UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON D.C., 20460 

MEMORANDUM 

PC Code: 101103 

DP Code: 415383 

December 3, 2013 

Subject: 

To: 

From: 

Through: 

Environmental Fate and Effects Division's Response to Public Comments on 

Registration Review: Preliminary Problem Formulation for Pymetrozine 

Steven Snyderman, Chemical Review Manager 

Patricia Parrott, Chief 

Risk Management and Implementation Branch III 

Pesticide Re-evaluation Division (7508P) 

Rochelle Bohaty, Ph.D., Chemi~ Katherine R. Stebbins, Biologist ~Jl/VUILc;. YJ-1~~ James Hetrick, Ph.D., Senior AdvisoQ~ 

Environmental Risk Branch III 

Environmental Fate and 

~ 

Effects Division (7507P) . ) 

~ .l-- \ '\.;I ~ z., \, 

Dana Spatz, Branch Chief~ ~ 

Environmental Risk Branch III V~ ~ fl .. f ~~1.1>/'6 Rosanna Louie-Juzwiak, RAPL /1) ~ ~ 

Environmental Fate and Effects Division (7507P) . 

This document contains the Environmental Fate and Effects Division's (EFED's) responses to 

Sygenta's comments on the Pymetrozine Registration Review Preliminary Problem formulation that 

are within the purview ofEFED (e.g., comments submitted related to the environmental fate, drinking 

water exposure and ecological assessments). Each comment received is numbered and includes the 

text within EPA's assessment for which a comment was received, a summary of the comment 

received, and then EFED's response to the comment. 

1. EPA Preliminary Problem Formulation: "Parent, CGA-23199, CGA-359009,. CGA-23199 

were not detected below 0- 6 inch depth" for the bareground plot (pg. 13). 

Comment Summary: CGA-294849 was also not detected below the 0-6" depth. 

EFED RESPONSE: EFED confirmed that CGA-294849 was also not detected below the 0-6" depth 

in the bareground plot [pg. 11 of the Terrestrial Field Dissipation (TFD) Study Data Evaluation 

(DER) MRIDs 44471703, 44411333, 44411337, 44411339, 44411332, 44411336, 44411335, and 

4464 7904)]. This information will be considered as part of the registration review risk assessment. 

2. EPA Preliminary Problem Formulation: "MRID 44647901, 44411334, 44471703, 44647904, 

44411338, 44647903 (supplemental) Analytical methods were inadequate for detecting CGA1 
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249257, storage stability for the CGA-180777, CGA-249257, and CGA-359009 were inadequate” 

pg. 13.

Comment Summary: An additional amendment to the final report (MRID 45387803) was not 

included in this review. This amendment includes additional storage stability data for CGA215944, CGA-359009, CGA-249257, CGA-294849, GS-23199, and CGA-180777. 

EFED RESPONSE: The amendment to the final report (MRID 45387803) was reviewed. This 

study provides additional storage stability data for the CGA-180777, CGA-294849 and GS23199. These data indicate that the aforementioned chemicals were stable during the TFD storage 

period. However, this amendment does not provide additional storage stability data for CGA249257 and CGA-359009 nor does it address the problems associated with the analytical methods 

for CGA- 249257. This additional information will be considered as part of the registration 

review risk assessment; however, additional data are still lacking for CGA-249257 and CGA359009.

3. EPA Preliminary Problem Formulation: “Parent and CGA-359009 were not detected below 0-

6 inch depth” for the cotton plot (pg. 13). 

Comment Summary: CGA-294849 was also not detected below 0-6" depth. 

EFED RESPONSE: EFED confirmed that CGA-294849 was also not detected below the 0-6" 

depth in cotton plot (pg. 12 the TFD DER MRIDs 44471703, 44411333, 44411337, 44411339, 

44411332, 44411336, 44411335, and 44647904)]). This information will be considered as part of 

the registration review risk assessment.

4. EPA Preliminary Problem Formulation: “MRID 44411334 (supplemental) 44647902 & 

44647901 Analytical methods were inadequate for detecting CGA-249257, storage stability for 

the CGA-180777, CGA-249257 and GA-359009 were inadequate,” pg. 13. 

