Document ID: EPA-HQ-OPP-2015-0375-0004
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2015-09-18T04:00Z

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

                                                           POLLUTION PREVENTION

MEMORANDUM

	Date:	4 June 2015

	SUBJECT:  	Fluensulfone  -  Revised Tolerance Recommendation for Tomato Paste.
 
PC Code:  050410
DP Barcode:  D427654
Decision No.: 505068
Registration No.:  66222-243
Petition No.:  5F8365
Regulatory Action:  Section 3
Risk Assessment Type:  Single Chemical Aggregate
Case No.:  None
TXR No.:  NA
CAS No.:  318290-98-1
MRID No.:  49556801
40 CFR:  180.680

	FROM:	Michael A. Doherty, Ph.D., Senior Chemist
		Risk Assessment Branch II (RAB II)
		Health Effects Division (HED; 7509P)

	THROUGH:	Christina Swartz, Chief
		RAB II 
		HED (7509P)

	TO:	Rita Kumar/Mark Suarez/Meredith Laws
		Invertebrate and Vertebrate Branch 3
		Registration Division (7505P)

The new nematicide fluensulfone was recently evaluated under a global joint review project, with Canada and Australia, for use on cucurbit and fruiting vegetables (crop groups 9 and 8-10, respectively). In the human health risk assessment (D403767, 18 June 2014; D422674, 4 September 2014), HED concluded that a tolerance for residues of fluensulfone in/on both crop groups was supported at 0.5 ppm, and tolerances were established in September 2014 (40 CFR 180.680). 

The tolerance expression specifies that for compliance, the analyte of interest is 3,4,4-trifluoro-but-3-ene-1-sulfonic acid (a.k.a. BSA, a metabolite and degradate found in crops treated with fluensulfone). Based on the information available to the Agency at that time, which showed no concentration of fluensulfone or the BSA metabolite, separate tolerances for residues in processed tomato products were not established. 

Recently, the Agency received a new tomato processing study which demonstrates concentration of BSA to a degree that warrants a separate tolerance for residues in tomato paste. The study, Magnitude of the Residue of Fluensulfone in Tomato Processed Commodities (Study No. AA120702; MRID 49556801), was reviewed by Health Canada's Pest Management Regulatory Agency (PMRA) and was found to be acceptable. EPA has not conducted additional review of the study. The PMRA evaluation is included as Attachment 1.

HED Conclusions

The processing study indicates that residues of BSA may concentrate in tomato puree (1.4X), tomato paste (3.5X), and dried tomato (6.6X). Based on these concentration factors and the highest average field trial (HAFT) residue (0.29 ppm) in tomato fruits, the tolerance for residues in tomato is sufficient to cover residues in puree. The registrant has not requested a tolerance for residues in dried tomato, dried tomato is not a significantly traded food commodity, and a tolerance is not necessary for harmonization purposes; therefore, a tolerance for residues in dried tomato is not necessary, per HED policy. For tomato paste, the product of the concentration factor and the HAFT residue supports a tolerance of 1.0 ppm.

Attachment 1  -  PMRA Evaluation of MRID 49556801 (Magnitude of the Residue of Fluensulfone in Tomato Processed Commodities, Study No. AA120702)

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B.7.7	Effects of Industrial Processing and/or Household Preparation
            (Annex IIA 6.5; Annex IIIA 8.5)

B.7.7.3	Magnitude of Residues on Set of Representative Processes
	(Annex IIA 6.5.3; Annex IIIA 8.5.3)
            
 B.7.7.3.1	TOMATO
 
Document ID:	MRID No. 49556801
		PMRA No. 2402078
Report:	Magnitude of the Residue of Fluensulfone in Tomato Processed Commodities, Study No. AA120702
Guidelines:	EPA OCSPP Harmonized Test Guideline 860.1520 Processed Food/Feed (August 1996)
PMRA Regulatory Directive DIR98-02  -  Residue Chemistry Guidelines, Section 10  -  Processed Food/Feed 
OECD Guideline 508 Magnitude of the Pesticide Residues in Processed Commodities (October 2008)
GLP Compliance:	No deviations from regulatory requirements were reported which would have an impact on the validity of the study.
Acceptability:	The study is considered scientifically acceptable.
Evaluator: 		Anne-Marie Boulanger, Ph.D., Scientific Evaluator III, EXP-1, HED

