   SEQ CHAPTER \h \r 1 

	UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF           

CHEMICAL SAFETY AND

POLLUTION PREVENTION

MEMORANDUM

Date:		09-FEB-2011

Subject:	Pyrasulfotole.  Section 3 Request for Use on Sorghum and Grass
Grown for Seed.  Summary of Analytical Chemistry and Residue Data.

PC Code:  000692  	DP Barcode:  D375391   

Decision No.:  425581	Registration No.:  264-1023

Petition No.:  9F7680	Regulatory Action:  Section 3 Registration

Risk Assessment Type:  NA	Case No.:  7272

TXR No.:  None	CAS No.:  365400-11-9 

MRID No.:  47815001 and 47815002	40 CFR:  180.631



From:		Jennifer R. Tyler, Chemist

		Risk Assessment Branch (RAB1)

		Health Effects Division (HED) (7509P)

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

		RAB1/HED (7509P)

To:		Bethany Benbow/Joanne Miller, RM Team 23

		Registration Division (RD) (7505P)

Bayer CropSciences has submitted a petition for the use of the active
ingredient (ai) pyrasulfotole
((5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl)[2-(methylsulfonyl)-4-(trifluor
omethyl)phenyl]methanone) on sorghum and grass grown for seed.  Bayer
has requested the establishment of permanent tolerances for
pyrasulfotole and its metabolite,
5-hydroxy-3-methyl-1H-pyrazol-4-yl)[2-(methylsulfonyl)-4-(trifluoromethy
l)phenyl]methanone, in or on the following raw agricultural commodities
(RACs):

Sorghum, grain	0.8 ppm

Sorghum, forage	1.2 ppm

Sorghum, stover	0.35 ppm

Grass, forage	10 ppm

Grass, hay	2.5 ppm



In addition, Bayer has requested permanent tolerances for pyrasulfotole
pyrasulfotole
((5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl)[2-(methylsulfonyl)-4-(trifluor
omethyl)phenyl]methanone) in or on the following commodities:

Milk	0.01 ppm	Hog, liver	8 ppm

Cattle, meat	0.04 ppm	Hog, meat byproducts	2 ppm

Cattle, fat	0.04 ppm	Sheep, meat	0.04 ppm

Cattle, liver	8 ppm	Sheep, fat	0.04 ppm

Cattle, meat byproducts	2 ppm	Sheep, liver	8 ppm

Goat, meat	0.04 ppm	Sheep, meat byproducts	2 ppm

Goat, fat	0.04 ppm	Horse, meat	0.04 ppm

Goat, liver	8 ppm	Horse, fat	0.04 ppm

Goat, meat byproducts	2 ppm	Horse, liver	8 ppm

Hog, meat	0.04 ppm	Horse, meat byproducts	2 ppm

Hog, fat	0.04 ppm





Executive Summary

Pyrasulfotole is a postemergence dicot herbicide currently registered
for use on small cereal grains, including wheat, barley, oat, rye, and
triticale.

™ Herbicide, an emulsifiable concentrate (EC) comprised of 37.5 g/L of
pyrasulfotole, bromoxynil (present as the mixed heptanoate and octanoate
esters), and the safener mefenpyr-diethyl for use on grain sorghum and
grass grown for seed.  The EC formulation is being proposed for two
ground or foliar applications per season to the above crops at rates of
0.073-0.078 lb pyrasulfotole/A.  HED notes that this document pertains
to the ai pyrasulfotole only.

The use directions provided by the petitioner are adequate to allow
evaluation of the residue data relative to the proposed uses on grain
sorghum and grass grown for seed, with the exception of instructions for
the use of adjuvants and the proposed application type/equipment or
spray volume for grass grown for seed.  The submitted magnitude of the
residue studies were performed without the use of adjuvants.  Therefore,
the label should be amended to prohibit the use of adjuvants on grain
sorghum and grass grown for seed.  In addition, the available magnitude
of residue data support broadcast foliar spray applications, and a spray
volume of 10-24 gal/A.  The proposed label should be revised to specify
instructions of application equipment and spray volume for grass grown
for seed.

