Page 1 of 11 

### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON D.C., 20460

OFFICE OF

CHEMICAL SAFETY AND

POLLUTION PREVENTION

PC Code: 129092

DP Barcode: D422666

Date: November 3 , 2014

MEMORANDUM

Subject: EFED Response to Comments on the Environmental Fate and Ecological Risk Assessment

for the Registration Review of Fenoxaprop

- p

- ethyl

To: Miguel Zavala

, Team Leader

Michael Goodis, Branch Chief Risk Management and Implementation Branch 3

Pesticide Reevaluation Division

Office of Pesticide Programs

From: Chuck Peck

, Environmental Engineer

Scott Glaberman, Ph.D., Biologist

Environmental Risk Branch 4 Office of Pesticide Programs

Reviewed By: Thomas Steeger, Ph.D., Senior Science Advisor

Jim Carleton, Ph.D., Senior Fate Scient ist

Environmental Risk Branch 4

Through: Thomas Steege r, Ph.D., Acti ng Branch Chief

Environmental Risk Branch 4

Environmental Fate and Effects Division

The Environmental Fate and Effects Division (EFED) has reviewed the document entitled “Bayer CropScience Comments to Environmental Fate and Ecological Risk Assessment and Drinking Water Assessment for the Registration Review of Fenoxaprop

- p

- ethyl. ” Responses by EFED to individual comments are provided below, including proposed modifications to the draft R egistration R eview risk

a ssessment for fenoxaprop

- p

- ethyl (PC Code: 129092).

BCS Comment (p. 4

) : Non

- definitive endpoints due to toxicity values greater than tested concentrations, especially at test concentrations well above Estimated Environmental Exposures (EECs), can be used for risk quotient calculation and characterization. The appropriate qualifiers can be included to explain the uncertainty. Not utilizing the “non

- definitive” endpoints when toxicity values are significantly greater exposure than gives the perce ption of a risk (and uncertainty) when in fact the risk is minimal and uncertainty is only in one direction.

EFED Response: EFED typically does not calculate risk quotient ( RQ ) values based on no n

definitive endpoints since precise RQ s can not be derived w here the specific toxicity of a chemicalPage 2 of 11

to a group of organisms is not known. However, in cases where the tox icity values are greater
than t he highest concentration tested and where exposure is estimated to be much lower than this concentration, the executive summary and risk characterization section s clearly indicate that that the likelihood of adverse effects from exposure ( i.e. , risk) is considered low for the particular group of organisms. For example, for potential risk to estuarine/marine f ish

, the Preliminary Risk Assessment (PRA) indicates the following:

RQ values for estuarine/marine fish are not presented in the Risk Estimation because the available acute toxicity endpoint is non

- definitive (sheepshead minnow LC50 >1,000 μg a.i./L)

and no chronic toxicity data have been submitted. To characterize the potential for acute risk to estuarine/marine fish associated with the labeled uses of FPE, peak surface water EECs are compared to the non

- definitive acute toxicity endpoint for sheepshead m innow. EECs for all uses are less than the acute risk LOC for listed species except for applications to rice (RQ =0.08). Given that the estimated release water concentrations from PFAM are several orders of magnitude below the Tier I Rice model EECs, the l ikelihood of acute mortality in listed or non

listed estuarine/marine fish from exposure to technical grade FPE is expected to be low.

This paragraph indicates that estimated exposure concentrations are lower than the “greater than” acute toxicity e ndpoint for the surrogate test species and therefore the likelihood of acute mortality in listed or non

- listed estuarine/marine fish from exposure to FPE is expected to be low. In addition, Table 1.1 of the PRA also indicat es that risks of conce rn to this group of organisms

are not expected. A similar comparison is made for non

- listed aquatic vascular plants and insect pollinators. Therefore, EFED believe s that the executive summary and risk characterization sections adequately communicate the low potential for risks of concern in cases where estimated exposure concentrations are expected to be substantially lower than available non

- definitive toxicity end points.

BCS Comment (p. 6

):

 As noted by both EPA and BCS, only one application per season can occur for wheat and barley. However, given the agronomic requirements of these crops, only one application will occur in any calendar year. The presentation of t he information in the format as provided in all 3 tables seems to indicate multiple applications for wheat and barley in any year, and misrepresents the

label.

