Document ID: EPA-HQ-OPP-2007-0398-0006
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-05-07T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF           

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

MEMORANDUM

	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 Number:	378132

PC Code:	124871	MRID No:	47105301

40 CFR 180	608

Chemical Class:	tetronic acid 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.

→ 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).  

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.

  SEQ CHAPTER \h \r 1 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	

Common name	Spirodiclofen

Company experimental name	BAJ2740

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

  

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/cm3

	Water solubility (20ºC at pH 4)	50μg/L

	Solvent solubility (g/L at 20°C)	n-heptane  

xylene  

dichloromethane 

2-propanol

1-octanol

polyethylene glycol

acetone

ethyl acetate

acetonitrile

dimethylsulfoxide	20

>250

>250

47

44

24

>250

>250

>250

75

	Vapor pressure (20ºC)	3 x 10-7 Pa

	Dissociation constant, pKa	Not determinable due to the instability in
aqueous solutions at >pH 4

	Octanol/water partition coefficient, Log(KOW) at pH 4 and 20ºC	5.83

	UV/visible absorption spectrum	λmax = 201 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 Spirodiclofen.

Applic. Timing, Type, and Equip.	Formulation

[EPA Reg. No.]	Applic. Rate 

(lb ai/A)	Max. No. Applic. per Season	Max. Seasonal Applic. Rate

(lb ai/A)	PHI

(days)	Use Directions and Limitations 1

Hops

Single foliar application at the early stages of mite infestation; 
Ground equipment	2 lb/gal FlC

[264-831]	0.28-0.39	1	0.39	14	Apply in a minimum of 50 gal/A using
conventional ground airblast spray

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.  

 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

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 NH2 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).  

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.

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

  SEQ CHAPTER \h \r 1 45696517.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.    SEQ CHAPTER \h \r 1 The 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 Applic. Rate  (lb ai/A)	PHI (days)	Residue Levels
(ppm) 1

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

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

  SEQ CHAPTER \h \r 1 860.1650 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 Tolerance (ppm)	Recommended Tolerance (ppm)	Comments;
Correct Commodity Definition

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

  SEQ CHAPTER \h \r 1 Attachments:  

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.

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

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

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

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-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).

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

Appendix II - International Tolerances.

-

,

.

X

d

g

i

n

‘

hR

蘆

ä

å

æ

ç

ú

û

 ‘

—

Ã

ç

è

ù

û

r

s

Ž

ž

Ÿ

«

±

²

¹

Î

hR

hR

hR

 hR

hR

 hR

H*

\

 h

 h

h

h

h

h

 h

h

 h

 h

h

h

h

h

h

hq

hq

hq

hq

 h±j

h±j

hq

 hq

hq

hq

h±j

 h

h

h

h

$

$

1$gd

$

'ð

'ð

'ð

'ð

'ð

'ð

'ð

'ð

'ð

'ð

'ð

'ð

'ð

h

$

愀Ĥ摧এrࠀ√ Proposed tolerance

 Reevaluated tolerance

 Other	Date:  12/09/2007

Codex Status (Maximum Residue Limits)	U. S. Tolerances

√ No Codex proposal step 6 or above

 No Codex proposal step 6 or above for the crops requested	Petition
Numbers: 7E7204

DP Number:  	346760

Other Identifier:  

Residue definition (step 8/CXL): NA	Reviewer/Branch:  M. Sahafeyan/RAB1

	Residue definition:  Spirodiclofen

Crop (s)	MRL (mg/kg)	Crop(s) 	Tolerance (ppm)

Hops, dried cones	30

	Limits for Canada	Limits for Mexico

 No Limits

√ No Limits for the crops requested	√  No Limits

  No Limits for the crops requested

Residue definition: N/A.

There is a label for use on stone fruit, pome fruit, and grapes.	Residue
definition: NA

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 Type	Growth stage	Rate	Volume	Matrix
PHI (days)	Residues (ppm)

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

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

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

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

	21	3.9

	28	3.1

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

	21	6.6

	28	4.0

Gebrontshausen, Germany  2004	Hallertauer Tradition	Foliar Directed	BBCH
71/79	0.43	0.38

	2100	225	dried cones	14	10.8

	28	10.0

Tettnang, Germany 2004	Hallertauer Mittelfruh	Foliar Directed	BBCH 75/79
0.43	0.38

	2100	225	dried cones	14	13.9

	28	9.0

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

	22	7.5

	28	8.8

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

	21	10.9

	28	7.5

Spirodiclofen	Summary of Analytical Chemistry and Residue Data	DP#: 
346760

PC Code: 124871

Page   PAGE  1  of   NUMPAGES  20