Document ID: EPA-HQ-OPP-2008-0478-0006
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2009-07-08T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460      

	OFFICE OF PREVENTION, PESTICIDE

                                                                        
                   AND TOXIC SUBSTANCES

	

  SEQ CHAPTER \h \r 1 MEMORANDUM

Date:  05/March/2009

SUBJECT:	Pyrimethanil; Section 3 Registration Request to Register New
Postharvest Uses on Stone Fruit, Crop Group 12 and a Preharvest Use on
Lemon.  Summary of Analytical Chemistry and Residue Data.  

 

PC Code:  288201	DP Barcode:  D361301

Decision No.:  393117	Registration No.:  43813-32 and 264-788

Petition No.:  8E7353	Regulatory Action:  Section 3 Registration

Risk Assessment Type:  None	Case No.:  None

TXR No.: None	CAS No.:  53112-28-0

MRID No.:  47425601 through 47425605	40 CFR:180.518

		              									

	          	

FROM:	  SEQ CHAPTER \h \r 1 Debra Rate, Ph.D., Biologist  SEQ CHAPTER \h
\r 1 

		Alternative Risk Integration and Assessment (ARIA)

		Risk Integration, Minor Use, and Emergency Response Branch (RIMUERB)

		Registration Division (RD; 7505P)

THROUGH:	William Cutchin, Acting Senior Branch Scientist

		ARIA/RIUMERB/RD (7505P)

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

		Risk Assessment Branch 1 (RAB1)

Health Effects Division (HED; 7509P)

TO:		Susan Stanton, Environmental Specialist  SEQ CHAPTER \h \r 1   SEQ
CHAPTER \h \r 1 

		Minor Use Team

		RIUMERB/RD (7505P)

I.	 CONCLUSIONS

Regulatory Recommendations 

Provided that a revised Section B, label (see requirements under
Directions for Use) and Section F (see requirements under Proposed
Tolerances) are submitted in addition to the submission of analytical
reference standards to replace expired samples; there are no residue
chemistry issues that would preclude granting a registration for uses of
pyrimethanil (Penbotec® 400SC (EPA Reg. No. 43813-32-2792) and Scala SC
(EPA Reg. No. 264-788)) on stone fruit and citrus fruit.  ARIA
recommends for the following permanent tolerances:

Fruits, stone, group 12	10 ppm

Fruit, citrus, group 10	11 ppm

ARIA recommends for the removal of the following tolerances
concomitantly with the establishment of the above tolerances:

Fruit, stone (except cherry), group 12	3.0 ppm

Fruit, citrus group 10 (postharvest)	10 ppm

Residue Chemistry Deficiencies

860.1200 Directions for Use

The label should be revised to prohibit the use of adjuvants with Scala
SC in the preharvest treatment of lemons.  The submitted label for
PENBOTEC 400SC states that stone fruit can be treated by high volume
spray, drench or dip; however, only stone fruit (except cherries) may be
treated with low-volume spray.  A revised Section B should be submitted
which accurately reflects the field trial data and label instructions
for both products.  

860.1550 Proposed Tolerances

A summary of the recommended tolerances along with recommendations for
commodity definitions are presented in Table 9.  The petitioner should
submit a revised Section F to reflect these tolerance and commodity
definitions.

860.1650 Submittal of Analytical Reference Standards

The petitioner should submit new analytical standards for pyrimethanil,
to replace the expired samples.  

II.	ACTION REQUESTED  

Interregional Research Project No. 4 (IR-4) has submitted a request to
add a new preharvest use of pyrimethanil on lemons and postharvest uses
on stone fruit, crop group 12.  Pyrimethanil is used to control brown
rot and gray mold.  The end-use products (EPs) relevant to this
registration request are Penbotec® 400SC (EPA Reg. No. 43813-32) and
Scala SC (EPA Reg. No. 264-788) which are soluble concentrate (SC)
formulations containing 37.14% (equivalent to 3.27 lb ai/gal) and 54.6%
(equivalent to 5.0 lb ai/gal) active ingredient (ai), respectively.  The
EPs are proposed for postharvest treatment of fruit at 400 g ai/100 gal
mix (dipping) or a high-volume application rate of 400 g ai/200,000 lb
fruit, or preharvest application of mature fruit at a rate of
approximately 0.70 lb ai/A, respectively.  The proposed preharvest
interval (PHI) is 7 days for lemons.

