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                 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                            WASHINGTON, D.C.  20460
                                       
                                                  OFFICE OF CHEMICAL SAFETY AND
                                                                                               POLLUTION PREVENTION
MEMORANDUM

Date:	14-August-2013

Subject:	Linuron.  Petition for the Establishment of Permanent Tolerances and Registration for Use on Coriander, Dill, Parsley, Pea (Dry), and Horseradish; and Submission of Residue Analytical Methods of Plants and Animal Matrices.  Summary of Analytical Chemistry and Residue Data.  

PC Code:  035506
DP Barcodes:  D404359, D411652
Decision No.:  469722
Registration No.:  61842-23
Petition No.:  2E8083
Regulatory Action:  Section 3
Risk Assessment Type:  NA
Case No.:  NA
TXR No.:  NA
CAS No.:  330-55-2
MRID No.:  See Appendix A
40 CFR:§180.184

From:	Nancy Tsaur, Chemist
	Risk Assessment Branch 3 (RAB3)
	Health Effects Division (7509P)

Through:	Steve Funk, Senior Chemist
	Risk Assessment Branch 3 (RAB3)
	Health Effects Division (7509P)

To: 	Kristin Rury, Biologist, Risk Assessor
	Risk Assessment Branch 3 (RAB3) 
	Health Effects Division (7509P)



                               Table of Contents

1.0	Executive Summary	3
2.0	Regulatory Recommendations	3
2.1	Tolerance Considerations	3
2.1.1	Enforcement Analytical Method	3
2.1.2	Recommended Tolerances	4
2.2.3	Revisions to Petitioned-For Tolerances	5
2.2.4	International Harmonization	5
3.0	Introduction	5
3.1	Chemical Identity	6
3.2	Physical/Chemical Characteristics	6
3.3	Pesticide Use Pattern/Directions for Use (860.1200)	7
4.0	Metabolite/Degradate Residue Profile	8
4.1	Nature of the Residue	8
4.2	Comparison of Metabolic Pathways	9
4.3	Residues of Concern Summary and Rationale	9
5.0	Residue Profile	10
5.1	Residue Analytical Methods (860.1340)	10
5.2	Submittal of Analytical Reference Standards (860.1650)	11
5.3	Storage Stability (860.1380)	11
5.4	Residue Data	12
5.4.1	Crop Field Trials (860.1500)	12
5.4.2	Meat, Milk, Poultry and Eggs (860.1480)	13
5.5	Food Residue Profile	13
6.0	Tolerance Derivation	13
Appendix A.  Summary of Submitted Residue Chemistry Studies	15
Appendix B.  International Residue Limits Table for Linuron	16
Appendix C.  OECD MRL Calculation Procedure Inputs/Outputs	17


1.0	Executive Summary

Interregional Research Project No. 4 (IR-4) has submitted a petition (PP#2E8083) for tolerances on coriander, dill, parsley, pea (dry), and horseradish; and has proposed to add these uses to the Tessenderlo Kerley label for Lorox(R) DF (EPA Reg. No. 61842-23).  IR-4 has submitted crop field trials utilizing comparable formulations, all of which consist of 50% active ingredient (ai) in a dry flowable formulation.  The residue chemistry database is adequate for tolerance assessment of the proposed uses.

Based on residues found in forage/foliage from three plant metabolism studies where the active ingredient was applied in a soil-directed fashion early in the growing season, linuron is understood to have systemic activity in plants.  The field trials indicate that finite residues are found in food commodities and that the residues concentrate upon drying herbs and/or processing dill for oil.  It has been shown that linuron and its metabolites, including unknown metabolites characterized as polar, can be converted quantitatively to 3,-4-dichloroaniline (3,4-DCA).  Therefore, linuron can be regulated by using the enforcement analytical method in which identified metabolites, unidentified polar components, and bound residues in plant and animal commodities are hydrolyzed to 3,4-DCA.  The total residue convertible to 3,4-DCA will be compared to the reference dose for parent linuron for purposes of dietary risk assessment.

Concomitant with this IR-4 petition, additional analytical method data have been submitted by Tessenderlo Kerley to support the newly proposed uses.  A new enforcement method for plant and livestock commodities was previously required as conditional data (K. Rury, DP375451, 04/01/2010).  A high performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) method based on extraction of residues and identification of parent and specific metabolites has been submitted.   Also submitted was a method that hydrolyzes commodities with base to transform the total linuron residue to 3,4-DCA.  Gas chromatography with mass spectrometry detection (GC/MS) is used to quantitate the 3,4-DCA.   Independent laboratory validation of the latter method has been provided.   In reviewing these data, HED has determined that the continued use of a common moiety definition (1,3-dichloraniline) is appropriate, and that the validated GC/MS method for 3,4-DCA will be adequate for tolerance enforcement purposes.  Thus, the requirement for additional enforcement analytical methods is fulfilled.

2.0	Regulatory Recommendations

HED has examined the residue chemistry database for linuron and concluded that, provided a revised label and a revised Section F, there are no residue chemistry deficiencies that would preclude granting Section 3 registration for the requested crop commodity uses of linuron, or establishment of tolerances for residues of linuron.  The specific tolerance recommendations are discussed in Section 2.1.2.

2.1	Tolerance Considerations

2.1.1	Enforcement Analytical Method

Various acceptable enforcement methods are available.

For linuron residues of concern in plant commodities, Method ABC-68406-M, is available and suitable for the enforcement of tolerances.  This method involves reflux of crop samples in strong base to hydrolyze residues of linuron and its metabolites to 3,4-DCA.  Then, 3,4-DCA is analyzed by gas chromatography with mass spectrometry detection (GC/MS).  Based on the lowest level of method validation (LLMV) from the independent laboratory validation (ILV) study, the validated limit of quantitation (LOQ) is 0.01 ppm for linuron and its metabolites hydrolyzable to 3,4-DCA in/on oily (soybean seed), watery (celery), and starch (potato) crop matrices.

