![](media/image1.png){width="0.7993055555555556in" height="0.8in"}

**UNITED STATES ENVIRONMENTAL PROTECTION AGENCY**

WASHINGTON, D.C. 20460

OFFICE OF

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

**[MEMORANDUM]{.underline}**

Date: 3-JAN-08

Subject: Spirodiclofen. Petition for Registration for Use on Hops.
Summary of Analytical Chemistry and Residue Data. Petition Number
7E7204.

  ------------- --------------- ------------- ---------------------------
  DP#:          346760          Decision      378132
                                Number:       

  PC Code:      124871          MRID No:      47105301

  40 CFR 180    608                           

  Chemical      tetronic acid                 
  Class:        insecticide                   
  ------------- --------------- ------------- ---------------------------

From: Mohsen Sahafeyan, Chemist

Registration Action Branch 1 (RAB1)

Health Effects Division (HED, 7509P)

Through: George F. Kramer, Ph.D., Senior Chemist

RAB1/HED (7509P)

To: Susan Stanton, Risk Manager Reviewer, RD

Daniel Rosenblatt, Risk Manager, RD

This document was originally prepared under contract by Dynamac
Corporation (1910 Sedwick Road, Building 100, Suite B, Durham, NC 27713;
submitted 09/12/2007). The document has been reviewed by HED and revised
to reflect current Office of Pesticide Programs (OPP) policies.

**Executive Summary**

Spirodiclofen is a tetronic acid acaricide registered in the U.S. for
use on fruit and nut crops for the control of mites and other damaging
insects. Permanent tolerances are established for spirodiclofen
(3-(2,4-dichlorophenyl)-2-oxo-1-oxaspiro\[4,5\]dec-3-en-4-yl
2,2-dimethylbutanoate) on grapes, citrus fruits, pome fruits, stone
fruits and the tree nut crop groups at 0.10-2.0 ppm, and on processed
commodities from these crops at 0.60-20 ppm \[40 CFR §180.608(a)\].
Tolerances are also established for the combined residues of
spirodiclofen and its free enol metabolite, BAJ 2510
(3-(2,4-dichlorophenyl)-4-hydroxy-1-oxaspiro\[4,5\]dec-3-en-2-one),
in/on livestock commodities at 0.01-0.10 ppm.

Spirodiclofen is currently registered to Bayer CropScience as a 2.0
lb/gal flowable concentrate formulation (FlC, Envidor^®^ 2 SC Miticide,
EPA Reg. No. 264-831) for use as a single broadcast foliar application
to grapes and fruit and nut trees at rates of 0.19-0.53 lb ai/A with
preharvest intervals (PHIs) of 14 days for grapes and 7 days for all
other crops. Interregional Research Project No. 4 (IR-4) is proposing
the use of spirodiclofen (FlC) on hops as a single foliar-directed
application at 0.28-0.39 lb ai/A with a PHI of 14 days. Applications are
restricted to the use of ground equipment in a minimum of 50 gal/A. In
conjunction with this use, IR-4 is proposing the following permanent
tolerance for spirodiclofen.

> Hop, dried cones 30 ppm

The nature of spirodiclofen residues in fruit and nut crops is
adequately understood based on the available apple, orange, lemon,
grapefruit and grape metabolism studies and the results of newly
submitted and reviewed apple and grape processing studies (T. Bloem,
D341847, 10-OCT-07). HED concludes the following: **(1)** citrus fruit,
pome fruit, stone fruit, and tree nut - the residue of concern for risk
assessment and tolerance enforcement is spirodiclofen *per se* and
**(2)** grape - the residue of concern for tolerance enforcement is
spirodiclofen *per se* and residues of concern for risk assessment are
spirodiclofen and BAJ 2510. Since the grape processing study
demonstrated degradation of spirodiclofen to BAJ 2510, HED is requesting
that the petitioner submit an orange processing study monitoring for
residues of spirodiclofen, BAJ 2510, 3-OH-enol, and 4-OH-enol. Pending
the submission of these data, human-health risk assessments should
assume default processing factors for all processed commodities
excluding the processed commodities for apple and grape. For the current
petition on hops, no additional plant metabolism data are required and
the residue of concern is spirodiclofen *per se*.

As the proposed use on hops does not include any regulated livestock
feedstuffs, issues pertaining to livestock metabolism, analytical
methods and storage stability data for animal commodities, and residues
in livestock commodities are not relevant to the current petition.

An adequate liquid chromatography/mass spectrometry/mass spectrometry
(LC/MS/MS) method (Bayer Report No. 109351) has been proposed for
enforcing tolerances of spirodiclofen *per se* in/on plant commodities.
For this method, residues in most commodities are extracted with
acetonitrile (ACN):water, acidified, and cleaned up using ENVI-carb or
NH~2~ cartridges. For nutmeats, residues are extracted sequentially with
acidic ACN:water and acetone:dichloromethane (DCM), and residues in the
combined extracts are partitioned into the organic fraction and cleaned
up by solvent partitioning. Purified residues are determined by LC/MS/MS
using the m/z 411→ 313 and 99 →71 ion transitions and deuterated
spirodiclofen as an internal standard. The validated limit of
quantitation (LOQ) is 0.01 ppm for spirodiclofen in/on citrus fruits,
stone fruits, pome fruits, nutmeats and almond hulls. This method has
undergone a successful independent laboratory validation (ILV) trial,
and has been reviewed by the Analytical Chemistry Branch (ACB). ACB
determined that the method would be adequate for tolerance enforcement
provided that a revised copy of the method was submitted incorporating
the changes and clarifications recommended by ACB (D308566, E. Kolbe,
5/18/05).

Samples of dried hop cones from the U.S. field trials were analyzed for
residues of spirodiclofen using a LC/MS/MS method that was derived from
the proposed enforcement method. Residues were extracted sequentially
with acidified ACN:water and acetone:DCM (1:2, v/v), combining the
extracts. Residue in the resulting organic fraction were then cleaned up
using NH~2~ and Florisil solid-phase extraction (SPE) cartridges and
analyzed by LC/MS/MS using the m/z 411→313 ion transition and external
standards. The method was adequately validated in conjunction with the
analysis of field trial samples. The lowest level of method validation
(LLMV) was 0.05 ppm, and the statistically calculated LOQ was 0.05 ppm
and the calculated limit of detection (LOD) was 0.02 ppm.