Concurrently, IR-4 has proposed for the establishment of permanent
tolerances for residues of the fungicide pyrimethanil,
4,6-dimethyl-N-phenyl-2-pyrimidinamine, in/on the raw agricultural
commodities:

Fruit, stone, group 12	10 ppm

Fruit, citrus (except lemon), group 10 (postharvest)	10 ppm

Lemon	11 ppm

Upon approval of the aforementioned tolerances, IR-4 requests the
removal of the following established tolerances of the fungicide
pyrimethanil, 4,6-dimethyl-N-phenyl-2-pyrimidinamine, in/on the raw
agricultural commodities:

Fruit, stone (except cherry), group 12	3.0 ppm

Fruit, citrus group 10 (postharvest)	10 ppm

III.	Executive Summary

Pyrimethanil [4,6-dimethyl-N-phenyl-2-pyrimidinamine] is an amino acid
synthesis inhibitor that inhibits the secretion of fungal enzymes
necessary for fungal infection.  Pyrimethanil is currently registered in
the U.S. for use on almonds, pome fruit, citrus fruit, stone fruit
(except cherry), bananas, grapes, onions, pistachios, strawberries,
tomatoes and tuberous and corm vegetables.  Pyrimethanil is applied to
the above crops as 1-6 broadcast applications (foliar or mature fruit)
per year not to exceed the maximum seasonal rate (0.7 - 2.1 lb ai/A),
depending on the crop.  Minimum preharvest intervals (PHIs) range from 0
to 7 days.

Permanent tolerances have been established for residues of pyrimethanil
per se in/on plant commodities at levels ranging from 0.05 ppm in/on
vegetable, tuberous and corm, subgroup 1C to 150 ppm in/on citrus oil
[40 CFR §180.518(a)(1)].  Tolerances have also been established for
pyrimethanil residues and its metabolite
4-[4,6-dimethyl-2-pyrimidinyl)amino]phenol in fat (0.01 ppm), kidney
(2.5 ppm) and byproducts (except kidney) (0.01 ppm) of cattle, goats,
horses and sheep and in milk (0.05 ppm) [40 CFR §180.518(a)(2)].

  SEQ CHAPTER \h \r 1 The qualitative nature of the pyrimethanil residue
in plant commodities is adequately understood based on acceptable
metabolism studies in lettuce, grapes, and tomatoes.  The HED Metabolism
Assessment Review Committee (MARC) has determined that for risk
assessment and tolerance expression that the parent is the only residue
of concern.  Future new uses on root crops whose tops are significant
food/feed items will require the analysis of metabolite AEC614278.

The crop uses proposed in this petition include dried citrus pulp (i.e.
proposed preharvest use on lemons) which is a regulated livestock
feedstuff; however, citrus pulp was addressed in a previous Agency
memorandum (DP# 284001, J. Morales and G. Kramer, 12/JAN/2004) and the
addition of this lemon use will not change previously calculated
livestock tolerances.  Therefore, issues pertaining to livestock
metabolism, analytical methods and storage stability data for and
residues in livestock commodities are not addressed in the current
petition.

A high-performance liquid chromatography (HPLC) residue analytical
method entitled, “Analytical Method for the Determination of Residues
of ZK 100309 in Vines, Strawberries, and Apples by HPLC” was submitted
in conjunction with an earlier pyrimethanil petition, PP#4E4384, for the
establishment of a tolerance on imported wine grapes.  The method has
been subjected to a successful independent laboratory validation (ILV)
and was subsequently forwarded to Analytical Chemistry Branch
(ACB)/Biological and Economics Analysis Division (BEAD) for a successful
petition method validation (PMV).

The data collection method used to generate residue data in conjunction
with magnitude of the residue studies associated with this petition is a
gas chromatography with mass selective detection (GC/MSD).  The limit of
quantitation (LOQ) ranged from 0.01-0.062 ppm; the calculated limit of
detection (LOD), ranged from 0.001 ppm to 0.021 ppm.  The adequacy of
the GC/MSD method for data collection was verified in each matrix by
fortifying control samples with pyrimethanil at tolerance-setting
levels.  Method recoveries were within the acceptable range of 70-120%
for all fortified samples.

Adequate field trial data, reflecting the proposed use pattern according
to the label directions, were submitted for lemons.  Maximum residues
following preharvest treatment at 0.690-0.817 lb ai/A (1.0x) and PHIs of
7 days were 0.27 ppm in/on lemons.  Maximum residues following
postharvest treatment by combinations of an aqueous drench (500 or 1000
ppm), storage wax line spray (2000 ppm), pack out wax line spray (2000
ppm), and an aqueous dip (1000 ppm) or line sprayer (2000 ppm) were 6.35
ppm in/on lemons.  The available data suggest that the recommended
tolerance of 11 ppm in/on citrus fruit for all of the labeled and
proposed uses (preharvest and postharvest) will not be exceeded when
maximum residues from all routes of pyrimethanil exposure are considered
(1 ppm for preharvest (lemon only) + 10 ppm for postharvest by line
spray aqueous and wax + postharvest by dipping). 

Adequate postharvest data were submitted for the representative crops of
fruit, stone, group 12 (tart cherries, sweet cherries, peaches, and
plums).  These data indicate that following one postharvest treatment
via dipping or spraying of stone fruits using an SC formulation at 0.882
lb ai/200,000 fruit (2.0x the proposed rate; except for tart cherries
(0.65x and 0.86x)), maximum residues of pyrimethanil were 1.39 ppm in/on
tart cherries, 13.0 ppm in/on sweet cherries, 8.2 ppm in/on peaches and
2.0 ppm in/on plums.  The available data suggest that the proposed crop
group tolerance of 10 ppm for stone fruits will be not be exceeded when
maximum residues from all routes of pyrimethanil exposure at the
labeled/proposed use rate to stone fruits are considered (preharvest +
postharvest by line spray aqueous and wax + postharvest by dipping).  

