Document ID: EPA-HQ-OPP-2011-0360-0010
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2013-06-12T04:00Z

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

MEMORANDUM

Date:	March 25, 2011

SUBJECT:	Tetrachlorvinphos.  Response to Comment on Storage Stability Residue Data Deficiencies.  
            
PC Code:  083701/083702
DP Barcodes:  D385359 & D386954
Decision No.:  359967
Registration No.:  Not Applicable
Petition No.: Not Applicable
Regulatory Action: Reregistration Follow-up
Risk Assessment Type: Not Applicable
Case No.: 0321
TXR No.: Not Applicable
CAS No.: 22248-79-9
MRID Nos.: 486378101 48319001
40 CFR: 180.252

FROM:	Christine L. Olinger, Chemist
		Risk Assessment Branch VII
		Health Effects Division (7509P)
		Office of Pesticide Programs

THRU:	Donna S. Davis, Chemist 
		Michael S. Metzger, Chief,
		Risk Assessment Branch VII
		Health Effects Division (7509P)
		Office of Pesticide Programs

TO:	James Parker, CRM
		Risk Management and Implementation Branch II
		Pesticide Re-evaluation Division (7508P)
		Office of Pesticide Programs

In response to deficiencies noted in a review of livestock magnitude of residue studies (C. Olinger; 10/7/10; D320848, D320858, D320859, and D381350) SRA International, on behalf of KMG Bernuth, has submitted data relating to the storage stability of tetrachlorvinphos residues in livestock tissues, eggs, and milk.  The Pesticide Re-evaluation Division (PRD) has requested HED review of this information to satisfy the outstanding data deficiencies.

CONCLUSIONS

No additional storage stability data are needed to support the use of tetrachlorvinphos on poultry.  The magnitude of residue study on poultry is adequate and there are no outstanding deficiencies with this study.  The magnitude of residue requirement is considered satisfied for poultry.

No storage stability data are available for livestock commodities.  The samples from the ruminant magnitude of residue study that reflect the maximum current use pattern were stored less than thirty days, so storage stability data are not needed.  Provided the registrant does not make changes to the current use pattern/application rates, no additional storage stability data are needed and the requirement for a magnitude of residue study for ruminants is satisfied.  Should the registrant wish to revise the existing use patterns such that the magnitude of residue data from other treatment groups would be used for tolerance and/or risk assessment, additional storage stability data demonstrating stability of tetrachlorvinphos and its metabolites for at least two months would be required. 

DETAILED CONSIDERATIONS

HED identified the following deficiencies regarding the storage stability data as well as detailed information on storage intervals in the review of poultry and ruminant magnitude of residue studies (C. Olinger; 10/7/10; D320848, D320858, D320859, and D381350).  

   * New storage stability studies should be conducted with quantifiable (i.e., fortified) residues of all analytes in all cattle and poultry matrices.  In addition, the registrant needs to submit information pertaining to dates of treatment, collection, extraction, and analysis to verify the maximum storage intervals of all samples collected from both the cattle and poultry studies.
   * Although a companion storage stability study was included in support of the cattle study, the submitted data were deemed inadequate because of the study design.  Selected samples of various matrices were re-assayed after the initial analysis.  Considerable degradation may have occurred prior to the initial analysis of storage stability samples.  Many of the matrices did not have quantifiable residues of one or more of the analytes at the time of initial analysis, so potential degradation upon storage cannot be accurately assessed.  

SRA International, on behalf of KMG Bernuth, has submitted additional information on the storage intervals for these studies, which is discussed below.

Data Submitted to Support MRID 47589301 Poultry Magnitude of Residue Study
The registrant has provided information on the storage intervals for samples from the original poultry study.  SRA submitted storage interval information in two volumes, MRID Nos. 486378101 and 48319001.  A summary of the storage intervals is presented in Table 1 below.