In conjunction with the field trials, adequate storage stability data
were submitted indicating that spirodiclofen is stable at -20ºC in dried
hops for up to 15.3 months of storage. These data adequately support the
maximum frozen storage interval (15.9 months) from the U.S. field
trials.

Adequate field trial data on hops are available from 3 trials conducted
in the U.S. in Zones 11 and 12 during 2004. In each trial, spirodiclofen
(2 lb/gal FlC) was applied to hops as a single foliar-directed
application at 0.387-0.412 lb ai/A (1x rate) during cone development and
maturation. Applications were made using ground equipment at volumes of
43-175 gal/A, and did not include the use of any spray adjuvants. The
resulting residues of spirodiclofen were 1.97-13.1 ppm in/on 6 samples
of dried hop cones harvested 21 days after treatment (DAT) and 2.85-5.72
ppm in/on 6 samples harvested at 28 DAT. Average spirodiclofen residues
were 6.42 and 3.99 ppm at 21 and 28 DAT, respectively.

The petitioner also submitted supplemental hops field trial data from 8
trials conducted in Germany during 2003 and 2004. In each of these
trials, spirodiclofen (240 g/L FlC) was applied to hops as a single
foliar application at 0.34-0.43 kg ai/ha (0.30-0.38 lb ai/A, \~1x
proposed U.S. rate) during cone development and maturation (BBCH 71-87),
using ground equipment at volumes of 2100-3547 L/ha (225-380 gal/A).
Residues of spirodiclofen were 3.9-24.0 ppm in/on 8 samples of dried
hops harvested at the proposed PHI of 14 days. Residues were 3.9-10.9
ppm in/on 4 samples by 21 DAT and 3.1-10.0 ppm in/on 6 samples by 28
DAT. Average residues were 11.6, 7.23, and 7.07 ppm at 14, 21 and 28
DAT, respectively, indicating that residues declined slowly from 14-28
DAT.

As there are no regulated processed commodities associated with hops, no
processing studies are required for this petition. Data pertaining to
residues in rotational crops are also not required as hops are a
perennial crop.

Number range CHAPTER**Regulatory Recommendations and Residue Chemistry
Deficiencies**

No deficiencies were noted in the subject petition that would preclude
establishing a permanent tolerance for spirodiclofen residues on dried
hops. Although adequate U.S. field trial data are available supporting a
minimum PHI of either 21 or 28 days, IR-4 is requesting a 14-day PHI for
hops in order to harmonize the U.S. and German use patterns. In
addition, IR-4 is requesting a 30-ppm tolerance on dried hop cones to
harmonize with the established German maximum residue limit (MRL).
Considering similarity in climatic conditions between the hops growing
regions in the U.S. and Germany and the German MRL of 30 ppm being
higher than the maximum residue values from the other two submitted
field trial data sets having similar application rates, but longer PHIs
(21 and 28 day), HED recommends establishing a permanent tolerance for
spirodiclofen on hops at 30 ppm to promote free trade between NAFTA and
non-NAFTA countries. A human-health risk assessment for spirodiclofen is
forthcoming.

**Background**

Spirodiclofen is a member of a new class of chemicals called tetronic
acid insecticides (MOA Group 23). These compounds are acaricides that
also have insecticidal activity at higher doses. Their mode of action is
through the inhibition of lipid biosynthesis, which inhibits the younger
insect's ability to develop through the various growth stages and the
ability of adults to reproduce.

Interregional Research Project 4 has submitted a petition (PP#7E7204)
proposing the use of spirodiclofen on hops for control of two-spotted
spider mites. Although IR-4 has conducted the required hops field trials
in the U.S., they proposed harmonizing the U.S. use pattern and
tolerance with the existing use pattern and tolerance in Germany. This
proposal was reviewed by chemistry science advisory council (ChemSAC)
(meeting of 2/28/07).

  ---------------------------------------------------------------------------------
  **Table 1.          
  Spirodiclofen       
  Compound            
  Nomenclature.**     
  ------------------- -------------------------------------------------------------
  Compound            ![](media/image2.wmf){width="2.0590277777777777in"
                      height="1.4986111111111111in"}

  Common name         Spirodiclofen

  Company             BAJ2740
  experimental name   

  IUPAC name          3-(2,4-dichlorophenyl)-2-oxo-1-oxaspiro\[4,5\]dec-3-en-4-yl
                      2,2-dimethylbutyrate

  CAS name            3-(2,4-dichlorophenyl)-2-oxo-1-oxaspiro\[4,5\]dec-3-en-4-yl
                      2,2-dimethylbutanoate

  CAS registry number 148477-71-8

  End-use product     2 lb/gal FlC (ENVIDOR^®^ 2 SC Miticide; EPA Reg. No. 264-831)
  (EP)                
  ---------------------------------------------------------------------------------

