Page 2 of 10 Clothianidin Registration Review: Response to Comments

1. Comment: Multiple commenters inquired as to whether the Agency has considered recent publications characterizing neonicotinoid exposure to honey bees in lab oratory settings ; specifically the 2012

Pettis et al . study with imida cloprid , “ Pesticide exposure in honeybe es results in increased levels of the gut pathogen Nosema

. ”

Response: This study is currently in review and all available data will be considered at the time of risk

assessment.

2. Comment:

Neonicotinoid particulate matter in seed planter exhaust has been discussed in some recently published articles ( Krupke CH, et a l. 2012 ; Tapparo et al. 2012). Is the Agency considering seed planter exhaust as a route of exposure to neonicotinoid compounds like clothianidin?

Response: As captured in the conceptual diagram on page 29 of the clothianidin problem formulation, the Agency will consider exposure resulting from abraded seed coat particulates in the registration

r eview risk assessment fo r clothianidin

.

3. Comment: Will the Agency consider risks to small birds and mammals exposed via treated seed consumption ?

Response:

T he Agency routinely considers risks to passerines (small birds) and small mammals when assessing ecological risk.

4. Comment: Multiple commenters discussed the toxicity profile of clothianidin in terms of acute exposure to bees, wondering how this information will be used in risk assessment.

Response: The EPA is aware of registrant

- submitted studies and other open liter ature studies regarding the potential effects of neonicotinoid insecticides on insect pollinators and specifically on honey

bees.

As part of the review process, the EPA examines the effects of chemicals on bees based on both laboratory and when appropriate, field studies to determine whether individual bees and entire bee colonies may be affected by the use of a compound and to support risk mitigation decisions.Page 3 of 10 The EPA is currently revising its process for assessing pesticide risks to bees to reflect advancements in the state of the science that underlie bee exposure and effects assessments. Interim guidance (USEPA 2011 1 ) on factors to consider when evaluating expos ure and effects to bees is available to ecological risk assessors. In 2012, the EPA will present to a FIFRA Scientific Advisory Panel (SAP) a proposed process for quantifying risks to honeybees and identifying exposure and effect studies needed to inform t hat process. Based on input from the SAP, the EPA will incorporate its revised assessment process to quantify risks to bees in a similar manner

as that used to evaluate risks to other taxa.

As the EPA’s understanding of the science evolves, its need for data and its evaluation of those data will evolve as well. Therefore, as with all taxa, the EPA reserves the right to require additional data it deems necessary to inform its understanding of potential ecological risks and support its associated risk man agement decisions. Additional data requirements for pollinators may extend beyond those identified in problem formulations and preliminary work p lans written in support of the registration r eview process.

5. Comment:

Roberta Firoved quoted Dr. Luis Esp ino , a University of California Cooperative Extension representative

, who provided information on rice and almonds and crop

- specific pest

management practice in California , noting the geographic coincidence of rice growing areas with

almond orchards in the Sacramento valley region

. Seedling pests in rice fields are commonly controlled via insecticide application, but these treatments are typically not applied before late April, weeks after the completion of almond bloom.

Response: The Agency will c ontinue to rely on the chemical

- specific usage data provided by the California Department of Pesticide Regulation to detect trends in both the amount and spatial distribution of

clothianidin applied in the state of California. The information regarding ti ming of insecticide applications may be useful for exposure characterization in the registration r eview assessment

.

6. Comment: Bayer CropScience (BCS) requests that section 7.1 Stressors of Concern (page 31) of the PF document be amended to omit aquatic invertebrates as species at risk with respect to seed

treatment uses. The correct screening level aquatic risk assessment indicates minimal chronic risk to all aquatic species, including invertebrates, s ince all RQ’s are less than 1.