No processed food and feed studies were necessary or submitted for the
proposed uses and requested tolerances of the current petition. 
Processing studies for citrus fruit and plum were previously reviewed
(DP# 284001 & 284870, J. Morales, 12/JAN/2004) and while pyrimethanil
residues were found not to concentrate in prunes, following an
exaggerated (5x) study, pyrimethanil residues concentrated 16x in citrus
oil.  

Stone fruits and lemons are typically not rotated.  Therefore, residue
data pertaining to confined and field accumulation in rotational crops
are not germane to this tolerance petition.



DETAILED CONSIDERATIONS

Background

  SEQ CHAPTER \h \r 1 Pyrimethanil is an anilinopyrimidine fungicide
that inhibits the secretion of fungal enzymes which are required during
the infection process.  Pyrimethanil blocks the ability of the fungus to
degrade and digest the plant tissues, thus stopping penetration and
development of the disease.  The precise mechanism of inhibition of
enzyme secretion has not been fully established.  Protein synthesis is
not inhibited, and evidence suggests that extracellular enzymes
accumulate inside the fungus, their release being blocked in the
presence of the fungicide.  Pyrimethanil penetrates rapidly into the
plant tissues, where it stops the development of the disease, providing
a significant curative action.  In vitro, germ tube extension and
mycelial growth are inhibited.

Pyrimethanil does not exhibit cross-resistance to sterol-inhibitors,
dicarboximides, benzimidazoles, quinone outside inhibitors, or
phenylamides, but may exhibit cross-resistance in certain plant
pathogenic fungi including anilinopyridine (AP) compounds such as
cyprodinil and mepanipyrim.  The nomenclature of pyrimethanil is
summarized in Table 1.  The physicochemical properties of pyrimethanil
are summarized in Table 2.

Table 1.  Test Compound Nomenclature

Chemical structure	

  

Common name	Pyrimethanil

Company experimental name	NR*

IUPAC name	N-(4,6-dimethylpyrimidin-2yl)aniline

CAS name	4,6-dimethyl-N-phenyl-2-pyrimidinamine

CAS #	53112-28-0

End-use product/(EP)	Penbotec® 400SC and Scala SC

*NR = Not Reported

Table 2.  Physicochemical Properties of the Technical Grade Test
Compound 

Parameter	Value	References

Melting point/range	96oC	The Pest Manual.  British Crop Protection
Council.  Twelfth Edition, Editor: C.D.S. Tomlin.

pH (water solution at 25oC)	6.1

	Specific gravity at 20oC	1.15

	Water solubility (g/l at 25oC)	0.121 

	Solvent solubility (g/l at 20oC)	 acetone – 389, ethyl acetate –
617, methanol – 176, methylene chloride – 1000, n-hexane – 23.7,
toluene – 412 

	Vapour pressure at 25oC	2.2 mPa

	Octanol/water partition coefficient log (KOW)  	2.84

	UV/visible absorption spectrum	No UV absorption above 290 nm	Pest
Management Regulatory Agency Health, Canada, 2006.

860.1200 Directions for Use

Table 3.  Summary of Section B Directions for Use of Pyrimethanil.

Applic. Timing, Type, and Equip.	Formulation

[EPA Reg. No.]	Applic. Rate	Max. No. Applic. per Season	Max. Seasonal
Applic. Rate	PHI

(days)	Use Directions and Limitations

Stone Fruit, Crop Group 12

High-Volume Spray, Drench or Dip

	PENBOTEC 400SC

[43813-32]

	16 fl.oz/100 gal water with water or wax/oil emulsion to treat 200,000
lbs. fruit	1

	16 fl.oz/100 gal water/200,000 lbs. fruit 

(0.0255 lb ai/oz)

	NA

	Do not make more than one postharvest application.  May be applied the
same day as sold or eaten.

Low-Volume Spray

	PENBOTEC 400SC

[43813-32]

	64 fl.oz/100 gal water with water or wax/oil emulsion.  Apply 10-25 gal
to treat 200,000 lbs. fruit	1

	64 fl.oz/100 gal water Apply 10-25 gal to 200,000 lbs. fruit

	NA

	Do not make more than one postharvest application.  May be applied the
same day as sold or eaten.  Do not use this method of application on
cherry.

Lemon

Foliar air blast

	SCALA SC

[264-788]

	18 fl oz/A (0.690 lb ai/A)

	1

	18 fl oz/A/season (0.690 lb ai/A/season)	7

	Do not apply with in 7 days of harvest (7-day PHI).  Do not apply more
than 18 fl oz /A/year in the field.