+------------------------+------------+------------+-----------------+
| **Table 2.             |            |            |                 |
| Physicochemical        |            |            |                 |
| Properties of          |            |            |                 |
| Spirodiclofen.**       |            |            |                 |
+========================+============+============+=================+
| Parameter              | Value      |            | Reference       |
+------------------------+------------+------------+-----------------+
| Melting point          | 94.8ºC     |            | DP# 315459, S.  |
|                        |            |            | Mathur, 4/20/05 |
+------------------------+------------+------------+-----------------+
| pH                     | 4.2        |            |                 |
+------------------------+------------+------------+-----------------+
| Density (20ºC)         | 1.29       |            |                 |
|                        | g/cm^3^    |            |                 |
+------------------------+------------+------------+-----------------+
| Water solubility (20ºC | 50μg/L     |            |                 |
| at pH 4)               |            |            |                 |
+------------------------+------------+------------+-----------------+
| Solvent solubility     | n-heptane  | 20         |                 |
| (g/L at 20°C)          |            |            |                 |
|                        | xylene     | \>250      |                 |
|                        |            |            |                 |
|                        | dichl      | \>250      |                 |
|                        | oromethane |            |                 |
|                        |            | 47         |                 |
|                        | 2-propanol |            |                 |
|                        |            | 44         |                 |
|                        | 1-octanol  |            |                 |
|                        |            | 24         |                 |
|                        | po         |            |                 |
|                        | lyethylene | \>250      |                 |
|                        | glycol     |            |                 |
|                        |            | \>250      |                 |
|                        | acetone    |            |                 |
|                        |            | \>250      |                 |
|                        | ethyl      |            |                 |
|                        | acetate    | 75         |                 |
|                        |            |            |                 |
|                        | ac         |            |                 |
|                        | etonitrile |            |                 |
|                        |            |            |                 |
|                        | dimethy    |            |                 |
|                        | lsulfoxide |            |                 |
+------------------------+------------+------------+-----------------+
| Vapor pressure (20ºC)  | 3 x 10^-7^ |            |                 |
|                        | Pa         |            |                 |
+------------------------+------------+------------+-----------------+
| Dissociation constant, | Not        |            |                 |
| pK~a~                  | de         |            |                 |
|                        | terminable |            |                 |
|                        | due to the |            |                 |
|                        | i          |            |                 |
|                        | nstability |            |                 |
|                        | in aqueous |            |                 |
|                        | solutions  |            |                 |
|                        | at \>pH 4  |            |                 |
+------------------------+------------+------------+-----------------+
| Octanol/water          | 5.83       |            |                 |
| partition coefficient, |            |            |                 |
| Log(K~OW~) at pH 4 and |            |            |                 |
| 20ºC                   |            |            |                 |
+------------------------+------------+------------+-----------------+
| UV/visible absorption  | λmax = 201 |            |                 |
| spectrum               | nm: Not    |            |                 |
|                        | expected   |            |                 |
|                        | to absorb  |            |                 |
|                        | UV at λ    |            |                 |
|                        | \>350 nm   |            |                 |
+------------------------+------------+------------+-----------------+

**860.1200 Directions for Use**

A 2 lb/gal FlC formulation of spirodiclofen (ENVIDOR^®^ 2 SC Miticide;
EPA Reg. No. 264-831) is currently registered to Bayer for use as
broadcast foliar applications to citrus fruits, pome fruits, stone
fruits, grapes, and tree nuts. IR-4 is proposing the use of this 2
lb/gal FlC on hops for the control of two-spotted spider mites
(*Tetranychus urticae*). An example label was provided, and the proposed
use directions are summarized below in Table 3.

+--------------+-------+------+-------+---------+----+----------------+
| **Table 3.   |       |      |       |         |    |                |
| Summary of   |       |      |       |         |    |                |
| Directions   |       |      |       |         |    |                |
| for Use of   |       |      |       |         |    |                |
| Spir         |       |      |       |         |    |                |
| odiclofen.** |       |      |       |         |    |                |
+==============+=======+======+=======+=========+====+================+
| Applic.      | F     | App  | Max.  | Max.    | P  | Use Directions |
| Timing,      | ormul | lic. | No.   | S       | HI | and            |
| Type, and    | ation | Rate | Ap    | easonal |    | Limitations    |
| Equip.       |       |      | plic. | Applic. | (d | ^1^            |
|              | \[EPA | (lb  | per   | Rate    | ay |                |
|              | Reg.  | a    | S     |         | s) |                |
|              | No.\] | i/A) | eason | (lb     |    |                |
|              |       |      |       | ai/A)   |    |                |
+--------------+-------+------+-------+---------+----+----------------+
| **Hops**     |       |      |       |         |    |                |
+--------------+-------+------+-------+---------+----+----------------+
| Single       | 2     | 0    | 1     | 0.39    | 14 | Apply in a     |
| foliar       | l     | .28- |       |         |    | minimum of 50  |
| application  | b/gal | 0.39 |       |         |    | gal/A using    |
| at the early | FlC   |      |       |         |    | conventional   |
| stages of    |       |      |       |         |    | ground         |
| mite         | \     |      |       |         |    | airblast spray |
| infestation; | [264- |      |       |         |    |                |
| Ground       | 831\] |      |       |         |    |                |
| equipment    |       |      |       |         |    |                |
+--------------+-------+------+-------+---------+----+----------------+

^1^ Do not apply through any type of irrigation equipment or using
aerial equipment.

*Conclusions*. The label directions are adequate to allow evaluation of
the residue data relative to the proposed use. Although samples from the
U.S. field trials were collected at 21 and 28 DAT, IR-4 is requesting a
14-day PHI in order to harmonize the U.S. and German use patterns. In
addition to the U.S. field trials, IR-4 has provided summaries from
eight field trials conducted on hops in Germany at 0.30-0.38 lb ai/A
(\~1x rate) with harvest intervals of 14, 21 and 28 DAT. As residue
levels in/on dried hops were similar between the U.S. and German field
trials at 21 and 28 DAT, HED will accept the use of the 14-DAT residue
data from Germany to support the proposed use directions on hops in the
U.S.

**860.1300 Nature of the Residue -- Plants**

PP#2F6469, DP# D285249, T. Bloem, 4/18/05

The nature of spirodiclofen residues in fruit and nut crops is
adequately understood based on the available apple, orange, lemon,
grapefruit and grape metabolism studies and the results of newly
submitted and reviewed apple and grape processing studies (T. Bloem,
D341847, 10-OCT-07). These studies indicate that the metabolism of
spirodiclofen in fruit crops involves the following steps: cleavage of
the ester linkage to form the free enol metabolite (BAJ 2510);
hydroxylation of BAJ 2510 on the cyclohexyl ring to form 3-OH-enol and
4-OH-enol metabolites; and cleavage of the enol ring structure to form
2,4-dichloro-mandelic acid-cyclohexylester, which undergoes
hydroxylation/conjugation and further degradation to yield
2,4-dichloro-mandelic acid (free and conjugated). The recently submitted
grape processing study indicates that residues of spirodiclofen degrade
to BAJ 2510 during processing of grapes to juice, juice concentrate,
jelly and raisin.

The majority of the residues in/on fruits in each study were comprised
of surface residues, with nearly all surface residues being comprised of
parent compound. Overall spirodiclofen accounted for 34-99% of the total
radioactive residues (TRR). Minor amounts of the following compounds
were also identified: BAJ 2510 (≤2% TRR), 3-OH-enol (≤3% TRR), 4-OH-enol
(\<1% TRR), 2,4-dichloro-mandelic acid-cyclohexylester compounds (free
and conjugated; ≤9% TRR), and 2,4-dichloro-mandelic acid (free and
conjugate; ≤12% TRR).