Table 1.  Storage Intervals for Samples from Tetrachlorvinphos Poultry Magnitude of Residue Study [1]
                                    Matrix
                                  Group(s) 2
                               Time Interval [3]
                               No. Days Storage
                                    Matrix
                                  Group(s) 2
                               Time Interval [3]
                               No. Days Storage
                                     Eggs
                                      1-4
                                      -7
                                      1-3
                                     Eggs
                                      1-4
                                      78
                                      11
                                     Eggs
                                      1-4
                                      -1
                                      1-2
                                     Eggs
                                      1-4
                                      82
                                       9
                                     Eggs
                                      1-4
                                       1
                                      2-3
                                     Eggs
                                      1-4
                                      84
                                     12-20
                                     Eggs
                                      1-4
                                       3
                                      2-3
                                     Eggs
                                      1-4
                                      86
                                      18
                                     Eggs
                                      1-4
                                       5
                                      2-3
                                     Eggs
                                      1-4
                                      88
                                      16
                                     Eggs
                                      1-4
                                       8
                                      1-3
                                     Eggs
                                      1-4
                                      91
                                      13
                                     Eggs
                                      1-4
                                      12
                                       2
                                     Eggs
                                      1-4
                                      95
                                      15
                                     Eggs
                                      1-4
                                      15
                                      2-4
                                     Eggs
                                      1-4
                                      98
                                      12
                                     Eggs
                                      1-4
                                      17
                                      2-4
                                     Eggs
                                      1-4
                                      101
                                       9
                                     Eggs
                                      1-4
                                      19
                                      2-4
                                     Eggs
                                      1-4
                                      105
                                       5
                                     Eggs
                                      1-4
                                      22
                                      1-4
                                    Muscle
                                      1-4
                                       0
                                      14
                                     Eggs
                                      1-4
                                      26
                                       2
                                    Muscle
                                      3R
                                       7
                                      22
                                     Eggs
                                      1-4
                                      29
                                      2-4
                                    Muscle
                                      3R
                                      14
                                      15
                                     Eggs
                                      1-4
                                      31
                                      3-4
                                    Muscle
                                      3R
                                      21
                                       8
                                     Eggs
                                      1-4
                                      33
                                      3-4
                                     Liver
                                      1-4
                                       0
                                      18
                                     Eggs
                                      1-4
                                      36
                                      1-4
                                     Liver
                                      3R
                                       7
                                      22
                                     Eggs
                                      1-4
                                      40
                                       2
                                     Liver
                                      3R
                                      14
                                      15
                                     Eggs
                                      1-4
                                      43
                                      2-6
                                     Liver
                                      3R
                                      21
                                       8
                                     Eggs
                                      1-4
                                      45
                                     3-10
                                    Kidney
                                      1-4
                                       0
                                      27
                                     Eggs
                                      1-4
                                      47
                                     3-10
                                    Kidney
                                      3R
                                       7
                                      22
                                     Eggs
                                      1-4
                                      50
                                     1-19
                                    Kidney
                                      3R
                                      14
                                      15
                                     Eggs
                                      1-4
                                      54
                                     2-17
                                    Kidney
                                      3R
                                      21
                                       8
                                     Eggs
                                      1-4
                                      57
                                      4-6
                                   Skin/Fat
                                      1-4
                                       0
                                      20
                                     Eggs
                                      1-4
                                      59
                                     4-10
                                   Skin/Fat
                                      3R
                                       7
                                      26
                                     Eggs
                                      1-4
                                      61
                                     6-10
                                   Skin/Fat
                                      3R
                                      14
                                      19
                                     Eggs
                                      1-4
                                      64
                                     11-19
                                   Skin/Fat
                                      3R
                                      21
                                      12
                                     Eggs
                                      1-4
                                      68
                                     9-17
                                 Abdominal Fat
                                      1-4
                                       0
                                      25
                                     Eggs
                                      1-4
                                      70
                                      12
                                 Abdominal Fat
                                      3R
                                       7
                                      26
                                     Eggs
                                      1-4
                                      71
                                     4-11
                                 Abdominal Fat
                                      3R
                                      14
                                      19
                                     Eggs
                                      1-4
                                      73
                                       4
                                 Abdominal Fat
                                      3R
                                      21
                                      12
                                     Eggs
                                      1-4
                                      75
                                       6
                                       
[1] MRID No. for poultry magnitude of residue study is MRID 47589301; storage intervals are reported in MRID Nos. 48378101 48319001.
2 Groups are described in MRID 47589301.
3 Time intervals for eggs are days after study initiation.  Negative numbers refer to number of days prior to first application.  Time intervals for tissues refer to days after sacrifice.

The Agency generally requires storage stability data when samples from magnitude of residue studies are stored for more than 30 days.  Since all samples were stored for less than 30 days, no storage stability data are needed to support the poultry magnitude of residue study.  There are no outstanding deficiencies for the poultry magnitude of residue study and the magnitude of residue requirement for poultry has been satisfied.