Text in bold-type is present on the label but is missing from the
Section B.

Conclusions  The submitted label for PENBOTEC 400SC states that stone
fruit can be treated by high volume spray, drench or dip; however, only
stone fruit (except cherries) may be treated with low-volume spray.  The
Section B should be revised and submitted to match the label for this
condition.  

The submitted label for SCALA SC does not include use directions for
lemon.  No adjuvants were used in the lemon studies.  The label should
be revised to include the proposed use for lemons, and to prohibit the
use of adjuvants in the preharvest treatment of lemons.

860.1300 Nature of the Residue – Plants

DP#s 284001 & 284870, J. Morales and G. Kramer, 12/JAN/2004 (PP#s
2F06439 and 2F06480)

  SEQ CHAPTER \h \r 1 The qualitative nature of the pyrimethanil residue
in plant commodities is adequately understood based on acceptable
metabolism studies in lettuce, grapes, and tomatoes.  The HED Metabolism
Assessment Review Committee (MARC) has determined that for risk
assessment and tolerance expression, parent only is the residue of
concern.  Future new uses on root crops whose tops are significant
food/feed items will require the analysis of metabolite AEC614278.

860.1340 Residue Analytical Methods

DP# 284866, D. Vogel, et al, 11/15/2004.

Enforcement methods

A residue analytical method entitled “Analytical Method for the
Determination of Residues of ZK 100309 in Vines, Strawberries, and
Apples by HPLC” was submitted in conjunction with an earlier
pyrimethanil petition, PP#4E4384, for the establishment of a tolerance
on imported wine grapes.  The method has been subjected to a successful
PMV by ACB/BEAD (DP# 288256, E. Kolbe, 7/JUL/2004). 

Data-collection method(s)

The data-collection method used to generate residue data in conjunction
with magnitude of the residue studies associated with this petition is a
GC/MSD method derived from “Fruit and Vegetables: Analytical Method
for the Determination of Residues (Improved Version), Pyrimethanil,
Active Substance.”  Briefly, pyrimethanil residues were extracted by
homogenization with acetone.  An aliquot of the extract was acidified
then washed with hexane before adding base to enable solvent partition. 
Final clean-up was by silica solid phase extraction (SPE), with
determination by GC/MSD.  The lowest level of method validation (LLMV)
was 0.05 ppm, the LOD and LOQ were calculated to range from 0.001 ppm to
0.021 ppm and 0.01-0.062 ppm, respectively.  The adequacy of the GC/MSD
method for data collection was concurrently verified by fortifying
control samples of each matrix with pyrimethanil at tolerance-setting
levels.  Method recoveries were within the acceptable range of 70-120%
for all fortified samples.

860.1360 Multiresidue Methods

DP# 284001 and 284870, J. Morales and G. Kramer, 12/JAN/2004 (PP#s
2F06439 and 2F06480)

  SEQ CHAPTER \h \r 1 Pyrimethanil was tested through Protocols C, D,
and E of the standard Food and Drug Administration (FDA) Multiresidue
Protocols.  Pyrimethanil was found to be nondetectable by the
electron-capture (EC) detector.  The use of a nitrogen-specific detector
is recommended.  Recovery was complete (>100%) using the Luke procedure
for grapes (non-fatty food) fortified at 0.05 and 5.0 ppm.  No recovery
was obtained from cottonseed oil (fatty food) fortified at 0.05 ppm. 
For cottonseed oil fortified at 0.5 ppm, average recoveries of 28%
(range 16-40%) and 78% (range 75-82%) were obtained when using the ether
and the methylene chloride system, respectively.  Pyrimethanil eluted
from the standardized Florisil column.  Recovery ranged from 86 to 98%
using two different systems.

860.1380 Storage Stability

47425601.der.doc, D. Rate, 03/NOV/2008. (Peach)

47425602.der.doc, D. Rate, 03/NOV/2008. (Plum)

47425603.der.doc, D. Rate, 03/NOV/2008. (Sweet Cherry)

47425604.der.doc, D. Rate, 03/NOV/2008. (Lemon)

47425605.der.doc, D. Rate, 03/NOV/2008. (Cherry)

Fruit samples that were collected from the pre- and postharvest residue
studies associated with this petition were stored frozen prior to
residue analysis for durations of 0 days to 523 days.  No additional
supporting storage stability data were included in the review package. 
However, it has been previously reported that residues of pyrimethanil
are reasonably stable under frozen storage conditions in/on apples for
up to 676 days (DP# 347247 and 347248, G. Kramer, 17/JUL/2008).

860.1480 Meat, Milk, Poultry, and Eggs

The crop uses proposed in this petition include dried citrus pulp (i.e.
proposed preharvest use on lemons) which is a regulated livestock
feedstuff; however, citrus pulp was addressed in a previous Agency
memorandum (DP# 284001, J. Morales and G. Kramer, 12/JAN/2004) and the
addition of this lemon use will not change previously calculated
livestock tolerances.  Therefore, issues pertaining to livestock
metabolism, analytical methods and storage stability data for and
residues in livestock commodities are not addressed in the current
petition.