HED concludes the following: **(1)** citrus fruit, pome fruit, stone
fruit, and tree nut - the residue of concern for risk assessment and
tolerance enforcement is spirodiclofen *per se* and **(2)** grape - the
residue of concern for tolerance enforcement is spirodiclofen *per se*
and residues of concern for risk assessment are spirodiclofen and BAJ
2510 (T. Bloem, D341847, 10-OCT-07). HED has requested data
demonstrating the stability of BAJ 2510, 3-OH-enol, and 4-OH-enol in/on
grape juice and raisins when stored frozen for 70 days and submission of
an orange processing study monitoring for residues of spirodiclofen, BAJ
2510, 3-OH-enol, and 4-OH-enol. Pending the submission of these data,
human-health risk assessments should assume default processing factors
for all processed commodities excluding the processed commodities for
apple and grape. For the current petition on hops, no additional plant
metabolism data are required and the residue of concern is
spirodiclofen, *per se*.

*Conclusions*. As hops are a minor crop, the available metabolism data
will be used to support the use on hops. However, additional plant
metabolism data may be required in the future for crop uses other than
fruits. For purposes of this tolerance petition, HED concludes that the
residue of concern in/on dried hops consists of spirodiclofen *per se.*

**860.1300 Nature of the Residue - Livestock**

As there are no livestock feedstuffs associated with hops, data
requirements for livestock metabolism are not relevant to this tolerance
petition.

**860.1340 Residue Analytical Methods**

PP#2F6469, DP# D285249, T. Bloem, 4/18/05

DP# 318055, T. Bloem, 6/1/05

[]{.mark}

*Enforcement method.* Bayer has proposed a LC/MS/MS method (Report No.
109351) for enforcing tolerances of spirodiclofen in/on plant
commodities. With the exception of nutmeats and oil, residues are
extracted with ACN:water (2:1), filtered, and acidified with HCl. For
nutmeats, residues are extracted sequentially with ACN:water (2:1,
acidified with 20% aqueous cysteine HCl) and acetone:DCM (1:2). The
filtrates are combined, and residues in the lower organic layer are
concentrated, reconstituted in hexane and partitioned into ACN.

With the exception of nutmeat and almond hull samples, residues are then
cleaned up using an ENVI-carb cartridge eluted with DCM. Residues from
hulls are cleaned using an NH~2~ cartridge eluted with ACN, and residues
from nutmeats are analyzed without further clean up. Purified residues
are determined by LC/MS/MS analysis with electrospray ionization in the
positive-ion single-reaction monitoring mode. The m/z 411→ 313 and 99
→71 ion transitions are monitored for spirodiclofen, and deuterated
spirodiclofen is used as an internal standard. The validated LOQ is 0.01
ppm for spirodiclofen in/on citrus fruits, stone fruits, pome fruits,
nutmeats and almond hulls.

Adequate validation data, a successful ILV trial, and radiovalidation
data are available for the proposed enforcement method. The method has
also been reviewed by ACB, without conducting a laboratory trial. ACB
determined that the method would be adequate for tolerance enforcement
provided that a revised copy of the method was submitted incorporating
the changes and clarifications recommended by ACB (D308566, E. Kolbe,
5/18/05).

*Data Collection Method.* Samples from the U.S. hops field trials were
analyzed for residues of spirodiclofen using a LC/MS/MS method, which
was derived from the proposed enforcement method. For samples of dried
hops, residues were extracted sequentially with acidified ACN:water
(2:1, v/v) and acetone:DCM (1:2, v/v). The filtrates were combined, and
residues were partitioned into the organic phase. Residues were then
cleaned up using a NH~2~ SPE cartridge eluted with acetone:DCM (1:2),
followed by a Florisil SPE cartridge eluted with 10% ethyl acetate in
hexane. Residues were then analyzed by LC/MS/MS using a reverse-phase
column (C~8~), a mobile phase gradient of water to methanol (each
containing 0.1% formic acid), and a MS/MS detector run in the positive
chemical ionization mode. Residues of spirodiclofen were detected and
quantified using the m/z 411→313 ion transition and external standards.
The LLMV was 0.05 ppm, and the statistically calculated LOQ and LOD were
0.05 ppm and 0.02 ppm, respectively. The above method was adequately
validated prior to and in conjunction with the analysis of field trial
samples.

[]{.mark}

*Conclusions*. The LC/MS/MS method used in the field trials is adequate
for determining residues of spirodiclofen in/on dried hops. Given the
similarity between the data collection method and the LC/MS/MS
enforcement method (nutmeats), the enforcement method will be adequate
for regulating residues in/on dried hops.

**860.1360 Multiresidue Methods**

Number range CHAPTER45696517.der, T. Bloem, 8/18/04

Spirodiclofen and BAJ 2510 were screened through the FDA MRM testing
protocols. As both compounds are not N-methylcarbamates, naturally
fluorescent, acids, phenols or substituted ureas, Protocols, A, B, and G
were not performed. Protocol C modules DG1 and DG10 (gas
chromatography/electron-capture detector, GC/ECD) gave acceptable
results for BAJ 2510 and spirodiclofen. Using fortified orange samples,
acceptable recoveries of spirodiclofen were attained through Protocols D
(80-103%) and E (54-77%). Using fortified ground beef samples,
unacceptable recoveries of spirodiclofen were attainted through protocol
F (16-30%). BAJ 2510 was not recovered through the Florisil clean-up
column, and therefore, gave unacceptable recoveries for Protocol D
(fortified orange samples) and F (fortified ground beef samples). Since
BAJ 2510 was not recovered through Protocol D, Protocol E was not
tested. These data have been forwarded to FDA for evaluation (DP#
D308565, T. Bloem, 9/29/04).

**860.1380 Storage Stability**

45696606.der2, T. Bloem, 9/22/04

Adequate data are available indicating that spirodiclofen is stable at
\<-15ºC for up to 13.3 months in peaches and grapes, 10 months in prunes
and almond hulls, and 7.6 months in raisins, dried apples, and fruit
juice concentrates (apple and grape). However, spirodiclofen residues
were shown to decline by 26% in almond nutmeats over 13.5 months of
storage.