The nature of the pyrasulfotole residues sorghum and grass is understood
based on previously submitted and reviewed metabolism studies on wheat
(Memo, J. Tyler, 6/8/07; D333412).  The metabolism of pyrasulfotole in
spring wheat involves the demethylation and subsequent glucosylation of
the parent compound, yielding pyrasulfotole-desmethyl-O-glucoside. 
There was also cleavage of the complete pyrazole moiety resulting in the
pyrasulfotole-benzoic acid metabolite.  Based on the results of the
wheat metabolism studies, parent and pyrasulfotole-desmethyl are the
residues of concern for tolerances and risk assessment purposes (Memo,
J. Tyler et al., 06/08/07; D328640).  Any future uses on other crops,
such as leafy vegetables, or legumes, may require the submission of
additional metabolism data.

The nature of the pyrasulfotole residues in livestock is understood
based on previously submitted and reviewed lactating goat and laying hen
metabolism studies (Memo, J. Tyler, 6/8/07; D333412).  The goat study
indicates that the metabolism of pyrasulfotole in lactating goats
involved either N-demethylation of pyrasulfotole to form
pyrasulfotole-desmethyl, or oxidation of pyrasulfotole to form
pyrasulfotole-hydroxymethyl.  The hen study indicates that the
metabolism of pyrasulfotole in laying hens involved the N-demethylation
of pyrasulfotole to yield the pyrasulfotole-desmethyl metabolite.  The
residues of concern in livestock for tolerance and risk assessment
purposes are parent and the desmethyl metabolite (Memo, J. Tyler,
06/08/07; D328640).

An adequate high-performance liquid chromatography (HPLC)/mass
spectrometry (MS)/MS method (Method AI-001-P04-02) is available for
collecting data on residues of pyrasulfotole and its metabolite
pyrasulfotole-desmethyl in/on plant commodities.  The limit of
quantitation (LOQ) is 0.010 ppm for each analyte.  A similar method,
Method AI-001-P04-01, which is also the proposed enforcement method for
plant commodities, has been adequately radiovalidated and undergone a
successful independent laboratory validation (ILV) trial.  Method
AI-001-P04-01 was forwarded to the Analytical Chemistry Branch of the
Biological & Economics Analysis Division (ACB/BEAD) for a petition
method validation (PMV; Memo, J. Tyler, 1/30/07; D335558).  ACB reviewed
the proposed enforcement method data without a laboratory validation,
but recommended the petitioner provide information for a second MS/MS
ion transition to provide a confirmation of analyte identities (Memo, C.
Stafford, 6/7/07; D335559).  In response, the company submitted Bayer
Method AI-001-P04-02, which includes the requested information for a
second MS/MS ion transition.  HED reviewed this method, and determined
it suitable for determination of pyrasulfotole and
pyrasulfotole-desmethyl in crop matrices (Memo, G. Kramer, 12/18/09;
D367796).

A HPLC-MS/MS method (Method AI-004-A05-01) for collecting data on
pyrasulfotole in livestock tissues, including milk, matrices was
previously submitted and reviewed by HED (Memo, J. Tyler, 06/08/07;
D333412).  However, based on the results of the livestock metabolism
studies, the residues of concern in livestock are pyrasulfotole and
pyrasulfotole-desmethyl for tolerance and risk assessment purposes
(Memo, J. Tyler et al., 6/8/07; D328640).  Therefore, HED requested the
petitioner submit a ruminant analytical enforcement method to determine
residues of pyrasulfotole and pyrasulfotole-desmethyl as well as
adequate radiovalidation and ILV data.  In response, the company
submitted a new HPLC-MS/MS (Method AI-006-A08-01) for collecting
pyrasulfotole and pyrasulfotole-desmethyl in livestock tissues and milk,
as well as ILV data.  HED reviewed these submissions; and, based on
validation data provided by the petitioner and the successful ILV,
determined that Method AI-006-A08-01 is suitable as an enforcement
method for livestock commodities as defined in Standard Operating
Procedure (SOP) No. ACB-019 (9/15/08) (Memo, G. Kramer, 12/18/09;
D367796).  HED also determined that radiovalidation data are not
necessary as the extraction procedures are identical to the previous
version of the method (for which adequate extraction efficiency data
were provided).