 For the aquatic exposure estimates (and given the above statement) it is not appropriate to mode l 2 applications to wheat and barley. A more appropriate approach would be to model different crops if the goal is to estimate annual loading from a single field.

 If a second application were to occur in a calendar year and on the same field it would be to a different crop. It appears that EPA assumes that wheat or barley could be followed by a soybean season, which is a correct assumption. However this scenario would not occur in ND or OR. This cropping scenario would only occur below interstate I70, and t he application interval would generally be 4 months. Therefore BCS recommends the ND and OR scenarios be updated.

 As scenarios are reconsidered, please note that there are factors on the label which may influence the application intervals. For example, the PUMA label does not allow harvest until 57

- 70 days after the last application.

 For the reasons noted above, for the terrestrial exposure estimates (TREX), it is inappropriate to model two applications to the same crop, when that scenario does not exist an d given that TREX is modeling in

-

field exposure. Greater consideration needs to be given to the agronomic practices and to the fact that the crop for the first application is no longer present when the second application occurs.Page 3 of 11

EFED Response: As discussed in the draft risk assessment

“For applications of FPE to barley/wheat, the label specifies that FPE can only be applied to barley/wheat once during crop season, so the second application date was modeled using the first day after the harvest date specified in the PRZM scenario. For applications of FPE to conservation reserves and soybeans (multiple applications), the label specifies that FPE can only be applied to conservation reserves and soybeans twice during crop season, so the third appli cation date was modeled using the first day after the harvest date specified in the PRZM scenario.”

The goal of the aquatic modeling effort was to estimate environmental concentrations that could

occur in a waterbody receiving runoff and drift from a fiel d receiving multiple applications of FPE. EFED currently does not have multiple crop scenarios, so the assumption was made that the second application was made to a fallow field, thus eliminat ing the need to consider what specific crop ( e.g. , soybeans) is planted after the main crop, but still allow EFED to assess the impact of the maximum annual application rate that could occur to a specific field.

BCS Comment (p

p .7

- 8 ): Within the season EPA assumed one application at the maximum rate (0.01 lb a.i./A) and on e at a significantly lower rate (0.028 lb a.i./A). The lower rate (0.028 lb a.i./A) is not a recommended label rate, and is below a rate to be observed in the field. Using a rat e that is below the

recommended rates could lead to issues with resistance and to dis

- satisfied customers who do not achieve the desired weed control. The appropriate in season rates would be either a single application at the highest rate (0.1 lb a.i./A) or two applications splitting the seasonal rate (2x0.064 lb a.i. /A).

EFED Response: E FED will revise it’s modeling to reflect the lowest recommended label rate

response for conservation reserves.

BCS Comment (p. 9

): In order to achieve the annual maximum use ra te, the EPA scenario included 3 applications at the seaso nal maximum (0.173 lb a.i./A), followed by one application at 0.012 lb a.i./A. The lower rate (0.012 lb a.i./A) is not a recommended label rate, and is below a rate to be observed in the field. Using a rat e that is below the recommended rates could lead to issues with resistance and to dis

satisfied customers who do not achieve the desired weed control. Therefore if 3 appli cations at the

seasonal maximum of 0.173 lb a.i./A are used, no further applications would be made. If the desired goal of achieving ann ual maximum loading at the annua l maximum rate per year, then a different scenario needs to be developed for multiple application rates at a lower rate.

EFED Response: For ornamental, right s

- of

- way, and turf, the maximum single application rate is

0.173 lbs a

. i

. /A, with a maximum seasonal and annual rate of 0.531 lbs a

. i

. /A. However, the rate

of 0.531 lbs a

. i

. /A is not evenly divisible by 0.173 (0.173 x 3 = 0.519) ; therefore, a fourth application is technically feasible. Given that the lowest recommende d single application rate for these uses is 0.02 lbs a.i./A, E FED will model four applications at 0.173, 0.173, 0.165, and 0.02

lbs a.i./A.