860.1500 Crop Field Trials

Lemon

47425604.der.doc, D. Rate, 03/NOV/2008. (Lemon)

Table 4.  Summary of Residue Data from Crop Field Trials with
Pyrimethanil.

Commodity	Total Applic. Rate

 (lb ai/A)	PHI 

(days)	Sample size (n)	Residue Levels (ppm)

Min.	Max.	HAFT*	Median	Mean	Std. Dev.

Lemon	0.690 – 0.817	7	10	0.068	0.31	0.27	0.22	0.20	0.080

*HAFT = Highest Average Field Trial

IR-4 submitted field trial data to support the establishment of a
tolerance for residue of pyrimethanil in or on lemon.  Five field trials
were conducted for this study during the 2004 – 2005 growing season in
CA (Region 10).  At each trial, one foliar air blast application of
Scala( SC (54.6 % pyrimethanil) with no adjuvants or additives was made
at a rate of approximately 0.70 lb ai/A.  Mature lemons were harvested 7
days after the application.

Residues of pyrimethanil were analyzed in the IR-4 Western Region
Laboratory, Davis, CA.  The procedure used for the analysis was derived
from the AgrEvo UK Limited method 140/01/012, “Fruit and Vegetables:
Analytical Method for the Determination of Residues (Improved Version),
Pyrimethanil, Active Substance.”  Pyrimethanil residues in lemon were
extracted by homogenization with acetone.  An aliquot of the extract was
acidified then washed with hexane before adding base to enable solvent
partition.  Final clean-up was by silica SPE, with determination by
GC/MSD.

Based on recoveries of samples fortified at the LLMV, 0.05 ppm, the LOD
and LOQ were calculated as 0.017 ppm and 0.052 ppm, respectively.  No
residue decline data was submitted.

Conclusions:  In combination with previously reviewed data and the
established tolerance of 10 ppm for postharvest treatment of citrus
fruit, ARIA recommends for a tolerance in/on fruit, citrus, group 10 at
11 ppm which will include the labeled preharvest and postharvest
applications of pyrimethanil to lemons and the postharvest applications
to the remainder of the citrus fruit group.  Concomitant with the
establishment of the recommended tolerance, ARIA recommends for the
removal of the current 10 ppm tolerance on fruit, citrus, group 10
postharvest.

Stone Fruit - Postharvest Studies 

47425601.der.doc, D. Rate, 03/NOV/2008. (Peach)

47425602.der.doc, D. Rate, 03/NOV/2008. (Plum)

47425603.der.doc, D. Rate, 03/NOV/2008. (Sweet Cherry)

47425605.der.doc, D. Rate, 03/NOV/2008. (Cherry)

Peach:

Table 5.  Summary of Residue Data from Crop Field Trials with
Pyrimethanil.

Commodity	Analyte	Total Application Rate,

(lb ai/100 gal mix)	Total Application  Rate

(ml ai /200,000 lb fruit)	Residue Levels (ppm)

Sample size (n)	Min.	Max.	HAFT*	Median	Mean	Std. Dev.

Peach	Pyrimethanil	0.868 – 0.882

6	3.4	8.2	7.4	5.7	5.5	1.8

	0.882 – 0.917	4	0.97	2.1	2.0	1.4	1.5	0.57

	0.926 – 0.935	4	2.3	3.3	2.9	2.6	2.7	0.43

*HAFT = Highest Average Field Trial

  SEQ CHAPTER \h \r 1 IR-4 submitted data for postharvest use of
pyrimethanil on peach.  To support the establishment of a tolerance for
pyrimethanil, the submitted data were obtained from 2 trials conducted
in California (EPA Region 10) and 1 trial in New Jersey (EPA Region 2). 
Postharvest trials were conducted to represent the main growing regions
and methods of application. 

At each test location peaches were dipped for approximately 30 seconds
in the fungicide solution with concentration 0.882 lb ai/100 gal
(treatment 2; 2x the proposed application rate).  Two additional
treatments were examined at the two California trials where peaches were
sprayed with Penbotec 400SC at a rate of approximately 0.882 lb
ai/200,000 lb fruit in a high-volume spray (treatment 3) and in a low
volume spray (treatment 4).  A fruit wax adjuvant was added to the
applied mixtures in all treatments.  After treatment, the peaches were
allowed to dry and the pits were removed.

Pyrimethanil residues were extracted from homogenized samples and after
clean-up analyzed by GC/MSD.  The procedure was derived from the AgrEvo
UK Limited method, “Fruit and Vegetables: Analytical Method for the
Determination of Residues (Improved Version), Pyrimethanil, Active
Substance.”  The method is acceptable as a data-gathering method.  



Plum:

Table 6.  Summary of Residue Data from Crop Field Trials with
Pyrimethanil.

