-16
                                      --
                                      15
Update to current group definition and harmonization with Codex MRL
                                 180.607(a)(2)
Cattle, fat
                                     0.10
                                     0.15
Harmonization with Codex MRL
Cattle, meat byproducts
                                     0.20
                                      0.3

Goat, fat
                                     0.10
                                     0.15

Goat, meat byproducts
                                     0.20
                                      0.3

Horse, fat
                                     0.10
                                     0.15

Horse, meat byproducts
                                     0.20
                                      0.3

Sheep, fat
                                     0.10
                                     0.15

Sheep, meat byproducts
                                     0.20
                                      0.3

                                  180.607(d)
Alfalfa, hay
                                      3.0
                                       3
Corrected values to be consistent with OECD Rounding Class Practice.
Beet, sugar, tops
                                     0.20
Remove; no longer considered a significant feed commodity
Oat, forage
                                     0.20
                                      0.2
Corrected values to be consistent with OECD Rounding Class Practice.
Wheat, forage
                                     0.20
                                      0.2

[1] Tolerances were established in association with proposed uses, but uses were not established due to concerns raised in the environmental assessment.  The Agency requests that the registrant's input on if tolerances should be retained for import purposes or if registration of the associated uses will be sought in the near future.
[2] Tolerance without a U.S. registration.

 Proposed Interim Registration Review Decision

The Agency is issuing this PID in accordance with 40 C.F.R. §§ 155.56 and 155.58. The Agency has made the following proposed interim decision: (1) a comparative metabolism study in rats, dogs, and humans; ECM/ILV for soil and water; a chronic larval honey bee toxicity study; and depending on the disposition of pollinator data currently under review, additional higher tier pollinator data are needed, and (2) EPA proposes that spiromesifen does not meet the registration standard without the changes to the affected registrations and their labeling proposed in Sections IV and Appendices A and B.

In this PID, the Agency is not making any human health or environmental safety findings associated with the Endocrine Disruptor Screening Program (EDSP) screening of spiromesifen. Similarly, the Agency is not making a complete endangered species finding, though the proposed mitigation is expected to reduce the extent of environmental exposure and may reduce risk to listed species whose range or critical habitat co-occur with the use of spiromesifen. The Agency will complete a listed-species assessment and any necessary Endangered Species Act (ESA) Section 7 consultation with the Services, and make an EDSP determination before issuing a final registration review decision for spiromesifen. For more information, see Appendices C and D.

V. NEXT STEPS AND TIMELINE

 Proposed Interim Registration Review Decision

A Federal Register Notice will announce the availability of the spiromesifen PID and open a 60-day comment period. The Agency may issue an Interim Registration Review Decision (ID) for spiromesifen after the close of this comment period if commenters do not submit significant comments or additional information that lead the Agency to change the proposed interim decision described in Section IV.C, above. The Agency may make a final registration review decision for spiromesifen without previously issuing an ID. However, a final registration review decision for spiromesifen will only be made after EPA completes (1) an endangered species determination and any necessary consultation with the Services, and (2) an EDSP determination.

 Implementation of Mitigation Measures

If EPA posts an ID to the public docket, the spiromesifen registrants must submit amended labels, include the label changes described in Appendices A and B, and requests for amendment of registrations within 60 days.

   Appendix A: Summary of Proposed Actions for Spiromesifen
                            Affected Population(s)
                              Source of Exposure
                               Route of Exposure
                             Duration of Exposure
                          Potential Risks of Concern
                               Proposed Actions
General Population
Infants and Children
Residues from application
Dietary
Chronic
Reproductive Toxicity