BCS Comment (p. 10

): The annual maximum use rate of 0.188 lb a.i./A is an error. As presented in the

November 2012 meeting, BCS agreed to limit the annual maximum use rate to 0.142 lb

a.i./A

. If an application of 0.108 lb a.i./A is used, a second applicat ion of 0.034 lb a.i./A will not be used. This rate is not a recommended label rate, and is below a rate to be obser ved in the field. Using a rate

that is below the recommended rates could lead to issues with resistance and to dis

- satisfied customers

who do not ac hieve the desired weed control. Generally speaking, another crop will not be grown within

the same calendar year

, and therefore for that field only the applications to rice shou ld be considered for

the annual application rate.Page 4 of 11

EFED Response: As provided in Attachment 1, the letter submitted by the registrant in

November 2012 indicates the maximum annual rate that can be applied is 0.188 lbs a

. i

. /A, not

0.1 42 lbs a

. i

. /A as indicated in the table provided in the comments from Bayer

. If the registrant

wishes to amend the labels to reflect a maximum annual application rate of 0.142 lbs a.i./A , then

EFED will revi se its modeling approach. As a second application of 0.034 lb a.i./A would be below the minimum recommended treatment rate of 0.05 lbs a.i./A, EFED will revise its modeling approach to account for minimum application rate of 0.05 lbs a.i./A, resulting in a second application rate of 0.078 lbs a.i./A to achieve the maximum application rate per season of

0.128 lbs a.i./A

. However, EFED recommends that if the single maximum application rate of

0.108 lbs a.i./A remains on the label, the label should specify that a second application should not be made, as it would be below the minimum recommended treatment rate. EFED will continue to model three applications to the field, regardless of whether only one crop is grown within a g iven calendar year, as the label will allow for a maximum annual application rate of 0.188 lbs a.i./A

.

BCS Comment (p. 11 ): For the scenario where EPA assumed 3 applications in a year, one of the application rates used was 0.028 lb a.i./A. This lower ra te is not a r ecommended label rate, and is below a rate to be observed in the field. Using a rat e that is below the recommended rates could lead to issues

with resistance and to dis

- satisfied customers who do not achieve the desired weed control. The

appro priate in sea son rates would be either a single application at the highest rate (0.1 lb a.i./A) or two applications splitting the seasonal rate (2x0.064 lb a.i./A). If one is to consider t he annual maximum rate

in order to assess potential annual loading, the more appropr iate approach would be to model different crop. The rate for the different crop would then ne ed to be the 0.06 lb a.i./A (as EPA assumed).

EFED Response: E FED will revise it’s modeling to reflect the lowest recommended label rate

for soybeans (0.043 lbs a.i./A) with a coupled second application rate of 0.085 lbs a.i./A

.

BCS Comment (p. 12 ): The current label restricts the use of grass grown for seed to the Oregon, Washington and Utah. The aquatic scenarios California, Pennsylvania and Florida, but especially PA and FL, do not represent the potential use area s for the crop of interest. BCS recommends that these

scenarios be revised to represent the weather and soil conditions in the states allowed this use on the

label.

EFED Response: Grass grown for seed was modeled using the turf scenarios from CA, FL, and PA, which are designed to represent protect ive estimates for applications throughout the nation. While the label restricts grass grown for seed to OR, WA, and UT, the three aquatic scenarios that were used in the modeling are designed to be protec tive reflections of EECs where grass grown

for seed is permitted.

BCS Comment (p. 12 ): Appendix D contains the output for TerrPlant.

BCS Comment (p. 12 ): TerrP lant example output is located in Appendix D.

EFED Response: EFED will make the appropriate corrections to labeling the appendices in the

revised r isk assessment.

BCS Comment (p. 12 ): This rate is correct for cotton and soybean, however, wheat and barley the maximum application rate is 0.083 lb a.i./A. BCS Comment (p. 18) : The maximum application rate for wheat is 0.83 lb a.i./A.

EFED Response: Although a maximum seasonal application rate of 0. 0 83 lbs a.i./A is specified for wheat, the maximum annual application rate across all uses that can be made to a field on which wheat is also grown in the same year is 0.188 lbs a.i./A, per the Bayer commitment letterPage 5 of 11

signed November 30, 2012 ( Attachment 1 ) . Therefore the use of 0. 0 83 lbs a.i./A as an exposure modeling input would underestimate the potential exposure to terrestrial animals.

BCS Comment (p. 1 3

): BCS agrees with the NOAEL of 180 ppm for the two

- generation reproduction study in rats, however the NOEL based on daily dose within the study is as follows [Table omitted]. BCS recommends EPA consider the measured dose ranges in the critical parts of the study in the risk
characterization.

