Page 2 of 12

Mesotrione Registration Review: Response to Comments

1. Syngenta Comment:

 Pag e 5

-- Guideline Number 835.4200, Anaerobic soil metabolism

. No data are available for anaerobic soil metabolism. It is expected that mesotrione anaerobic soil metabolism is pH dependent hence data for soils with typical pH for mesotrione use areas are

recommended.

Syngenta resp ectfully requests that two previously submitted anaerobic soil metabolism studies (MRID 44505131 [ 14 C

- phenyl label, RR96

- 033B] and 44505132 [ 14 C

- cyclohexane label, R95

- 048B]) along with other relevant e

- fate study findings be considered by the EPA to fulfi ll this data guideline. Although top water layers were dosed (0.32

- 0.34 ppm or equivalent to 322

- 340 g a i/ha), these two 1996 soil studies were primarily designed/conducted to satisfy the guideline (GL) requirements under Subdivision N: 162

- 2 (anaerobic so il; with a <60 day incubation duration per GL). However, these two studies were submitted by a Syngenta legacy company to satisfy 162

- 3 (anaerobic aquatic

- sediment) since prior to the October 2007 40 CFR part 158 changes, N series

162

- 2 and 162

- 3 requireme nts were satisfied by a sole anaerobic aquatic

- sediment study.

These two anaerobic soil studies were conducted in slightly acidic (pH 6.2) WI silt loam soil and were terminated upon either: after

- 60 days of incubation (MRID 445051

- 31, phenyl radiolabel), or after >90% of parent was transformed along with > 5% of dose transformed to CO 2 (MRID

445051

- 32, cyclohexane radiolabel).

In the 14 C

- phenyl

- mesotrione anaerobic soil metabolism study (MRID 445051

- 31), parent degraded quickly by way of bridge cleavage a nd subsequent reduction of the nitro group to an amine to form primarily 2

- amino

- 4

- (methylsulfonyl)benzoic acid (AMBA). No other major degradate or volatile component was detected. Formation to 4

- (methylsulfonyl)

- 2

- nitrobenzoic acid (MNBA) enroute to AMBA was apparently transitory, since MNBA was not de tected. The estimated parent DT 50 was ~4 days and parent was undetectable in both water and soil extracts at

30

- 59 days after treatment (DAT). AMBA was first detected in both water and sediment extracts

at 3 DAT and peaked in the total test system at 30 DAT (mean of 0.138 ppm or

- 41% of applied radioactivity, AR) before declining almost in half by the next sampling interval (59 DAT; mean 0.075 of ppm or

- 22 % AR). The study was terminated at

- 60 days per guide line N series 162

- 2 guidance.

In the 14 C

- cyclohexane

- mesotrione anaerobic soil metabolism study (MRID 445051

- 32), parent similarly degraded quickly (DT 50 of ~4 days) by way of bridge cleavage (confirmed by MRID

445051

- 31) and subsequent volatilization, pr imarily t o CO 2 , and/or 14 C

- incorporation and/or complexing of polar components into/with soil organic matter fractions. Per Table IV within the report, the level of parent was 102% AR (0.328 ppm) at 0 DAT and rapidly declined to 9.32% AR (0.030 ppm) by 14 DAT, reflecting > 90% AR transformation of parent. Also by 14 DAT, >5% AR (mean) mineralized to CO2 (based on NaOH traps); thus, the study was terminated follow the 30 DAT sample analyses.

Based on the key findings within these two anaerobic soil metabolism studies, Syngenta doesPage 3 of 12

not believe that conducting an additional separate anaerobic soil metabolism study will provide any additional information that will be useful for risk assessment purposes. Thus, Syngenta respectfully requests that the ana erobic soil metabolism data guideline (OCSPP Guideline 835.4200) be categorized as fulfilled based on previously submitted data (MRIDs 44505131

- 32)

or be waived for mesotrione.

EPA Response: EPA will perform a thorough review of the provided information and the

additional studies which were submitted by Syngenta concurrent with the above comments . EPA

will determine whether enough information is available to reduce the uncertainty that resulted in the original request for an anaerobic soil metabolism stu dy. This study remains a data gap until

the review has been completed

.

