# Test Material: Nicosulfuron

MRID 49169703

Title: Sarff, P. 2004. Rate of 14 

# C-Nicosulfuron Degrada tion in Three Soils.

EPA PC Code: 129008

OCSPP Guideline: 835.4100

For CDM Smith

Primary Reviewer: Joan Harlin Signature:

Date: 3/20/14

Secondary Reviewer: Kathleen Ferguson Signature:

Date: 3/20/14

QC/QA Manager: Joan Gaidos Signature:

Date: 3/20/14

## Nicosulfuron (PC 129008) MRID 49169703

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# Aerobic degradation of Ni cosulfuron in three soils

Report: MRID 49169703. Sarff, P. 2004. Rate of 14 

# C-Nicosulfuron Degradation in Three Soils. Unpublished study performed by ABC Laboratories, Inc., Columbia, Missouri and DuPont Crop Protection, Newark, Delaware; sponsored and submitted by E.I. du Pont de Nemours and Company, Wilmington, Delaware. DuPont Study No.: 10929; ABC Study No.: 47547. Experimental work conducted between August 13, 2002 and N ovember 19, 2003 (p. 6). Final report issued April 1, 2004.

Document No.: MRID 49169703

Guideline: OCSPP 835.4100
Statements: The study was conducted according to US EPA Principles of Good Laboratory Practice (p. 3). Signed and dated Data C onfidentiality, GLP, Quality Assurance, and a certification of authenticity st atement were provided (pp. 2-5).

Classification: This study is Supplemental . The soil extraction proce dures were not adequate to extract all identifiable [ 14 

# C]residues in the soils; une xtracted residues totaled a maximum of 30.0-40.2% of the applied. Th e pesticide use history at the soil source sites was not reported, and it was not confirmed that the soils were free of pesticide residues.

PC Code: 129008

Reviewer: Gabe Rothman Signature: Environmental Scientist Date: August 24, 2015

EXECUTIVE SUMMARY

The aerobic transforma tion of [pyridine-2- 14 

# C]- and [pyrimidine-2- 14 

# C]-labeled nicosulfuron was studied in three European souls: a sandy loam from Denmark (Fla kkebjerg; pH 6.14), a clay loam from France (Champenoux, pH 5.35), and a loam from Germany (Gross-Umstadt, pH 7.48). The samples were incubated in darkness at 20  C and ca. 50% of the 0 bar moisture holding capacity.
The aerobic metabolism of nicosu lfuron (both labels) was also studied in the Champenoux clay
loam soil at 10 ° C under the same test conditions. The soil wa s treated at 0.08 mg a.i./kg, equivalent to a field rate of 0.06 kg a.i./ha. A continuous fl ow-through volatile trapping system was used. It
was not confirmed that aerobic conditions were maintained in the soils throughout the study. The soils were viable at study initiation and termination.

20°C experiments: The overall material balance averag ed 100.0 ± 3.2% (range 95.8-106.0%) of the applied for the pyridine label and 98.6 ± 2.3% (r ange 95.2-102.7%) for the pyr imidine label in the Flakkebjerg sandy loam soil; 97.2 ± 4.4% (range 85.7-101.8%) for the pyridine label and 94.6 ± 3.3% (range 87.5-98.5%) for the pyrimidine label in the Champenoux clay loam soil; and 96.0 ± 2.8% (range 90.8-99.6%) of the applied for the pyridine label and 96.3 ± 3.1% (range 91.3-100.8%) for the pyrimidine label in the Gross-Umstadt loam soil. There were no patterns of decline in
recoveries over time. Recoveries generally met guideline criteria.

10°C experiments: The overall material balance averag ed 99.6 ± 2.9% (range 95.3-106.9%) for the pyridine label and 99.8 ± 3.1% (r ange 96.0-107.0%) for the pyrimid ine label in the Champenoux

## Nicosulfuron (PC 129008) MRID 49169703

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# clay loam soil. There were no patterns of declin e in recoveries over time . Recoveries met guideline
criteria.

DT 50 

# values, calculated half-lives, and informa tion on transformation products are listed in Table 1

. For the 20oC experiments, half-lives were 51.4 days in the Flakkebjerg sandy loam soil, 15.8 days in the Champenoux clay loam soil, and 18.4 days in the Gross-Umstadt loam soil. Major transformation products identified were 

# IN-HYY21, IN-J0290, and IN-V9367. For the 10oC experiment, the half-life was 156 days for the Champenoux clay loam soil. Major transformation products identified we re IN-J0290 and IN-V9367.

20oC experiments: In the Flakkebjerg sandy loam soil (c ombined labels), total extractable radioactivity declined from 97.1% of the applied at time 0 to 88.7% at 120 days posttreatment. Unextracted radioactivity increased to a ma ximum of 32.5% of the applied at 120 days.
Evolved 14 

# CO 2 

# totaled a maximum of 9.0% of the applied at study termination; other volatiles were
not detected.

In the Champenoux clay loam soil (combined labels), total extractable radioa ctivity declined from 95.5% of the applied at time 0 to 84.4% at 120 da ys posttreatment. Unextracted radioactivity
increased to a maximum of 30.0% of the a pplied at 120 days posttreatment. Evolved 14 

# CO 2 

# totaled a maximum of 3.6% of the applied at study term ination; other volatile s were not detected.

In the Gross-Umstadt loam soil (combined labels), total extractable radioactivity declined from 98.8% of the applied at time 0 to 59.7% at 120 da ys posttreatment. Unextracted radioactivity increased to a maximum of 40.2% of the applied at 90 days, and was 39.0% at 120 days. Following
humic/fulvic extraction of the Gross-Umstadt lo am 120-day sample, fulvic acid was 25.0% of the applied, humic acid was 6.0%, and humin was 8.0%.

10oC experiments: In the Champenoux clay loam soil (c ombined labels), total extractable radioactivity declined from 97.1% of the applied at time 0 to 86.7% at 120 days posttreatment. Unextracted radioactivity increased to a maximum of 19.0% of the applied at 90 days posttreatment and was 18.3% at 120 days. Evolved 14 

# CO 2 

# totaled a maximum of 0.6% of the applied at study termination; other volatiles were not detected.Nicosulfuron (PC 129008) MRID 49169703Page 4 of 30Table 1. Results Synopsis: Aerobic Soil Metabolism of NicosulfuronSoil Location andTexture(Temperature,pH)ObservedDT50(days)CalculatedHalf-lifeA(days)ModelParameters andStatisticsTransformation Products (maximum % AR, associated interval)BMajor MinorDenmarkFlakkebjergSandy loam soil(20C, pH 6.14)ca. 4151.4DFOPC0= 95.4f = 0.27K0= 0.0605K1= 0.00784Slow t1/2= 88.4IN-J0290 (21.3% at 90 days)IN-HYY21 (13.8% at 90 days)IN-V9367 (52.2% at 120 days)Unextracted residues (32.5% at 120days)IN-74427 (1.4% at 90, 120 days)IN-69188 (2.2% at 120 days)CO2(9.0% at 120 days)FranceChampenouxClay loam soil(20C, pH 5.35)ca. 1415.8IOREC0= 93.8N = 1.6k = 0.0035tR IORE= 27.7IN-J0290 (48.8% at 62 days)IN-V9367 (72.4% at 120 days)Unextracted residues (30.0% at 120days)IN-HYY21 (4.6% at 90 days)IN-37740 (2.9% at 14 days)IN-74427 (2.5% at 120 days)IN-77799 (3.1% at 30 days)IN-69188 (2.6% at 62 days)CO2(3.6% at 120 days)GermanyGross-UnstadtLoam soil(20C, pH 7.48)ca. 1818.4IOREC0= 96.9N = 1.35k = 0.00865tR IORE= 24.9IN-HYY21 34.9% at 120 days)Unextracted residues (40.2% at 90 days)IN-GDC42 (7.0% at 120 days)IN-V9367 (6.2% at 120 days)IN-37740 (5.5% at 14 days)CO2(5.5% at 120 days)FranceChampenouxClay loam soil(10C, pH 5.35)>120156DFOPC0= 94.8f = 0.351K0= 0.0214K1= 0.00184Slow t1/2= 378IN-J0290 (16.7% at 90 days)IN-V9367 (35.3% at 120 days)Unextracted residues (19.0% at 90 days)CO2(0.6% at 120 days)AModel was selected in accordance with the NAFTA kinetics guidance (USEPA, 2012). Double First Order in Parallel (DFOP), and Indeterminate Order RateEquation (IORE)BAR means “applied radioactivity”.