EXECUTIVE SUMMARY

Tomato field trials for fluensulfone were conducted in the United States during the 2012 growing season. Fluensulfone, formulated as an emulsifiable concentrate (EC) of 480 g/L, was applied 7 days before transplanting of tomatoes as one pre-plant incorporated (PPI) application at rates of ca. 12 kg ai/ha (TRT #1) and ca. 20 kg ai/ha (TRT #2). Tomatoes were harvested only from one test plot of one trial (TRT #2 of T-CA) at commercial maturity (PHIs of 118-133 days).  The tomato fruits were processed into juice, purée, paste, wet pomace and dry pomace using simulated commercial practices.

All RAC samples were frozen at the testing facility and remained frozen during shipping and storage prior to analysis. All RAC samples harvested for processing were kept cool at the testing facility until shipping to the processing facility and remained frozen during storage after to processing and prior to analysis. The maximum storage interval for samples was 83 days (i.e. from harvest to processing to analysis). Storage conditions and durations are supported by studies showing that residues of fluensulfone are stable for up to 469 days in tomato RAC, and 181 days for tomato paste and purée under frozen conditions.

Samples were analyzed using Method 1977W, a HPLC-MS/MS method to determine residues of fluensulfone and M-3627 in tomato matrices. Acceptable concurrent recoveries were reported for tomato samples at various fortification levels, thus validating the method. The limit of quantitation (LOQ) was 0.01 ppm per analyte for tomato RAC, juice and purée, and 0.10 ppm per analyte for tomato paste, wet pomace and dry pomace.

A comparison of the residues in the raw agricultural commodity tomato fruit with those in each processed fraction resulted in processing factors of 1-fold for residues of fluensulfone in all tomato processed fractions, and processing factors of 0.66- to 6.57-fold for residues of M-3627 in tomato processed fractions. These processing factors were less than the theoretical concentration factors for tomato juice, purée, paste and dry pomace.

I.  MATERIALS AND METHODS

A.  MATERIALS

Table 7.7.3.1-1.  Nomenclature for Fluensulfone.
Common name
Fluensulfone
Identity
5-chloro-2-[(3,4,4-trifluoro-3-buten-1-yl)sulfonyl]thiazole
CAS no.
318290-98-1
Company experimental name
MCW-2

B.  Study Design

1.  Test Procedure
Location and detailed use pattern for the trial are provided in Table B.7.7.3.1-2. At each trial location, two treated plots were established at ca. 12 kg ai/ha (TRT #1; 4.2-fold maximum US registered GAP) and ca. 20 kg ai/ha (TRT #2; 7.1-fold maximum US registered GAP). The trials using the lower application rate were conducted due to concerns with phytotoxicity at 7.1-fold max GAP. However, tomato fruit samples were only collected from the 7.1-fold Californian trial (TRT#2) as the tomatoes matured first in California and no phytotoxicity was observed.

Table B.7.7.3.1-2.  Study Use Pattern.
               Location:  City, State/Province; Year (Trial ID)
                         End-use Product/ Formulation
                       Method and Timing of Application
                                    Volume
                                    [L/ha]
                             Rate per Application
                                  [kg ai/ha]
                          Retreatment Interval (days)
                                  Total Rate
                                   [kg ai/ha]
                             Surfactant/ Adjuvant
Porterville, CA; 2012; (T-CA)
                            Fluensulfone 480 g/L EC
TRT #1: one pre-plant incorporated application using backpack sprayer, 7 days before transplanting
                                    336.15
                                     11.84
                                      N/A
                                     11.84
                                     None

TRT #2: one pre-plant incorporated application using backpack sprayer, 7 days before transplanting
                                    339.04
                                     19.92
                                      N/A
                                     19.92
                                     None
Dover, FL; 2012; (T-FL)
                            Fluensulfone 480 g/L EC
TRT #1: one pre-plant incorporated application using backpack sprayer, 7 days before transplanting
                                    276.59
                                     11.72
                                      N/A
                                     11.72
                                     None

TRT #2: one pre-plant incorporated application using backpack sprayer, 7 days before transplanting
                                    284.50
                                     20.13
                                      N/A
                                     20.13
                                     None

Duplicate tomato fruit samples (minimum of 12 fruits; ca. 2 kg per sample) were harvested, for analysis of tomato RAC, at normal commercial harvest. In addition, single bulk tomato fruit samples (ca. 40 kg per sample) were also harvested at normal commercial harvest and transferred to the processing facility for preparation of tomato juice, purée, paste and pomace (wet and dry).