EFED Response: Mammalian chronic toxicity studies are reviewed by OPP’s Health Effects Division (HED). EFED will work with HED to extract dose

- based endpoints based on measured dietary intake and integrate them into the final version of the ERA for FPE.

BCS Comment (p. 13

): BCS asks for clarification in Table 3.12 where the honeybee acute contact is marked as the most sensitive endpoint that will be used in RQ calculation. Text on page 68 states “RQs

were not calculated for terrestrial invertebrates” and Table 1.1 indicates that no RQs were calculated for insect pollinators.

EFED Response: The toxicity endpoint for honeybees was incorrectly labeled as being used in RQ calculations since it is a non

- definitive endpoint. Rather, this endpoint is considered in conjunction with predicted exposure levels to qualitatively characterize the potential for risk to

bees in the risk descr iption section. Therefore

, the asterisk for this endpoint will be removed from

the table in the revised risk assessment.

BCS Comment (pp. 14

- 15 ): BCS Response: The radicle is the initial root like structure or embryonic root that forms prior to the develo pment of the primary root system. Radicle length inhibition measurements are not representative, nor do they satisfy the objective of the seedling emergence test. Growth during germination is mainly driven by intrinsic factors of the seed, such as nutrient reserves, rather than external parameters. This can result in high variability in radicle length without accounting for external factors such as concentration of the test substance in the soil. The radicle length test design and endpoint is not required o r supported in current or previous EPA guidelines. In the 1982 Pesticide Assessment Guidelines, Subdivision J Hazard Evaluation for NTPs, radicle length was only indicated as a visual marker of seed germination. In this evaluation, if the radicle length wa s >5mm the seed was considered germinated.

In the table above, only MRID 47333423 quantifies actual root length. In this study following the 1996 guideline on Tier II seedling emergence testing (OPPTS 850.4225), root lengths were measured on day 14 after test termination. Similarly, the replacement 2012 OCSPP 850.4230 guideline for seed germination uses root length as one of the studies effect endpoints. Root length is measured on day 14 from seedlings upon termination of the test. The root length endpoint is reported as root inhibition IC10 and IC50 values. Endpoints given for MRID 41276904 and 41276905 are for radicle length. Root length is not the same as radicle length and these endpoints are not comparable.

In MRIDs 4126904 and 4126905, radicle length testing was performed in a petri dish by sprouting 10 seeds, without soil, on FPE treated filter paper. This petri dish is then incubated in the dark for 6 to 7 days. This exposure scenario is not environmentally relevant and unrealistic in determining ri sk characterization for seedling emergence. Radicle length does not reflect an endpoint that mimics an in

field application scenario for seedling emergence testing. Variability in this test design is high. For corn and oat, no dose response relationship ex isted for seed germination. In oat, a dose response was observed for radicle length, however for corn, no dose response relationship existed in radicle length measurements. In corn, at an exposure concentration of 0.0006 lb a.i./A, 13% inhibition was obser ved. At the next dose, 0.0012 lb a.i./A, 7% stimulation occurred, followed by a 33% stimulation in the 0.0024 lbPage 6 of 11

a.i./A treatment. The highest treatment level tested with corn, 0.0096 lb a.i./A resulted in a 14% inhibition, comparable to the lowest concent ration tested. In bo th oat and corn, radicle length measurements had no correlation with seedling survival, germination, or emergence giving this endpoint no relevance in predicting effects on survival and growth.

As fenoxaprop

-

p

- ethyl has been registered with the US EPA since 1987, several older study reports exist that are comprised of provisional test des igns, often containing multiple endpoints that are no longer

considered valid or accurate. BCS wo uld like to clarify the correct conservative endpoints to be used to estimate risk to NTPs, based off of endpoints correlated with survival and growth. The endpoints below

are su pported by the current seedling emergence guideline OCSPP 850.4100, as this is the most scientifically up

- to

- date methodology.

EFED Response: The reviewer concurs that radicle length endpoints are highly variable and

therefore will not be used in the final version of the risk asse ssment. The next most sensitive endpoint ( s ) from available terrestrial plant toxicity studies will be eval uated for appropriateness and integrated in the risk characterization and risk discussion sections of the assessment accordingly

.