## Nicosulfuron (PC 129008) MRID 49169703

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# I. Materials And Methods

A. Materials:

1. Test Material [Pyridine-2- 14 

# C]- and [pyrimidine-2- 14 

# C]-labeled nicosulfuron (DPX-V9360; p. 20, Figure 1, p. 68) Pyridine-2-label Specific activity: 62.9 μCi/mg (pp. 19-20) Radiochemical purity: 98.0% (HPLC) Chemical purity: Not reported

Lot No.: 2385-050

Pyrimidine-2-label Specific activity: 62.2 μCi/mg (pp. 19-20) Radiochemical purity: 98.6% (HPLC) Chemical purity: Not reported

Lot No.: 2406-007

Solubility in water: Not reported

2. Reference Compounds: The following standards were used in the analysis ( Table 2 ).

Table 2. Reference Compounds

Applicant’s
Code Name Chemical Name Purity (%) Lot No.

Nicosulfuron(DPXV9360) 2-{{{{(4,6-Dimethoxy-2-pyrimidinyl )amino]carbonyl]a mino]sulfonyl]- N,N-dimethyl-3-pyridinecarboxamide 97.9 116

IN-V9367 2-(Aminosulfonyl)-N,N-dimethyl-3-pyridinecarboxamide 99.7 3

IN-37740 2-[[(3,4-Dihydro-6-methoxy-4-oxopyrimidin-2- yl]aminocarbonyl)aminosulfonyl]-N,N-dimethyl-3-pyridinecarboxamide NR 4

IN-J0290 4,6-Dimethoxy-2-pyrimidinamine 99.9 3
IN-H1043 2-Amino-6-hydroxy-4(1H)-pyrimidinone 99.2 7

IN-74427 2-[(4,6-Dimethoxy-2-pyrimidinyl)-amino]-N,N-dimethyl-3- pyridinecarboxamide 99.4 2

IN-W9807 2-[[(4,6-Dimethoxypyrimidin-2-yl)aminocarbonyl]aminosulfonyl]-Nmethyl-3-pyridinecarboxamide 97.2 3

IN-64554 Isothiaxolo[5,4-B]pyridine-3(2H)-one, 1,1-dioxide 99.5 2

IN-GDC42 2-[[[[(Aminocarbonyl)amino]carbonyl]amino]sulfonyl]-N,N-dimethyl-3- pyridine-carboxamide -- --

IN-77799 2-[(Aminocarbonyl)[4-methoxy-6-(methyldioxy)-2-pyrimidinyl]amino]- N,N-dimethyl-3-pyridinecarboxamide -- --

IN-69188 --
-- -- IN-H9235 --
-- --

IN-HYY21 2-[[[[(Amonoiminomethyl)amino]-carbonyl]amino]sulfonyl]-N,Ndimethyl-3-pyridinecarboxamide -- --
Data obtained from pp. 20-21 and Figure 1, pp. 68-72 of the study report. -- = not reported.

## Nicosulfuron (PC 129008) MRID 49169703

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# 3. Soil: Soil collection and characteri zation are summarized in Table 3 and Table 4 , respectively.

Table 3. Description of Soil Collection and Storage
Description Flakkebjerg Champenoux Gross-Umstadt
Geographic location Flakkebjerg, Denmark Champenoux, France Gross-Umstadt, Germany
Soil series Not reported
Pesticide use history at
the collection site Not reported

Collection date Not reported
Collection procedures Not reported
Sampling depth Not reported
Storage temperature ca . 4 ° C
Storage length Not reported.
Soil preparation Sieved ( ca. 2 mm) Data obtained from pp. 22, 37; and Table 1, p. of the study report.



# Table 4. Properties of the Soil Property Flakkebjerg Champenoux Gross-Umstadt Soil Texture (USDA) Sandy loam Clay loam 1 

## Loam

% Sand 53.2 21.2 37.2

% Silt 32.8 50.8 46.8 % Clay 14.0 28.0 16.0 pH (in water) 6.14 5.35 7.48 Organic carbon (%) 1 

## 1.0 1.6 1.0 Organic matter (%) (Walkley-Black) 2.1 2.1 1.8 Cation Exchange Capacity (meq/100 g) (method not reported) 9.90 17.73 10.66

CaCO 3 

## equivalence (%) Soil Moisture Content (%)

0 bar 34.1 51.3 41.4

0.1 bar 21.1 34.8 28.2

0.33 bar 20.2 28.4 24.6 Bulk density (g/cm 3 

## ) 1.14 1.12 1.14

Microbial Biomass in untreated soil (mg C/100 g soil)

At initiation 92.6 132.8 128.6

At termination 98.7 153.9 167.7

Soil taxonomic classification Not re ported Not reported Not reported Data obtained from p. 22, Table 1, p 49, and Table 2, p. 51, of the study report. The soil textures for the Flakkebjerg and Gross-Umstadt soils were confirmed using USDA-NRCS technical support tools. The soil texture for the Champenoux soil was determined by the reviewer to be a clay loam (see Reviewer’s Comment). 1 Organic carbon = organic matter (%)/1.724.

## Nicosulfuron (PC 129008) MRID 49169703

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# B. STUDY DESIGN

1. Experimental Conditions: (Summarized in Table 5 ).

Table 5. Experimental Design

Property Details Duration of the test (days) 120 Soil condition (Air dried/fresh) Fresh Soil (g/replicate) 50 g (dry wt) Application rates Nominal 0.08 μg a.i./g, equivalent to 60 g a.i./ha 1



## Actual Pyridine = 0.0782 μg a.i./g (reviewer-calculated) Pyrimidine = 0.0786 μg a. i./g (reviewer-calculated) Control conditions (if used) Sterile controls were not used. Number of Replicates Controls (if used) Sterile controls were not used. Treatment Single samples of each soil and labe l were collected at each sampling interval. Test apparatus

Type/material/volume The test system consisted of 250-mL glass Erlenmeyer flasks containing moist treated soil (50 g dry wt) that were connected to a continuous flow throughvolatile trapping system. The bottles were kept in the dark in a temperaturecontrolled chamber. The test system is illustrated in Figure 2, p. 73. Details of traps for CO 2 

## and other volatiles (if any) Humidified, CO 2 

## -free air was pulled through the samples, then through one bottle of ethylene glycol and two bottles of 1N KOH traps. If no traps were used, is the system closed/open? Volatile traps were used.

Identity and concentration of
co-solvent Not applicable. Application solutions brought to volume with 10 mM ammonium
acetate solution.

Test Material:

Volume of the test
solution used/treatment Pyridine-2- 14 

## C label: 247 μL/vessel Pyrimidine-2- 14 

## C label: 241 μL/vessel

Application method Applied with automatic pipette to samp le surface, water added to bring to ca

. 50% of 0 bar moisture, and then soil mixed with a spatula.

Is the co-solvent evaporated? Not applicable

Any indication of the test material adsorbing to the walls of the test apparatus? No

Experimental conditions:

Temperature (  C) 20 ± 2  C, range 22.9-27.6  C

10 ± 2  C, range 12.7-13.6  C: Gross-Unstadt soil only

Continuous darkness Yes Moisture content (MHC) ca . 50% of 0 bar moisture

Moisture maintenance
method Moisture levels adjusted as needed at least monthly with reagent water.

Other details (if any) None Data obtained from pp. 23-26, 37; Table 2, pp. 50-51; and Figure 2, p. 73 of the study report. 1 Field equivalence calculated by the study author assuming an incorporation depth of 5 cm and a soil bulk density of 1.5 g/cm 3 

## (p. 19).



# 2. Sampling During Study Period: (Details summarized in Table 6 ).

## Nicosulfuron (PC 129008) MRID 49169703

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# Table 6. Sampling During Study Period

Criteria Flakkebjerg Champenoux Gross-Umstadt
Sampling intervals (days)
Both labels 0, 3, 7, 14, 21, 30, 45, 62, 76 (Gross-Umstadt only), 90, and 120

Sampling method The entire flask was collected at each sampling interval.