Reduce application rates
Residential post- application
Residues from application
Dermal
Incidental Oral
Short- and Intermediate Term
Reproductive Toxicity
Reduce application rates
Occupational Handler
Mixing/loading/
application
Dermal
Short- and Intermediate Term
Reproductive Toxicity
PPE
EC
Restrict application methods
Occupational post-application
Residues from application
Dermal
Short- and Intermediate Term
Reproductive Toxicity
Re-entry restrictions
Mammals
Residues from application
Drift
Dietary
Chronic
Chronic Toxicity
Reproductive Toxicity
Reduce application rates
Drift management
Pollinators
Residues from application
Drift
Dietary
Chronic
Chronic Toxicity
Reproductive Toxicity
Reduce application rates
Drift management
Advisory
Terrestrial Plants
Residues from application
Drift
Run-off
Contact
N/A
Seedling Emergence
Vegetative Vigor
Reduce application rates
Drift management
Advisories
Freshwater Invertebrates
Drift
Run-off
Contact
Chronic
Chronic Toxicity
Reproductive Toxicity
Reduce application rates
Drift management
Advisories

   Appendix B: Proposed Labeling Changes for Spiromesifen Products
                                  Description
               Proposed Label Language for Spiromesifen Products
                              Placement on Label

                               End-Use Products

Site of Action Group Number

Note to registrant -- Include:
 Name of the ACTIVE INGREDIENT in the first column
  "GROUP" in the second column
 PRIMARY SITE OF ACTION CODE in the third column
 "INSECTICIDE/MITICIDE" in the fourth column.

                                 SPIROMESIFEN
                                     GROUP
                                      23
                             INSECTICIDE/MITICIDE

Front Panel, upper right quadrant.
All text should be black, bold face and all caps on a white background, except the mode of action code, which should be white, bold face and all caps on a black background; all text and columns should be surrounded by a black rectangle.
Resistance-management labeling statements for insecticides
Include resistance management label language for insecticides/acaricides from PRN 2017-1 (https://www.epa.gov/pesticide-registration/pesticide-registration-notices-year)
Directions for Use, prior to directions for specific crops
Surface Water Advisory Statements

"This product may impact surface water quality due to runoff of rain water. This is especially true for poorly draining soils and soils with shallow ground water. This product is classified as having a high potential for reaching surface water via runoff for several months or more after application.
A level, well-maintained vegetative buffer strip between areas to which this product is applied and surface water features such as ponds, streams, and springs will reduce the potential loading of spiromesifen from runoff water and sediment. Runoff of this product will be reduced by avoiding applications when rainfall or irrigation is expected to occur within 48 hours. Sound erosion control practices will reduce this product's potential to reach aquatic sediment via runoff."
Environmental Hazards
Groundwater Advisory Statements
"This chemical has properties and characteristics associated with chemicals detected in groundwater. This chemical may leach into groundwater if used in areas where soils are permeable, particularly where the water table is shallow."
Environmental Hazards
Updated Gloves Statement

Update the gloves statements to be consistent with Chapter 10 of the Label Review Manual. In particular, remove reference to specific categories in EPA's chemical-resistance category selection chart and list the appropriate chemical-resistant glove types to use.

In the Personal Protective Equipment (PPE) within the Precautionary Statements and Agricultural Use Requirements, if applicable
Personal Protective Equipment
Liquid products
(Registrants should only add PPE for the uses/equipment allowed on current labels)
"All handlers must wear:
 long sleeved shirt,
 long pants,
 shoes and socks.

In addition:
::	Mixer/Loaders (M/Ls) supporting the application of spiromesifen via aerial equipment to carrots, cucurbits, fruiting vegetables, leafy greens (Brassica spp. and others), and low growing berries
    M/Ls supporting application via chemigation to field crops
::	M/Ls supporting application via ground boom to corn; cotton; mint, peppermint, spearmint; potatoes; and tuberous and corm vegetables
::	Applicators using ground boom and airblast equipment to treat ornamentals, vegetables, trees, and container stock in nurseries)
must also wear chemical-resistant gloves.