Comment Summary: Storage stability data for CGA-359009 and CGA-249257 included in 

MRID 44411334 span 0-353 days. The longest sample holding time was 318 days for CGA359009 with the exception of 3 reanalyzed samples. No appreciable losses for CGA-359009 

relative to fresh spikes were observed under freezer storage conditions. An additional amendment 

to the final report (MRID 45387801) was not included in this review. This amendment includes 

additional storage stability data for CGA-294849, GS-23199, and CGA-180777. These chemicals 

exhibited no appreciable losses under freezer storage conditions. 

EFED RESPONSE: An additional amendment (MRID 45387803) to the final report (MRID 

45387801) was not included in the problem formulation. This amendment includes additional 

storage stability data for CGA-294849, GS-23199, and CGA-180777. These data indicate that the 

aforementioned chemicals were stable during the TFD storage period. However, this amendment 

does not provide additional storage stability data for CGA-249257 and CGA-359009 nor does it 

address the problems associated with the analytical methods for CGA- 249257. This information 

will be considered as part of the registration review risk assessment; however, data are still 

lacking for CGA-249257 and CGA-359009.

5. EPA Preliminary Problem Formulation: “No residues were not detected below 0-6 inch depth” 

for the bareground plot (pg. 14). 
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Comment Summary: No residues were detected below the 0-6 inch depth for the bareground 

plot. 

EFED RESPONSE: This typographical error will be corrected and accurately reflected in the 

registration review risk assessment.

6. EPA Preliminary Problem Formulation: “No residues were not detected below 0-6 inch 

depth,” in the tomato plot (pg. 14). 

Comment Summary: No quantifiable residues were detected below the 0-6 inch depth for the 

tomato plot. 

EFED RESPONSE: This typographical correction will be reflected in the registration review 

risk assessment. 

7. EPA Preliminary Problem Formulation: “MRID 44411338, 44647903 (supplemental) 

analytical methods were inadequate for detecting CGA-249257, storage stability for the CGA294849 and GS-23199 were inadequate” pg. 14. 

Comment Summary: An additional amendment to the final report (MRID 45387802) was not 

included in the problem formulation. This amendment includes additional storage stability data 

for CGA-294849, GS-23199, and CGA-180777. None of these analytes exhibited appreciable 

losses under freezer storage conditions; therefore Syngenta believes the storage stability data are 

sufficient to support the terrestrial field dissipation studies. 

EFED RESPONSE: The amendment to the final report (MRID 45387802) was reviewed. This 

study provides additional storage stability data for the CGA-180777, CGA-294849 and GS23199. These data indicate that the aforementioned chemicals were stable during the TFD storage 

period. However, this amendment does not provide additional storage stability data for CGA249257 and CGA-359009 nor does it address the problems associated with the analytical methods 

for CGA- 249257. This information will be considered as part of the registration review risk 

assessment; however, data are still lacking for CGA-249257 and CGA-359009.

8. EPA Preliminary Problem Formulation: “Bobwhite quail (Colinus virginianus); NOAEC = 

100 mg a.i./kg; LOAEC = 300 mg a.i./kg based on number of 14-day old survivors of eggs set; 

MRID 44024911 (Acceptable)” pg. 22

Comment Summary: Consistent with the original study report, no treatment-related effects 

were detected in the variables tested and the NOAEC value should be 300 mg a.i./kg based on 

statistical analysis of the dataset with the removal of the outlier in the highest treatment group 

(Cage 64 - assumed to have an infertile male or female, infertility was not treatment related). 

EFED RESPONSE: The EFED reviewer agrees that one replicate in the highest treatment level 

(cage 64) is an outlier (as a result of an infertile male or female) and this replicate was removed 

from the dataset in a second analysis within the DER review. After the replicate pen was 

removed from the analysis, the percentage of 14-day old survivors of eggs set at the highest 

treatment level (300 ppm) was still significantly less than the control (Dunnett’s, α = 0.05) and 

the reviewer believes that this response is a treatment related effect. Hence, the resulting 

NOAEC is 100 mg a.i./kg. 
4

9. EPA Preliminary Problem Formulation: “Storage stability for the CGA-180777, CGA249257, and CGA-359009 were inadequate. Because CGA-359009 is one of the identified 

residues of concern, submission of storage stability studies are needed” (pg. 29).