Sample Handling and Preparation

Tomato RAC samples were frozen after harvest and shipped frozen to the laboratory. Tomato samples harvested for processing were kept cool following harvest and shipped unfrozen to the processing facility.

Sample Processing

Untreated tomato samples were processed before the treated tomato samples. Tomatoes were processed according to simulated industrial practice as closely as possible. Tomato fruits were first sorted for any fruits unsuitable for processing. Whole tomatoes were then placed in warm water at 52-57°C for 3-5 minutes to loosen extraneous material, rinsed with water, and defects or off-color areas were trimmed off the tomato fruits prior to processing.

Cleaned tomatoes were chopped to a fine consistency and fed into a pulper/finisher with a 6/64″ screen. The material that passed through the screen was collected and heated rapidly to 91-97°C by pumping through a heat exchanger. The pulp material that did not pass through the screen was set aside. The hot break material was fed through another pulper/finisher with a 0.033″ screen; the material that did not passed through the screen was pulp. The resulting juice was checked for acidity and percent solids. If necessary, the acidity was adjusted to pH 4.5 or less with citric acid.

The pulp material was combined and a portion was taken for the wet pomace fraction. The remaining pulp was dried in an oven at 54-71°C for 20-24 hours. The resulting dry pomace was collected. Fractions of tomato wet and dry pomace were then stored frozen.

A portion of tomato juice was heated to 85-91°C for ca. 3 minutes, placed in a can and sealed. The sealed can was pressure cooked for 40-45 seconds at 121-124°C; cooled in a water bath at 16-27°C for 28-32 minutes. Fractions of tomato juice were then stored frozen.

The remaining tomato juice was used to produce tomato paste and purée. Both paste and purée were produced by vacuum evaporation of water at the lowest possible temperature and highest possible vacuum. The juice was concentrated to percent solids of 8-24% for purée and 24-30% for paste. Purée and paste were then heated to 85-91°C, placed in metal cans, sealed and cooled in water bath at 16-27°C for 28-32 minutes. Fractions of tomato purée and paste were then stored frozen.

2.  Description of Analytical Procedures

Samples of tomato were analyzed for residues of fluensulfone and metabolites M-3625, M-3626 and M-3627 using the Analytical Method 1977W (PMRA # 2181331; 2181930 (ILV)). The method was fully validated in the Annex B.5.2 (OECD). Note: Metabolite M-3626 (i.e. methyl sulfone) is a soil metabolite and not a plant metabolite. Metabolite M-3625 (i.e. thiazole sulfonic acid) is a plant metabolite. However, these two metabolites are not included in the residue definitions in plant commodities for enforcement and risk assessment purposes. As such, they will not be discussed in this document.

Briefly, samples were extracted once with acetonitrile:water (ACN:H2O). For determination of fluensulfone (i.e. MCW-2), an aliquot of the extract was subjected to HPLC-MS/MS using atmospheric pressure chemical ionization in positive polarity mode (APCI(+)) with multiple reaction monitoring (MRM). For determination of metabolite M-3627, an aliquot of the extract was cleaned up by SPE (i.e. Bond Elut) and the resulting extract was analyzed HPLC-MS/MS using electrospray ionization in negative polarity mode (ESI(-)) with MRM.  The LOQ for each analyte in tomato RAC, juice and purée was 0.01 ppm. The LOQ for all analytes in tomato paste, wet pomace and dry pomace was 0.10 ppm. The LODs were determined to be the lowest calibrant for each analyte resulting in values of 0.003 ppm (MCW-2) and 0.004 ppm (M3627).

II.  RESULTS AND DISCUSSION

Method performance was evaluated by use of concurrent recovery samples by fortifying tomato RAC and processed commodities (i.e. juice, purée, paste, pomace (wet and dry)) with fluensulfone at 0.01 ppm and 0.10 ppm (n = 1-4 per fortification level); M-3627 at 0.01 ppm, 0.10 ppm, 2.5 ppm, 5.0 ppm, 10 ppm and/or 20 ppm (n = 1-6 per fortification level) (Table B.7.7.3.1-3). The fortification levels bracketed the measured residues.