Response: In the Section 3 New Use assessment for clothianidin uses on mustard and cotton (December 2010; D378994, D377955) an acute level of concern (LOC) was inadvertently used in some

cases to evaluate the chronic risk to aquatic invertebrates and that this resul ted in some erroneous LOC exceedences for chronic aquatic invertebrate testing

. Despite this, chronic exceedances to

1 USEPA. 2011. Pesticides: Science and Policy. Interim Guidance on Honey Bee Data Requirements. http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/terrestrial_biology_tech_team/hone

y bee_data_interim_guidance.htmPage 4 of 10 benthic invertebrates did persist using the chronic LOC of 1.0 based on sediment bound (organic carbon normalized) EECs. More importantly ; the language describing aquatic invertebrates as a

taxon at risk was intentionally retained in the problem formulation so as to capture the uncertainty surrounding the chronic toxicity of clothianidin to the sediment

- dwelling midge

, which available data ( MRID 45422414 ) indicate to be more than three orders of magnitude more acutely sensitive than daphnid s (MRID 45422338)

. The EFED’s logic behind a request for 28

- day chronic study with midge using spiked water is that the 10

- day midge study (MRID

46826902 ) does not assess fecundity, which was the most sensitive endpoint in both chronic daphnid and mysid testing. It is noted that the NOAEC in the daphnid chronic test is greater than three orders of magnitude more sensitive than the daphnid 48

- hour EC 50 , wh ich indicates that a

28

- day chronic test with the midge could reveal considerably heightened sensitivity compared to

the 48

- hour testing

.

7. Comment: BCS requests that the Agency reconsider its identification of non

- guideline midge studies using

TGAI and the degradates TZNG and TMG as a data gap. The current aquatic data package is robust and includes sufficient laboratory and field data to allow the Agency to conclude minimal risk for all aquatic organisms, including threatened and endangered species.

Response: As described above, uncertainty regarding the chronic sensitivity of midge exists because this species has tested to be more acutely sensitive than daphnia. Further, the available 10

- day midge study (conducted with clothianidin technical) did n ot evaluate the most sensitive endpoint from the daphnid chronic study (i.e., reproduction). T he Agency is not aware of an acute midge study that indicates equal or lesser toxicity of degradate TMG as compared to daphnia response. Such data would likely preclude the need for additional midge chronic testing with TMG

. However, since the publication of the preliminary work plan, EFED has reconsidered the need for further midge toxicity testing with degradate TZNG. This is principally because available acute toxicity data for midge exposed to TZNG indicate lesser toxicity than acute exposure to clothianidin

technical. The final work plan will be revised accordingly.

8. Comment:

BCS reiterated comments submitt ed to the Agency in January 2011.

• The Agency has mistakenly indicated that the chronic LOC for endangered and threatened species is 0.05 in Table 13 of the EFED document. The correct chronic LOC is 1.0 as noted in Appendix C, page 72 in the EFED documen t. This error in Table 13 led to a chronic LOC that was 20x lower than the appropriate value (1.0 vs. 0.05). Due to this mistake in the process of evaluating the chronic RQ, the EFED memo and science chapter incorrectly conclude that there is a major ris k to free

- swimming aquatic invertebrates. These statements should be removed from the memo and removed from subsequent related sections of the EFED document.

• The Agency mistakenly used the lower range of the 95% confidence interval for the mysid 48

- hour

EC 50 , rather than the EC 50 value, itself.Page 5 of 10 Response: The aquatic invertebrate toxicity characterization errors in the 2010 EFED risk assessment have been noted. EFED will revise this risk characterization as appropriate for the registration review

risk assessment

.

EFED has investigated the concern that a lower bound of a 95% confidence interval for an EC 50 was used instead of the EC 50 value itself. While the endpoint of 22 parts per billion (ppb) is the

lower bound of the EC 50 that was calculated by the study author, the statistical analysi s completed by the EPA reviewer; described in the Data Evaluation Record (DER) for MRID 45422414; determined an EC 50 of 22 ppb with lower and upper 95% confidence bounds of 18 and 27 ppb , res pectively

.

9. Comment:

BCS opposes the use of the language “degradates of concern” on the grounds that it will be misconstrued by the general public as a risk determination rather than a hazard classification.

Response:

T he “degradate of concern” terminology reflects both exposure and hazard components. At this time, degradate TMG is of potential concern to the midge, pending submission of additional

data.