Comment Summary: Storage stability data for CGA-359009 in soils from California, Georgia, 

and New York are included in the terrestrial field dissipation studies and related amendments: 

MRID 44411338, 44471703, 45387803, and 44411334. Although there is an apparent loss of 

recovery in the Georgia soil at the last time point, this is not consistent with studies from 

California and New York which cover longer time spans and show no appreciable losses. 

Existing data demonstrate CGA-359009 is stable under freezer storage conditions and sufficiently 

support the terrestrial field dissipation studies. 

EFED RESPONSE: Storage stability studies for CGA-359009 in California and New York soils 

suggest stability in these two soils under the storage conditions; however, data are lacking for the 

Georgia soil or a rationale on why CGA-359009 was stable in California and New York soils, but 

not stable in the Georgia soil. The storage stability of CGA-359009 in the Georgia soil remains an 

uncertainty. 

10. EPA Preliminary Problem Formulation: “Results are not consistent between hydrolysis studies 

(MRIDs 44024964 and 44024963) for pH 5, with half-lives ranging from 12 to 28 days. Because 

hydrolysis appears to be an important route of dissipation in acidic environments, additional 

abiotic hydrolysis data for pH 5 are needed.” pg. 28. 

Comment Summary: Results are not consistent between studies at pH=5 (at 25 °C). Half-lives 

range between 5 d and 12 d. At pH=7 and pH =9 (at 25 °C) the compound is relatively stable. 

EFED RESPONSE: The three hydrolysis studies (MRIDs 44024962, 44024963, and 44024964) 

submitted to EPA for pymetrozine were reexamined. The inconsistencies between hydrolysis 

half-life values (ranges from 16.9 to 26.8 d using non-linear single first order kinetic model) for 

pH 5 were confirmed. Reported and recalculated half-life values are shown in the table below for 

pH 5. In the absence of new data, the hydrolysis half-life of pymetrozine at pH at 5 will be 

assumed to be 28 days. 

Source 

Classification

pH 5 

DT50 Value1 Comments

MRID 44024962 

(triazine ring labeled) 

supplemental 

12.1 days 

Value reported in DER and preliminary problem 

formulation; values was calculated using linear regression 

of log transformed concentration data for parent 

22.0 days Value calculated using non-linear single first order model2

14.9 Value calculated using DFOP model2 

MRID 44024963 

Supplemental 

(triazine ring-labeled) 

28.4 days Value reported in DER and preliminary problem 

formulation; values was calculated using linear regression 

of log transformed concentration data for parent 

26.7 days Value calculated using non-linear single first order model2

MRID 44024964 

Draft DER; 

Supplemental 

(pyridine ring-labeled) 

14.4 days Value reported in DER and preliminary problem 

formulation; values was calculated using linear regression 

of log transformed concentration data for parent 

16.9 days Value calculated using non-linear single first order model2

11.6 days Value calculated using IORE model2 

1. DER noted that hydrolysis of pymetrozine was biphasic; however, due to the discrepancy in the 

half-life values the quality of the data are questionable. 

2. DT50 were calculated using nonlinear regression and single first-order (SFO), double first- order 
5

in parallel (DFOP), or indeterminate- order equation (IORE). The equations can be found in the 

document, Standard Operating Procedure for Using the NAFTA Guidance to Calculate 

Representative Half-life Values and Characterize Pesticide Degradation, Agency December 21, 

2012. 

11. EPA Preliminary Problem Formulation: In the aqueous photolysis experiment “A major 

degradate (up to 28.9% AR) was not identified. Identification of this transformation product is 

needed to rule out the potential that it is a residue of toxicological concern. In absence of the data, 

this residue may be considered as part of a TTR approach in modeling to account for this 

uncertainty” (pg. 28). 