Data Submitted to Support MRID 47193001 Ruminant Magnitude of Residue Study
The registrant provided storage intervals for the samples from the original ruminant study.  In addition, the registrant submitted an inadequate storage stability study to support the ruminant magnitude of residue study.  In response to the deficiencies identified in the October 2010 review the registrant submitted detailed information on storage intervals from the magnitude of residue study (MRID Number pending).  

The magnitude of residue study included five different treatment groups, which are described in Table 2 below.  Treatment group 4 represents the current maximum label rate for both the feed-through and dermal treatment uses.  A summary of the storage intervals from treatment group 4 is presented in Table 3 below.

Table 2.  Summary of Treatment Groups from Ruminant Magnitude of Residue Study
                                     Group
                             Treatment Description
                                       1
Control
                                       2
Nominal 1x rate Oral Only
                                       3
Nominal 1x rate Oral; Nominal 0.5x rate Dermal
                                       4
Nominal 1x rate Oral; Nominal 1x rate Dermal
                                       5
Nominal 3x rate Oral; Nominal 0.5x rate Dermal

Table 3.  Storage Intervals for Samples from Tetrachlorvinphos Ruminant Magnitude of Residue Study (Group 4 Only)[1]
                                    Matrix
                                   Cow No.2
                             Time Interval (Days)3
                               No. Days Storage
                                     Milk
                                     8-10
                                      -7
                                       9
                                     Milk
                                     8-10
                                      -1
                                       3
                                     Milk
                                     8-10
                                       1
                                       6
                                     Milk
                                     8-10
                                       2
                                       7
                                     Milk
                                     8-10
                                       4
                                      16
                                     Milk
                                     8-10
                                       7
                                      26
                                     Milk
                                     8-10
                                      10
                                      20
                                     Milk
                                     8-10
                                      14
                                       9
                                     Milk
                                     8-10
                                      17
                                       8
                                     Milk
                                     8-10
                                      21
                                       7
                                     Milk
                                     8-10
                                      24
                                      11
                                     Milk
                                     8-10
                                      28
                                      14
                                   Skim Milk
                                     8-10
                                      14
                                      25
                                   Skim Milk
                                     8-10
                                      29
                                      15
                                     Cream
                                     8-10
                                      14
                                      23
                                     Cream
                                     8-10
                                      29
                                      22
                                    Muscle
                                       8
                                       0
                                   23 (63)4
                                    Muscle
                                       9
                                       0
                                    22 (62)
                                    Muscle
                                      10
                                       0
                                    21 (61)
                                Peritoneal Fat
                                       8
                                       0
                                      28
                                Peritoneal Fat
                                       9
                                       0
                                      27
                                Peritoneal Fat
                                      10
                                       0
                                      26
                               Subcutaneous Fat
                                       8
                                       0
                                    23 (63)
                               Subcutaneous Fat
                                       9
                                       0
                                    22 (62)
                               Subcutaneous Fat
                                      10
                                       0
                                    21 (61)
                                    Kidney
                                       8
                                       0
                                      31
                                    Kidney
                                       9
                                       0
                                      30
                                    Kidney
                                      10
                                       0
                                      29
                                     Liver
                                       8
                                       0
                                      34
                                     Liver
                                       9
                                       0
                                      33
                                     Liver
                                      10
                                       0
                                      32
[1] MRID No. for ruminant magnitude of residue study is MRID 47193001; storage intervals are reported in email sent 3/23/11; MRID number pending.
2 Cow identification numbers are described in MRID 47193001.
3 Time intervals for milk are days after study initiation.  Negative numbers refer to number of days prior to first application.  Time interval for tissues refers to days after sacrifice.
4 Number of days storage prior to TCPEdiol analysis (where different from other analytes) is shown in parentheses

The samples from treatment group 4 represent the application rates and retreatment intervals that represent current product labels.  Almost all samples were analyzed within 30 days; all were analyzed within 34 days with the exception of the analyses for one metabolite, TCPEdiol, in muscle and subcutaneous fat.  HED does not need additional storage stability data to support this treatment group since samples were analyzed within 30 days or slightly later.  Although some samples were analyzed for one metabolite after two months of storage, most samples were analyzed within an appropriate interval for this metabolite and residues were non-detectable.  Since significant exposure is not expected, a storage stability study for this metabolite will not be required to support treatment group 4.

However, samples from other treatment groups were stored up to two months.  The data from these groups have not been used directly in tolerance and/or risk assessment, but have only been used for risk characterization.  Should the registrant amend use directions such that these data would be needed for tolerance assessment, storage stability data would be required.