Commodity	Total Applic. Rate

 (lb ai/100 gal)	PHI (days)	Residue Levels (ppm)

	Sample size (n)	Min.	Max.	HAFT*	Median	Mean	Std. Dev.

Plum	0.879 – 0.881	NA	6	0.612	2.00	1.90	0.908	1.146	0.597

	0.890	NA	2	0.200	0.204	0.202	0.202	0.202	–

	0.916	NA	2	0.295	0.347	0.321	0.321	0.321	–

*HAFT = Highest Average Field Trial

  SEQ CHAPTER \h \r 1 IR-4 submitted data for postharvest use of
pyrimethanil on plum.  To support the establishment of a tolerance for
pyrimethanil, the submitted data were obtained from 1 trial conducted in
California (EPA Region 10), 1 trial in Washington (EPA Region 11) and
one in Michigan (EPA Region 5) during the 2004 growing season.  The
number of field trials and geographic representation are not in
accordance with OPPTS Guideline 860.1500 as this is a postharvest study.
 Postharvest trials were conducted to represent the main growing regions
and methods of application.

At each trial, plums were dipped for approximately 30 seconds in the
fungicide solution with a concentration of approximately 0.881 lb ai/100
gal mix (treatment 2; 2x the proposed application rate).  Two additional
treatments were examined at the California trial where plums were
sprayed with Penbotec 400SC at rates of approximately 0.890 lb ai/
200,000 lb fruit in a high-volume spray (treatment 3) and 0.917 lb ai/
200,000 lb fruit and in a low-volume spray (treatment 4).  A fruit wax
adjuvant was added to the applied mixtures in all treatments.  After
treatment, the plums were allowed to dry and the pits were removed.  

Pyrimethanil residues were extracted from homogenized samples and after
clean-up analyzed by GC/MSD.  The procedure was derived from the AgrEvo
UK Limited method, “Fruit and Vegetables: Analytical Method for the
Determination of Residues (Improved Version), Pyrimethanil, Active
Substance.”  The method is acceptable as a data-gathering method.  

Tart Cherry:

Table 7.  Summary of Residue Data at 0 day after application from Crop
Field Trials with Pyrimethanil

Commodity	Total Applic. Rate

 (ppm)	Sample size (n)	Residue Levels (ppm)

	Min.	Max.	HAFT*	Median	Mean	Std. Dev.

Cherry	323	16	0.61	1.21	1.16	1.03	0.98	0.20

	430	16	0.93	1.39	1.25	1.22	1.19	0.14

*HAFT = Highest Average Field Trial

  SEQ CHAPTER \h \r 1 IR-4 submitted data to support the establishment
of a tolerance for pyrimethanil postharvest use on cherry.  The
submitted data were obtained from 4 trials with cherries from different
origins (Chile and Argentina) of South America.  Cherries were purchased
at the local German market.  The field portion of the study was
conducted by eurofins-GAB GmbH in Niefern-Öschelbronn, Germany.  The
analytical portion of the study was conducted by eurofins-GAB GmbH at
Pforzheim, Germany.

Control samples were taken before the application.  One postharvest
application of active ingredient LAG 2002 259 (synonym: Penbotec 400 SC)
was made using two different treatments with two different
concentrations: ~300 ppm and ~400 ppm (0.65x and 0.86x the proposed
rate, respectively).  The fruits were dipped once into the treatment
solution for 30 – 60 seconds (treatment 1) and for 45 seconds
(treatment 2).  After being dried at room temperature, fruit samples
were stored at different testing conditions: chilled (CS), ambient (AS)
or at a combination of chilled and ambient storage conditions (CAS). 
Treated samples were taken at different storage time intervals.  After
stones were removed from the fruits, treated and untreated samples were
placed and stored in deep freezing conditions at ≤ –19o C until
analysis.

Residues were extracted with acetonitrile and were analyzed by HPLC with
tandem mass spectrometry (MS/MS) detection.  Method validation recovery
at fortification levels 0.01 ppm – 2.0 ppm was 93 ( 5 % with a LOQ of
0.01 ppm.  This method is adequate for data collection.

Sweet Cherry:

Table 8.  Summary of Residue Data from Crop Field Trials with
Pyrimethanil.

Commodity	Total Applic. Rate

 (g ai/ 100 gal)

[Dip]	Total Applic. Rate

 (g ai/ 25,000 lb fruit)

[High volume]	Sample size (n)	Residue Levels (ppm)

Min.	Max.	HAFT*	Median	Mean	Std. Dev.

Sweet Cherry	398.89 – 399.70

6	2.1	13.0	12.5	5.7	6.8	4.7

399.05 –  418.10	4	1.2	12.0	12.0	6.6	6.6	6.2

*HAFT = Highest Average Field Trial

  SEQ CHAPTER \h \r 1 IR-4 submitted data for postharvest use of
pyrimethanil on sweet cherry.  To support the establishment of a
tolerance for pyrimethanil in/on sweet cherry, the submitted data were
obtained from one trial conducted in California (EPA Region 10), one
trial in Washington (EPA Region 11) and one in Michigan (EPA Region 5)
during the 2006 growing season.  The number of field trials and
geographic representation are not in accordance with OPPTS Guideline
860.1500 as this is a postharvest study.  Postharvest trials were
conducted to represent the main growing regions and methods of
application.