Method of collection of CO 2 

## and organic volatile compounds Triplicate aliquots of th e trapping solutions were collected at each sampling interval. The volatile trapping solutions were replaced with fresh material at each sampling event.
Sampling intervals/times for:
Sterility check (if used) Sterile controls were not used.

Moisture content Moisture levels were adjusted as needed at least monthly with reagent water.
Redox potential, other The redox potential was not measured.

Sample storage before analysis Soils were extracted immediat ely or stored frozen for ≤ 9 days. Extracts were stored frozen until analysis. Samples were generally analyzed within ca . 1
month.

Other observation (if any 

# ) None Data obtained from pp. 26-27 of the study report.



# 3. Analytical Procedures

Extraction Methods: The soil was extracted three ti mes by shaking for 30 minutes with acetone:0.01M ammonium carbonate (4:1, v:v; p. 27; Figure 2,p. 74). The extracts were combined, concentrated, and filtered. Aliquots were analyzed by LSC. Additional aliquots were concentrated to near dryness under nitrogen, reconstituted in wate r:methanol (95:5, v:v), filtered, and analyzed by
LSC and HPLC.

Determination of Unextracted Residues: The extracted soils were air-dried and homogenized via mechanical shaking (wrist acti on or horizontal platform shak er; p. 27). Due to inadequate homogenization, the samples after day 60 and select samples that showed poor replication in the original combustions were homogenized using a mort ar and pestle (p. 28). Tr iplicate aliquots of the soil samples were analyzed by combustion followed by LSC.

Determination of Volatile Compounds: Aliquots of the ethylene glycol and KOH trapping solutions were analyzed by LSC (p. 27). The presence of CO 2 

# in the KOH solutions was confirmed by precipitation with bari um chloride (p. 28).

Total radioactivity measurement: Total [ 14 

# C]residues were determined by summing the
concentrations of residues in the soil extracts, extracted so il, and volatile traps (p. 38).

Derivatization method A derivatization method was not employed.

Identification and quantification of Parent and Transformation Compounds: The concentrated soil extracts were analyzed using reverse phase HPLC using Supelco Discovery C18 columns eluted with a mobile gradient phase of (A) methanol a nd (B) 0.1% formic acid (p. 30). The metabolites INV9367 and IN-GDC42 were separa ted using reverse phase HPLC using a Phenomenex Aqua column with a mobile phase of (A) methanol wi th 0.2% formic acid and (B) 0.2% formic acid (p. 31).

Extract solutions were cochromatographed w ith unlabeled reference standards (p. 30).

## Nicosulfuron (PC 129008) MRID 49169703

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# Transformation products were separated and posit ively identified in th e soil extracts using LC/MS/MS (p. 27).

Detection Limits (LOD, LOQ) for the Parent and Transformation Products: The LOD for LSC analysis was twice background (pp. 30- 31). For combustion LSC, the LOD was ca . 3.6 ppb (4.5% of the applied radioactivity (p. 35). Fo r LSC of the soil extracts, the LOD was ca. 8.6 ppb (11% AR). For LSC of the KOH and ethylene glycol trapping solutions, the LOD was ca . 0.8 ppb (1% AR) and ca. 0.4 ppb (0.5% AR), respectively. For HPLC of the soil extracts, the LOD was ca. 0.3 ppb (0.38% AR).

II. Results and Discussion

A. Data

Study results including total mass balances and di stribution of radioactivity are presented in Table
7 . No determinations were made to verify that aer obic conditions were maintained in the soils. Soils were viable at study initiation a nd termination (Table 2, p. 51).

B. Mass Balance

20 ° C experiments: The overall material balance averag ed 100.0 ± 3.2% (range 95.8-106.0%) of the applied for the pyridine label and 98.6 ± 2.3% (r ange 95.2-102.7%) for the pyr imidine label in the Flakkebjerg sandy loam soil; 97.2 ± 4.4% (range 85.7-101.8%) for the pyridine label and 94.6 ± 3.3% (range 87.5-98.5%) for the pyrimidine label in the Champenoux clay loam soil; and 96.0 ± 2.8% (range 90.8-99.6%) of the applied for the pyridine label and 96.3 ± 3.1% (range 91.3-100.8%) for the pyrimidine label in the Gross-Umstadt lo am soil (Tables 3-4, pp. 52-55; Table 6, pp. 58-59). There were no patterns of decline in recoveries over time. Rec overies generally met guideline
criteria.

10°C experiments: The overall material balance averaged 99.6 ± 2.9% (range 96.0-107.0%) for the pyridine label and 99.8 ± 3.1% (r ange 95.9-106.9%) for the pyrimid ine label in the Champenoux clay loam soil (Table 5, pp. 56-57) . There were no patterns of dec line in recoveries over time. Recoveries met guideline criteria.

C. Unextracted and Extractable Residues

20 ° C experiments: In the Flakkebjerg sandy loam soil (c ombined labels), total extractable radioactivity declined from 97.1% of the applied at time 0 to 88.7% at 120 days posttreatment (Table 3, pp. 52-53). Unextracted ra dioactivity increased to a maxi mum of 32.5% of the applied at 120 days.

In the Champenoux clay loam soil (combined labels), total extractable radioa ctivity declined from 95.5% of the applied at time 0 to 84.4% at 120 days posttreatment (Table 4, pp. 54-55). Unextracted radioactivity increased to a maximum of 30.0% of the applied at 120 days posttreatment.

In the Gross-Umstadt loam soil (combined labels), total extractable radioactivity declined from 98.8% of the applied at time 0 to 59.7% at 120 days posttreatment (Table 6, pp. 66-67). Unextracted

## Nicosulfuron (PC 129008) MRID 49169703

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# radioactivity increased to a ma ximum of 40.2% of the applied at 90 days, and was 39.0% at 120 days. Following humic/fulvic extraction of the Gr oss-Umstadt loam 120-day sample, fulvic acid was 25.0% of the applied, humic acid was 6.0%, and humin was 8.0% (p. 42).

10oC experiments: In the Champenoux clay loam soil (c ombined labels), total extractable radioactivity declined from 97.1% of the applied at time 0 to 86.7% at 120 days posttreatment (Table 5, pp. 56-57). Unextracted ra dioactivity increased to a maxi mum of 19.0% of the applied at 90 days posttreatment and was 18.3% at 120 days.

D. Volatilization

At 120 days posttreatment evolved 14 

# CO 2 

# totaled a maximum of 9.0% in the Flakkebjerg sandy loam soil, 3.6% in the Champenoux clay loam so il, and 5.5% in the Gross-Unstadt loam soil (Tables 3-4, pp. 52-55; Table 6, pp. 58-59). Vo latile organics we re not detected.