In conjunction with the hops field trials, a storage stability study was
conducted using control samples of dried hop cones fortified with
spirodiclofen at 0.10 ppm. The fortified samples were stored under the
same conditions as the field trial samples. At the end of the analytical
phase of the study, the stored sample was analyzed in triplicate along
with a control sample and a freshly fortified sample. The average
corrected recovery from the stored samples was 102%, indicating that
spirodiclofen is stable in dried hops at -20ºC for up to 460 days (15.1
months).

In the hops field trials conducted in the U.S., samples of dried hops
were stored at -20ºC for 470-476 days (15.6 months) prior to analysis.

*Conclusions*. The submitted storage stability data on hops are adequate
and support the storage intervals and conditions incurred by the field
trial samples.

**860.1400 Water, Fish, and Irrigated Crops**

There are no registered uses that are relevant to this guideline topic.

**860.1460 Food Handling**

There are no registered uses that are relevant to this guideline topic.

**860.1480 Meat, Milk, Poultry, and Eggs**

As there are no livestock feedstuffs associated with the proposed use on
hops, data requirements pertaining to meat, milk, poultry, and eggs are
not relevant to this tolerance petition.

**860.1500 Crop Field Trials**

47105301.der (hops)

To support the use of spirodiclofen (FlC) on hops in the U.S., IR-4 has
submitted field data from three trials conducted in the U.S. during
2004. In Section G of the submitted petition, IR-4 also provided the
German review of the data from eight field trials conducted in Germany
during 2003-2004. Number range CHAPTERThe results from these tests are
discussed below and the residue data are summarized in Table 4.

  --------------------------------------------------------------------------------------------
  **Table 4.                                                                           
  Summary of                                                                           
  Residue Data                                                                         
  from Crop Field                                                                      
  Trials with                                                                          
  Spirodiclofen                                                                        
  (FlC).**                                                                             
  --------------- ----------- -------- --------- ------ ------ ------ -------- ------- -------
  Crop matrix     Total       PHI      Residue                                         
                  Applic.     (days)   Levels                                          
                  Rate (lb             (ppm) ^1^                                       
                  ai/A)                                                                

                                       n         Min.   Max.   HAFT   Median   Mean    Std.
                                                               ^2^                     Dev.

  **Hops,                                                                              
  proposed U.S.                                                                        
  use rate - 0.39                                                                      
  lb ai/A with                                                                         
  14-day PHI**                                                                         

  **U.S. Field                                                                         
  Trial Data                                                                           
  (2004)**                                                                             

  Dried hop cones 0.39-0.41   21       6         1.97   13.1   13.0   4.26     6.42    5.16

                              28       6         2.85   5.72   4.83   3.90     3.99    0.982

  **German Field                                                                       
  Trial Data                                                                           
  (2003-2004)**                                                                        

  Dried hop cones 0.30-0.39   14       8         3.9    24.0   24.0   10.65    11.60   6.62

                              21-22    4         3.9    10.9   10.9   7.05     7.23    2.89

                              28       6         3.1    10.0   10.0   8.15     7.07    2.85
  --------------------------------------------------------------------------------------------

^1^ The method LOQ is 0.05 ppm for residues of spirodiclofen in dried
hops.

^2^ HAFT = Highest average field trial result.

**U.S. Field Trials.** In 3 field trials conducted during 2004 in Zones
11 and 12, spirodiclofen (2 lb/gal FlC) was applied to hops as a single
foliar-directed application at 0.387-0.412 lb ai/A (1x rate) during cone
development and maturation. Applications were made using ground
equipment at volumes of 43-175 gal/A, and did not include the use of any
spray adjuvants. Duplicate control and treated samples of mature fresh
hop cones were collected from each test site at 21 and 28 DAT, and dried
within one day of harvest using commercial dryers. In one field trial,
additional samples were also collected at 6 and 14 DAT to assess residue
decline. Samples of dried hop cones were stored frozen for up to 15.6
months prior to analysis, and a concurrent storage stability study was
conducted supporting the stability of spirodiclofen in hops at -20ºC for
up to 15.1 months.

[]{.mark}

The LC/MS/MS method used to determine residues of spirodiclofen in/on
hops was adequately validated in conjunction with the analysis of field
trial samples. The calculated LOQ and LOD were 0.05 and 0.02 ppm,
respectively, and the LLMV was 0.05 ppm.

Following a single foliar-directed application of spirodiclofen (FlC) at
0.387-0.412 lb ai/A, residues of spirodiclofen were 1.97-13.1 ppm in/on
6 samples of dried hop cones harvested 21 DAT and 2.85-5.72 ppm in/on 6
samples of dried hop cones harvested 28 DAT. Average residues were 6.42
and 3.99 ppm at 21 and 28 DAT, respectively, and the HAFT residues were
13.0 and 4.83 ppm. In the residue decline trial, average residues in/on
hops decline relatively linearly from 6.68 ppm at 6 DAT to 3.59 ppm by
28 DAT.

**German Field Trials.** In 8 field trials conducted during 2003 and
2004 in Southern Germany (see Appendix III), a 240 g/L suspension
concentrate formulation of spirodiclofen was applied to hops as a single
foliar application at 0.34-0.43 kg ai/ha (0.30-0.38 lb ai/A, \~1x U.S.
rate) during cone development and maturation (BBCH 71-87). Applications
were made using ground equipment at volumes of 2100-3547 L/ha (225-380
gal/A). Fresh green hops were harvested at 14 DAT from each trial, and
at 21-22 DAT from 4 trials and at 28 DAT from 6 trials. Green hops were
dried to yield a single treated sample of dried hops from each trial at
each interval.

The German report did not include information on sample storage
conditions or intervals prior to analysis. Residues were determined
using a LC/MS/MS method, but no details of the method were provided.

Following a single foliar application of spirodiclofen (FlC) at
0.30-0.38 lb ai/A (\~1x the proposed U.S. use rate), residues of
spirodiclofen were 3.9-24.0 ppm in/on 8 samples of dried hops harvested
at the proposed PHI of 14 days. Residues were 3.9-10.9 ppm in/on 4
samples by 21 DAT and 3.1-10.0 ppm in/on 6 samples by 28 DAT. Average
residues were 11.6, 7.23, and 7.07 ppm at 14, 21 and 28 DAT,
respectively, indicating that residues declined slowly from 14-28 DAT.

*Conclusions*. The three hops field trials conducted in the U.S. are
adequate and would support PHIs of either 21 or 28 days, independently
from the German field trial data. An adequate number of trials were
conducted on hops in the U.S. in the appropriate geographical regions.
Samples were analyzed for the residues of concern using an adequate
method and the samples storage conditions and intervals are supported by
the available storage stability data.