BCS Comment (p. 16) : The correct NOAEC value from the study report is 0.081 lb a.i./A. The nondefinitive endpoint (<0.081 lb a.i./A) was obtained by visually interpreting the results as stated in the DER “The reviewer felt that the 16.9 and 15.7% inhibitions at the tomato and cucumber treatment levels, respectively, were biologically significant.” DER (MRID 47333423). The ori ginal study reported p

values associated with the control and limit (0.081 lb a.i./A) treatment for tomato and cucumber are p=0.132 and p=0.091, respectively. BCS seeks clarification on the reviewers visual determination of these endpoints reported in Tabl e 2 of the DER for shoot dry weight/plant (MRID 47333423), as these values do not indicate significant difference from the controls in the submitted study report, Table 9 (page 21).

EFED Response: EFED continues to rely on its previous de termination that the inhibition to tomato dry weight is biologically significant based on the fact that the variance surrounding the measurements was reasonably low for control ( = 10, s 2 =0.76) and treated ( =8.3, s 2 =3.5) plants;

however

, EFED acknowledges that the finding of biological significance for the cucumber endpoint is weak due to the fact the variance was high and was greater than the mean

measurements for both control ( =56, s 2 =105) and treated ( =47, s 2 =54) plants.

BCS Comment (p. 16) : BCS agrees that the most sensitive endpoints are corn plant height; however, BCS disagrees that these endpoints be derived by visual interpr etation of the data. In the DER (MRID 41276907), the reviewer reported “the no

- effect lev el at or below which no ad verse effects were observed
in the data”. BCS believes that stati stical no

- effect level be used, representing the highest test level that is statistically similar to the control group. The correct mathe matically derived endpoints for corn plant height are as fol lows: Corn plant height EC25 of 0.006 lb a.i./A with a NOEL of 0.0048 lb a.i./A.

EFED Response : Based on the analysis provided in the DER for MRID 41276906, it is not possible to determine the appropriate NOAEC for corn. The DER indicates a NOAEC of <0.0006

lbs a

. i

. /A for corn in the conclusions, but the reviewer results section indicates a definitive value

of 0.0 006 lbs a.i./A as the NOAEC with a footnote indicating that a 7% reductio n in plant height

was observed at this treatment level. Based o n this dis crepancy, EFED will re

- examine this study

in order to derive an appropriate endpoint for use in the final version of the risk assessment.

BCS Comment (p. 16) : The MRID number listed (41276904) is for Tier I Seedling Emergence studies.

The correct MRID for the vegetative vigor Tier I studies is 41276906.Page 7 of 11

EFED Response : The appropriate correction in MRID numbers will be made in the final version

of the risk assessment.

BCS Comment (p. 17) : BCS seeks clarification on this endpoint selection . In EPA’s DER for MRID 47333424, the reviewer calculated endpoint agrees with the BCS calculated endpoint of 0.020 lb a.i./A for Bluejoint marsh grass (page 17 of the DER MRID 47333424).

EFED Response : The NOAEC for root length (p. 18 of DER MRID 47333424) is 0.01 lbs a.i./A

, which is the most sensitive endpoint for b luejoint grass

. However, given that root measurements are no longer required in the current version of the OCSPP 850.4150 guideline, the next most sensitive endpoint 0.02 lbs a.i./A fo r shoot length and shoot dry weight will be used for risk

assessment.

BCS Comment (p. 17) : Root biomass is no longer an endpoint measured in current vegetative vigor test guideline OCSPP 850.4150. Root related endpoints are difficult due to inability to c ompletely separate roots from organic material after harvesting. Also, the removal of seedlings from the soil media often results in separation and destruction of the root system. This results in a false inflation or deflation of biomass value. Depending o n the amount of root material lost during harvest, or the amount of organic matter attached to root surfaces, the accuracy of this endpoint is greatly reduced. For these reasons, current guidelines do not indicate root based measurements.

Fenoxaprop

-

p

- eth yl is known for its selective toxicity to monocots. This selectivity is seen in Tier I vegetative vigor and seedling emergence testing with FPE without safener, resulting in no exceedence for dicot species. Carrot resulted in IC25 values greater than 0.1 l b a.i./A. Correct conservative endpoints for carrot are for shoot dry weight, with EC25 >0.081 lb a.i./A and NOEL of 0.081 lb a.i./A.