10 ° C - At 120 days posttreatment evolved 14 

# CO 2 

# totaled a maximum of 0.6% in the Champenoux clay loam soil (Table 5, pp. 55-56). Volatile organi cs were not detected.Nicosulfuron (PC 129008) MRID 49169703Page 11 of 30Table 7a. Transformation of [pyridine-2-14C]nicosulfuron, expressed as a percentage of the applied radioactivity, in Flakkebjerg sandyloam soil at 20°C.Sampling Interval (days) 0 3 7 14 21 30 45 62 90 120Nicosulfuron (DPX-V9360)91.0 97.6 83.2 67.1 68.7 56.1 41.7 40.6 29.0 22.2IN-HYY21 nd nd ndnd 1.32.5 5.3 1.6 13.8 10.0IN-V9367 nd 4.6 10.6 19.0 17.8 30.4 39.9 40.9 40.5 52.2IN-74427 nd nd nd nd nd nd nd nd 1.2 1.2IN-69188 nd nd nd 0.7 1.0 0.7 0.9 1.4 1.5 1.6Unassigned radioactivity10.5 nd 0.9 1.7 1.7 1.1 1.2 2.7 1.5 1.4Extracted residues91.5 102.4 95.1 88.9 90.4 90.7 89.0 87.3 87.6 88.7Unextracted residues 6.1 3.5 4.8 10.2 7.4 8.1 10.2 8.4 12.3 15.514CO2na nd nd nd nd 0.1 0.1 0.2 0.4 0.7Organic volatiles na nd ndnd nd nd nd nd nd ndMass balance97.7 106.0 99.9 99.1 97.8 98.9 99.4 95.8 100.4 104.9Data obtained from Table 3, p. 52 and Table 7, p. 60 of the study report.na = not analyzed; nd= not detected.1 Unidentified radioactivity in extracts.Table 7b. Transformation of [pyrimidine-2-14C]nicosulfuron, expressed as a percentage of the applied radioactivity, in Flakkebjerg sandyloam soil at 20°C.Sampling Interval (days) 0 3 7 14 21 30 45 62 90 120Nicosulfuron (DPX-V9360)96.9 83.9 88.0 70.8 64.4 66.3 58.4 48.3 35.7 34.5IN-HYY21nd 1.4 nd 0.9 0.7 1.1 2.0 2.0 2.4 3.7IN-J0290nd 2.4 4.9 11.4 13.3 13.4 11.4 19.5 21.3 14.7IN-74427nd nd nd nd nd nd nd 0.4 1.4 1.4IN-69188nd nd nd 0.6 0.9 1.2 1.5 1.7 1.9 2.2Unassigned radioactivity1nd 4.5 0.5 0.7 1.0 0.5 0.4 1.1 2.5 2.4Extracted residues97.1 93.4 93.8 84.4 80.4 82.4 73.7 73.1 65.2 59.0Unextracted residues1.2 3.8 4.4 16.3 13.9 12.9 20.7 20.5 31.0 32.514CO2na 0.05 0.2 0.7 0.8 1.8 3.0 4.0 6.4 9.0Organic volatilesna nd nd nd nd nd nd nd 0.2 0.2Mass balance98.3 97.2 98.4 101.4 95.2 97.1 97.4 97.6 102.7 100.7Data obtained from Table 3, p. 53 and Table 7, p. 61 of the study report.na = not analyzed; nd =not detected.1 Unidentified radioactivity in extracts.Nicosulfuron (PC 129008) MRID 49169703Page 12 of 30Table 7c. Transformation of [pyridine-2-14C]nicosulfuron, expressed as a percentage of the applied radioactivity, in Champenoux clayloam soil at 20°C.Sampling Interval (days) 0 3 7 14 21 30 45 62 90 120Nicosulfuron (DPX-V9360) 94.9 73.6 66.5 46.0 35.8 32.5 21.1 15.4 8.2 4.6IN-HYY21 nd nd 0.4nd nd0.8 1.1 1.6 4.6 ndIN-V9367 0.6 8.4 21.5 34.9 40.9 49.7 56.1 66.4 68.7 72.4IN-37740 nd 0.5 1.3 2.9 1.8 1.8 1.2 1.1 0.7 0.7IN-74427 nd nd nd 0.7 nd nd nd nd 1.8 1.6IN-77799 nd nd 1.0 nd 2.4 3.1 1.7 2.5 nd 1.8IN-69188 nd nd 0.5 nd nd nd 1.7 0.4 2.3 1.2Unassigned radioactivity1nd nd nd 2.5 0.6 nd 2.4 1.5 1.3 2.0Extracted residues 95.5 82.7 91.1 87.8 82.0 88.0 85.2 88.9 87.9 84.4Unextracted residues 2.9 2.9 6.4 10.8 16.2 11.9 11.3 10.3 13.6 11.014CO2na nd nd nd nd 0.04 0.1 0.2 0.4 0.7Organic volatiles na nd ndnd nd nd nd nd nd ndMass balance 98.4 85.7 97.5 98.6 98.2 100.0 96.6 99.4 101.8 96.1Data obtained from Table 4, p. 54 and Table 8, p. 62 of the study report.na = not analyzed; nd= not detected.1 Unidentified radioactivity in extracts.Nicosulfuron (PC 129008) MRID 49169703Page 13 of 30Table 7d. Transformation of [pyrimidine-2-14C]nicosulfuron, expressed as a percentage of the applied radioactivity, in Champenoux clayloam soil at 20°C.Sampling Interval (days) 0 3 7 14 21 30 45 62 90 120Nicosulfuron (DPX-V9360) 94.3 81.2 74.9 47.7 41.7 31.0 22.0 15.5 10.6 5.8IN-HYY21 nd 2.7 nd nd 0.4 nd 0.6 1.2 1.7 1.8IN-J0290 0.4 6.8 9.7 17.3 25.3 36.0 35.9 48.8 46.2 48.5IN-37740 nd 0.6 0.8 2.1 2.2 1.9 1.5 1.4 0.7 0.7IN-74427 nd nd nd nd 0.8 nd 1.0 1.7 2.0 2.5IN-77799 nd nd 1.0 nd 0.9 0.9 1.0 0.4 nd ndIN-69188 nd nd nd 1.9 1.9 1.9 2.1 2.6 2.0 2.4Unassigned radioactivity1nd nd 0.5 nd nd 1.3 0.6 nd nd ndExtracted residues 94.9 91.8 87.1 69.4 73.4 73.1 64.9 71.6 63.2 62.2Unextracted residues 3.4 6.7 9.8 25.1 18.7 19.0 21.4 20.2 29.6 30.014CO2na nd 0.05 0.2 0.4 0.7 1.2 1.5 2.5 3.6Organic volatiles na nd ndnd nd nd nd nd nd ndMass balance 98.3 98.5 96.9 94.7 92.5 92.8 87.5 93.3 95.3 95.8Data obtained from Table 4, p. 55 and Table 8, p. 63 of the study report.na = not analyzed; nd =not detected.1 Unidentified radioactivity in extracts.Nicosulfuron (PC 129008) MRID 49169703Page 14 of 30Table 7e. Transformation of [pyridine-2-14C]nicosulfuron, expressed as a percentage of the applied radioactivity, in Gross-Unstadt loam soilat 20°C.Sampling Interval (days) 0 3 7 14 21 30 45 62 76 90 120Nicosulfuron (DPX-V9360) 96.5 84.1 72.9 56.8 44.7 33.5 22.0 14.7 9.3 7.7 4.8IN-HYY21 nd 1.9 4.2 11.3 18.4 21.3 27.5 29.8 34.1 34.2 34.6IN-GDC42 nd nd nd nd 2.8 2.3 4.3 4.8 nr 5.5 6.2IN-V9367 nd 1.1 2.6 4.7 2.8 4.6 4.3 4.8 nr 5.5 6.2IN-37740 nd 3.6 4.1 4.0 2.7 2.1 0.9 0.7 nd 0.6 0.5Unassigned radioactivity1nd 1.1 0.4 2.6 2.8 3.2 3.4 4.8 4.5 4.9 9.0Extracted residues 96.7 91.8 84.1 79.5 74.3 66.9 62.4 59.5 57.3 58.6 59.7Unextracted residues nd 5.2 15.2 18.0 25.1 23.6 33.0 34.7 34.3 38.3 31.614CO2na 0.04 0.1 0.1 0.2 0.3 0.6 0.7 0.9 1.2 1.8Organic volatiles na nd nd ndnd nd nd nd nd nd 0.1Mass balance 96.7 97.0 99.3 97.6 99.6 90.8 96.0 94.9 92.5 98.0 93.1Data obtained from Table 6, p. 58 and Table 10, p. 66 of the study report.na = not analyzed; nd = not detected; nr = not reported.1 Unidentified radioactivity in extracts.Table 7f. Transformation of [pyrimidine-2-14C]nicosulfuron, expressed as a percentage of theapplied radioactivity, in Gross-Umstadt loamsoil at 20°C.Sampling Interval (days) 0 3 7 14 21 30 45 62 76 90 120Nicosulfuron (DPX-V9360) 98.8 85.2 73.1 54.4 44.1 33.6 27.2 14.6 10.2 8.3 5.2IN-HYY21 nd 2.8 4.8 10.6 12.5 22.1 24.8 31.5 27.6 32.8 34.9IN-GDC42 nd nd 0.6 2.6 2.9 3.7 4.1 5.2 6.4 5.7 7.0IN-37740 nd 3.1 4.2 5.5 2.9 2.2 1.4 0.6 0.7 0.6 0.6Unassigned radioactivity1nd 1.5 0.9 1.9 9.7 3.2 3.5 3.6 7.2 4.6 4.8Extracted residues 98.8 92.8 83.5 75.0 72.0 64.9 61.0 55.6 52.0 52.2 52.5Unextracted residues nd 7.6 16.5 18.8 22.6 25.3 32.9 35.4 35.3 40.2 39.014CO2na 0.1 0.7 1.0 1.5 2.0 2.7 3.4 3.9 4.4 5.5Organic volatiles na nd nd ndnd nd nd nd nd nd ndMass balance 98.8 100.6 100.8 94.9 96.1 92.1 96.6 94.4 91.3 96.7 96.9Data obtained from Table 6, p. 59 and Table 10, p. 67 of the study report.na = not analyzed; nd =not detected.1 Unidentified radioactivity in extracts.Nicosulfuron (PC 129008) MRID 49169703Page 15 of 30Table 7g. Transformation of [pyridine-2-14C]nicosulfuron, expressed as a percentage of theapplied radioactivity, in Champenoux clay loamsoil at 10°C.Sampling Interval (days) 0 3 7 14 21 30 45 62 90 120Nicosulfuron (DPX-V9360) 96.4 91.1 87.7 78.3 81.4 72.5 67.5 62.7 52.7 47.1IN-V9367 0.8 2.2 3.5 8.7 9.3 12.1 17.2 22.5 24.9 35.3Unassigned radioactivity1nd 0.4 0.6 2.0 1.5 1.7 3.3 3.8 6.9 4.3Extracted residues 97.1 93.6 91.9 89.0 92.2 86.3 88.0 89.0 84.5 86.7Unextracted residues 2.7 5.4 7.5 17.9 8.0 9.0 9.9 9.8 14.5 12.314CO2na nd nd nd nd nd nd nd nd ndOrganic volatiles na nd ndnd nd nd nd nd nd ndMass balance 99.8 99.1 99.4 106.9 100.2 95.3 98.0 98.9 99.0 99.0Data obtained from Table 5, p. 56 and Table 9, p. 64 of the study report.na = not analyzed; nd= not detected.1 Unidentified radioactivity in extracts.Table 7h. Transformation of [pyrimidine-2-14C]nicosulfuron, expressed as a percentage of the applied radioactivity, in Champenoux clayloam soil at 10°C.Sampling Interval (days) 0 3 7 14 21 30 45 62 90 120Nicosulfuron (DPX-V9360) 94.5 92.4 89.0 92.8 81.9 76.3 69.8 67.8 59.7 57.2IN-J0290 0.4 1.3 1.8 4.3 5.9 7.4 10.7 11.7 16.7 15.5Unassigned radioactivity10.7 0.5 1.9 1.5 2.1 2.1 3.5 5.8 5.3 9.7Extracted residues 95.6 94.3 92.7 98.7 89.9 85.9 84.1 85.3 81.8 82.4Unextracted residues 3.2 5.6 5.9 8.3 9.5 13.2 11.8 11.0 19.0 18.314CO2na nd nd nd nd nd 0.09 0.2 0.4 0.6Organic volatiles na nd ndnd nd nd nd nd nd ndMass balance 98.8 99.9 98.6 107.0 99.4 99.1 96.0 96.5 101.1 101.4Data obtained from Table 5, p. 57 and Table 9, p. 65 of the study report.na = not analyzed; nd =not detected.1 Unidentified radioactivity in extracts.