In tomato RAC and processed commodities, the majority of individual recoveries for residues of fluensulfone were within the acceptable range of recoveries with a few exceptions in tomato paste and dry pomace at 0.01 ppm. For metabolite M-3627, very few individual recoveries were outside the acceptable range of recoveries. The standard deviations were also less than +- 20%.

Concurrent recoveries for each analyte were measured using both the quantitation and confirmation ion transitions. The data are reported in Table B.7.7.3.1-3. The confirmatory data are in agreement with the quantitation data but are not reported herein.

The detector response was linear (coefficient of determination, r[2] > 0.99) for each analyte within the range of 0.0005-0.100 ug/mL. Representative chromatograms of control samples, fortified samples and treated samples were provided. The control chromatograms generally had no peaks of interest above the chromatographic background at the retention time of the analytes of interest. Peaks were usually symmetrical and well defined.

Table B.7.7.3.1-3.  Summary of Procedural/Concurrent Recoveries* of Fluensulfone and Metabolite M-3627 from Tomato RAC and Processed Commodities.
Matrix
                           Fortification Level (ppm)
                          Quantitation Ion Transition

                                       
                                Recoveries (%)
                             Mean +- SD (RSD) (%)
                             Fluensulfone (MCW-2)
Tomato RAC
                                     0.01
                                      80
                                       

                                     0.10
                                      87
                                       
Tomato juice
                                     0.01
                                    90, 120
                                      105

                                     0.10
                                    99, 93
                                      96
Tomato purée
                                     0.01
                                   100, 100
                                      100

                                     0.10
                                   100, 100
                                      100
Tomato paste
                                     0.01
                                   130, 100
                                      115

                                     0.10
                                    97, 89
                                      93
Tomato wet pomace
                                     0.01
                                    90, 80
                                      85

                                     0.10
                                    90, 92
                                      91
Tomato dry pomace
                                     0.01
                               150, 170, 140, 98
                                140 +- 30 (22)
                                       
                                     0.10
                                   111, 115
                                      113
                                    M-3627
Tomato RAC
                                     0.01
                                      130
                                       

                                     0.10
                                      100
                                       

                                      2.5
                                    80, 83
                                      82
Tomato juice
                                     0.01
                                    110, 80
                                      95

                                     0.10
                                98, 97, 70, 83
                                 87 +- 13 (15)

                                      5.0
                                    90, 73
                                      82
Tomato purée
                                     0.01
                                   100, 100
                                      100

                                     0.10
                               105, 104, 91, 102
                               101 +- 6.5 (6.4)

                                      5.0
                                    100, 92
                                      96
Tomato paste
                                     0.01
                                   100, 100
                                      100

                                     0.10
                            92, 118, 92, 86, 98, 91
                                 96 +- 14 (15)

                                      10
                                98, 84, 111, 87
                                 95 +- 12 (13)
Tomato wet pomace
                                     0.01
                                    120, 90
                                      105

                                     0.10
                                100, 77, 79, 93
                                 87 +- 11 (13)

                                      5.0
                                    85, 87
                                      86
Tomato dry pomace
                                     0.01
                                    80, 100
                                      90

                                     0.10
                                76, 85, 79, 75
                                79 +- 4.5 (5.7)
                                       
                                      20
                                    99, 100
                                      100
* Recoveries in bold and red are outside the acceptable ranges of (1) 60-120% for fortification levels of <= 0.01 ppm; (2) 70-120% for > 0.01 ppm to <= 0.10 ppm; (3) 70-110% for > 0.1 ppm. Relative standard deviations in bold and red are greater than the acceptable value of (1) 30% for fortification levels of <= 0.01 ppm; (2) 20% for > 0.01 ppm to <= 0.10 ppm; (3) 15% for > 0.1 ppm <= 1.0 ppm; (4) 10% > 1 ppm, as per OECD Guidance Document on Pesticide Residue Analytical Methods [ENV/JM/MONO(2007)17].

All the processed samples except tomato dry pomace were stored frozen 30 days or less from harvest to processing to analysis while tomato dry pomace was stored for a maximum of 83 days from harvest to processing to analysis (Table B.7.7.3.1-4). The available freezer storage stability data indicate that residues of fluensulfone (MCW-2) and metabolite M-3627 were stable when stored frozen between -12°C and -20°C in tomato RAC for up to 469 days, and in tomato paste and purée for up to 181 days. Thus, the storage intervals of the tomato RAC and processed commodities are covered by the demonstrated storage intervals.