10. Comment:

BCS notes that the summary of a field study conducted by researchers at the Unive rsity of Minnesota and University of Guelph inaccurately characterizes several key findings (Appendix E) . The PF document states “Several effects parameters on honey bees, including mortality, pollen foraging activity, mean number of foragers observed, an d mean honey yield appeared to be negatively impacted by seed treatment, however replicate data for honey bees and hives were not provided, so statistical analysis of the data could not be conducted.” This statement

mischaracterizes the results of the stu dy in question.

Response: Submission of the raw data for this study (MRID 45422435) would allow for verification of the study authors ’ reported results. A statistical re

- analysis would necessarily precede any changes to study characterization.

11. Comment: BCS discusses the following:

• Page 11, Table 3, Aerobic Aquatic Metabolism: There are two studies with acceptable data for the assessment of the aerobic aquatic half

- life

-- MRID 46826903 (half

- life = 187 days; core study with thiazolyl

- radiolab el and one water/sediment system) and MRID 45422324 (half

- lives 48 days and 65 days; supplemental study with phenyl

- radiolabel and two water/sediment systems). All three values should be considered when deriving aerobic aquatic half

- life used for the aqua tic exposure assessment.Page 6 of 10 • Page 38, Table 7.1, Aerobic Aquatic Metabolism: The supplemental aerobic aquatic metabolism study should be listed (MRID 45422324).

Response:

All data for aerobic aquatic metabolism will be evaluated at the time of risk assessment.

12. Comment: BCS discusses the following: Exposure Modeling Input Data: In addition to using the appropriate aerobic aquatic metabolism half

- life, the exposure assessments must also use the appropriate aqueous photolysis half

- life (half

- lives of 0.6 days and 1.1 days for the sterile aqueous buffer solution (MRID 45422318) and natural water (MRID 45422318) studies) and appropriate application methods for the seed treatment uses (i.e. CAM=8).

Response: The Agency will use a ll available data and current guidance on model inputs at the time of risk

assessment.

13. Comment:

Valent suggests that the Agency consider harmonizing data requirements for honey bee testing

with the California Department of Pesticide Regulation (CDPR) and Health Canada’s Pest Management Regulatory Agency (PMRA) i n order to avoid duplicative or contradictory testing requirements

.

Response: The Agency is working with the C DPR and Health Canada’s PMRA to ensure that the necessary data will be available for assessing risk to insect pollinators by the time of registration review. It is the Agency’s intention to avoid requesting data that is duplicative, contradictory, or otherwise unduly burdensome.

14. Comment:

Valent encourages the EPA to develop and implement a state

- of

- the

- art pollinator risk

assessment process based on the findings of the SETAC Pellston and FIFRA SAP.

Response:

Comments and recommendations from both the SETAC Global W orkshop on Pollinator Risk

A ssessment and the 2012 FIFRA SAP on estimating risk to insect pollinators will influence the approach of the clothianidin registration review risk assessment.

15. Comment: Both Valent and BCS submitted edits regarding Appendix A, Maximum Labeled Application Rates for Clothianidin

.Page 7 of 10 Response:

EFED will work with the Biological and Economic Analysis Division (BEAD) to insure all use

rates are accurate at time of risk assessment and BCS and Valent comments will be cons idered

.

16. Comment:

Mass bee die

- offs could have far

- reaching impacts on the food supply.

Response: Concerns regarding impacts to pollinators that could potentially affect food security should be directed to the United States Department of Agriculture.

17. Comment:

Commenter self

- identifies as a commercial beekeeper that has determined varroa mites ( Varroa spp.) to be a major factor in colony health in recent years.

Response:

The USDA and EPA are considering Varroa spp. as a potential contributor among a number of stressors that have been implicated in honey bee health issues.

18. Comment: Beyond Pesticides suggests that the Agency consider a study (Iwasa et al., 2004) with an LD 50 value that is lower than the current 0.0439 μg ai/bee endpoint.

Response: The Agency will consider all available open literature which passes the ECOTOX and OPP acceptability criteria screens 2 at the time of risk assessment.