In addition, Method ABC-65790 is a confirmatory method that is also available that may be used to confirm results from the use of Method ABC-68406-M.  In this method, extractions are conducted with methanol and each analyte is analyzed by liquid chromatography/tandem mass spectrometry (LC/MS/MS).  This method separately determines residues of linuron and metabolites 3-(3,4-dichlorophenyl)-1-methylurea (DCPMU), N-(3,4-dichlorophenyl)urea (DCPU), and desmethyl linuron in crop commodities.  Based on the LLMV, the validated LOQ is 0.01 ppm each for linuron, DCPMU, DCPU, and desmethyl linuron.

For linuron residues of concern in livestock commodities Method ABC-67638-M is available and suitable for the enforcement of tolerances.  This method involves reflux of livestock commodity samples in strong base to hydrolyze residues of linuron and its metabolites to 3,4-dichloroaniline (3,4-DCA).  Then, 3,4-DCA is analyzed by gas chromatography with mass spectrometry detection (GC/MS).  Based on the LLMV, the validated LOQ is 0.01 ppm for linuron and its metabolites hydrolyzable to 3,4-DCA in milk, muscle, and liver.

2.1.2	Recommended Tolerances
 
In addition to the recommended tolerances listed below in Table 2.2.2, the tolerance with regional registration under 40 CFR §180.184(c) for parsley, leaves (0.25 ppm) should be deleted.

Table 2.2.2.  Tolerance Summary for Linuron.
                                   Commodity
                     Established/Proposed Tolerance (ppm)
                        HED-Recommended Tolerance (ppm)
                                   Comments
                        (correct commodity definition)
                            Cilantro, fresh leaves
                                      3.0
                                      1.5
                               coriander, leaves
                            Cilantro, dried leaves
                                      27
                                      10
                            coriander, dried leaves
                                Coriander, seed
                                     0.01
                                     0.05
                                       
                            Dillweed, fresh leaves
                                      1.5
                                      0.6
                                       
                            Dillweed, dried leaves
                                      7.1
                                      3.0
                                       
                                  Dill, seed
                                      0.3
                                      0.5
                                       
                                   Dill, oil
                                      4.8
                                      2.0
                                       
                                  Horseradish
                                     0.05
                                     0.05
                                       
                                Parsley, leaves
                                      3.0
                                      4.0
                                       
                             Parsley, dried leaves
                                      8.3
                                      3.0
                                       
                                Pea, dry, seed
                                     0.08
                                     0.06
                                       


2.2.3	Revisions to Petitioned-For Tolerances

All of the petitioned-for tolerance levels(except for horseradish) must be revised to reflect the tolerance levels recommended by HED for linuron (3-(3,4-dichlorophenyl)-1-methoxy-1-methylurea) and its metabolites convertible to 3,4-dichloroaniline, calculated as linuron, in or on the commodities.

The Organization for Economic Cooperation and Development (OECD) calculation procedures were used to calculate the tolerance levels for the following three commodities: cilantro, fresh leaves; dillweed, fresh leaves; and pea, dry, seed.  Based on the OECD calculations, all three tolerance levels should be decreased.

Instead of using the OECD calculator due to a limited number of field trials, the formula of 5X the mean was used to establish tolerance levels for the following three commodities: coriander, seed; dill, seed; and parsley, leaves.  Based on this calculation method, all three tolerance levels should be increased.

For the dried herbs (cilantro, dillweed, and parsley) and the dill oil, the formula of the highest average field trial (HAFT) multiplied by the concentration factor was used to calculate the recommended tolerance levels (the concentration factors were derived from dividing the average dried/oil commodity residue by the average fresh commodity residue).  Based on this calculation method, all four tolerance levels should be decreased.

2.2.4	International Harmonization

There are no established maximum residue limits (MRLs) for linuron in Codex for any agricultural commodity.  Furthermore, no Canadian or Mexican MRLs have been established for linuron.  Therefore, there are no harmonization issues that exist with respect to U.S. tolerances.

2.3	Label Recommendations

Since there are livestock feed items associated with field pea, the following restriction should be added to the label: "Do not apply to field pea used for livestock feed."

3.0	Introduction

Linuron is a selective phenylurea herbicide used to control broadleaf weeds and annual grasses by systemically inhibiting photosynthesis.  It may be applied pre-plant, pre-emergence, post-emergence or post-transplant to various field crops and noncrop areas.


3.1	Chemical Identity

Table 3.1.  Linuron Nomenclature.
Compound

Common name
Linuron
Company experimental name
DPX-Z0326
IUPAC name
3-(3,4-dichlorophenyl)-1-methoxy-1-methylurea
CAS name
N`-(3,4-dichlorophenyl)-N-methoxy-N-methylurea
CAS #
330-55-2
End-use product/EP

Metabolite
                                       
Common name
DCPMU
Chemical name
3-(3,4-dichlorophenyl)-1-methylurea
Metabolite
                                       
Common name
DCPU
Chemical name
N-(3,4-dichlorophenyl)urea
Metabolite
                                       
Common name
Desmethyl linuron
Chemical name
N-(3,4-dichlorophenyl)-N`-methoxyurea

3.2	Physical/Chemical Characteristics

Linuron is an off-white powder with a molecular weight of 249.1 g/mol, which indicates that the potential to cross biological barriers, such as the skin, is somewhat limited.  Furthermore, the low log of the octanol/water partition coefficient (log Pow = 2.76 at 25C) suggests low potential for dermal absorption; the relatively low water solubility and low lipophilic potential, indicate that linuron is not likely to bioaccumulate.  The vapor pressure for linuron is low (3.011x10[-7] mm Hg at 25C), and linuron is considered relatively insoluble in water. The Henry's Law constant was calculated to be 1.97x10[-9] atm·m[3]/mol.  Thus, linuron is unlikely to volatilize significantly, and inhalation via chemical vaporization is unlikely.  