## Nicosulfuron (PC 129008) MRID 49169703

Page 16 of 30 

# E. Transformation of the Test Compound

20oC experiments: Using Single First Order and ModelManager v. 1.1, the study author calculated combined label half-lives of 50 days in the Flakkebjerg sandy loam soil; 16 days in the Champenoux clay loam soil, and 18 days in the Gross-Umstadt loam soil (pp. 33, 43). The halflives calculated by the study author were similar to the combined la bel half-lives calculated by the
reviewer.

10oC experiments: Using Single First Orde r and ModelManager® version 1.1, the study author
calculated a combined label hal f-life of 150 days in the Cham penoux clay loam soil (pp. 33. 43). The half-life calculated by the st udy author was identical to the combined labe l half-life calculated by the reviewer using the IORE model (the DF OP model was the most appropriate model).



# A erobic metabolism of Nicosulfuron in sandy loam at 20°C

Days % AR

0 0 3 3 7 7 14 14 21 21 30 30 45 45 62 62 90 90 120 120 91.0 96.9 97.6 83.9 83.2 88.0 67.1 70.8 68.7 64.4 56.1 66.3 41.7 58.4 40.6 48.3 29.0 35.7 22.2 34.5 0 20 40 60 80 100 120 0 20 40 60 80

TimeConcentration SFO
DFOP
IORE

-10 -5 0 5 10

-10 -5 0 5 10

-10 -5 0 5 10

0 20 40 60 80 100

DT 50 DT 90  2 C 0 Parameters

SFO 59.1 196 5.2 90 k  0.0117

DFOP 51.4 254 3 95.4 f  0.27

 k 0  0.0605

 k 1  0.00784

IORE 50.2 479 2.9 94.9 N  2.05

 k  0.00017 S C S SFO Slow t 1 2

t R IORE 628

784

88.4

144



# A erobic metabolism of Nicosulfuron in clay loam soil at 20°C

Days % AR

0 0 3 3 7 7 14 14 21 21 30 30 45 45 62 62 90 90 120 120 94.9 94.3 73.6 81.2 66.5 74.9 46.0 47.7 35.8 41.7 32.5 31.0 21.1 22.0 15.4 15.5 8.20 10.6 4.60 5.80 0 20 40 60 80 100 120 0 20 40 60 80

TimeConcentration SFO
DFOP
IORE -5 0 5

-5 0 5

-5 0 5

0 20 40 60 80 100120

DT 50 DT 90  2 C 0 Parameters

SFO 19.8 65.8 8.7 88.7 k  0 .035

DFOP 15.5 89.5 4.2 94 f  0.5

 k 0  0.0 909

 k 1  0.0 18

IORE 15.8 91.9 4.2 93.8 N  1.6

 k  0.0035 S C
S SFO Slow t 1 2

t R IORE 199

485

38.5

27.7

## Nicosulfuron (PC 129008) MRID 49169703

Page 17 of 30 Kinetics models: Single First-Order (SFO); Double First- Order in Parallel (DFOP), an d Indeterminate Order Rate Equation (IORE). Model was elected in accordance with the NAFTA kinetics guidance (USEPA, 2012).



# Transformation products identified in the soil are presented in Table 8 . No major transformation products were isolated. 

# A erobic metabolism of Nicosulfuron in loam soil at 20°C

Days % AR

0 0 3 3 7 7 14 14 21 21 30 30 45 45 62 62 76 76 90 90 120 120 96.5 98.8 84.1 85.2 72.9 73.1 56.8 54.4 44.7 44.1 33.5 33.6 22.0 27.2 14.7 14.6 9.30 10.2 7.70 8.30 4.80 5.20 0 20 40 60 80 100 120 0 20 40 60 80



### TimeConcentration 

### SFO
DFOP
IORE

-6 -4 -2 0 2 4 6

-6 -4 -2 0 2 4 6

-6 -4 -2 0 2 4 6



### 0 20 40 60 80 100



### DT 50 

### DT 90 

###  2 

### C 0 

### Parameters

SFO 21.2 70.4 5.3 93.6 k  0.0327



### DFOP 18.1 81 1.7 97.5 f  0.342

 k 0 

###  0.0894

 k 1 

###  0.0233



### IORE 18.4 82.7 1.9 96.9 N  1.35

 k  0.00865 

### S C 

### S SFO 

### Slow t 1 2



### t R IORE 

### 43.9

180

29.7

24.9



# A erobic metabolism of Nicosulfuron in clay loam soil at 10°C

Days % AR

0 0 3 3 7 7 14 14 21 21 30 30 45 45 62 62 90 90 120 120 96.4 94.5 91.1 92.4 87.7 89.0 78.3 92.8 81.4 81.9 72.5 76.3 67.5 69.8 62.7 67.8 52.7 59.7 47.1 57.2 0 20 40 60 80 100 120 0 20 40 60 80