However, IR-4 is requesting that the use pattern for hops in the U.S. be
harmonized with the use pattern in Germany, which allows for a PHI of 14
days. Although no residue data for a 14-day PHI are available from the
U.S., IR-4 has supplied summaries of German field trials that included
harvest intervals of 14, 21, and 28 DAT and were conducted at
approximately the same rates as proposed for the U.S. Average residues
in/on hops were 6.42 and 3.99 ppm at 21 and 28 DAT in the U.S. field
trials, and were 7.23 and 7.07 ppm at 21 and 28 DAT in the German field
trials. At 14 DAT, average residues were 11.60 ppm in the German field
trials.

Considering the similarity in climatic conditions between the hops
growing regions in the U.S. and Germany, and the similarity in the
residue data from both countries at the 21- and 28-day harvest
intervals, ChemSAC recommended in favor of allowing the use of the
German field trial data to support the U.S. use pattern and tolerance
(meeting 2/28/07). In order to harmonize with the previously established
Germany MRL, HED has decided to set the U.S. tolerance for spirodiclofen
on hops at 30 ppm to promote free trade between NAFTA and non-NAFTA
countries (for more discussion see section 860.1550 Proposed Tolerances
below).

**860.1520 Processed Food and Feed**

HED does not require residue data for any processed commodities
associated with hops. Therefore, data requirements for processed food
and feed are not relevant to this tolerance petition

Number range CHAPTER**860.1650 Submittal of Analytical Reference
Standards**

Analytical reference standards for spirodiclofen are available at the
EPA National Pesticide Standard Repository as of 8/8/07.

**860.1850-1900 Confined and field Accumulation in Rotational Crops**

Because hops are not rotated, no data pertaining to rotational crops are
required to support the proposed use.

**860.1550 Proposed Tolerances**

HED has concluded that the residue of concern in fruit, except grape,
and nut crops is spirodiclofen *per se,* for both the tolerance
expression and risk assessment purposes; for grape, the residue of
concern for tolerance enforcement is spirodiclofen *per se* and residues
of concern for risk assessment are spirodiclofen and BAJ 2510. For
purposes of this tolerance petition, the residue of concern is parent
spirodiclofen. Permanent tolerances are established for spirodiclofen on
grapes, citrus fruits, pome fruits, stone fruits and the tree nut crop
groups at 0.1-2.0 ppm, and on processed commodities from these crops at
0.6-20 ppm \[40 CFR §180.608(a)(1)\]. Tolerances are also established
for the combined residues of spirodiclofen and its free enol metabolite
BAJ 2510 in/on livestock commodities at 0.01-0.10 ppm \[40 CFR
§180.608(a)(2)\].

Using the Agency's *Guidelines for Setting Pesticide Tolerances Based on
Field Trial Data*, potential tolerances for dried hops were calculated
using the 21- and 28-DAT residue data from the adequate U.S. field
trials conducted at a 1x rate. The calculated tolerances for dried hops
harvested at the 21 and 28-day intervals were 35 and 7 ppm, respectively
(Appendix I).

However, IR-4 is requesting a minimum PHI of 14 days for hops in order
to harmonize the U.S. use directions with the use pattern in Germany.
IR-4 has also requested that the U.S. tolerance on hops be harmonized
with the proposed German MRL of 30 ppm (Table 6).

HED calculated a tolerance for spirodiclofen on hops with a PHI of 14
days using field trial data conducted in Germany. These field trial data
were originally submitted to European regulatory authorities in order to
establish a German MRL. Following the guidance used by NAFTA countries
(Guideline for Setting Pesticide Tolerances Based on Field Trial Data
SOP), the suggested tolerance for this data set would be 45 ppm, which
is rounded up from 40.73 ppm (the point estimate of the 99th
percentile). However, the European regulatory community employs
different methods for calculating tolerances. As such, the German MRL
was set at 30 ppm, which is above the highest residue value of 24 ppm.
The German MRL of 30 ppm is also higher than the maximum residue values
from two other submitted field trial data sets having similar
application rates, but longer PHIs (21 and 28 day). Thus, in order to
harmonized with the previously established Germany MRL, HED has decided
to set the U.S. tolerance for spirodiclofen on hops at 30 ppm to promote
free trade between NAFTA and non-NAFTA countries.

Mexican and Codex MRLs have not been established for spirodiclofen
(Appendix II), but Canadian MRLs have been established on a number of
crops and processed commodities. No MRLs have been established by
Canada, Mexico or Codex for spirodiclofen on hops. However, Germany is
currently using an assessment level (Beurteilungsempfehlungen) of 30
mg/kg to evaluate the safety of spirodiclofen use on hops.

  ------------------ -------------- ------------- -----------------------------
  **Table 6.                                      
  Tolerance Summary                               
  for                                             
  Spirodiclofen.**                                

  Commodity          Proposed       Recommended   Comments; *Correct Commodity
                     Tolerance      Tolerance     Definition*
                     (ppm)          (ppm)         

  Hop, dried cones   30             30            
  ------------------ -------------- ------------- -----------------------------

**References**

DP Number: D285249

Subject: Spirodiclofen in/on Citrus Fruit, Grape, Pome Fruit, Stone
Fruit, and Tree Nut Crops. Summary of Analytical Chemistry and Residue
Data.

From: T. Bloem

To: D. Kenny

Dated: 4/18/05

MRID(s): 45696504, 45696505, 45696506, 45696507, 45696508, 45696510,
45696513, 45696514, 45696515, 45696516, 45696517, 45696518, 45696519,
45696520, 45696521, 45696601, 45696602, 45696603, 45696604, 45696605,
45696606, 45696611, 45696612, 46028301

DP Number: D315459

Subject: Product Chemistry Review of TGAI. Joint Review with PMRA
(NAFTA)

From: S. Mathur

To: R. Kumar / D. Kenny

Dated: 4/20/05

MRID(s): NA

DP Number: D308566

Subject: PP# 2F6469. Review of Proposed Tolerance Enforcement Methods
for Spirodiclofen in/on Plant and Livestock Commodities.