2. Syngenta Comment:

 Page 5

-- Guideline Number 835.4300, Aerobic aquatic metabolism

. This data for

mesotrione are limited to two British natural water

- sediment systems with experimental pH 7.9 and 6.9. These experimental pHs are higher than those of most of the many soils used in the aerobic soil metabolism studies, and we might expect longer half

- live s at lower aquatic system pHs. In addition, it is not certain that the microbial makeup of the British

water

- sediment systems is similar to the one in the US. Therefore, a new study conducted

on a US natural

- water sediment system at a variety of pHs typic al for mesotrione use areas is needed. Study should be conducted until patterns of decline of parent and patterns of formation and decline of transformation products are established. For the purpose of modeling a very conservative approach will be taken in selecting the input parameters if

the data are not available.

In an earlier aerobic aquatic

- sediment study (MRID 45196011, RJ2724B, both 14 C

- labels), two different British test systems were used, both with slightly alkaline sediment pHs, but near neutral water pHs (report Tables 2, 4

- 6): Old Basing with a sediment pH of 7.8 and water pH of 7.2, and Virginia Water with a sediment pH of 7.5 and water pH of 6.8 (pHs measured following collection). Mesotrione degraded rapidly to primarily AMBA (via tra nsitory formation of MNBA) in both test systems. The estimated total system DT 50 was 3

- 6 days.

In a recent 2013 study entitled "Mesotrione

- Aerobic and Anaerobic Aquatic Sediment Metabolism of [Phenyl

14 C]

- Mesotrione" ( MRID 49458103 Smithers Viscient rep ort number: 8236956, Syngenta task number: TK0045812, being submitted concurrently to the EPA), slightly acidic and slightly alkaline test systems with significantly different organic matter (OM) levels were used/compared. The initial pHs and % OM of the B ritish two test systems at their collections were: Swiss Lake's sediment (sand) pH of 5.2 (using soil:0.01M CaCl 2 ), 0.7

- 1.6 OM% with a natural water pH of 6.7; and Calwich Abbey's sediment (silt loam) pH of 7.3 (using

soil:0.01M CaCl 2 ), 7.9

- 8.1 OM% with a natural water pH of 7.9. The calculated total system single f irst order (SFO) half

- life (DT 50 ) for the acidic test system with low OM under aerobic and anaerobic conditions were 11.1 and 1.4 days, respectively. In the alkaline test system with high OM, the calculated total system SFO DT 50 under aerobic and anaerobic conditions were 6.6 and 14.4 days, respectively. Likely other soil parameters, including OM, may have influenced degradation besides just pH.Page 4 of 12

The EPA's concern on whether "the microbial makeup of the British water

- sediment systems is similar to the one in the US," is addressed in a separate comparative report being concurrently submitted to the EPA (entitled: "Microbial Profile Comparison of USA Soils to European and Brazilian Soils as of 2013, " MRID 49458102 Syngenta Report Number: TK0249517). In brief, this microbial profile comparison statistically demonstrates no significant difference in microbial makeup between US and European (including British) soils. The comparison is also applicable to sediment (originating from eroding soils). Thus, studies using European soils/sediments should not be deemed supplemental or unacceptable based on uncertainties in microbial profile similarities. In addition, "soil taxonomy is not required for sediments u sed in aquatic metabolism studies" per earlier EPA guidance (page 5 of EPA's Memorandum on "Prodiamine: Response to Waiver Requests" dated December 21, 2012, PC code 110201, DP barcode 406170). Therefore, Syngenta believes MRID 45196011 (RJ2724B) and the n ew 2013 study being submitted concurrently ( MRID 49458103 Syngenta task number: TK0045812) should adequately address and satisfy the data guideline for Aerobic Aquatic Metabolism for Mesotrione: Guideline

835.4300.

EPA Response: EPA will review the newly submitted data (MRIDs: 49458103 and 49458102 )

and determine if the new data satisfy the data requirement for a erobic a quatic m etabolism for

m esotrione

, Guideline 835.4300. If the data are found to satisfy the guideline requirement

, they

will be consider ed at the time of the r egistration r eview risk assessment

.

3. Syngenta Comment:

 Page 5

- 6

-- Guideline Number 835.4400, Anaerobic aquatic metabolism. Currently the data for mesotrione are limited to one flooded Radford U.S. soil system with purified water (two radiolabels and pH 6.9 to 7) and the obtained half

- life is comparable to the aerobic soil metabolism rate, and essentially the same as those from the two different aerobic aquatic systems. These results indicate that metabolism pr ogresses under suboxic conditions, and may be more influenced by pH than lower oxygen content. If this is true, an additional study is requested to further understand mesotrione metabolism under anaerobic aquatic conditions in natural systems at a variety of pHs. Study should be conducted until patterns of decline of parent and patterns of formation and decline of transformation products are established. For the purpose of modeling a very conservative approach will be taken in selecting the input parameters if the data are not available.