At each trial, fruit was dipped for approximately 30 seconds in the
fungicide solution (Penbotec 400 SC) with a concentration of
approximately 400 g ai/100 gal mix (treatment 2; 2x the proposed
application rate).  Two additional treatments were examined at a
high-volume application rate of 400 g ai/25,000 lb fruit at the
California and Washington trials, where cherries were sprayed on a
packing line (treatment 3) and with a backpack sprayer (treatment 4),
respectively. A fruit wax was added to the applied mixtures in all
treatments.  After treatment, the fruit was allowed to dry and the stems
and pits were removed. 

Pyrimethanil residues were extracted from homogenized samples, and
analyzed by GC/MSD after SPE clean-up.  

Conclusions:  The petitioner requested a tolerance of 10 ppm on stone
fruit.  Preharvest uses currently have an established tolerance of 3 ppm
on stone fruit (except cherry).  The data submitted with this petition
are for the postharvest application to representative crops of peaches,
plums and cherries.  The field trial studies were performed at 2x the
proposed application rate for all commodities except the tart cherries
for which the two submitted studies were performed at 0.65x and 0.86x
the proposed use rate.  Due to the nature of the postharvest
applications, the Agency will allow on a case-by-case basis for the
residues to be normalized to the proposed 1x application rate. 
Following a normalization process for all submitted data and
commodities, the highest postharvest application residues would likely
occur at a level of 6.5 ppm on sweet cherries.  The highest postharvest
application residues (6.5 ppm) + the established tolerance for
preharvest uses on stone fruit (except cherry) (3 ppm) are not expected
to exceed the requested tolerance of 10 ppm. 

The submitted data in conjunction with previously reviewed data support
a tolerance of 10 ppm on the proposed/labeled pre- and postharvest uses
of stone fruit.  Thus, ARIA recommends for the following tolerances: 10
ppm in/on fruit, stone.  ARIA also recommends for the removal of the
current tolerance of 3.0 ppm on fruit, stone (except cherry)
(postharvest).

860.1520 Processed Food and Feed

Processing studies for plum and citrus fruit were previously reviewed
(DP# 284001 and 284870, J. Morales, 12/JAN/2004) and pyrimethanil
residues were found not to concentrate in prunes, following an
exaggerated (5x) study.  However, pyrimethanil residues did concentrate
(16x) in citrus oil.  No additional processed food and feed studies were
necessary or submitted for the proposed uses and requested tolerances of
the current petition.  

  SEQ CHAPTER \h \r 1 860.1650 Submittal of Analytical Reference
Standards

Analytical standards for pyrimethanil, with an expiration date
01/SEP/2008, are currently available in the EPA National Pesticide
Standards Repository.  The petitioner should submit new analytical
standards for pyrimethanil, to replace the expired samples.  

860.1850 and 1900 Confined and Field Accumulation in Rotational Crops

Stone fruits and lemons are typically not rotated.  Therefore, residue
data pertaining to confined and field accumulation in rotational crops
are not germane to this tolerance petition.

860.1550 Proposed Tolerances

The Agency has determined that the residue of concern for the purpose of
tolerance expression in plants is parent only.  The residues of concern
for tolerance expression in ruminant tissues are parent + Metabolite
AEC614276, and for milk are parent + Metabolite AEC614277; see Figure 1
(Attachment 1) for chemical names and structures of these regulated
compounds.  The tolerance expressions proposed by the petitioner in its
submission of Section F are consistent with the tolerance definitions
for pyrimethanil in 40 CFR §180.518.

A summary of the recommended tolerances for the commodities addressed in
the current petition is listed in Table 9.

The recommended tolerance of 10 ppm for stone fruits (crop group 12) is
adequate and is supported by the submitted residue data.  When the
maximum residues from all routes of pyrimethanil exposure to stone
fruits (crop group 12) are considered (i.e., postharvest by high-volume
spray, drench or dip, or low-volume spray + preharvest application), the
total residues (ppm) are expected to be below the recommended tolerance.

The proposed tolerance of 10 ppm for citrus fruits (crop group 10)
(except lemon) is adequate and is supported by previously reviewed
residue data reflecting the proposed use pattern (DP#   SEQ CHAPTER \h
\r 1 284001 and 284870,   SEQ CHAPTER \h \r 1 J. Morales and   SEQ
CHAPTER \h \r 1 G. Kramer,   SEQ CHAPTER \h \r 1 12/JAN/2004).  However,
when the maximum residues from all routes of pyrimethanil exposure to
citrus fruits (crop group 10), are considered (i.e., postharvest by line
spray aqueous and wax + postharvest by dip or drench + preharvest use on
lemons), the expected total residues (ppm) will exceed the proposed
tolerance.  Thus, ARIA recommends for a tolerance of 11 ppm for all
labeled uses of pyrimethanil on fruit, citrus (crop group 10).