### TimeConcentration 

### SFO
DFOP
IORE

-10 -5 0 5 10

-10 -5 0 5 10

-10 -5 0 5 10

0 20 40 60 80 100



### DT 50 

### DT 90 

###  2 

### C 0 

### Parameters

SFO 128 425 2.5 92 k  0.00542



### DFOP 156 1019 1.1 94.8 f  0.351

 k 0  0.0214

 k 1  0.00184



### IORE 150 4051 1.1 95 N  2.85

 k  2.02e-06 

### S C 

### S SFO 

### Slow t 1 2



### t R IORE 259

322

378

1.22e+03

## Nicosulfuron (PC 129008) MRID 49169703

Page 18 of 30 

# Table 8. Transformation Products of Nicosulfuron in Soil

Transformation
Products Maximum
%AR Observed Associated
Interval

(days) Final %AR
Observed Final Interval (days)

Denmark Flakkebjerg sandy loam soil (20  C, pH 6.14) IN-HYY21 13.8 90 10.0 120

IN-J0290 21.3 90 14.7 120

IN-V9367 52.2 120 52.2 120
IN-74427 1.4 90, 120 1.4 120

IN-69188 2.2 120 2.2 120

France Champenoux clay loam soil (20  C, pH 5.35) IN-HYY21 4.6 90 1.8 120

IN-J0290 48.8 62 48.5 120

IN-V9367 72.4 120 72.4 120

IN-37740 2.9 14 0.7 120

IN-74427 2.5 120 2.5 120

IN-77799 3.1 30 1.8 120

IN-69188 2.6 62 2.4 120

Germany
Gross-Unstadt
loam soil (20  C, pH 7.48) IN-HYY21 34.9 120 34.9 120

IN-GDC42 7.0 120 7.0 120

IN-V9367 6.2 120 6.2 120

IN-37740 5.5 14 0.6 120

France Champenoux clay loam soil (10  C, pH 5.35) IN-J0290 16.7 90 15.5 120

IN-V9367 35.3 120 35.3 120

Data obtained from pp. 40-41 and Tables 7-10, pp. 60-67 of the study report.

## Nicosulfuron (PC 129008) MRID 49169703

Page 19 of 30 

# A transformation pathway was provided by the study author (Figure 23, p. 115).

III. STUDY DEFICIENCIES AND REVIEWER’S COMMENTS

1. The soil extraction procedures were not adequate to extract all identifiable [14C]residues in the soils. Unextracted radioactivity in the test soils incubated at 20oC increased to maximums of 30.0-40.2% of the applied at 90 or 120 days postt reatment (Table 3, pp. 52-53; Table 4, pp. 54- 55; Table 6, pp. 58-59). Only the Day 120 Gross- Umstadt loam soil samples treated with [pyrimidine-2- 14 

# C]nicosulfuron were subjected to hu mic/fulvic extraction for further
characterization of the unextracted resi dues (p. 28). At 120 days, fulvic acid was 25.0% of the applied, humic acid was 6.0%, and humin was 8.0% (p. 42); further characterization was not performed. For all of the test soils, the more a ggressive extraction should have been done at more sampling intervals.

2. Champenoux clay loam soil experiment conducted at 10 ° C was terminated at 120 days, at which time undegraded nicosulfuron comprised 47.1-57.2% of the applied radioa ctivity, accounting for
>50% of the initial radi oactivity (94.5-96.4% of th e applied; Table 9, pp. 64- 65). It is preferable that metabolism experiments are conducted for seve ral intervals past the observed half-life, so that the pattern of decline of the parent compound and the pattern s of formation and decline of

## Nicosulfuron (PC 129008) MRID 49169703

Page 20 of 30 

# the transformation products are clearly established.

3. Information on the aerobic soil metabolism of nico sulfuron in three different soils is presented in this study. To satisfy OCSPP guidelines, info rmation on aerobic metabolism in four different soil types is required.

4. The study author incorrectly identified the Champenoux soil as a sandy loam using the USDA Soil Textural Classification System . The reviewer determined that this soil is a clay loam, and
refers to it as such in this review.

5. Single samples were collected for sample analysis at all sampling intervals. It is preferable for duplicate samples to be collected so that betw een replicate variability can be assessed.

6. Complete descriptions of the unlabeled refere nce standards were not reported. Chemical names were not provided for the reference standard s IN-69188 and IN-H9235. Also, the purity and lot number were not provided for the fo llowing reference standards: IN-GDC42, IN-77799, IN-69188, IN-H9235, and IN-HYY21. The purity was not provided for IN-37740.

7. During the 20oC experiments, the incubati on temperature was re ported to be 20 ± 2  C (p. 37). The study author reported that there were f our deviations lasting up to seven hours. The temperature range was 22.9-27.6  C. During the 10°C experiment , the incubation temperature was reported to be 10 ± 2  C. The study author reported that th ere were three deviations lasting up to 1 hour. The temperature range was 12.7-13.6  C.

8. Storage stability analysis of a Day 0 soil extract from a soil sample treated with [pyridine-2-

14 

# C]nicosulfuron and analyzed ca . 6 months after the initial extr action showed that nicosulfuron comprised >99% of the radioactivity (p. 44).

9. In order to produce sufficient material for iden tification, additional samp les were prepared and
treated at 1  g a.i./g (pp. 19, 25).

IV. REFERENCES

1. U.S. Environmental Protection Agency. 2008. Fate, Transport and Transformation Test Guidelines, OCSPP 835.4100, Aerobic Soil Metabo lism. Office of Chemical Safety and Pollution Prevention, Washington, DC. EPA 712-C-08-016.