As indicated above, Syngenta is submitting a new study entitled "Mesotrione

- Aerobic and Anaerobic Aquatic Sediment Metabolism of [Phenyl

14 C]

- Mesotrione" ( MRID 49458103 Smithers Viscient report number: 8236956, Syngenta task number: TK0045812) to satisfy the data guideline for Anaerobic Aquatic Metabolism for Mesotrione: Guideline 835.4400. As also indicated above, Syngenta is concurrently submitting a comparative report addressing EPA's concern/uncertainty of the microbial profile similarities between US and European test systems (entitled: "Microbial Profile Comparison of USA Soils to European and Brazilian Soils as of 2013," MRID 49458102 Syngenta Report Number: TK02495 17). In brief, this microbial profile comparison statistically demonstrates no significant difference in microbial makeup between USPage 5 of 12

and European (including British) soils. The comparison is also applicable to sediment (originating from eroding soils).

EP A Response: EPA will review the newly submitted data (MRIDs: 49458103 and 49458102)

and determine if the data satisfy the data guideline for a na erobic a quatic m etabolism for

m esotrione

, Guideline 835.44 00. If the data are found to be acceptable

, the stud i es will be

considered at the time of the r egistration r eview risk assessment.

4. Syngenta Comment:

 Page 6

— Guideline Number 835.4100, Aerobic Soil Metabolism for MNBA. There are no separate aerobic soil metabolism study for MNBA alone, as there was for AMBA, thus is not certain if there is concern for exposure from MNBA from mesotrione use. Fate data indicate that MNBA would be a major product in many soils in which corn is grown. (In three of seventeen aerobic soils with more neutral pHs (more desirable for growing corn), maximum concentrations of MNBA reached approximately 30, 50, and 60% of the dose.) Even though the registrant attempted to estimate half

- lives for MNBA from mesotrione metabolism data, EFED concludes that the available data are insuffic ient for the purpose. In at least two soils, MNBA "half

- lives" appeared to be one to several months, but much shorter in others. The submitted data will alleviate the uncertainty associated with the metabolite persistence and uncertainty with its availabil ity in soil for potential transport to surface water. Without this data it will be assumed that the degradate 's aerobic soil metabolism half

- life is three times the most conservative estimated half

- live obtained from a formation and decline curve.

Within the EPA's October 26, 2007 40 CFR part 158 the following is stated regarding conducting e

- fate lab studies with degradates (per section XIV. Discussion of Key Comments on Environmental Fate Data Requirements (Subpart N), 3. Data requirements, ix. Degradat es): "The Agency does not require degradate substances to undergo the set of fate data requirements as it requires of the active ingredients. The set of fate studies as currently designed and conducted with the TGAI provide adequate information on the form ation, decline and mobility of the major degradates. Testing with degradates as the primary test substance is not required for the environmental fate data requirements." Per this agency statement, it is unclear why a degradate study is cited as a data

- gap.

Nonetheless, Syngenta believes a previously submitted MNBA aerobic soil metabolism study (MRID 45196008, entitled MNBA

- Rate of Degradation in Soil under Aerobic Laboratory Conditions, study # PMS 472, report #RR 99

- 098B) should satisfy this agency requ est.

Furthermore, a comprehensive summary of kinetics for mesotrione, AMBA and MNBA under aerobic soil conditions is being submitted concurrently ( MRID 49458110 report # NC/11/059C, Syngenta task # TK0046971, entitled: "Mesotrione

- Kinetic Modelling Anal ysis of Data from Aerobic Soil Degradation Studies to Derive Modelling and Persistence Endpoint DT 50 Values"),

which includes DT 50 values for MNBA from parent aerobic soil metabolism studies. Within this report ( MRID 49458110 NC/11/059C), five mesotrione

- related aerobic soil metabolism studiesPage 6 of 12

are cited, including one study investigating 13 different US soils for up to 28 DAT (RR 93

- 092, MRID 44505129).