Linuron is moderately persistent with an aerobic soil metabolism half-life ranging from 57 to 100 days.  Because parent linuron is sufficiently persistent and may be mobile under certain environmental conditions, it has the potential to impact ground water quality.  More detailed physicochemical properties of the technical grade of linuron are summarized in Table 3.2.

Table 3.2.  Physicochemical Properties of the Technical Grade Test Compound Linuron.
Parameter
Value
Reference
Molecular weight (g/mole)
249.1
42213301
Melting point/range
91-94+-1°C
42213301
pH
6.98, 7.09 for a 0.2% solution and 9.38, 9.41, for a 2.5% solution at 22.5+-0.5C
42213301
Density
1.4963 g/mL at 22.3+-0.5C 
(air comparison pycnometer)
42213301
Water solubility (20.5 +- 0.5 C)
5.88x10[-3] g/100 mL
42213301
Solvent solubility (20 C)
dichloromethane	44.1 g/100 mL
toluene	7.91 g/100 mL
methanol	12.6 g/100 mL
hexane	0.220 g/100 mL
42213301
Vapor pressure at 25°C
4.015x10[-5] Pa
3.011x10[-7] mm Hg
42213303
Henry's Law Constant at 25°C
1.97x10[-9] atm·m[3]/mol
http://toxnet.nlm.nih.gov
Dissociation constant (pKa)
dissociation constant could not be determined; physical and chemical properties deemed all methods in OECD guidelines inappropriate
42213302
Octanol/water partition coefficient Log(KOW)
8.2x10[2] at 23+-1C (GC method)
log Pow = 2.76
42213301
 
3.3	Pesticide Use Pattern/Directions for Use (860.1200)

IR-4 is proposing new uses for the 50% DF formulation Lorox(R) DF (EPA Reg. No. 61842-23).  The use directions are summarized below in Table 3.3.

Table 3.3.  Summary of Proposed Directions for Use of Linuron (Lorox(R) DF, EPA Reg. No. 61842-23).
                       Application, Type, and Equipment
                                   App Rate
                                   (lb ai/A)
                                    Timing
                            Max No. App per Season
                            Max. Seasonal App Rate
                                   (lb ai/A)
                                      PHI
                                    (days)
                    Product Use Directions and Limitations
                                   Coriander
                                   Broadcast
                                       
                              Ground, Chemigation
                                   0.5 - 1.0
                                 preemergence
                                       1
                                      2.0
                              East of Rocky Mtns
                                       
                                      1.5
                              West of Rocky Mtns
                                      21
Do not apply by air.  Do not apply to sand or loamy sand soil types to avoid crop injury.  Do not use on soils with less than 1% organic matter to avoid crop injury.  Do not exceed 4 lbs. LOROX(R) DF per acre per year East of Rocky Mountains.  Do not exceed 3 lbs. LOROX(R) DF per acre per year West of Rocky Mountains.  Additional applications allowed, but do not exceed maximum rate.  Do not apply within 155 days of harvest for seed.
                                       
                                   0.5 - 1.0
                                 postemergence
                                       2
                                       
                                       

                                     Dill
                                   Broadcast
                                       
                              Ground, Chemigation
                                      1.0
                                 preemergence
                                       1
                                      2.0
                              East of Rocky Mtns
                                       
                                      1.5
                              West of Rocky Mtns
                                      21
Do not apply by air.  Do not apply to sand or loamy sand soil types to avoid crop injury.  Do not use on soils with less than 1% organic matter to avoid crop injury.  Do not exceed 4 lbs. LOROX(R) DF per acre per year East of Rocky Mountains.  Do not exceed 3 lbs. LOROX(R) DF per acre per year West of Rocky Mountains.  Additional applications allowed, but do not exceed maximum rate.
                                       
                                   0.5 - 1.0
                                 postemergence
                                       2
                                       
                                       

                                    Parsley
                                   Broadcast
                                       
                              Ground, Chemigation
                                   0.5 - 1.5
                                 preemergence
                                       1
                                      1.5
                                      30
Do not apply by air.  Apply after planting, but before the crop emerges.  Do not exceed a total of 3 lbs. of LOROX(R) DF per acre per season.  Use lower rates on coarse soils and higher rates on heavier soils.
                                       
                                      0.5
                                 postemergence
                                       1
                                      0.5
                                       

              Parsley Grown for Seed (Oregon and Washington Only)
                                   Broadcast
                                       
                              Ground, Chemigation
                                   0.5 - 1.0
                                 preemergence
                                       2
                                      2.0
                                      NA
Do not apply by air.  For best results apply preemergence to weeds or early postemergence while weeds are small.  Wait at least 21 days between applications.  Do not make more than two applications in the first growing season and do not make more than two applications in the second growing season.
                                   Pea (Dry)
                                   Broadcast
                                       
                              Ground, Chemigation
                                      1.0
                                 preemergence
                                       1
                                      1.0
                                      NA
Do not apply by air.  Do not apply to sand or loamy sand soil types.  Do not use on soils with less than 1% organic matter.  Apply post planting but preemergence to the crop.  Use lower rates on coarse soils and higher rates on heavier soils.
                                  Horseradish
                                   Broadcast
                                       
                              Ground, Chemigation
                                      1.5
                                 preemergence
                                       1
                                      1.5
                                      NA
Do not apply by air.  Apply after planting or during dormancy, but before the leaves emerge in spring.  Use lower rates on lighter soils and higher rates on heavier soils.

Conclusions:  The submitted use directions are adequate to allow evaluation of the residue data relative to the proposed use pattern for coriander, dill, parsley, pea (dry), and horseradish.

