Document ID: EPA-HQ-OPP-2012-0791-0012
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2014-02-12T05:00Z

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

Date:	17-December-2013

Subject:	Addendum to DP Barcodes D404359 and D411652: 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:  D416651
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.:  NA
40 CFR:§180.184

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

Through:	Christine Olinger, Branch Chief
	Risk Assessment Branch 3 (RAB3)
	Health Effects Division (7509P)

To: 	Kristin Rury, Biologist, Risk Assessor
	Risk Assessment Branch 3 (RAB3) 
	Health Effects Division (7509P)
	
	and
	
	Laura Nollen/Barbara Madden, RM05
	Risk Integration Minor Use and Emergency Response Branch (RIMUERB)
	Registration Division (7505P)

This document serves as an addendum to the original residue data review from August 14, 2013.  The addendum updates corrected values for the recommended tolerances, tolerance derivation, and input/output values for the Organization for Economic Cooperation and Development (OECD) tolerance calculation procedures.

                               Table of Contents

1.0	Executive Summary	3
2.0	Regulatory Recommendations	3
2.1	Tolerance Considerations	3
2.1.1	Recommended Tolerances	3
2.1.2	Revisions to Petitioned-For Tolerances	4
2.1.3	International Harmonization	4
3.0	Residue Data: Crop Field Trials (860.1500)	4
4.0	Tolerance Derivation	5
Appendix A.  OECD MRL Calculation Procedure Inputs/Outputs	8

1.0	Executive Summary

The 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.

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 are submitted, 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 2.1.1.

2.1	Tolerance Considerations

2.1.1	Recommended Tolerances
 
In addition to the recommended tolerances listed below in Table 1, the tolerance with regional registration under 40 CFR §180.184(c) for parsley, leaves (0.25 ppm) should be deleted.

Table 1.  Tolerance Summary for Linuron.
                                   Commodity
                           Proposed Tolerance (ppm)
                        HED-Recommended Tolerance (ppm)
                                  Comments[a]
                 (OECD calculation adjustments to tolerances)
                                       
                                       
                                   DP404359
                                   DP416651
                                       
                            Cilantro, fresh leaves
                                      3.0
                                      1.5
                                      3.0
                  Corrected OECD Calculation Procedure values
                            Cilantro, dried leaves
                                      27
                                      10
                                      10
                          9X PF x HAFT of 1.055 ppm
                                Coriander, seed
                                     0.01
                                     0.05
                                     0.01
                                LOQ of 0.01 ppm
                            Dillweed, fresh leaves
                                      1.5
                                      0.6
                                      1.5
                  Corrected OECD Calculation Procedure values
                            Dillweed, dried leaves
                                      7.1
                                      3.0
                                      5.0
                           9X PF x HAFT of 0.56 ppm
                                  Dill, seed
                                      0.3
                                      0.5
                                      0.5
                             5 x Mean of 0.09 ppm
                                   Dill, oil
                                      4.8
                                      2.0
                                      2.0
                          3.21 PF x HAFT of 0.56 ppm
                                  Horseradish
                                     0.05
                                     0.05
                                     0.05
                                LOQ of 0.05 ppm
                                Parsley, leaves
                                      3.0
                                      4.0
                                      4.0
                             5 x Mean of 0.75 ppm
                             Parsley, dried leaves
                                      8.3
                                      3.0
                                      9.0
                          9X PF x HAFT of 1.015 ppm
                                Pea, dry, seed
                                     0.08
                                     0.06
                                     0.09
                  Corrected OECD Calculation Procedure values
a	OECD = Organization for Economic Cooperation and Development. PF = processing factor. HAFT = highest average field trial. LOQ = limit of quantitation.

2.1.2	Revisions to Petitioned-For Tolerances

All of the petitioned-for tolerance levels (except for fresh cilantro, coriander seed, fresh dillweed, and 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 (DCA), 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, the tolerance level for pea, dry, seed should be increased.

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 two commodities: dill, seed; and parsley, leaves.  Based on this calculation method, both tolerance levels should be increased.

For the dried herbs (cilantro, dillweed, and parsley), the formula of the highest average field trial (HAFT) multiplied by the herb processing (drying) factor of 9X was used to calculate the recommended tolerance levels (the processing factor was derived from dividing the average  dried cilantro commodity residue by the average fresh cilantro residue).  Based on this calculation method, the tolerance levels for dried cilantro and dillweed should be decreased, and the tolerance for dried parsley should be increased.

For dill oil, the formula of the HAFT multiplied by the herb processing (oil extraction) factor of 3.21X was used to calculate the recommended tolerance level (the processing factor was derived from dividing the average dill oil commodity residue by the average fresh dill residue).  Based on this calculation method, the dill oil tolerance should be decreased.

2.1.3	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.

3.0	Residue Data: 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.

The available residue data, as shown in Table 2, 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.

Table 2.  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
                                       3
                                   <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.

4.0	Tolerance Derivation

As shown in Appendix A, the statistical goal of the OECD calculation procedures is to produce an MRL/tolerance 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 3,4-DCA were quantifiable (LOQ = 0.01 ppm) in/on samples.  

For fresh coriander, data from four field trials were used in the OECD tolerance calculation procedures for fresh coriander, resulting in a recommended tolerance of 3.0 ppm.  (Note that the correct commodity term is cilantro, fresh leaves).