See Engineering Controls for additional requirements."
In the Personal Protective Equipment (PPE) within the Precautionary Statements
Engineering Controls for products that allow aerial application on the following crops: corn; cotton; mint, peppermint, and spearmint; potatoes; and tuberous and corm vegetables
"Engineering Controls"
In addition to the PPE for all handlers, mixer/loaders supporting aerial applications to [registrants edit list as appropriate: corn; cotton; mint, peppermint, and spearmint; potatoes; and tuberous and corm vegetables must use closed mixing/loading systems that meet the requirements listed in the WPS for agricultural pesticides [40 CFR 170.607(d)(2)(i) &(ii)] for dermal protection."
Precautionary Statements under the heading "Hazards to Humans and Domestic Animals" under the heading "Engineering Controls"
REI statement for the Agricultural Use Requirements Box when there are multiple crops with different REIs
"Do not enter or allow workers to enter during the restricted-entry interval (REI). The REI is listed in the Directions for Use associated with the crop."
Within the Agricultural Use
Requirements Box
Prohibited Entry for Tuberous and Corm Vegetables (Crop Subgroup 1C)
 "Tuberous and Corm Vegetables (Crop Subgroup 1C): The REI is 12 hours.  Do not allow workers to perform hand-set irrigation activities until 11 days after application."
Directions for Use Under the Appropriate Crop Specific Directions
Prohibited Entry for Carrots

 "Carrots: The REI is 12 hours. Do not allow workers to perform hand-set irrigation activities until 11 days after application."

Directions for Use Under the
Appropriate Crop Specific
Directions
Prohibited Entry for Mint/Peppermint/Spearmint

 "Mint/Peppermint/Spearmint: The REI is 12 hours.  Do not allow workers to perform hand-set irrigation activities until 11 days after application."
Directions for Use Under the
Appropriate Crop Specific
Directions
Prohibited Entry for Potato

 "Potato: The REI is 12 hours.  Do not allow workers to perform hand-set irrigation activities until 11 days after application."

Directions for Use Under the
Appropriate Crop Specific
Directions
Prohibited Entry for Leafy Brassica Greens

 "Leafy Brassica Greens: The REI is 12 hours.  Do not allow workers to harvest until 14 days after application."

Directions for Use Under the
Appropriate Crop Specific Directions
Prohibited Entry for cauliflower

 "Cauliflower: The REI is 12 hours Do not allow workers to perform tying/training or harvest until 14 days after application."

Directions for Use Under the
Appropriate Crop Specific
Directions
Maximum Application Rates

Maximum annual application rate:

"For all crops and use sites do not use more than 0.35 lbs spiromesifen per acre per year."

Maximum single application rates:

Cotton: 0.168 lbs ai/A
Ornamentals (ornamentals for commercial production, residential trees and greenhouses): 0.125 lbs ai/A
Ornamentals (garden): 0.0625 lbs ai/A
Directions for Use Under the
Appropriate Crop Specific
Directions
Pollinator Protection Statements

(For products formulated for outdoor foliar applications to agricultural crops.)

"Following best management practices can help reduce risk to terrestrial pollinators.  Examples of best management practices include checking to confirm hive locations before spraying and applying pesticides at twilight and at night when pollinators are less likely foraging.  For additional resources on pollinator best management practices, visit https://www.epa.gov/pollinator-protection/find-best-management-practices-protect-pollinators."
"Pollinator protection plans are developed by states/tribes to promote communication between growers, landowners, farmers, beekeepers, pesticide users, and other pest management professionals to reduce exposure of bees to pesticides. Visit available state/tribal plans for additional information on how to protect pollinators."