4.0	Metabolite/Degradate Residue Profile

4.1	Nature of the Residue

New metabolism data were not submitted to support this registration request.  The qualitative nature of the residue in plants and animals is adequately understood.  The chemical structures of the metabolites of concern are listed in Table 3.1.

Plant metabolism studies show the major plant metabolites to be DCPMU and DCPU.  There was a significant amount of unidentified polar components in corn, potato, and soybean plant metabolism studies; however, it was concluded that the components in plants are hydrolyzable to 3,4-dichloroaniline (3,4-DCA).  There was almost quantitative conversion (via base hydrolysis) of the total radioactive residue (TRR) to 3,4-DCA in the metabolism studies. 

In animals, linuron is metabolized to DCPU and hydroxy-norlinuron (through DCPMU and desmethyl-linuron intermediates).  Small amounts of 3,4-DCA were detected in both the corn and poultry studies.  

Water degradates identified in linuron aerobic soil metabolism are the same as the identified plant metabolites.  

4.2	Comparison of Metabolic Pathways

The metabolic pathways in plants and livestock are similar.   Linuron is converted to DCPMU, DCPU, hydroxy-norlinuron, and unidentified polar metabolites, all of which may be converted to 3,4-DCA via base hydrolysis..

Metabolism studies also illustrate the distribution of residues of linuron within plant and animals.  Radiolabeled [14]C-linuron equivalents were found at the highest levels in the forage or foliage of corn, potato, and soybean following early season soil-directed application of linuron.  Detectable residues (0.01  -  0.03 ppm) were also found in the potato tuber and corn grain, and quantifiable residues were found in soybean seed.  Linuron and/or its metabolites are systemic.

 In animals, the highest levels of [14]C-linuron equivalents were found in the liver of both goat and poultry.  No intact linuron (<0.001 ppm) was detected in the milk, tissues, or urine of the test animals, except egg yolk.  Approximately 95% of the radioactivity in milk was characterized as polar metabolites.

For both livestock and plant commodities, the residues listed in the tolerance expression are the same as those that will be included in the dietary risk assessment, linuron and metabolites convertible to 3,4-DCA.  This essentially encompasses the entire total radioactive residues from plant and livestock metabolism studies.

In rats, the major metabolites identified in the urine were hydroxy-norlinuron, DCPU, and DCPMU; and those in feces were hydroxy-norlinuron and DCPU.  The major metabolites DCPU and DCPMU were identified in the rat metabolism study, in both plant and animal metabolism studies, and as water metabolites in the aerobic soil metabolism study.   These metabolites, in addition to desmethyl-linuron, are the metabolites of toxicological concern referenced in the tolerance expression and considered in this risk assessment.  Neither hydroxy-3,4-dichloroanaline, 3,4-dichloroanaline nor 3,3',4,4'-tetrachloroazobenzene (TCAB) were present in any of the samples in the rat metabolism study.  

4.3	Residues of Concern Summary and Rationale
D. McNeilly. 11/17/1993. Linuron Plant and Animal Metabolism: Results of the HED Metabolism Committee Meetings held October 21, and October 29, 1993.  MARC Decision Memo.

The residue definitions for enforcement of tolerance and for risk assessment are identical, namely, linuron and metabolites convertible to 3,4-DCA.

The terminal residues of concern in plants and animals are linuron (parent) and metabolites convertible to 3,4-DCA including DCPMU, DCPU, desmethyl linuron, and hydroxy-norlinuron.  3,4-DCA is not of regulatory concern in connection with the registered use of linuron due to the very low levels at which the chemical is detected in plants and animals (<0.01ppm).  Metabolites convertible to 3,4-DCA are not likely to be more toxic than the parent compound.  Linuron can therefore be regulated by using the enforcement analytical method in which known metabolites and unidentified polar components in plants and bound residues in animal tissues are hydrolyzed to 3,4-DCA.  The total residue convertible to 3,4-DCA will be compared to the reference dose for parent linuron for purposes of dietary risk assessment.  

The linuron drinking water exposure assessment is based upon review of environmental fate studies for parent linuron, modeling and monitoring results for parent linuron, and modeling results for the degradates of linuron based upon parent linuron model input parameters.  Parent linuron appears to be moderately persistent and relatively immobile.  Water degradates identified in the linuron aerobic soil metabolism study are desmethyl linuron, DCPMU, and DCPU.  The degradate 3,4-DCA was not included in the water assessment as it was not detected in the aerobic soil metabolism study (0.01 ppm detection limit).  According to acceptable fate studies, 3,4-DCA is formed under anaerobic aquatic conditions rarely found in the environment and is not relevant to drinking water assessment.  The environmental fate assessment for linuron is incomplete and tentative because information on the persistence, mobility and dissipation pathways of several degradates of linuron is not available.  However, none of the linuron water degradates are present at levels greater than 10% of the applied parent, and therefore not considered major water metabolites.

Table 4.3.  Summary of Metabolites and Degradates to be included in the Risk Assessment and Tolerance Expression
Matrix
Residues included in Risk Assessment
Residues included in Tolerance Expression
Plants
Primary Crop
linuron and 
metabolites convertible to 3,4-DCA
linuron and metabolites convertible to 3,4-DCA

Rotational Crop


Livestock
Ruminant



Poultry


Drinking Water

Not Applicable

5.0	Residue Profile

5.1	Residue Analytical Methods (860.1340) 

Various adequately validated analytical methods are now available for linuron.

For linuron residues of concern in plant commodities, Method ABC-68406-M is available and suitable for residue collection as well as enforcement of tolerances.  This method has been used previously for data collection and is used with the current field trial submissions.  This method involves reflux of crop samples in strong base to hydrolyze residues of linuron and its metabolites to 3,4-DCA.  Then, 3,4-DCA GC/MS.  Based on the LLMV from the ILV study, the validated LOQ is 0.01 ppm for linuron and its metabolites hydrolyzable to 3,4-DCA in/on oily (soybean seed), watery (celery), and starch (potato) crop matrices.