From: E. Kolbe

To: K. Whitby/ M. Laws

Dated: 5/18/05

MRID(s): 45696514, 45699604, 45696515, 45696603

DP Number: 318055

Subject: Spirodiclofen. Results of Petition Method Validation (PMV).

From: T. Bloem

To: D. Kenny

Dated: 6/1/05

MRID(s): None

**Number range CHAPTERAttachments:**

Appendix I -- Tolerance Assessment Calculations

Appendix II -- International Residue Limit Status sheet

Appendix III -- Residue Data from German Field Trials

Template Version September 2005

**Appendix I -- Tolerance Assessment Calculations**

The Agency's *Guideline for Setting Pesticide Tolerances Based on Field
Trial Data* was utilized for determining appropriate tolerance levels on
dried hop cones. Residues levels in this commodity were \>LOQ in all
samples. The dataset used to calculate tolerances for spirodiclofen
residues on hops consisted of U.S. and German field trial data
representing applications of the appropriate formulation at \~1x the
maximum proposed use rate but at different PHIs (U.S. PHI = 21 and 28
days; German PHI = 14 days).

The datasets for spirodiclofen on hops harvested at 21- and 28-DAT were
entered into the tolerance spreadsheet. The results form the approximate
Shaprio-Francia test statistic (Figures I-2 and -4) and visual
inspection indicated that mathematically, the residues from samples
harvested at 21-DAT are lognormal; lognormality, however, was rejected
for residues from samples harvested at 28-DAT. The calculated tolerance
for 21-day and 28-day PHI were respectively 35 and 7 ppm.

HED also calculated a tolerance for spirodiclofen on hops with a PHI of
14 days using field trial data conducted in Germany. These field trial
data were originally submitted to European regulatory authorities in
order to establish a German MRL. Following the guidance used by NAFTA
countries (Guideline for Setting Pesticide Tolerances Based on Field
Trial Data SOP), the suggested tolerance for this data set would be 45
ppm, which is rounded up from 40.73 ppm (the point estimate of the 99th
percentile). However, the European regulatory community employs
different methods for calculating tolerances. As such, the German MRL
was set at 30 ppm, which is above the highest residue value of 24 ppm.
The German MRL of 30 ppm is also higher than the maximum residue values
from two other submitted field trial data sets having similar
application rates, but longer PHIs (21 and 28 day). Thus in order to
harmonized with the previously established Germany MRL, HED has decided
to set the U.S. tolerance for spirodiclofen on hops at 30 ppm to promote
free trade between NAFTA and non-NAFTA countries.

  ---------------------- ------------------------ ------------------------
  **Table I-1.                                    
  Spirodiclofen Residues                          
  in/on Dried Hop Cones,                          
  U.S. Field Trial                                
  Data.**                                         

  **Regulator:**         EPA                      

  **Chemical:**          Spirodiclofen            

  **Crop:**              Hops, dried cones        

  **PHI:**               21 days                  28 days

  **App. Rate:**         0.39-0.41 lb ai/A        

  **Submitter:**         IR-4                     

  **MRID Citation:**     MRID 41705301            

                         **Residues**             **Residues**

                         1.97                     2.85

                         2.13                     3.32

                         3.95                     3.86

                         4.57                     3.93

                         12.8                     4.23

                         13.1                     5.72
  ---------------------- ------------------------ ------------------------

**Figure I-1. Lognormal Probability Plot of Spirodiclofen Residues in/on
Dried Hop Cones Harvested at 21 DAT.**

![](media/image3.wmf){width="5.854166666666667in"
height="4.004166666666666in"}

Figure I-2. Data Summary Sheet for Residues of Spirodiclofen in/on Dried
Hop Cones at 21 DAT.

![](media/image4.wmf){width="5.249305555555556in"
height="3.801388888888889in"}

**Figure I-3. Lognormal Probability Plot of Spirodiclofen Residues in/on
Dried Hop Cones Harvested at 28 DAT.**

![](media/image5.wmf){width="5.986805555555556in"
height="4.101388888888889in"}

Figure I-4. Data Summary Sheet for Residues of Spirodiclofen in/on Dried
Hop Cones at 28 DAT.

![](media/image6.wmf){width="5.516666666666667in"
height="4.004166666666666in"}

**Table I-2. Spirodiclofen Residues in/on Dried Hop Cones, German Field
Trial Data (PHI = 14 days).**

  ---------------------- ------------------------------------------------
  **Regulator:**         EPA

  **Chemical:**          spirodiclofen

  **Crop:**              hops

  **PHI:**               14 days

  **App. Rate:**         0.32 - 0.38 lb ai/A

  **Submitter:**         [IR-]{.underline}4 (German Study)

                         **Residues**

                         17.000

                         24.000

                         3.900

                         5.200

                         10.800

                         13.900

                         7.500

                         10.500
  ---------------------- ------------------------------------------------

**Figure I-5. Lognormal Probability Plot of Spirodiclofen Residues in/on
Dried Hop Cones Harvested at 14 DAT (German Study).**

![](media/image7.wmf){width="6.497222222222222in"
height="3.529861111111111in"}

Figure I-6. Data Summary Sheet for Residues of Spirodiclofen in/on Dried
Hop Cones at 14 DAT (German Study).