In the latter report (MRID 44505129), all soils were slightly acidic (per in

- house

mea surements) except for one silty clay loam soil from IL (soil # 742) which was slightly alkaline (pH 7.2, % OM of 4.5, cation

- exchange capacity [CEC] of 25.5 meq/100g). In soil #742,

14 C

- mestotrione degraded comparably to or faster than the other 12 soils, but MNBA did not degrade as rapidly as the other soils within the 0

- 28 DAT incubation period. However, in another separate study (RR96

- 099B, MRID # 44505208), two soils with slightly alkaline pHs of 7.1 (clay loam, % OM of 5.7, CEC of 22.9) and 7.7 (loam, % OM of 1.46, CEC of 8.6) showed rapid degradation/dissipation of MNBA within a 0

- 28 DAT incubation period. Thus, the MNBA persistence seen with soil # 742 in MRID 44505129 may have been an anomaly and likely not pH

- related. Nonetheless, within ( MRID 49458110 NC/11/059C, b eing submitted), a statistical test (Dixon's test) deemed the MNBA findings for soil #742 (MRID 44505129) as an outlier.

Among the remaining soils ( MRID 49458110 NC/11/059C, being submitted), DT 50 values for MNBA ranged from 0.5 to 15.7 days in soils of pH 5.3

- 7.7 (n = 10), which is comparable to the range calculated in MRID 45196008 (0.6

- 10.6 days in soils of pH 5.5

- 7.9; n = 4). Thus, MNBA's persistence is not strongly correlated to pH, nor to % OM or CEC (R 2 <0.23 for all three soil parameters as shown in F igure 1 below) across all DTso values (n = 14 soils, see

T able 1 below ), excluding soil #742, but declines rapidly in a wide variety of soil types.

Table 1 : MNBA DT 50 values under a range of soil types and characteristi cs (reprinted from MRID 49458110 ) . Does not include

soil #742 ’

Soil Texture Soil Name MNBA *D T 50 (days) per

NC/ll/059C soil pH

(water:soil, 1:1

wt. ratio ) %Organic

Matter (OM) CEC

( meq/lOOg ) EPAMRID

# Syngenta study

#

lA silty clay

loam 722 0.6 5.7 3.2 16.2 44505129 RR 93

- 092B

KS loam 725 0.5 5.8 2.3 11.9 44505129 RR 93

- 092B

IN sandy loam 728 5.1 5.9 1.6 6.2 44505129 RR 93

- 092B

WI Silt Loam 729 0.7 5.6 1.9 9.4 44505129 RR 93

- 092B

OHclayloam 730 0.7 5.3 1.7 10.9 44505129 RR 93

- 092B

MO silty clay

loam 731 15.7 6.1 2 18.2 44505129 RR 93

- 092B

WI Silt Loam Richmond 1.1 6.2 2.72 12.02 44373531 RR 95

- 082B

NC Sandy

Loam ERTC 6.2 6.4 0.98 2.44 44505208 RR 96

- 099B

French Loam Toulouse 5 7.7 1.48 8.6 44505208 RR 96

- 099B

UK clay loam Pickett Place ** 7.1 5.7 22.9 44505208 RR 96

- 099B

WI Silt Loam Richmond 6.3 6.1 2.16 10.51 45196006 RR 97

- 033B

MILoamy

Sand*** Spinks 8.6 6.7 1.4 6.1 45196008 RR 99

- 098B

WI Silt

Loam*** Delavan 10.1 6 2.4 13.2 45196008 RR 99

- 098B

UK Loam*** Wisborough

Green 0.6 5.5 5.1 11.7 45196008 RR 99

- 098B

UK sand*** East Anglia 10.6 7.9 2.2 11.1 45196008 RR 99

- 098BPage 7 of 12

* MNBA D T

50 (days) calculated per NC/11/059C (to be submitted), except for data from MNBA aerobic s01l metabolism study (MRID 45196008). Note: All studies conducted at 20 °

- 25°C.

** MNBA not detected between 0

- 28 DAT incubation, except at 3 DAT at <5% AR (thus, data excluded in figures below ).

***Data taken from a MNBA aerobic soil metabolism study, rather than parent mesotrione aerobic soil metabolism studie s

.

Figure 1 : (Reprinted from MRID 49485110 )

EPA Response: In circumstances where evidence suggests that a degradate of concern is more

toxic then the parent

, it is a common practi ce to request an aerobic soil metabolism study for the degradate

. The available ecotoxicity dataset is fairly limited for MNBA. Although apparently less toxic to nonvascular aquatic plants than parent mesotrione, it does appear to be more toxic to

freshwater invertebrates. MNBA

, once formed in the soil

, potentially will reach surface water via

runoff and will be available for exposure to aquatic organisms. Therefore

, understanding of MNBA kinetics is crucial for conducting ecological risk assessment.