In addition, Method ABC-65790 was presented.  It is a multi-residue method that is suitable for screening for enforcement of tolerances for linuron residues in plant commodities.  It may also be used as a confirmatory method for Method ABC-68406.  In this method, extractions are conducted with methanol and each analyte is analyzed by LC/MS/MS.  This method separately determines residues of linuron and metabolites DCPMU, DCPU, and desmethyl linuron in crop commodities.  Based on the LLMV, the validated LOQ is 0.01 ppm each for linuron, DCPMU, DCPU, and desmethyl linuron.  Transition ions monitored were:  m/z 249-->160 for linuron, m/z 219-->127 for DCPMU, m/z 205-->127 for DCPU, and m/z 235-->160 for desmethyl linuron.  HED notes that this method is not acceptable as the primary enforcement method because of the following reasons: (1) the residue definition contains components in addition to those determined; and (2) the method does not include a secondary ion transition for each analyte, which is required for enforcement methods.

For linuron residues of concern in livestock commodities Method, ABC-67638-M, is available and suitable for residue collection as well as enforcement of tolerances.  This method involves reflux of livestock commodity samples in strong base to hydrolyze residues of linuron and its metabolites to 3,4-DCA.  Then, 3,4-DCA is analyzed by GC/MS.  Based on the LLMV, the validated LOQ is 0.01 ppm for linuron and its metabolites hydrolyzable to 3,4-DCA in milk, muscle, and liver.

Conclusions.  The analytical methods, ABC-68406-M and ABC-67638-M, are adequate for enforcement of the tolerance expression and they been validated.

5.2	Submittal of Analytical Reference Standards (860.1650)

The analytical reference standard of linuron at the EPA National Pesticide Standards Repository, expired as of April 18, 2013.  The registrant must send an updated COA, or five grams of new material to the Repository as soon as possible.  The reference standard can be sent to the Analytical Chemistry Branch, to the attention of either Theresa Cole or Thuy Nguyen, at the address listed below:
      USEPA
      National Pesticide Standards Repository/Analytical Chemistry Branch/OPP
      701 Mapes Road
      Fort George G. Meade, MD  20755-5350

The full 9 digit zip code is mandatory or the mail will be returned to the sender.

5.3	Storage Stability (860.1380)

The storage durations and conditions of samples from the submitted crop field trials are presented in Table 5.3.  Freezer storage stability data were generated concurrently with the crop field trials.  Data showed that linuron residues were stable in all matrices under frozen storage for the duration of the storage period.


Table 5.3  Stability of  Linuron Residues in Following Storage.
                                    Matrix
                              Storage Temperature
                            Actual Storage Duration
                                    (days)
               Interval of Demonstrated Storage Stability (days)
                       Coriander Fresh Leaves and Stems
                                   -21+-7°C
                                   378 - 514
                                      530
                       Coriander Dried Leaves and Stems
                                       
                                      468
                                      427
                                Coriander Seed
                                       
                                      271
                                      288
                          Dill Fresh Leaves and Stems
                                       
                                   64 - 165
                                      212
                          Dill Dried Leaves and Stems
                                       
                                      164
                                      160
                                   Dill Seed
                                       
                                   31 - 128
                                      193
                                   Dill Oil
                                       
                                      147
                                      139
                        Parsley Fresh Leaves and Stems
                                       
                                      264
                                      264
                        Parsley Dried Leaves and Stems
                                       
                                      220
                                      220
                                   Pea (Dry)
                                       
                                   125 - 138
                                   145 - 147
                                  Horseradish
                                       
                                    62 - 70
                                    62 - 70

Conclusions: The storage stability data are adequate to support the storage intervals and conditions for the residue samples of coriander, dill, parsley, pea (dry), and horseradish from the field trials.  

5.4	Residue Data

5.4.1	Crop Field Trials (860.1500)
DER References: MRIDs 48928501, 48928502, 48928503, 48928504, 45633501, 45633502

All of the field trials were conducted according to the proposed label use directions in the appropriate representative geographical regions.  Adjuvants were not used in any of the field trials.  Residue decline studies were not conducted. 

Table 5.4.1.  Summary of Residues from Field Trials with Linuron.
                                  Crop Matrix
                                  Analyte[b]
                                 Applic. Rate
                                 (lb ai/acre)
                                  PHI (days)
                                       n
                             Residues[a][,b] (ppm)
                                       
                                       
                                       
                                       
                                       
                                     Min.
                                     Max.
                                     HAFT
                                     Mean
                                      SD
 Coriander: Proposed Use = 2.0 lb ai/acre total application rate, 21-day PHI.
                            Fresh Leaves and Stems
                                    Linuron
                                 1.997 - 2.118
                                     19-21
                                       8
                                     0.08
                                     1.14
                                     1.055
                                     0.65
                                      0.4
                            Dried Leaves and Stems
                                       
                                       
                                      19
                                       1
                                      8.5
                                      NA
                                      NA
                                      NA
                                     Seed
                                       
                                       
                                      155
                                       2
                                   <0.01
                                      NA
                                      NA
                                      NA
    Dill: Proposed Use = 2.0 lb ai/acre total application rate, 21-day PHI.
                            Fresh Leaves and Stems
                                    Linuron
                                 2.005 - 2.026
                                    20 - 22
                                       7
                                      0.3
                                     0.67
                                     0.56
                                     0.48
                                      0.1
                            Dried Leaves and Stems
                                       
                                       
                                      22
                                       2
                                      1.8
                                      3.5
                                     2.65
                                     2.65
                                      1.2
                                     Seed
                                       
                                       
                                    59 - 85
                                       4
                                     0.06
                                     0.12
                                     0.12
                                     0.09
                                     0.03
                                      Oil
                                       