Codex maximum residue limits (MRLs) have been established for
pyrimethanil per se in/on plant commodities.  Codex MRLs are listed for
citrus fruit at 7 ppm (postharvest); cherry (postharvest), peach and
nectarine at 4 ppm; apricot at 3 ppm; and plum at 2 ppm.  Presumably due
to differences in application and use patterns, harmonization is not
feasible at this time.

A Canadian MRL for citrus fruit (Calamondins, citrus citron, citrus
hybrids, grapefruits, kumquats, lemons, limes, oranges, pummelos,
satsuma mandarins, tangerines) is established at 10 ppm and for stone
fruit (apricots,  nectarines, peaches, plumcots, plums, prune plums)
established at 3 ppm.  There are no Mexican MRLs established for
residues of pyrimethanil in commodities associated with this review.  

An International Residue Limit (IRL) form is appended to this Summary
Document and follows this section.

Table 9.  Tolerance Summary for Pyrimethanil.

Commodity	Proposed / Established Tolerance (ppm)	Recommended Tolerance
(ppm)	Comments; Correct Commodity Definition

40 CFR §180.518 (a)(1)

Stone Fruits (Crop Group 12) 	10	10	Fruit, stone, group 12

Citrus Fruits (Crop Group 10) 	10	11	Fruit, citrus, group 10

	Fruit, stone (except cherry), group 12	3.0	Remove

	Fruit, citrus, group 10 (postharvest)	10	Remove

	

References

DP#:	NA

Subject:	Magnitude of the Residue Studies

From:	S. Usachenko

To:	D. Rate

Dated:	03/NOV/2008

MRIDs:	47425601, 47425602, 47425603, 47425604, 47425605

DP#:		284866

Subject:	  SEQ CHAPTER \h \r 1 PP#s: 2F6480, 9E6054, 2F6439. 
Pyrimethanil in/on Tree Nuts, Bulb Vegetables, Grapes, Stone Fruit
(except Cherry), Pome Fruit, Citrus Fruit, Tuberous and Corm Vegetables,
Strawberry, Tomato, and Imported Banana.  Health Effects Division (HED)
Risk Assessment.  PC Code: 288201.

From:	D. Vogel and Y. Yang

To:	S. Gardner and M. Waller

Dated:	15/NOV/2004

MRIDs:	  SEQ CHAPTER \h \r 1 NA

DP#:	  SEQ CHAPTER \h \r 1 284001 and 284870

Subject:	  SEQ CHAPTER \h \r 1 PP#s 2F06439 & 2F06480.  Pyrimethanil on
Tree Nuts, Stone Fruit, Bulb

Vegetables, Grapes, Pome Fruit, Tuber & Corm Vegetables, Strawberries,

and Tomatoes.  Summary of Analytical Chemistry and Residue Data.

From:		J. Morales and G. Kramer

To:		D. Vogel and M. Waller

Dated:		12/JAN/2004

MRIDs:	Various

  SEQ CHAPTER \h \r 1 Attachment:

International Residue Limit Status sheet



INTERNATIONAL RESIDUE LIMIT STATUS

Chemical Name: 

4,6-Dimethyl-N-phenyl-2-pyrimidinamine	Common Name:

Pyrimethanil

	√ Proposed/Recommended Tolerance

( Reevaluated tolerance

( Other	Date:  01/13/2008

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
Number:  PP#  8E7353

DP#:  361301

Other Identifier:  

Residue definition (step 8/CXL): pyrimethanil for plant commodities. 
For compliance with MRLs and estimation of dietary intake for plant
commodities: pyrimethanil

For compliance with MRLs for milk: the sum of pyrimethanil and
2-anilino-4,6-dimethylpyrimidin-5-ol, expressed as pyrimethanil, and for
livestock tissues (excluding poultry) is the sum of pyrimethanil and
2-(4-hydroxyanilino)-4,6-dimethylpyrimidine, expressed as pyrimethanil.

	Reviewer/Branch:  D. Rate/ARIA/RIMUERB 

	Residue definition:

Plants  - Parent only

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

Citrus fruit (post harvest)	7	Citrus Fruit (Crop Group 10), 	11

Cherry (post harvest)	4	Stone Fruit (Crop Group 12) 	10

Apricot	3

Peach	4

Nectarine	4

Plum	2

Limits for Canada	Limits for Mexico

( No Limits

( No Limits for the crops requested	( No Limits

 √ No Limits for the crops requested

Residue definition: 

4,6-dimethyl-N-phenyl-2-pyrimidinamine

	Residue definition:  pyrimethanil

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

Calamondins, citrus citron, citrus

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Pyrimethanil	Summary of Analytical Chemistry and Residue Data	DP# 361301

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