EPA will review the recently su bmitted data and determine if the data satisfy the data guideline

for aerobic s oil m etabolism for MNBA

, Guideline 835.41 00. If the data are found to be acceptable

, the study (MRID 45196008) will be considered at the time of the r egistration r eview

risk assessment.

5. Syngenta Comment:

 p. 6

— Guideline Number 835.4300, Aerobic Aquatic Metabolism for MNBA. The Agency has no data on the fate of MBNA under aer obic aquatic conditions. The longer MBNA persists in the soil, the greater the opportunity for it to move into surface water, where its fate is unknown and where it potentially could impact aquatic species. Data from this study

would address the uncertaint y in regards to MNBA behavior in the aquatic environment under aerobic conditions. The study should be conducted at a variety of pHs.

Per the agency statement quoted previously from the EPA's October 26, 2007 40 CFR partPage 8 of 12

158 (XIV. Discussion of Key Comments on Environmental Fate Data Requirements (Subpart N), 3. Data requirements, ix. Degradates), it is again unclear why a degradate study is cited

as a data

- gap.

With the new aquatic

- sediment study being submitted concurrently entitled "Mesotrione

- A erobic and Anaerobic Aquatic Sediment Metabolism of [Phenyl

14 C]

- Mesotrione" ( MRID

49458103 Smithers Viscient report number: 8236956, Syngenta task number: TK0045812) no MNBA was detected under aerobic conditions in either test system/matrix. MNBA (NOA4371 30) was found only at <2% of applied dose in one test system under anaerobic

conditions.

In an earlier aerobic aquatic

- sediment study (MRID 45196011, RJ2724B), Mesotrione degraded rapidly to primarily AMBA (via transitory formation of MNBA) in both test s ystems. The highest level (total test system) of MNBA reached was 7.9% AR at 3 DAT; declining to <0.9% AR by 42

- 101 DAT in one test system; and not detected in the other total test system. Again, these finding demonstrate that MNBA under aquatic

- sediment conditions was a transitory degradate with no persistence. Thus, Syngenta believes the parent (mesotrione) aquatic

- sediment studies adequately describe the formation/decline of MNBA and respectfully request that this data guideline for a MNBA aquatic sedi ment study be categorized as fulfilled based on existing data ( MRID 49458103 study submitted concurrently and MRID 45196011) or be waived.

EPA Response : EPA will review the recently submitted study and determine if there is enough information available to reduce the uncertainty that resulted in the original request for an aerobic aquatic metabolism study for MNBA. The Agency ’s main concern is that the data from the

formation and decli ne of the major degradates from the TGAI studies can serve as the bas is for

the total toxic residue (TTR) half

- life calculation s and be used in a TTR risk asses sment, but will

not allow for an individual degradate assessment. In circumstances where there i s a lack of data

for a modeling purpose , a conservative estimate of the modeling parameter s will be made

.

6. Syngenta Comment:

 Page 5

-- 6

— Guideline Number 835.6100, Environmental Chemistry Methods and Independent Laboratory Validation on Soil, Water, and Sediment (835.6100) with the Storage Stability Characteristics for Surface Water Monitoring (MRID 47244503) It is requested for the purpose of upgrading an unacceptable Surface Water Monitoring study to supplemental because surface water samples were store d for up to 18 months before analysis. If upgraded, the available surface water data could be used for qualitative characterization or even used more quantitatively (chronic exposure results) in the risk

assessment.

While there is not a storage stability report specific to the surface water monitoring program, storage stability data were generated in a 2004 study entitled, "Mesotrione: Stability of Mesotrione, MNBA and AMBA in Ground Water and Lysimeter Water when Stored at Room Temperature for up to 14 Da ys, <7°C for up to Nine Months and Deep Frozen at <

- 18°C for up to Four Years

- Final Rep ort." ( MRID 49458104 Syngenta study number: 00 JH009, being submitted concurrently with this response to the EPA). Therein, suction lysimeter water and ground water were stored over aPage 9 of 12

period of 9 months at <7°C and analyzed for parent mesotrione and degradation products, MNBA and AMBA. All three analyt es were found to be stable for the duration of the study.