"How to Report Bee Kills
It is recommended that users contact both the state lead agency and the U.S. Environmental Protection Agency to report bee kills due to pesticide application.  Bee kills can be reported to EPA at<EMAIL_ADDRESS> To contact your state lead agency, see the current listing of state pesticide regulatory agencies at the National Pesticide Information Center's website:  http://npic.orst.edu/reg/state_agencies.html."
Directions for Use, prior to crop specific directions
Application Prohibition:
For all products that do not prohibit hand-held application equipment
"Applications using mechanically-pressurized handguns are prohibited."
Directions for Use
Additional Required Labelling Action
Applies to all products delivered via liquid spray applications
Remove information about volumetric mean diameter from all labels where such information currently appears.
Directions for Use
Spray Drift Management Application Restrictions for all products that allow aerial application
"MANDATORY SPRAY DRIFT MANAGEMENT
Aerial Applications:
 --------------------------------------------------------------------------------
   Do not release spray at a height greater than 10 ft above the ground or vegetative canopy unless a greater application height is necessary for pilot safety.
    Applicators must select nozzle and pressure that deliver medium or courser droplets in accordance with American Society of Agricultural & Biological Engineers Standard 641 (ASABE S641). If the windspeed is 10 miles per hour or less, applicators must use (1/2) swath displacement upwind at the downwind edge of the field. When the windspeed is between 11-15 miles per hour, applicators must use (3/4) swath displacement upwind at the downwind edge of the field.
    Do not apply when wind speeds exceed 15 mph at the application site. If the windspeed is greater than 10 mph, the boom length must be 65% or less of the wingspan for fixed wing aircraft and 75% or less of the rotor diameter for helicopters. Otherwise, the boom length must be 75% or less of the wingspan for fixed-wing aircraft and 90% or less of the rotor diameter for helicopters.
 --------------------------------------------------------------------------------
   Do not apply during temperature inversions."
Directions for Use, in a box titled "Mandatory Spray Drift Management" under the heading "Aerial Applications"
Placement for these statements should be in general directions for use, before and use-specific directions for use.
Spray Drift Management Application Restrictions for products that allow airblast applications
"MANDATORY SPRAY DRIFT MANAGEMENT

Airblast applications:
    Sprays must be directed into the canopy.
    Do not apply when wind speeds exceed 15 miles per hour at the application site.
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   User must turn off outward pointing nozzles at row ends and when spraying outer row.
    Do not apply during temperature inversions."
Directions for Use, in a box titled "Mandatory Spray Drift Management" under the heading "Airblast Applications"
Spray Drift Management Application Restrictions for products that allow ground boom applications
"MANDATORY SPRAY DRIFT MANAGEMENT
Ground Boom Applications:
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User must only apply with the release height recommended by the manufacturer, but no more than 4 feet above the ground or crop canopy.
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Applicators must select nozzle and pressure that deliver medium or courser droplets in accordance with American Society of Agricultural & Biological Engineers Standard 572 (ASABE S572).
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Do not apply when wind speeds exceed 15 mph at the application site.
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Do not apply during temperature inversions."
Directions for Use, in a box titled "Mandatory Spray Drift Management" under the heading "Ground Boom Applications"
Advisory Spray Drift Management Language for all products delivered via liquid spray application
"SPRAY DRIFT ADVISORIES
THE APPLICATOR IS RESPONSIBLE FOR AVOIDING OFF-SITE SPRAY DRIFT.
BE AWARE OF NEARBY NON-TARGET SITES AND ENVIRONMENTAL CONDITIONS.

IMPORTANCE OF DROPLET SIZE
An effective way to reduce spray drift is to apply large droplets. Use the largest droplets that provide target pest control. While applying larger droplets will reduce spray drift, the potential for drift will be greater if applications are made improperly or under unfavorable environmental conditions.

Controlling Droplet Size  -  Ground Boom (note to registrants: remove if ground boom is prohibited on product labels)
:: Volume - Increasing the spray volume so that larger droplets are produced will reduce spray drift. Use the highest practical spray volume for the application. If a greater spray volume is needed, consider using a nozzle with a higher flow rate.
:: Pressure - Use the lowest spray pressure recommended for the nozzle to produce the target spray volume and droplet size.
:: Spray Nozzle - Use a spray nozzle that is designed for the intended application. Consider using nozzles designed to reduce drift.

Controlling Droplet Size  -  Aircraft (note to registrants: remove if aerial application is prohibited on product labels)
:: Adjust Nozzles - Follow nozzle manufacturers' recommendations for setting up nozzles. Generally, to reduce fine droplets, nozzles should be oriented parallel with the airflow in flight.

BOOM HEIGHT  -  Ground Boom (note to registrants: remove if ground boom is prohibited on product labels)
For ground equipment, the boom should remain level with the crop and have minimal bounce.

RELEASE HEIGHT - Aircraft (note to registrants: remove if aerial application is prohibited on product labels)
Higher release heights increase the potential for spray drift.

SHIELDED SPRAYERS
Shielding the boom or individual nozzles can reduce spray drift. Consider using shielded sprayers. Verify that the shields are not interfering with the uniform deposition of the spray on the target area.