19. Comment:

From the Beyond Pesticides letter: “The application rates for clothianidin and thiamethoxam on corn range from 0.25 to 1.25 mg/kernel. A single kernel contains several orders of magnitude of active ingredient more than the published LD 50 values for honey bees. ”

Response: The exposure routes that are relevant to the seed treatment coating and that the EFED is planning to evaluate at the time of risk assessment are captured by the terrestrial organism exposure and effects conceptual models (See Figures 6.2 and 6.3 on page 29 of the Problem Formulation for the Ecological Risk, Endangered Species, and Drinking Water Exposure Assessments in Support of the Registration Review of Clothia nidin)

. Those media include: nectar, pollen, guttation droplets/dew, abraded seedcoat dust, and puddled surface water.

2 Evaluation Guidelines for Ecological Toxicity Data in the Open Literature : http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/endangered_species_reregistra tion_workgroup/esa_evaluation_open_literature.htmPage 8 of 10 Please note that no response to comments 20 through 24 is included in this document On March 20, 2012, the EPA received an emergency citizen petition seeking suspension of registration for clothianidin. The petition requested action within 90 days. The agency is reviewing the petition and plans to respond to the petitioners' allegation th at clothianidin poses an imminent hazard to pollinators. Many of the comments received in the March 20, 2012 petition were also received during the 60 day comment period. Comments received in both the petition and during the comment period for the PWP su ch as comments 20 through 24 below will not be responded to in this document but instead will be posted in the Clothianidin Petition for Emergency Suspension Docket (EPA

- HQ

- OPP

- 2012

- 0334) at www.regulations.gov

.

20. Comment: From the Beyond Pesticides letter: “ Lethal and sublethal exposures have been shown to decrease foraging activity, along with olfactory learning performance and decrease hive activity.”

21. Comment: From the Beyond Pesticides letter: “ One of the greatest sources for exposure is from the exhaust

of the tractor

- drawn planters that spew small residues (dust) of treated seeds into the air while sowing. One Italian study found that bee mortality increased right after seed sowing and

confirmed these fin dings with post mortem chemical analysis that found high concentrations of

neonic otinoid insecticides (imidaclopr id and clothianidin) as high as 500 n ano g rams active ingredient /bee (Girolami V, et al. 2011). A similar study involving the seed sower found comparable results of increased bee mortality on the day of sowing and decreased foraging days after sowing, this time with thiamethoxam (Tremolada P, et al

. 2010). ”

22. Comment: From the Beyond Pesticides letter: “ Clothianidin residues remain present in the surface soil of agricultural fields long after treated seed had been planted, as long as two g rowing seasons (Krupke CH, et a l. 2012)

. ”

23. Comment: From the Beyond Pesticides letter: “ The rapid disappearance of the honey bees, also dubbed “Colony Collapse Di sorder” or CCD, has been observed in the U.S. since 2006. Even though researchers have indicated that there may be several variables associated with CCD, clothianidin, and other chemicals in its class, cannot be ruled out as a major contributor and this mu st be factored into the agency’s assessment. ”

24. Comment: From the Beyond Pesticides letter: “ Looking at SETAC’s recommendations and EPA’s data requirements, pesticide risks to honey bees have not been extensively studied and the agency is playing catch

- up with bee data. Much remains unknown about the effects of pesticide contaminants and exposure pathways on the honey bee and other bee and pollinator populations. The members of the SETAC workshop agreed that the most significant routes of exposure for

both honey bees and other bees (from foliar and systemic seed treatments), are through dermal contact and oral exposure of foraging adults, hive adults, and larvae to contaminated pollen,Page 9 of 10 nectar, and processed food (honey, bee bread, etc) (Krupke CH, et a l. 20 12)

. Contact with contaminated soil, sprayed leaves and petals were also notable exposure pathways, especially for other bees. In light of this and independent studies demonstrating that these routes of exposures do occur resulting in bee mortality and im paired bee health, serious action is warranted. Thus far the agency has not sufficiently reviewed pertinent honey bee data regarding clothianidin. As a result, the agency has not fulfilled its statutory mandate under FIFRA to pose no unreasonable

adverse effect on the environment. ”

25. Comment: Steve Ellis of Old Mill Honey looks to update a previously submitted incident report by specifying the number of hives affected.