Comment Summary: “ID via HPLC between 92 and 97% AR ((pyridinyl-label); 21-24% CGA215944 and 71-73% CGA-300407 and 98% ((triazinyl-label); 23-24% CGA-215944, 65-68% 

CGA-2155525) and 23% CGA249257)...[critical endpoints listed]” 

EFED RESPONSE: The comment received is unclear. EFED interpreted the comment as 

suggesting that the unidentified residues could be either CGA-215944 or CGA-215525; however, 

the major (28.9%) transformation product not identified in the study cannot be identified by 

EFED as the necessary data were not supplied to support this comment. Additional data that 

indentifies this unidentified major (28.9%) transformation product would reduce uncertainty. In 

absence of the data, this residue may be considered as part of a TTR approach in modeling to 

account for this uncertainty. If this comment was misinterpreted, the commenter should clarify 

the comment and submit any supporting data that has not previously been reviewed by the 

Agency. 

12. EPA Preliminary Problem Formulation: Soil Photolysis: A large amount of unextracted 

residues (>75%) was observed in the irradiated samples compared to the dark control (<20%) at 

study termination.” pg. 28. 

Comment Summary: MRID 45208702 employed four extraction techniques and removal of 

bound residues was improved; more components identified, however, approximately 30% of 

applied radioactivity (AR) not identified (pyridinyl-label) and approximately 50% of AR not 

identified (triazine-label). Non single first order kinetics was observed; however, in all previous 

studies first order kinetics was observed. All residues higher than 10% were identified. 

EFED RESPONSE: MRID 45208702 will be considered as part of the registration review 

process; however, the extraction methods [extraction 1) 80:20 acetonitrile:water and extraction 2) 

3:1 acetonitrile:water] employed in this study prior to fractionation are not considered exhaustive. 

Residues extracted using extraction methods 1 and 2 were identified at concentrations greater 

than 10%. Nevertheless, up to 11% and 13% of the applied radioactivity was reported as 

“residue” and not identified in the cited study (MRID 45208702), for the control and irritated 

samples. Furthermore, a large amount (up to an additional 30%) of radioactivity was isolated as 

part of extraction 3 (fractionation) and not identified. No data are available to determine if the 

isolated radioactivity was associated with residues that could have been extracted using a solvent 

system other than the acetonitrile and water systems mentioned above (extractions 1 and 2) or if 

the residues are truly bound residues). Additional solvent systems should have been explored 

prior to fractionation (extractions 3 and 4). While soil photolysis does not appear to result in the 

formation of unique phototransformation products, additional information would reduce the 

uncertainty associated with the unextracted/unidentified residues in both soil photolysis studies. 
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13. EPA Preliminary Problem Formulation: “Current guidelines recommend aerobic soil 

metabolism data be submitted for a total of five different soils. In the absence of these data the 

calculated aerobic soil metabolism half-life value will be multiplied by 3 to generate model input 

values. This adjustment factor is applied to account for the uncertainty associated with the 

variation in transformation in different soil systems.” pg. 28. 

Comment Summary: Several additional aerobic soil metabolism half-life values as well as 

maximum observed concentrations of a number of transformation products were cited. 

EFED RESPONSE: The half-life values and the maximum observed concentrations provided 

cannot be verified by EFED as the necessary data were not supplied to support this comment 

received on the preliminary problem formation. The cited study should be submitted for the 

Agency to review. 

Any additional data to address this issue will be considered as part of the registration review risk 

assessment. In absence of these data, the calculated aerobic soil metabolism half-life value will be 

multiplied by 3 to generate model input values. This adjustment factor is applied to account for 

the uncertainty associated with the variation in transformation in different soil systems.

14. EPA Preliminary Problem Formulation: Aerobic aquatic metabolism “data have not been 

submitted to the EPA. In absence of these data the calculated aerobic soil metabolism half-life 

input values will be multiplied by 2 (6 times the aerobic soil half-life value) to generate model 

input value for aerobic aquatic metabolism. This adjustment factor is applied to account for the 

uncertainty associated with the difference between aerobic soil and aerobic aquatic metabolism.” 

pg. 29. 