![](media/image8.wmf){width="6.495138888888889in"
height="4.236805555555556in"}

**Appendix II - International Tolerances.**

+-------------------+-----------------+-----------------+--------------+
| INTERNATIONAL     |                 |                 |              |
| RESIDUE LIMIT     |                 |                 |              |
| STATUS            |                 |                 |              |
+===================+=================+=================+==============+
| Chemical Name:    | Common Name:    | √ Proposed      | Date:        |
| 3-(2,4-d          | Spirodiclofen   | tolerance       | 12/09/2007   |
| ichlorophenyl)-2- |                 |                 |              |
| oxo-1-oxaspiro\[4 |                 |  Reevaluated   |              |
| ,5\]dec-3-en-4-yl |                 | tolerance       |              |
| 2,2-              |                 |                 |              |
| dimethylbutanoate |                 |  Other         |              |
+-------------------+-----------------+-----------------+--------------+
| **Codex Status    |                 | **U. S.         |              |
| (Maximum Residue  |                 | Tolerances**    |              |
| Limits)**         |                 |                 |              |
+-------------------+-----------------+-----------------+--------------+
| √ No Codex        |                 | **Petition      |              |
| proposal step 6   |                 | Numbers**:      |              |
| or above          |                 | 7E7204          |              |
|                   |                 |                 |              |
|  No Codex        |                 | **DP Number:**  |              |
| proposal step 6   |                 | 346760          |              |
| or above for the  |                 |                 |              |
| crops requested   |                 | **Other         |              |
|                   |                 | Identifier:**   |              |
+-------------------+-----------------+-----------------+--------------+
| **Residue         |                 | **Rev           |              |
| definition (step  |                 | iewer/Branch:** |              |
| 8/CXL):** NA      |                 | M.              |              |
|                   |                 | Sahafeyan/RAB1  |              |
+-------------------+-----------------+-----------------+--------------+
|                   |                 | **Residue       |              |
|                   |                 | definition:**   |              |
|                   |                 | Spirodiclofen   |              |
+-------------------+-----------------+-----------------+--------------+
| **Crop (s)**      | **MRL (mg/kg)** | **Crop(s)**     | **Tolerance  |
|                   |                 |                 | (ppm)**      |
+-------------------+-----------------+-----------------+--------------+
|                   |                 | Hops, dried     | 30           |
|                   |                 | cones           |              |
+-------------------+-----------------+-----------------+--------------+
|                   |                 |                 |              |
+-------------------+-----------------+-----------------+--------------+
| **Limits for      |                 | **Limits for    |              |
| Canada**          |                 | Mexico**        |              |
+-------------------+-----------------+-----------------+--------------+
|  No Limits       |                 | √ No Limits     |              |
|                   |                 |                 |              |
| √ No Limits for   |                 |  No Limits for |              |
| the crops         |                 | the crops       |              |
| requested         |                 | requested       |              |
+-------------------+-----------------+-----------------+--------------+
| Residue           |                 | Residue         |              |
| definition: N/A.  |                 | definition: NA  |              |
|                   |                 |                 |              |
| There is a label  |                 |                 |              |
| for use on stone  |                 |                 |              |
| fruit, pome       |                 |                 |              |
| fruit, and        |                 |                 |              |
| grapes.           |                 |                 |              |
+-------------------+-----------------+-----------------+--------------+
| Crop(s)           | MRL (mg/kg)     | Crop(s)         | MRL (mg/kg)  |
+-------------------+-----------------+-----------------+--------------+
|                   |                 |                 |              |
+-------------------+-----------------+-----------------+--------------+
|                   |                 |                 |              |
+-------------------+-----------------+-----------------+--------------+
|                   |                 |                 |              |
+-------------------+-----------------+-----------------+--------------+
|                   |                 |                 |              |
+-------------------+-----------------+-----------------+--------------+
|                   |                 |                 |              |
+-------------------+-----------------+-----------------+--------------+
|                   |                 |                 |              |
+-------------------+-----------------+-----------------+--------------+
|                   |                 |                 |              |
+-------------------+-----------------+-----------------+--------------+
|                   |                 |                 |              |
+-------------------+-----------------+-----------------+--------------+
|                   |                 |                 |              |
+-------------------+-----------------+-----------------+--------------+
|                   |                 |                 |              |
+-------------------+-----------------+-----------------+--------------+
|                   |                 |                 |              |
+-------------------+-----------------+-----------------+--------------+
|                   |                 |                 |              |
+-------------------+-----------------+-----------------+--------------+
|                   |                 |                 |              |
+-------------------+-----------------+-----------------+--------------+
| Notes/Special     |                 |                 |              |
| Instructions:     |                 |                 |              |
| S.Funk,           |                 |                 |              |
| 12/10/2007.       |                 |                 |              |
+-------------------+-----------------+-----------------+--------------+

**Appendix III -- German Field Trail Data on Hops.**

  ------------------- ------------- --------------- ---------- ---------- -------- ------------ ----------- ------------ ---------- ------------
  **Table III- 1.                                                                                                                   
  Residues of                                                                                                                       
  Spirodiclofen in/on                                                                                                               
  Dried Hops From                                                                                                                   
  German Field Trials                                                                                                               
  Conducted during                                                                                                                  
  2003 and 2004.**                                                                                                                  

  **Location/year**   **Variety**   **Application   **Growth   **Rate**            **Volume**               **Matrix**   **PHI      **Residues
                                    Type**          stage**                                                              (days)**   (ppm)**

                                                               **kg       **lb     **l/ha**     **gal/A**                           
                                                               ai/ha**    ai/A**                                                    

  Gebrontshausen,     Perle         Foliar Directed BBCH 84/87 0.36       0.32     3300         353         dried cones  14         17.0
  Germany 2003                                                                                                                      

  Gebrontshausen,     Hallertauer   Foliar Directed BBCH 84/87 0.36       0.32     3300         353         dried cones  14         24.0
  Germany 2003        Tradition                                                                                                     

  Tettnang, Germany   Spalter       Foliar Directed BBCH 79    0.34       0.30     3109         333         dried cones  14         3.9
  2003                Hopfen                                                                                                        

                                                                                                                         21         3.9

                                                                                                                         28         3.1

  Tettnang, Germany   Hallertauer   Foliar Directed BBCH 79    0.39       0.35     3547         380         dried cones  14         5.2
  2003                Mittelfruh                                                                                                    

                                                                                                                         21         6.6

                                                                                                                         28         4.0

  Gebrontshausen,     Hallertauer   Foliar Directed BBCH 71/79 0.43       0.38     2100         225         dried cones  14         10.8
  Germany 2004        Tradition                                                                                                     

                                                                                                                         28         10.0

  Tettnang, Germany   Hallertauer   Foliar Directed BBCH 75/79 0.43       0.38     2100         225         dried cones  14         13.9
  2004                Mittelfruh                                                                                                    

                                                                                                                         28         9.0

  Gebrontshausen,     Perle         Foliar Directed BBCH 71/75 0.43       0.38     2100         225         dried cones  14         7.5
  Germany 2004                                                                                                                      

                                                                                                                         22         7.5

                                                                                                                         28         8.8

  Tettnang, Germany   Spalter       Foliar Directed BBCH 75/79 0.43       0.38     2100         225         dried cones  14         10.5
  2004                Hopfen                                                                                                        

                                                                                                                         21         10.9

                                                                                                                         28         7.5
  ------------------- ------------- --------------- ---------- ---------- -------- ------------ ----------- ------------ ---------- ------------