Response: The Agency will consider all available incident information at the time of r isk

assessment.

26. Comment:

Steve Ellis claims to speak for other beekeepers in Minnesota who have experienced bee kill incidents in early spring

. Mr. Ellis suspect s p esticide poisoning may be the cause

.

Response: All available incident reports will be considered at the time of risk assessment. The following information, taken from the National Pesticide Information Center (NPIC) website ( http://npic.orst. edu/reportprob.html#env ), explains how to report a pesticide incident. NPIC is a cooperative agreement between Oregon State University and the U.S. Environmental Protection Agency

.

Reporting an Environmental Incident (wildlife, air, soil or water):

1. If a pesticide incident has occurred involving wildlife, air, soil or water, contact your State Environmental Agency to report the problem.

2. Next, call the National Pesticide Information Center (NPIC) at 1

- 800

- 858

- 7378 to report the incident. NPIC provides these reports to the EPA under a cooperative agreement. Trained pesticide specialists are available to document the incident and provide information that could be helpful in your unique situation. NPIC is open from 7:30am

- 3:30pm PST.

3. Also, consider repor ting the incident to the product's manufacturer . Manufacturers are required by

law to submit reports of adverse effects to the US EPA. Attention government organizations, academia, wildlife rehabilitation centers, conservation societies, and bee keepers:

I f you want to report pesticide

- related illness in wildlife or an environmental problem associated with a pesticide, please submit a report using our quick and easy Ecological Pesticide Incident Reporting portal ( http://pi.ace.orst.edu/erep/ ). Reports will improve the quality of environmental incident data the EPA

receives.Page 10 of 10 27. Comment: Northern tier beekeepers rely on early spring blooming plants such as dandelion for colony

build

- up. The persistence of clothianidin in the soil, in conjunction with the compound’s systemic nature, could affect the quality of this type of forage.

Response: EFED risk assessments consider both the treatment area and surrounding habitat that may be

affected as a result of pesticide application. Potential impacts to edge habitat and coincident forage resources resulting from clothianidin use will be characterized in the r egistration r eview

risk assessment.

28. Comment: Could the Agency consider a di fferent toxicological paradigm to address the mode of action of systemic compounds like clothianidin, rather than continued reliance on the LD 50 methodology?

The commenter further expressed concern of unintended consequences resulting from the concurrent use of systemic pesticides and plant

- incorporated protectants (PIPs).

Response: The Agency intends to convene a Scientific Advisory Panel meeting to obtain expert scientific advice regarding risk assessment methodology for systemic compounds which may effect pollinators. The r egistration review risk assessment for clothianidin is expected to be conducted in 2017 after submission of clarifying toxicity and exposure information. For the registration review risk assessment, EPA will consider clothianidin exposure and hazard issues in a manner

consistent with the recommendations of the FIFRA SAP.

It is likely that EPA will continue to rely on tradition measures of acute toxicity which are

consistent with those used with other taxa. While the use of LD 50 data may not be confined to acute contact studies with young adult bees, this measure of toxi city remains a recognized standard in toxicity testing whether it is based on contact toxicity or oral toxicity and it is used extensively by other regulatory partners globally, particularly for screening

- level assessments.

Where there are sufficient data to indicate that a compound is toxic, higher tiered studies will be required to address specific uncertainties and these tests will typically be conducted to examine effects at the whole colony level. Such tests may be conducted under controlled environm ental

conditions such as semi

- field studies where colonies are confined to tented enclosures or they may extend to full field studies where exposure conditions are intended to reflect actual usage patterns of the chemical. However, as ecological effect te sting is refined, the studies are intended to focus on specific uncertainties which have been determined through the lower tier studies; the need for such studies will also depend on the risk managers' need for additional information to support decision ma king efforts.