                                       
                                      48
                                       1
                                      1.8
                                      NA
                                      NA
                                      NA
  Parsley: Proposed Use = 1.5 lb ai/acre total application rate, 30-day PHI.
                            Fresh Leaves and Stems
                                    Linuron
                                     1.510
                                    29 - 32
                                       4
                                     0.43
                                      1.3
                                     1.02
                                     0.75
                                     0.387
                            Dried Leaves and Stems
                                       
                                     1.511
                                      29
                                       1
                                      2.8
                                      2.8
                                      2.8
                                      NA
Pea (Dry): Proposed Use = 1.0 lb ai/acre total application rate, unspecified PHI.
                                   Pea (Dry)
                                       
                                 0.972 - 1.015
                                    65 - 92
                                      12
                                   <0.01
                                     0.052
                                     0.051
                                     0.014
                                     0.018
Horseradish: Proposed Use = 1.5 lb ai/acre total application rate, unspecified PHI.
                                     Roots
                                    Linuron
                                 1.43  -  1.55
                                   77 - 100
                                       
                                   <0.05
                                      NA
                                      NA
                                      NA
a	HAFT = highest average field trial.  SD = Standard Deviation.  For samples with no detectable residues (< 0.01 ppm) the LOQ value (0.01 ppm) was used to calculate the Mean and Standard Deviation.
b	Residues were converted to and measured as 3,4-DCA.  Values were converted to linuron equivalents.

Conclusions:  The available residue data are acceptable and reflect the proposed use patterns provided in Section B.  The number and geographical locations of the field trials are in accordance with the test guidelines.  Furthermore, an acceptable method was used for residue quantitation and the data are supported by adequate storage stability data.

5.4.2	Meat, Milk, Poultry and Eggs (860.1480)

There are no feed items associated with this current petition.  Cowpea commodities would affect the dietary burden of cattle but since they are a bean rather than a pea, they are not included in the petition for dry peas.  Dry peas only includes the following commodities listed under 40 CFR§180.1(g): Cajanus cajan (includes pigeon pea); Cicerspp. (includes chickpea and garbanzo bean); Lens culinaris (lentil);Pisumspp. (includes dwarf pea, garden pea, green pea, English pea, field pea, and edible pod pea).  Therefore, the previous livestock dietary intake calculations and resulting tolerance recommendations are not changed.  However, since there are livestock feed items associated with field pea, the following restriction should be added to the label: " Do not apply to field pea used for livestock feed."

5.5	Food Residue Profile

The residue data on coriander, dill, parsley, pea (dry), and horseradish are adequate for tolerance assessment and for use in dietary risk assessment.  Based on detectable residues found in forage/foliage of a few metabolism studies, linuron is assumed to have systemic activity in plants.  Finite residues of linuron and/or its metabolites are anticipated on food and feed commodities, even from early season soil-directed applications.   Transfer to livestock commodities has been demonstrated, although the residue is primarily metabolites and unidentified polar components.   The analytical methods account for the total residue by conversion of parent, metabolites, and polar, and bound (non-releasable) components to 3,4-DCA.

6.0	Tolerance Derivation

As shown in Appendix C, the statistical goal of the OECD calculation procedures is to produce an MRL proposal in the region of the 95[th] percentile of the underlying residues distribution.  

Coriander (MRID 48928501)
The dataset used to establish a tolerance for linuron consisted of field trial data on coriander representing two applications within -5% to +10% of 1 lb ai/A per application for a total of 2 lb ai/A per crop, and 19- to 21-day PHIs.  The average residue values used to calculate the tolerance are provided below.  Combined residues of linuron and its metabolites hydrolyzed to 2,4-DCA were quantifiable (LOQ = 0.01 ppm) in/on samples.  Data from four field trials were used in the OECD tolerance calculation procedures for fresh coriander, resulting in a recommended tolerance of 1.5 ppm.  For dried coriander, a 9X concentration factor was derived from a single residue field trial where the coriander was dried, resulting in a recommended tolerance of 10 ppm (calculated by: HAFT of fresh coriander residue 1.055 ppm x concentration factor 9).  For coriander seed, no detectable residues were found, resulting in a recommended tolerance of 0.05 ppm (calculated by: 5 x LOQ 0.01 ppm).

Dill (MRID 48928502)
The dataset used to establish a tolerance for linuron consisted of field trial data on dill representing two applications within -5% to +10% of 1 lb ai/A per application for a total of 2 lb ai/A per crop, and 20- to 22- day PHIs.  The average residue values used to calculate the tolerance are provided below.  Combined residues of linuron and its metabolites hydrolyzed to3,4-DCA were quantifiable (LOQ = 0.01 ppm) in/on all samples.  Data from three field trials were used in the OECD tolerance calculation procedures for fresh dill, resulting in a recommended tolerance of 0.6 ppm.  For dried dill, a 4.73X concentration factor was derived from a single residue field trial where the dill was dried, resulting in a recommended tolerance of 3.0 ppm (calculated by: HAFT of fresh dill 0.56 ppm x concentration factor 4.73).  For dill seed, the OECD calculation procedures could not be used because there were only two field trials, thus resulting in a recommended tolerance of 0.5 ppm (calculated by: 5 x mean dill oil residue 0.9 ppm).  For dill oil, a 3.21X concentration factor was derived from a single residue field trial, resulting in a recommended tolerance of 2.0 ppm (calculated by: HAFT of fresh dill 0.56 ppm x concentration factor 3.21).