In the surface water monitoring study (MRID 47244503), 2895 of 3274 samples (88.4%) were refrigerated less than 9 months prior to analysis for mesotrione. Among the 2895 samples stored

less than 9 months, only 477 (16.5%) contained mesotrione above the limit of quantitation (LOQ

= 0. 05 μ g/L). The highest concentration of mesotrione detected in these samples was 2.40 μ g/L,

and the 90th ce ntile concentration was 0.12 μ g/L.

Given that a large majority of the surface water samples were cold

- stored for a period of time less than the duration of the storage stability study under the same conditions, Syngenta believes the available mesotrione surface water monitoring data can be used for qualitative charac terization or quantitative risk assessment.

EPA Response: EPA documentation indicates that some samples were stored for up to 18 months prior to analysis , but the storage conditions we re not provided in the study report

, hence the submitted study may be insufficient for the purpose of upgrading the surface water monitoring study. EPA will review the submitted storage stability data

, and after i t receive s relevant information on the storage conditions of the monitoring samples

, it will make a final

dete rmination whether provided data are sufficient to upgrade the currently unacceptable study

.

It should be noted that the monitoring data report is also lacking in information about the sampling methods

, the ana lytical methods used, the method description, method validation, the procedural recove ries, or other relevant information. Since this mesotrione monitoring was a subset of the Atrazine Monitoring Program (AMP ) , for which sampling protocols were reviewed by the EPA

, if applicable, a reference to relevant documentation may be sufficient for this study.

7. Syngenta Comment:

 Page 5, Table 1

— Guideline Number 850.6100, Analytical method in soil Enclosed with this submission is data that has not been previously submitted to EPA to address this anticipated data need ( MRID 49458108 T001200

- 03 and MRID 49458107 T00265 5

- 03).

EPA Response: EPA will review the submitted analytical method data. This study remains a data gap until the review has been completed and the studies are found to be acce ptable.

8. Syngenta Comment:

 Page 6, Table 1

— Guideline Number 850.6100, Analytical method in water and sediment

Enclosed with this submission is data that has not been previously submitted to EPA to address this anticipated data need ( MRID 49458106 T006179

- 04 and MRID 49458109 T006179/04

.

EPA Response: EPA will review the submitted analytical methods data. This study remains a data gap until the review has been completed and the studies are found to be acceptable.Page 10 of 12

9. Syngenta Comment:

 Page 6

— Data are requested for the following mesotrione ecological data gap: Estuarine/Marine Invertebrate Acute Toxicity Study Using MNBA (OCSPP Guideline 850.1035)

A waiver request for this data requirement is being submitted concurrently with this response ( MRID 49 458105 TK0249521)

EPA Response: EPA will review the data waiver request and determine whether enough information is available to reduce the uncertainty that resulted in the original request for an estuarine/marine invertebrate acute toxicity study using M NBA.

10. Syngenta Comment:

 Page 7

— Data are requested for the following mesotrione ecological data gap: Terrestrial Plant Seedling Emergence Tier II Study (OCSPP Guidelines 850.4100) with the degradate MNBA on onion, lettuce and cabbage

Enclosed w ith this submissi on is MRID 49458101 Report Number: TK0249516 entitled "Discussion and Waiver Requests for Mesotrione

- Related Environmental Fate Data Guidelines

Listed in the EPA's June 3

, 2014 Memorandum"

. This document states that:

"In the 14C

- phenyl

- mesot rione anaerobic soil metabolism study (MRID 44505131 )

, parent degraded quickly by way of bridge cleavage and subsequent reduction of the nitro group

to an amine to form primarily 2

- amino

- 4

- (methylsulfonyl)benzoic acid (AMBA). No other major degradate or vo latile component was detected. Formation to 4

- (methylsulfonyl)

- 2

- nitrobenzoic acid (MNBA) enroute to AMBA was apparently transitory, since MNBA was not detected. The estimated parent DT 50 was ~ 4 days and parent was undetectable in both water and soil extra cts at
30

- 59 days after treatment (D AT). AMBA was first detected in both water and sediment extracts

at 3 D AT and peaked in the total test system at 30 D AT (mean of 0.138 ppm or ~ 41% of applied radioactivity, AR) before declining almost in half by the next sampling interval (59 D AT; mean 0.075 of ppm or

- 22 % AR ). The study was terminated at ~ 60 days per guideline N series 162

- 2 guidance ...