2. U.S. Environmental Protection Agency. 2012. Guidance for Evaluating and Calculating Degradation Kinetics in Environmental Media.Nicosulfuron (PC 129008) MRID 49169703Page 21 of 30DER ATTACHMENT 1. Nicosulfuron and Its Environmental Transformation Products.ACode Name/ SynonymChemical NameChemical StructureStudy TypeMRIDMaximum %AR (day)Final %AR(study length)PARENTNicosulfuron (DPXV9360; IN-V9360)IUPAC:2-[(4,6-Dimethoxypyrimidin-2-ylcarbamoyl)sulfamoyl]-N,NdimethylnicotinamideCAS:2-[[[[(4,6-Dimethoxy-2-pyrimidinyl)amino]carbonyl]amino]sulfonyl]-N,N-dimethyl-3-pyridinecarboxamideCAS No.:111991-09-4Formula:C15H18N6O6SMW:410.4 g/molSMILES:CN(C)C(=O)c1cccnc1S(=O)(=O)NC(=O)Nc2nc(OC)cc(OC)n2835.4100Aerobic soilmetabolism49169703Sandy loam(20°C)97.6%(3 d)34.5%(120 d)Clay loam(20°C)94.9%(0 d)5.8% (120 d)Loam(20°C)98.8%(0 d)5.2% (120 d)Clay loam(10°C)96.4%(0 d)57.2%(120 d)MAJOR (>10%) TRANSFORMATION PRODUCTSIN-V9367CAS:2-(Aminosulfonyl)-N,Ndimethyl-3-pyridinecarboxamideCAS No.:112006-75-4Formula:C8H11N3O3SMW:229.25 g/molSMILES:CN(C)C(=O)c1cccnc1S(=O)(=O)N835.4100Aerobic soilmetabolism49169703Sandy loam(20°C)52.2%(120 d)52.2%(120 d)Clay loam(20°C)72.4%(120 d)72.4%(120 d)Loam(20°C)6.2% (120 d) 6.2% (120 d)Clay loam(10°C)35.3%(120 d)35.3%(120 d)IN-J0290CAS:4,6-Dimethoxy-2-pyrimidinamineCAS No.:36315-01-2Formula:C6H9N3O2MW:155.15 g/molSMILES:[H]N([H])c1nc(cc(n1)OC)OC835.4100Aerobic soilmetabolism49169703Sandy loam(20°C)21.3%(90 d)14.7%(120 d)Clay loam(20°C)48.8%(62 d)48.5%(120 d)Clay loam(10°C)16.7%(90 d)15.5%(120 d)Nicosulfuron (PC 129008) MRID 49169703Page 22 of 30Code Name/ SynonymChemical NameChemical StructureStudy TypeMRIDMaximum %AR (day)Final %AR(study length)IN-HYY21CAS:2-[[[[Aminoiminomethyl)amino]carbonyl)amino]sulfonyl]-N,N-dimethyl-3-pyridinecarboxamideFormula:C10H14N6O4SMW:314.33 g/molSMILES:CN(C)C(=O)c1cccnc1S(=O)(=O)NC(=O)NC(=N)NONC H3CH3SOOON H2N HNHNHN835.4100Aerobic soilmetabolism49169703Sandy loam(20°C)13.8%(90 d)10.0%(120 d)Clay loam(20°C)4.6% (90 d) 1.8% (120 d)Loam(20°C)34.9%(120 d)34.9%(120 d)Unextractable residuesNA NA835.4100Aerobic soilmetabolism49169703Sandy loam(20°C)32.5%(120 d)32.5%(120 d)Clay loam(20°C)30.0%(120 d)30.0%(120 d)Loam(20°C)40.2%(90 d)39.0%(120 d)Clay loam(10°C)19.0%(90 d)18.3%(120 d)MINOR (<10%) TRANSFORMATION PRODUCTSIN-74427CAS:2-[(4,6-Dimethoxy-2-pyrimidinyl)-amino]-N,N-dimethyl-3-pyridinecarboxamideFormula:C14H17N5O3MW:303.32 g/molSMILES:[H]N(c1c(cccn1)C(=O)N(C)C)c2nc(cc(n2)OC)OCNHO CH3O CH3NNNONCH3CH3835.4100Aerobic soilmetabolism49169703Sandy loam(20°C)1.4% (90, 120 d) 1.4% (120 d)Clay loam(20°C)2.5% (120 d) 2.5% (120 d)IN-69188IUPAC:1-(4,6-Dimethoxypyrimidin2-yl)pyrido[2,3-d]pyrimidine-2,4-dioneFormula:C13H11N5O4MW:301.26 g/molSMILES:COc1cc(nc(n1)n2c3c(cccn3)c(=O)[nH]c2=O)OC835.4100Aerobic soilmetabolism49169703Sandy loam(20°C)2.2% (120 d) 2.2% (120 d)Clay loam(20°C)2.6% (62 d) 2.4% (120 d)Nicosulfuron (PC 129008) MRID 49169703Page 23 of 30Code Name/ SynonymChemical NameChemical StructureStudy TypeMRIDMaximum %AR (day)Final %AR(study length)IN-37740CAS:2-[[(3,4-Dihydro-6-methoxy-4-oxopyrimidin-2-yl]aminocarbonyl]aminosulfonyl]-N,N-dimethyl-3-pyridinecarboxamideFormula:C14H16N6O6SMW:396.38 g/molSMILES:[H]n1c(=O)cc(nc1N([H])C(=O)N([H])S(=O)(=O)c2c(cccn2)C(=O)N(C)C)OCSOONHONHO CH3ONHNNONCH3CH3835.4100Aerobic soilmetabolism49169703Clay loam(20°C)2.9% (14 d) 0.7% (120 d)Loam(20°C)5.5% (14 d) 0.6% (120 d)IN-77799CAS:2-[(Aminocarbonyl) [4-methoxy-6-(methyldioxy}-2-pyrimidinyl] amino]-N,N-dimethyl-3-pyridinecarboxamideFormula:C15H18N6O4MW:346.34 g/molSMILES:CN(C)C(=O)c1cccnc1N(c2nc(cc(n2)OC)OC)C(=O)N835.4100Aerobic soilmetabolism49169703Clay loam(20°C)3.1% (30 d) 1.8% (120 d)IN-GDC42CAS:2-[[[[(Aminocarbonyl)amino]carbonyl]amino]sulfonyl]-N,Ndimethyl-3-pyridinecarboxamideFormula:C10H13N5O5SMW:315.3 g/molSMILES:CN(C)C(=O)c1cccnc1S(=O)(=O)NC(=O)NC(=O)NONC H3CH3SOON H2ONHNHON835.4100Aerobic soilmetabolism49169703Loam(20°C)7.0% (120 d) 7.0% (120 d)Carbon dioxideIUPAC:Carbon dioxideFormula:CO2MW:44 g/molSMILES:C(=O)=OCOO835.4100Aerobic soilmetabolism49169703Sandy loam(20°C)9.0% (120 d) 9.0% (120 d)Clay loam(20°C)3.6% (120 d) 3.6% (120 d)Loam(20°C)5.5% (120 d) 5.5% (120 d)Clay loam(10°C)0.6% (120 d) 0.6% (120 d)Nicosulfuron (PC 129008) MRID 49169703Page 24 of 30Code Name/ SynonymChemical NameChemical StructureStudy TypeMRIDMaximum %AR (day)Final %AR(study length)REFERENCE COMPOUNDS NOT IDENTIFIEDIN-64554CAS:Isothiaxolo[5,4-B]pyridin3(2H}-one,1,1-dioxideCAS No.:138417-40-0Formula:C6H4N2O3SMW:184.17 g/molSMILES:c1cc2c(nc1)S(=O)(=O)NC2=O835.4100Aerobic soilmetabolism49169703 NA NAIN-W9807CAS:2-[[(4,6-Dimethoxypyrimidin2-yl)aminocarbonyl]arninosulfonyl]-Nmethyl-3-pyridinecarboxamideFormula:C14H16N6O6SMW:396.38 g/molSMILES:[H]N(C)C(=O)c1cccnc1S(=O)(=O)N([H])C(=O)N([H])c2nc(cc(n2)OC)OCSOONHONHO CH3O CH3NNNONCH3H835.4100Aerobic soilmetabolism49169703 NA NAIN-H1043CAS:2-Amino-6-hydroxy-4(1H)-pyrimidinoneCAS No.:56-09-7Formula:C4H5N3O2MW:127.1 g/molSMILES:c1c(nc(nc1O)N)O835.4100Aerobic soilmetabolism49169703 NA NAIN-H9235IUPAC:2-Amino-6-methoxypyrimidin-4-olFormula:C5H7N3O2MW:141.13 g/molSMILES:[H]N([H])c1nc(cc(n1)OC)O835.4100Aerobic soilmetabolism49169703 NA NAAAR means “applied radioactivity”. MW means “molecular weight”. NA means “not applicable”.Nicosulfuron (PC 129008) MRID 49169703Page 25 of 30

## Nicosulfuron (PC 129008) MRID 49169703

Page 26 of 30 

# Attachment 2: Statistics Spreadsheets and Graph

Chemical: Nicosulfuron
MRID:
PC:
Guideline: 835.4100

Aerobic metabolism of Nicosulfuron in sandy loam at 20 ° C Days % AR

0 91.0
0 96.9
3 97.6
3 83.9
7 83.2
7 88.0
14 67.1
14 70.8
21 68.7
21 64.4
30 56.1
30 66.3
45 41.7
45 58.4
62 40.6
62 48.3
90 29.0
90 35.7
120 22.2
120 34.5 

## 49126703
129008

Data obtained from Table 7, pp. 60-61 of the study report. 

# A erobic metabolism of Nicosulfuron in sandy loam at 20°C

Days % AR

0 0 3 3 7 7 14 14 21 21 30 30 45 45 62 62 90 90 120 120 91.0 96.9 97.6 83.9 83.2 88.0 67.1 70.8 68.7 64.4 56.1 66.3 41.7 58.4 40.6 48.3 29.0 35.7 22.2 34.5 0 20 40 60 80 100 120 0 20 40 60 80

TimeConcentration SFO
DFOP
IORE

-10 -5 0 5 10

-10 -5 0 5 10

-10 -5 0 5 10

0 20 40 60 80 100

DT 50 DT 90  2 C 0 Parameters

SFO 59.1 196 5.2 90 k  0.0117

DFOP 51.4 254 3 95.4 f  0.27

 k 0  0.0605

 k 1  0.00784

IORE 50.2 479 2.9 94.9 N  2.05

 k  0.00017 S C S SFO Slow t 1 2

t R IORE 628

784

88.4

144

## Nicosulfuron (PC 129008) MRID 49169703

Page 27 of 30 Aerobic metabolism of Nicosulfuron in clay loam soil at 20°C Days % AR

0 94.9
0 94.3
3 73.6
3 81.2
7 66.5
7 74.9
14 46.0
14 47.7
21 35.8
21 41.7
30 32.5
30 31.0
45 21.1
45 22.0
62 15.4
62 15.5
90 8.2
90 10.6
120 4.6
120 5.8

Data obtained from Table 8, pp. 62-63 of the study report. 