Table B.7.7.3.1-4.  Summary of Storage Conditions.
                                    Matrix
                               (RAC or Extract)
                           Storage Temperature (°C)
                            Actual Storage Duration
                                    (days)
               Interval of Demonstrated Storage Stability (days)
                                  Tomato RAC
                                      -20
                                       2
                                      469
                                 Tomato juice
                                       
                                     27-28
                              181 (paste, purée)
                                 Tomato purée
                                       
                                     22-26
                                       
                                 Tomato paste
                                       
                                     25-30
                                       
                               Tomato wet pomace
                                       
                                     25-26
                                       
                               Tomato dry pomace
                                       
                                     82-83
                                       

Residues of fluensulfone (MCW-2) and metabolite M-3627, found in the various tomato samples, and their respective processing factors are given in Tables B.7.7.3.1-5.1 and B.7.7.3.1-5.2.
The residue levels were reported using both the quantitation and confirmation ion transitions. The data are in agreement. However, only the data obtained using the quantitation ion transitions for fluensulfone and M-3627 are reported herein.

The experimental processing factors of fluensulfone and M-3627 are less than the theoretical concentration factors (based on water loss or separation into components) for tomato juice and purée (1.4-fold) and tomato paste (5.5-fold), and the maximum observed (experimental) concentration factor for tomato dry pomace (80-fold) (DIR98-02; Section 10  -  Processed Food/Feed; Appendix A; Tables 2-4).

Table B.7.7.3.1-5.  Residue Data from Tomato Processing Study with Fluensulfone.
Commodity
                                Residues1 (ppm)
                              Processing Factors

                                       
                                     MCW-2
                                    M-3627
                                     MCW-2
                                    M-3627
Tomato (RAC)
                                       
                               <0.01; <0.01
                                 2.196; 2.145
                                      ---
                                      ---

                                     Mean
                                   <0.01
                                     2.17
                                       
                                       
Tomato Juice
                                       
                                   <0.01
                                  1.56; 2.06
                                       1
                                     0.83

                                     Mean
                                      ---
                                     1.81
                                       
                                       
Tomato Purée
                                       
                                   <0.01
                                  3.296; 2.71
                                       1
                                     1.38

                                     Mean
                                      ---
                                     3.00
                                       
                                       
Tomato Paste
                                       
                                   <0.10
                              8.765; 7.374; 6.917
                                      12
                                     3.54

                                    Median
                                      ---
                                     7.69
                                       
                                       
Tomato Wet Pomace
                                       
                                   <0.10
                                  1.54; 1.309
                                      12
                                     0.66

                                     Mean
                                      ---
                                     1.42
                                       
                                       
Tomato Dry Pomace
                                       
                                   <0.10
                                 15.51; 13.013
                                      12
                                     6.57

                                     Mean
                                      ---
                                     14.3
                                       
                                       
[1] If residues were < LOQ, they were accounted as 0.01 ppm (tomato RAC, juice, purée) or 0.10 ppm (tomato paste, wet and dry pomace) in the calculations. [2] The LOQs for fluensulfone in tomato RAC, and tomato paste, dry and wet pomace differ due to the nature of the matrix (0.01 ppm vs 0.10 ppm). However, as residues of fluensulfone were not quantifiable in any tomato matrix, a processing factor of 1 was assigned to tomato paste, wet and dry pomace.

III.  CONCLUSIONS

The tomato processing study is considered scientifically acceptable. A comparison of the residues in tomato fruit with those in each processed tomato fraction indicated that residues of fluensulfone do not concentrate in any of the other processed commodities of tomato. Residues of M-3627 concentrate in tomato purée, tomato paste and tomato dry pomace but do not concentrate in any other tomato processed commodities. Adequate storage stability data are available to support sample storage durations and conditions.

REFERENCES

PMRA # 2448366, Annex B.5.2 (OECD), Analytical methods (residue) for plants, plant products, foodstuffs of plant and animal origin, feedingstuffs, 26 pages.

PMRA # 2448367, Annex B.7 (OECD), Residue Data, 115 pages.