Parsley (MRID 48928503)
The dataset used to establish a tolerance for linuron consisted of field trial data on parsley representing one application of 1.51 lb ai/A and 29- to 32-day PHIs.  The average residue values used to calculate the tolerance are provided below.  Although the LOQ were not statistically calculated in this study, all combined residues of linuron and its metabolites hydrolyzed to 2,4-DCA were quantifiable in/on samples above the LLMV (0.05 ppm).  For fresh parsley, the OECD calculation procedures could not be used because there were only two field trials, thus resulting in a recommended tolerance of 4.0 ppm (calculated by: 5 x mean fresh parsley residue 0.75 ppm).  For fresh parsley, the recommended tolerance is 4.0 ppm.  For dried parsley, a 2.76X concentration factor was derived from a single residue field trial where parsley was dried, resulting in a recommended tolerance of 3.0 ppm (calculated by: HAFT of fresh parsley 1.015 ppm x concentration factor 2.76).

Pea (Dry) (MRID 48928504)
The dataset used to establish a tolerance for linuron consisted of field trial data on peas (dry) representing one application within -5% to +10% of 1 lb ai/A, and 65- to 92-day PHIs.  The average residue values used to calculate the tolerance are provided below.  Combined residues of linuron and its metabolites hydrolyzed to 2,4-DCA were quantifiable in/on two of six trials.  Data from all six field trials were used in the OECD calculation procedures, resulting in a recommended tolerance of 0.06 ppm.

Horseradish (MRIDs 45633501 and 45633502)
The dataset used to establish a tolerance for linuron consisted of field trial data on horseradish representing one application within -5% to +10% of 1.5 lb ai/A per application, and 76- to 100-day PHIs.  The average residue values used to calculate the tolerance are provided below.  An LOQ was not statistically calculated in this study, but the LLMV was determined to be 0.05 ppm.  Data from three field trials indicated that detectable residues were not found.  Thus, data consisting of <LOQ values from three field trials were used in the OECD tolerance calculation procedures, resulting in a recommended tolerance equivalent to the LOQ of 0.05 ppm.
Appendix A.  Summary of Submitted Residue Chemistry Studies 

Table A1.  Summary of Submitted Residue Chemistry Studies
                                OCSPP Guideline
                                     MRID
Title
                                   860.1340
                                       
                           Residue Analytical Method
                                   48832101
Determination of the Substituted Urea Herbicide Linuron and its Metabolites in Oily, Watery, and Starch Crop Matrices
                                       
                                   48832102
Independent Laboratory Validation of "Determination of the Substituted Urea Herbicide Linuron and its Metabolites in Soil and Agricultural Products" for Oily, Watery, and Starch Crop Matrices
                                       
                                   48832103
Determination of the Substituted Urea Herbicide Linuron and its Metabolites in Animal Tissue
                                       
                                   48832104
Independent Laboratory Validation of the Draft Method "Determination of the Substituted Urea Herbicide Linuron and its Metabolites in Animal Tissues"
                                       
                                   48832105
Method Transfer and Validation of "Determination of the Substituted Urea Herbicide Linuron and its Metabolites in Soil and Agricultural Products" for Animal Matrices
                                       
                                   48832106
Analytical Method for the Determination of Linuron and Metabolites in Crops using LC/MS/MS
                                       
                                   48832107
Independent Laboratory Validation of "Determination of the Substituted Urea Herbicide Linuron and its Metabolites in Soil and Agricultural Products" for Oily, Watery, and Starch Crop Matrices
                                       
                                   48832108
Independent Laboratory Validation of Residue Analytical Method 20001407/01-RVP, "Residue Analysis of Diuron and Metabolites in Plants Method Validation" for the Determination of Residues of Linuron and Metabolites in Grapes, Olives, and Wheat Grain
                                       
                                   48832109
Analytical Method for the Determination of Linuron and Metabolites in Animal Tissue using LC/MS/MS
                                       
                                   48832110
Independent Laboratory Validation of "Analytical Method for the Determination of Linuron and Metabolites in Animal Tissue using LC/MS/MS" and "Analytical Method for the Determination of Diuron and Metabolites in Animal Tissue using LC/MS/MS"
                                   860.1500
                                       
                               Crop Field Trial
                                   48928501
Linuron: Magnitude of the Residue on Coriander
                                       
                                   48928502
Linuron: Magnitude of the Residue on Dill
                                       
                                   48928503
Linuron: Magnitude of the Residue on Parsley
                                       
                                   48928504
Linuron: Magnitude of the Residue on Pea (Dry)
                                       
                                   45633501
                                   45633502
Linuron: Magnitude of the Residue on Horseradish

Appendix B.  International Residue Limits Table for Linuron

Table B1.  Summary of US and International Tolerances and Maximum Residue Limits of Linuron
                              Residue Definition
                                      US
                                    Canada
                                   Mexico[b]
                                     Codex
40 CFR 180.184:
Plant and Livestock:
(3-(3,4-dichlorophenyl)-1-methoxy-1-methylurea) and its metabolites convertible to 3,4-dichloroaniline
None

None
                                 Commodity[a]
                Tolerance (ppm) /Maximum Residue Limit (mg/kg)
                                       
                                      US
                                    Canada
                                   Mexico[b]
                                     Codex
                            Cilantro, fresh leaves
                                      1.5
                                                                               

                                                                               
                            Cilantro, dried leaves
                                      10
                                                                               

                                                                               
                                Coriander, seed
                                     0.05
                                                                               

                                                                               
                            Dillweed, fresh leaves
                                      0.6
                                                                               

                                                                               
                            Dillweed, dried leaves
                                      3.0
                                                                               

                                                                               
                                  Dill, seed
                                      0.5
                                                                               

                                                                               
                                   Dill, oil
                                      2.0
                                                                               

                                                                               
                                  Horseradish
                                     0.05
                                                                               

                                                                               
                                Parsley, leaves
                                      4.0
                                                                               

                                                                               
                             Parsley, dried leaves
                                      3.0
                                                                               

                                                                               
                                Pea, dry, seed
                                     0.06
                                                                               

                                                                               
Completed:  M. Negussie; 07/30/2013
a	Includes only commodities of interest for this action.  Tolerance values should be the HED recommendations and not those proposed by the applicant.
b	Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