TEMPERATURE AND HUMIDITY
When making applications in hot and dry conditions, use larger droplets to reduce effects of evaporation.

TEMPERATURE INVERSIONS
Drift potential is high during a temperature inversion. Temperature inversions are characterized by increasing temperature with altitude and are common on nights with limited cloud cover and light to no wind. The presence of an inversion can be indicated by ground fog or by the movement of smoke from a ground source or an aircraft smoke generator. Smoke that layers and moves laterally in a concentrated cloud (under low wind conditions) indicates an inversion, while smoke that moves upward and rapidly dissipates indicates good vertical air mixing.

WIND
Drift potential generally increases with wind speed. Applicators need to be familiar with local wind patterns and terrain that could affect spray drift."
Directions for Use, just below the Spray Drift box, under the heading "Spray Drift Advisories"
Advisory Spray Drift Management Language for products that allow boomless ground sprayer applications
"SPRAY DRIFT ADVISORIES
Boomless Ground Applications:
 Setting nozzles at the lowest effective height will help to reduce the potential for spray drift."
Directions for Use, just below the Spray Drift box, under the heading "Spray Drift Advisories"
Advisory Spray Drift Management Language for all products that applications with handheld technologies
"SPRAY DRIFT ADVISORIES
Handheld Technology Applications:
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   Take precautions to minimize spray drift."

Directions for Use, just below the Spray Drift box, under the heading "Spray Drift Advisories"

    Appendix C: Listed-Species Assessment
In 2013, EPA, along with the Fish and Wildlife Service (FWS), the National Marine Fisheries Service (NMFS), and the United States Department of Agriculture (USDA) released a summary of their joint Interim Approaches for assessing risks to endangered and threatened (listed) species from pesticides. These Interim Approaches were developed jointly by the agencies in response to the National Academy of Sciences'(NAS) recommendations that discussed specific scientific and technical issues related to the development of pesticide risk assessments conducted on federally threatened and endangered species.

Since that time, EPA has conducted biological evaluations (BEs) on three pilot chemicals representing the first nationwide pesticide consultations. These initial consultations were pilots and were envisioned to be the start of an iterative process. The agencies are continuing to work to improve the consultation process. For example, advancements to the initial pilot interim methods have been proposed based on experience conducting the first three pilot BEs.  Public input on those proposed revisions is currently being considered.

Also, a provision in the December 2018 Farm Bill included the establishment of a FIFRA Interagency Working Group to provide recommendations for improving the consultation process required under section 7 of the Endangered Species Act for pesticide registration and Registration Review and to increase opportunities for stakeholder input. This group includes representation from EPA, NMFS, FWS, USDA, and the Council on Environmental Quality (CEQ). Given this new law and that the first nationwide pesticide consultations were envisioned as pilots, the agencies are continuing to work collaboratively as consistent with the congressional intent of this new statutory provision. EPA has been tasked with a lead role on this group, and EPA hosted the first Principals Working Group meeting on June 6, 2019.

Given that the agencies are continuing to develop and work toward implementation of approaches to assess the potential risks of pesticides to listed species and their designated critical habitat, the ecological risk assessment supporting this PID for spiromesifen does not contain a complete ESA analysis that includes effects determinations for specific listed species or designated critical habitat. Although EPA has not yet completed effects determinations for specific species or habitats, for this PID, EPA's evaluation assumed, for all taxa of non-target wildlife and plants, that listed species and designated critical habitats may be present in the vicinity of the application of spiromesifen. This will allow EPA to focus its future evaluations on the types of species where the potential for effects exists once the scientific methods being developed by the agencies have been fully vetted. Once that occurs, these methods will be applied to subsequent analyses for spiromesifen as part of completing this registration review.

    Appendix D: Endocrine Disruptor Screening Program
As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, sub-chronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of its most recent registration decision for spiromesifen, EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA § 408(p), spiromesifen is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a "naturally occurring estrogen, or other such endocrine effects as the Administrator may designate." The EDSP employs a two-tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine-related effects caused by the substance, and establish a dose-response relationship between the dose and the E, A, or T effect.