For dried coriander, a 9X concentration factor was derived from a single residue field trial where the coriander was dried (calculated by dividing the average dried cilantro commodity residue by the average fresh cilantro residue), resulting in a recommended tolerance of 10 ppm (calculated by: HAFT of fresh coriander residue 1.055 ppm x processing factor 9).  (Note that the correct commodity term is cilantro, dried leaves).

For coriander seed, no detectable residues were found, resulting in a recommended tolerance of 0.01 ppm (at the 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.  

For fresh dill, data from three field trials were used in the OECD tolerance calculation procedures for fresh dill, resulting in a recommended tolerance of 1.5 ppm.

For dried dill, the 9X processing factor derived for coriander was used, resulting in a recommended tolerance of 5.0 ppm (calculated by: HAFT of fresh dill 0.56 ppm x concentration factor 9).  Since all fresh herbs contain comparable water content, the processing factor for dried herbs should be the same.  By using the highest processing factor value derived from coriander (at 9X), HED is being sufficiently protective that the residues of linuron are not underestimated in dried herb commodities.

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 0.09 ppm).

For dill oil, a 3.21X concentration factor was derived from a single residue field trial (calculated by dividing the average dill oil commodity residue by the average fresh dill residue), resulting in a recommended tolerance of 2.0 ppm (calculated by: HAFT of fresh dill 0.56 ppm x concentration factor 3.21).

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 Lowest Limit of Method Validation (LLMV) was determined to be 0.05 ppm.  

For horseradish, 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.

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 3,4-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 dried parsley, the 9X processing factor derived for coriander was used, resulting in a recommended tolerance of 9.0 ppm (calculated by: HAFT of fresh parsley 1.015 ppm x concentration factor 9).  Since all fresh herbs contain comparable water content, the processing factor for dried herbs should be the same.  By using the highest processing factor value derived from coriander (at 9X), HED is being sufficiently protective that the residues of linuron are not underestimated in dried herb commodities.

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 to3,4-DCA were quantifiable in/on two of six trials.  

For dry peas, data from all six field trials were used in the OECD calculation procedures, resulting in a recommended tolerance of 0.09 ppm.
Appendix A.  OECD MRL Calculation Procedure Inputs/Outputs

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

                               Residues (mg/kg)
                                     0.940
                                       1
                                     0.086
                                       1
                                     0.525
                                       1
                                     1.055
                                       1

Compound
 
                                    Linuron
Crop
 
                                Fresh Coriander
Region / Country
 
                                  CA/OR/TN/TX
GAP
 
                                       
 
 
 
                                       
Total number of data (n)
 
                                       4
 
 
                                       
                                       
Percentage of censored data
 
                                      0%
Number of non-censored data
 
                                       4
 
 
                                       
                                       
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)
 
                                     1.000
 
 
                                       
                                       
Proposed MRL estimate
 
 
                                       
 
 
                                       
                                       
- Highest residue
 
                                     1.055
- Mean + 4 SD
 
                                     2.414
- CF x 3 Mean
 
                                     1.954
Unrounded MRL
 
                                     2.414
 
 
                                       
                                       
Rounded MRL
 
                                       3
 
 
 
                                       
 
High uncertainty of MRL estimate due to small dataset.

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

                               Residues (mg/kg)
                                     0.335
                                       1
                                     0.490
                                       1
                                     0.560
                                       1

Compound
 
                                    Linuron
Crop
 
                                  Fresh Dill
Region / Country
 
                                   CA/FL/WA
GAP
 
                                       
 
 
 
                                       
Total number of data (n)
 
                                       3
 
 
                                       
                                       
Percentage of censored data
 
                                      0%
Number of non-censored data
 
                                       3
 
 
                                       
                                       
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)
 
                                     1.000
 
 
                                       
                                       
Proposed MRL estimate
 
 
                                       
 
 
                                       
                                       
- Highest residue
 
                                     0.560
- Mean + 4 SD
 
                                     0.922
- CF x 3 Mean
 
                                     1.385
Unrounded MRL
 
                                     1.385
 
 
                                       
                                       
Rounded MRL
 
                                      1.5
 
 
 
                                       
 
High uncertainty of MRL estimate due to small dataset.

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

                               Residues (mg/kg)
                                     0.015
                                       1
                                     0.010
                                       *
                                     0.010
                                       *
                                     0.010
                                       *
                                     0.051
                                       1
                                     0.010
                                       *

Compound
 
                                    Linuron
Crop
 
                                   Pea (Dry)
Region / Country
 
                                   ID/ND/WA
GAP
 
                                       
 
 
 
                                       
Total number of data (n)
 
                                       6
 
 
                                       
                                       
Percentage of censored data
 
                                      67%
Number of non-censored data
 
                                       2
 
 
                                       
                                       
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)
 
                                     0.556
 
 
                                       
                                       
Proposed MRL estimate
 
 
                                       
 
 
                                       
                                       
- Highest residue
 
                                     0.051
- Mean + 4 SD
 
                                     0.083
- CF x 3 Mean
 
                                     0.029
Unrounded MRL
 
                                     0.083
 
 
                                       
                                       
Rounded MRL
 
                                     0.09
 
 
 
                                       
 
High uncertainty of MRL estimate due to small dataset and high level of censoring.

Horseradish (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
 
                                     0.050
 
 
                                       
                                       
Rounded MRL
 
                                     0.05
 
 
 
                                       

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