. Furthermore, a comprehensive summary of kinetics for mesotrione, AMBA and

MNBA under aerobic soil conditions is bein g submitted concurrently ( MRID 49458110 report# NC/11/059C, Syngenta task# TK0046971, entitled: "Mesotrione

- Kinetic Modelling Analysis of Data from Aerobic Soil Degradation Studies to Derive Modelling and Persistence Endpoint DT 50 Values"), which includes DT 50 values for MNBA from parent aerobic soil metabolism studies. Within this report ( MRID 49458110 NC/11/059C), five mesotrione

- related aerobic soil metabolism studies are cited, including one study investigating 13 different US soils for up to 28

D AT (R R 93

- 092, MRID 44505129)."

Therefore, based on this analysis DT 50 values for MNBA range from 0.5 to 15.7 days in soils of pH 5.3

- 7.7 (n = 10)

, which is comparable to the range calculated in MRID 45196008 (0.6

- 10.6 days in soils of pH 5.5

- - 7.9; n = 4)

. Given these environmental fate data for MNBA

, Syngenta believes that environmental exposure will be very limited and generation of terrestrial plant data for MNBA would be unnecessary and uninformative for risk assessment purposes.Page 11 of 12

EPA Response:

EPA has requested the seedling emergence study ( Guideline 850.4100) with MNBA on onion, lettuce and cabbage (the most sensitive species from the terrestrial plant studies with parent mesotrione) due to its formation at rates up to 60% in the aerobic soil metabolis m studies and

because plants may be exposed via runoff. The seedling emergence study is not meant to evaluate

test substance residues over time , but is designed to evaluate phytotoxic effects after a single application of the test substance. A half

- life ranging from as short as 12 hours, but up to nearly 16 days (suggested by Syngenta’s comment) may still be sufficient for exposure of non

- target plants to runoff containing MNBA r esidues in eroded soil to occur. Therefore, seedling emergence data

is still needed to remove uncertainties in the risk assessment.

1 1

. Syngenta Comment

 Page 13

- 14

—

Endangered Species discussion

Syngenta has previously submitted a document summarizing the types of refinements that should be considered for an endangered species ri sk assessment (Risk Assessment Considerations Concerning the Potential Impacts of Pesticides on Endangered Species, MRID 49200601). It is respectfully requested that EPA review this document and consider these refinements when conducting an endangered spec ies risk assessment for mesotrione. An expanded document entitled "Risk Assessment Considerations With Regard to the Potential Impacts of Pesticides on Endangered Species" has recently been published in the peer reviewed journal Integrated

Environmental Assessment and Management and a copy of the unformatted article is enclosed; the citation is provided below:

Brain R, Teed S, Bang J, Thorbek P, Perine J, Peranginangin N, Kim M, Valenti T, Chen
W, Breton R; Rodney S, and Moore D. 2014. Risk Assessment Considerations With Regard

to the Potential Impacts of Pesticides on Endangered Species. Integrated Environmental

Assessment and Management DO I 10, 1 002/ieam.1572.

EPA Response :

EPA will consider the cited documents at the time of the r egistration r eview risk assessment (in addition to other open literature documents) in the context of EPA’s agreements with the Services regarding the conduct of risk assessments for potential impacts of pesticides to listed species and determine their applicability for use in the risk assessment.

12. Syngenta Comment

 Page 18

— MNBA; “No Data” for “Aquatic plants and algae”

Table 8 of the problem formulation states that there are no data available for aquatic plants; however, data for P. subcapitata (S. capricomutum) are available in MRID 44901710 and are subsequently discussed on page 19 of the problem formulation.Page 12 of 12

EPA Response:

Table 8 of the problem formulation is intended to indicate that there is no data of quantitative value

for use in risk assessment on effects of MNBA to aquatic plants or algae. The study that Syngenta cites (MRID 44901710), investigating the effect of MNBA on green algae, is discussed on page 19 of the problem formulation and is being downgraded to S upplemental

— Q ualitative due to

issues of extre mely high pH in controls and extreme acidic condition in the highest treatment doses that contribute to uncertainty around IC 50 and NOAEC endpoints. A more thorough discussion of the reevaluation and downgrade of this study has been completed under a sepa rate cover (DP 422484). The study may be used to characterize that MNBA is likely not as toxic as parent mesotrione to green algae . N o new data are currently being requested to evaluate the effect of MNBA on aquatic plants.