EFED Response : EFED agrees with the registrant that root endpoints are no longer evaluated in the OCSPP 850.4150 guidelin e. Therefore, based on shoot weight, shoot length, and survival, the most sensitive dicot species is lettuce with a corresponding NOAEC and EC 25 values of 0.041 and

>0.081 lbs a.i./A , respectively . These values will be used to represent dicots for vegetative vigor endpoints in the updated risk assessment.

BCS Comment (p. 17) : The text refers to incorrect table numbers: Table 4.2 represents acute and chronic RQs for direct effects to freshwater invertebrates. Table 4.3 represents acute and chronic RQs for direct effects to estuarine/marine invertebrates Table 4.4 represents RQ values for direct effects to aquatic vascular and nonvascular plants

EFED Response : The appropriate correction s will be made in the table captions in the final

version of the risk assessment.

BCS Comment (p. 18

) : The endpoint in question (<0.081 lb a.i./A) for vegetative vigor studies was derived from visual interpretation of the data for cucumber and tomato plants. Although the BCS study reported p

- values of 0.132 and 0.091 when compared to the controls, the DER indicated that the review “felt that the 16.9 and 15.7% inhibitions at the tomato and cucumber treatment levels, respectively, were biologically significant” (DER MRID 47333423). The correct conservative endpoint for these dicots, based on statistical analysis, is 0.081 lb a.i./A. Tier I studies support this as vegetative vigor testing resulted in IC25 values >0.1 lb a.i./A for tomato and cucumber plants (MRID 41276904).

As comments above address the definitive NOECs for monocots, a qu ick summary is included as follows: Corn dry weight (MRID 41276905) resulted in a NOEC of 0.006 lb a.i./A.Page 8 of 11

EFED Response : The above comment is similar to a previous comment calling into question the determination of biological significan ce for tomato and cucumber endpoints in the seedling emergence study (MRID 47333424). EFED believes that the responder mistakenly identified these as vegetative vigor endpoints. Therefore, this issue has already been addressed above.

BCS Comment (p. 18) : Effect distances need to be updated with the endpoints noted above. Additionally. EPA should incorporate current nozzle technology and the updated drift data that has been developed si nce the spray drift task force.

EFED Response : EFED will update all ter restrial plant analyses including effect distances with updated endpoints as needed. With regards to the use of current nozzle technology and drift data, EFED is currently evaluating drift data submitted by Crop Life America, but does not anticipate

the re view to be completed in time for incorporation into this assessment. EFED will continue to use the AgDRIFT model for use in its assessments.

BCS Comment (p. 18) : Footnote 4 is not indicated in Table 5.1

EFED Response : All footnotes will be appropriately updated in the final version of the risk

assessment.

BCS Comment (p. 19

) : “Based on this screening

- level assessment, there are potential risks from direct effects to listed mammals, freshwater fish, estuarine/marine invertebrates, and to monocot plants fr om the use of FPE on some of its registered use sites.” BCS seeks clarification of this statement. Table 5.1 indicates that direct effects only exist for terrestrial and semi

- aquatic plants

- monocots, and for

mammals.

EFED Response : EFED agrees with the r egistrant that there are no direct effects to listed

freshwater fish n or estuarine/marine invertebrates and will update the text to reflect these

conclusions.

BCS Comment (p. 19) : Table G

- 4 showed hydrolysis considered in PFAM modeling is stable.

EFED Response : The registrant is correct, the stable hydrolysis value depicted in Appendix G was inadvertently inserted in T able G

- 4 . The correct value of 24.6 days was actually used in the modeling and the Appendix T able G

- 4 will be corrected accordingly

.

BCS Comment (p. 23

) : Drinking water exposure assessments used the same use pattern assumptions and interpretations as noted in the EFED documents and commented here. BCS recommends that the use pattern inputs be updated for ALL exposure assessments (drinki ng water, surface water, terrestrial

vertebrates and terres trial plants (as appropriate)).

EFED Response : E FED will coordinate with the Health Effects Division to correct the application rates in the drinking water assessment, based on the preceding discussions.Page 9 of 11

Attachment 1. Bayer Commitment LetterPage 10 of 11Page 11 of 11