Appendix C.  OECD MRL Calculation Procedure Inputs/Outputs

Coriander (MRID 48928501)
2.0 lb ai/A; 19-21 day PHIs

                               Residues (mg/kg)
                                     0.940
                                     4.000
                                     0.086
                                     4.000
                                     0.525
                                     4.000
                                     1.055
                                     4.000

Compound
 
                                    Linuron
Crop
 
                                Fresh Coriander
Region / Country
 
                                  CA/OR/TN/TX
GAP
 
                                       
 
 
 
                                       
Total number of data (n)
 
                                       4
 
 
                                       
                                       
Percentage of censored data
 
                                     100%
Number of non-censored data
 
                                       0
 
 
                                       
                                       
Lowest residue
 
                                     0.086
Highest residue
 
                                     1.055
Median residue
 
                                     0.733
 
 
                                       
                                       
Mean
 
                                     0.651
Standard deviation (SD)
 
                                     0.441
 
 
                                       
                                       
Correction factor for censoring (CF)
 
                                     0.333
 
 
                                       
                                       
Proposed MRL estimate
 
 
                                       
 
 
                                       
                                       
- Highest residue
 
                                     1.055
- Mean + 4 SD
 
                                     2.414
- CF x 3 Mean
 
                                     0.651
Unrounded MRL
 
                                     1.055
 
 
                                       
                                       
Rounded MRL
 
                                      1.5
 
 
 
                                       
 
High uncertainty of MRL estimate due to small dataset and high level of censoring.



Dill (MRID 48928502)
2.0 lb ai/A; 20-22 day PHIs

                               Residues (mg/kg)
                                     0.335
                                     3.000
                                     0.490
                                     3.000
                                     0.560
                                     3.000

Compound
 
                                    Linuron
Crop
 
                                  Fresh Dill
Region / Country
 
                                   CA/FL/WA
GAP
 
                                       
 
 
 
                                       
Total number of data (n)
 
                                       3
 
 
                                       
                                       
Percentage of censored data
 
                                     100%
Number of non-censored data
 
                                       0
 
 
                                       
                                       
Lowest residue
 
                                     0.335
Highest residue
 
                                     0.560
Median residue
 
                                     0.490
 
 
                                       
                                       
Mean
 
                                     0.462
Standard deviation (SD)
 
                                     0.115
 
 
                                       
                                       
Correction factor for censoring (CF)
 
                                     0.333
 
 
                                       
                                       
Proposed MRL estimate
 
 
                                       
 
 
                                       
                                       
- Highest residue
 
                                     0.560
- Mean + 4 SD
 
                                     0.922
- CF x 3 Mean
 
                                     0.462
Unrounded MRL
 
                                     0.560
 
 
                                       
                                       
Rounded MRL
 
                                      0.6
 
 
 
                                       
 
High uncertainty of MRL estimate due to small dataset and high level of censoring.


Pea (Dry) (MRID 48928504)
1.0 lb ai/A; 65-92 day PHIs

                               Residues (mg/kg)
                                     0.015
                                     6.000
                                     0.010
                                       *
                                     0.010
                                       *
                                     0.010
                                       *
                                     0.051
                                     6.000
                                     0.010
                                       *

Compound
 
                                    Linuron
Crop
 
                                   Pea (Dry)
Region / Country
 
                                   ID/ND/WA
GAP
 
                                       
 
 
 
                                       
Total number of data (n)
 
                                       6
 
 
                                       
                                       
Percentage of censored data
 
                                     100%
Number of non-censored data
 
                                       0
 
 
                                       
                                       
Lowest residue
 
                                     0.010
Highest residue
 
                                     0.051
Median residue
 
                                     0.010
 
 
                                       
                                       
Mean
 
                                     0.018
Standard deviation (SD)
 
                                     0.016
 
 
                                       
                                       
Correction factor for censoring (CF)
 
                                     0.333
 
 
                                       
                                       
Proposed MRL estimate
 
 
                                       
 
 
                                       
                                       
- Highest residue
 
                                     0.051
- Mean + 4 SD
 
                                     0.083
- CF x 3 Mean
 
                                     0.018
Unrounded MRL
 
                                     0.051
 
 
                                       
                                       
Rounded MRL
 
                                     0.06
 
 
 
                                       
 
High uncertainty of MRL estimate due to small dataset and high level of censoring.


Horeseradish (MRIDs 45633501 and 45633502)
1.5 lb ai/A; 76-100 day PHIs

                               Residues (mg/kg)
                                   <0.05
                                   <0.05
                                   <0.05

Compound
 
                                    Linuron
Crop
 
                                  Horseradish
Region / Country
 
                                   MD/WI/NJ
GAP
 
                                       
 
 
 
                                       
Total number of data (n)
 
                                       3
 
 
                                       
                                       
Percentage of censored data
 
                                     100%
Number of non-censored data
 
                                       0
 
 
                                       
                                       
Lowest residue
 
                                     0.050
Highest residue
 
                                     0.050
Median residue
 
                                     0.050
 
 
                                       
                                       
Mean
 
                                     0.050
Standard deviation (SD)
 
                                     0.000
 
 
                                       
                                       
Correction factor for censoring (CF)
 
                                     0.333
 
 
                                       
                                       
Proposed MRL estimate
 
 
                                       
 
 
                                       
                                       
- Highest residue
 
                                     0.050
- Mean + 4 SD
 
                                     0.050
- CF x 3 Mean
 
                                     0.050
Unrounded MRL
 
                                     0.05
 
 
                                       
                                       
Rounded MRL
 
                                     0.05
 
 
 
                                       

High uncertainty of MRL estimate due to small dataset and high level of censoring.