# A erobic metabolism of Nicosulfuron in clay loam soil at 20°C

Days % AR

0 0 3 3 7 7 14 14 21 21 30 30 45 45 62 62 90 90 120 120 94.9 94.3 73.6 81.2 66.5 74.9 46.0 47.7 35.8 41.7 32.5 31.0 21.1 22.0 15.4 15.5 8.20 10.6 4.60 5.80 0 20 40 60 80 100 120 0 20 40 60 80



### TimeConcentration 

### SFO
DFOP
IORE -5 0 5

-5 0 5

-5 0 5

0 20 40 60 80 100120



### DT 50 

### DT 90 

###  2 

### C 0 

### Parameters

SFO 19.8 65.8 8.7 88.7 k  0.035



### DFOP 15.5 89.5 4.2 94 f  0.5

 k 0  0.0909

 k 1  0.018



### IORE 15.8 91.9 4.2 93.8 N  1.6

 k  0.0035 

### S C 

### S SFO 

### Slow t 1 2



### t R IORE 199

485

38.5

27.7



### Aerobic metabolism of Nicosulfuron in loam soil at 20 ° C Days % AR

0 96.5
0 98.8
3 84.1
3 85.2
7 72.9
7 73.1
14 56.8
14 54.4
21 44.7
21 44.1
30 33.5
30 33.6
45 22.0
45 27.2
62 14.7
62 14.6
76 9.3
76 10.2
90 7.7
90 8.3
120 4.8
120 5.2

Data obtained from Table 10, pp. 66-67 of the study report. 

# A erobic metabolism of Nicosulfuron in loam soil at 20°C

Days % AR

0 0 3 3 7 7 14 14 21 21 30 30 45 45 62 62 76 76 90 90 120 120 96.5 98.8 84.1 85.2 72.9 73.1 56.8 54.4 44.7 44.1 33.5 33.6 22.0 27.2 14.7 14.6 9.30 10.2 7.70 8.30 4.80 5.20 0 20 40 60 80 100 120 0 20 40 60 80



### TimeConcentration 

### SFO
DFOP
IORE

-6 -4 -2 0 2 4 6

-6 -4 -2 0 2 4 6

-6 -4 -2 0 2 4 6



### 0 20 40 60 80 100



### DT 50 

### DT 90 

###  2 

### C 0 

### Parameters

SFO 21.2 70.4 5.3 93.6 k  0.0327



### DFOP 18.1 81 1.7 97.5 f  0.342

 k 0 

###  0.0894

 k 1 

###  0.0233



### IORE 18.4 82.7 1.9 96.9 N  1.35

 k  0.00865 

### S C 

### S SFO 

### Slow t 1 2



### t R IORE 

### 43.9

180

29.7

24.9

## Nicosulfuron (PC 129008) MRID 49169703

Page 28 of 30 Aerobic metabolism of Nicosulfuron in clay loam soil at 10°C Days % AR

0 96.4
0 94.5
3 91.1
3 92.4
7 87.7
7 89.0
14 78.3
14 92.8
21 81.4
21 81.9
30 72.5
30 76.3
45 67.5
45 69.8
62 62.7
62 67.8
90 52.7
90 59.7
120 47.1
120 57.2

Data obtained from Table 9, pp. 64-65 of the study report. 

# A erobic metabolism of Nicosulfuron in clay loam soil at 10°C

Days % AR

0 0 3 3 7 7 14 14 21 21 30 30 45 45 62 62 90 90 120 120 96.4 94.5 91.1 92.4 87.7 89.0 78.3 92.8 81.4 81.9 72.5 76.3 67.5 69.8 62.7 67.8 52.7 59.7 47.1 57.2 0 20 40 60 80 100 120 0 20 40 60 80



### TimeConcentration 

### SFO
DFOP
IORE

-10 -5 0 5 10

-10 -5 0 5 10

-10 -5 0 5 10

0 20 40 60 80 100



### DT 50 

### DT 90 

###  2 

### C 0 

### Parameters

SFO 128 425 2.5 92 k  0.00542



### DFOP 156 1019 1.1 94.8 f  0.351

 k 0  0.0214

 k 1  0.00184



### IORE 150 4051 1.1 95 N  2.85

 k  2.02e-06 

### S C 

### S SFO 

### Slow t 1 2



### t R IORE 259

322

378

1.22e+03

## Nicosulfuron (PC 129008) MRID 49169703

Page 29 of 30 

# Attachment 3: Calculations

Calculations were performed by the reviewer us ing R software, and the following equations.

Single First-Order (SFO) Model

(eq. 1)

where,
C t 

# = concentration at time t (%)
C 0 

# = initial concentration (%) e = Euler’s number (-) k = SFO rate constant of decline (d -1 

# ) t = time (d)

The SFO equation is solved with R kinetics software by adjusting C 0 

# and k to minimize the objective function (S SFO 

# ) shown in equation 9.

DT 50 

# = natural log (2)/k (eq. 2)

DT 90 

# = ln (10)/k (eq. 3)

Indeterminate Order Rate Equation (IORE) Model

(eq. 4)

where, N = order of decline rate (-)
k IORE 

# = IORE rate constant of decline (d -1 

# )

This equation is solved with R kinetics softwa re by adjusting C0, kIORE, and N to minimize the objective function for IORE (SIO RE) (See equation 9). Half-liv es for the IORE model are calculated using equation 5, which represents a fi rst-order half-life that passes through the DT 90 

# of the IORE model. (Traditional DT 50 

# and DT 90 

# values for the IORE model can be calculated using equations 6 and 7.)

(eq. 5)

DT 50 

# = 1)

- k(N C

- /2) (C N)

- (1 0 N)

- (1 0 

# (eq. 6)

DT 90 

# = 1)

- k(N C

- /10) (C N)

- (1 0 N)

- (1 0 

# (eq. 7)

## Nicosulfuron (PC 129008) MRID 49169703

Page 30 of 30 

# Double First-Order in Parallel (DFOP) Model

(eq. 8)

where, g = the fraction of C 0 

# applied to compartment 1 (-)
k 1 

# = rate constant for compartment 1 (d -1 

# )
k 2 

# = rate constant for compartment 2 (d -1 

# )

If C 0 

# x g is set equal to a and C 0 

# (1-g) is set equal to c , then the equation can be solved with R
kinetics software for a , c , k 1 

# , and k 2 

# by minimizing the objective function (S DFOP 

# ) as described in equation 9.

DT 50 

# and DT 90 

# values can be calculated us ing equations 2 and 3, with k 1 

# or k 2 

# in place of k.

Objective Function: SFO, IORE, and DFOP are solved by minimizing the objective function (S SFO 

# , S IORE 

# , or S DFOP 

# ).

(eq. 9)

where,
S SFO 

# , S IORE 

# , or S DFOP 

# = objective function of kinetics model fit (% 2 

# ) n = number of data points (-)
C model,t 

# = modeled value at time corresponding to C d,t 

# (%)
C d,t 

# = experimental concentration at time t (%)

Critical Value to Determine Whether SFO is an Adequate Kinetics Model

If S SFO 

# is less than S C 

# , the SFO model is adequate to describe kinetics. If not, the faster of t IORE 

# or the DFOP DT 50 

# for compartment 2 should be used.

(eq. 10)

where,
S c 

# = the critical value that de fines the confidence contours (% 2 

# ) p = number of parameters (3 in this case)

α = the confidence level (0.50 in this case) F( α , p, n-p) = F distribution with α level of confidence and degr ees of freedom p and n-p