Comment Summary: Aerobic aquatic metabolism half-life values as well as maximum observed 

concentrations of a number of transformation products were cited. 

EFED RESPONSE: The half-life values and the maximum observed concentrations cannot be 

verified by EFED as the necessary data were not supplied to support this comment received on 

the preliminary problem formation. The cited study should be submitted for the Agency to 

review. 

Any additional data to address this issue will be considered as part of the registration review risk 

assessment. In absence of these data the calculated aerobic soil metabolism half-life input values 

will be multiplied by 2 (6 times the aerobic soil half-life value) to generate model input value for 

aerobic aquatic metabolism. This adjustment factor is applied to account for the uncertainty 

associated with the difference between aerobic soil and aerobic aquatic metabolism 

15. EPA Preliminary Problem Formulation: “Anaerobic Aquatic Metabolism: Current guidelines 

recommend anaerobic aquatic metabolism data be submitted for a total of two different sediment: 

water systems.” pg. 29. 

Comment Summary: Anaerobic aquatic metabolism half-life values as well as maximum 

observed concentrations of a number of transformation products were cited for one sediment 

water system. 

EFED RESPONSE: The half-life values and the maximum observed concentrations cannot be 

verified by EFED as the necessary data were not supplied to support this comment received on 
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the preliminary problem formation. The cited study should be submitted for the Agency to 

review. 

Any additional data to address this issue will be considered as part of the registration review risk 

assessment.

16. EPA Preliminary Problem Formulation: “Consistent with the Agency's responsibility under 

the Endangered Species Endangered Species Act (ESA), the Agency will evaluate risks to 

federally listed threatened and/or endangered species (“listed species") from registered uses of 

pesticides in registration review. These assessments will be conducted in accordance with 

standard EPA procedures and good scientific judgment. 

Comment Summary: Syngenta has submitted a document to the registration review docket 

summarizing the types of refinements that should be considered for an endangered species 

assessment (Risk Assessment Considerations Concerning the Potential/Impacts of Pesticides on 

Endangered Species, Syngenta Report Number TK0181948).

EFED RESPONSE: EPA will considered the submitted document and plans to address concerns 

raised for assessing the risks of pesticides to listed species based on the recommendations of the 

April 2013 National Academy of Sciences (NAS) report. EPA will address concerns specific to 

pymetrozine in connection with the development of its registration review decision document. 

The NAS report, available at http://www.nap.edu/catalog.php?record_id=18344, outlines 

recommendations on specific scientific and technical issues related to the development of 

pesticide risk assessments that are compliant with the Endangered Species Act and the Federal 

Insecticide, Fungicide, and Rodenticide Act. In November, the EPA, along with the U.S. Fish & 

Wildlife Service (USFWS), the National Marine Fisheries Service (NMFS) (collectively, the 

Services), and the U.S. Department of Agriculture (USDA), released a summary of their joint 

Interim Approaches for assessing risks to listed species from pesticides. The Interim Approaches 

were developed jointly by the Agencies in response to the NAS’ recommendations and reflect a 

common approach to risk assessment shared by the Agencies as a way of addressing scientific 

differences between EPA and the Services. The joint Interim Approaches were released prior to 

the stakeholder workshop held on November 15, 2013. EPA is presenting the joint Interim 

Approaches at the December 2013 PPDC and SFIREG meetings, allowing additional 

opportunities for stakeholders to comment on the Interim Approaches. The Agencies will 

consider public comments on the Interim Approaches prior to implementing them. The Agencies 

intend to jointly implement these approaches as part of a phased iterative process. EPA will 

refine its listed species risk assessments based on these interim approaches. The details of the 

joint Interim Approaches are contained in the white paper “Interim Approaches for NationalLevel Pesticide Endangered Species Act Assessments Based on the Recommendations of the 

National Academy of Sciences April 2013 Report,” dated November 1, 2013, available at 

http://www.epa.gov/espp/2013/nas.html.