Pyrasulfotole and the metabolite pyrasulfotole-desmethyl were subjected
to analysis by selected Protocols of the Food and Drug Administration
(FDA) Pesticide Analytical Manual, Volume I (PAM I), third edition.  The
results indicate that pyrasulfotole is partially recovered through
Protocol B, and completely recovered through Protocol C module DG-17. 
Pyrasulfotole-desmethyl was not recovered through any of the Protocols. 
The report has been forwarded to FDA for inclusion in PAM I (Memo, J.
Tyler, 1/30/07; D335562). 

No storage stability data were submitted in conjunction with the
proposed uses.  The available storage stability data are acceptable and
indicate that residues of pyrasulfotole and pyrasulfotole-benzoic acid
are stable in soybean seed and wheat matrices for up to 11 months, and
residues of pyrasulfotole-desmethyl decline in wheat forage and hay (ca.
0.12% per day) in frozen storage.  The storage stability data support
the sample storage intervals and conditions in the submitted crop field
trials.  Corrections to residues of pyrasulfotole due to in-storage
dissipation are not necessary, but residues of pyrasulfotole-desmethyl
in sorghum forage and stover, and grass forage and hay will require
corrections for in-storage dissipation.

The results of the cattle feeding study are adequate for purposes of
this action.  HED assumed the transfer of pyrasulfotole-desmethyl from
plant to livestock to be equivalent to that of the parent pyrasulfotole
based on the similar structure.  For any new uses which significantly
increase the maximum reasonable dietary burden (MRDB) of the metabolite,
the petitioner may be required to submit a feeding study with
pyrasulfotole-desmethyl.

Based on the MRDB for dairy cattle (45 ppm), the actual dose levels in
the feeding study are equivalent to 0.067x, 0.2x, and 0.67x the MRDB for
dairy cattle.  Based on the residues at the 0.67x feeding level, the
current tolerances of 0.02 ppm for meat of cattle, goat, horse and sheep
are adequate to support the proposed uses.  However, tolerances should
be established for residues of pyrasulfotole and pyrasulfotole-desmethyl
in/on milk at 0.03 ppm; fat of cattle, goat, horse and sheep at 0.03
ppm; liver of cattle, goat, horse, and sheep at 3.0 ppm; and meat
byproducts, except liver, of cattle, goat, horse, and sheep at 0.70 ppm.
 A revised Section F should be submitted to include the above
tolerances, as well as correct commodity definitions and tolerance
expression for livestock commodities.

Based upon a MRDB of 0.56 ppm for hogs, there is no reasonable
expectation of finding quantifiable residues of pyrasulfotole and
pyrasulfotole-desmethyl in hog muscle and fat; thus, the current
tolerances of 0.02 ppm are adequate.  There is reasonable expectation of
residues of pyrasulfotole and pyrasulfotole-desmethyl in hog liver and
kidney.  Therefore, the following tolerances for residues of
pyrasulfotole and pyrasulfotole-desmethyl are necessary:  hog, meat
byproducts, except liver at 0.05 ppm; and hog, liver at 0.30 ppm.  A
revised Section F should be submitted to include the above tolerances,
as well as correct commodity definitions and tolerance expression for
livestock commodities.

The results of the poultry feeding study are inadequate to determine the
need for poultry tolerances as only residues of pyrasulfotole-benzoic
acid were measured in the study.  However, the results of the poultry
metabolism studies can be used to determine the need for a new poultry
feeding study and/or poultry tolerances.  Based on the MRDB of 0.52 ppm
for poultry, the phenyl-labeled (8.6 ppm) and pyrazole-labeled (10.5
ppm) poultry metabolism studies were conducted at 16x and 20x the MRDB
for poultry, respectively.  Based on the results of the poultry
metabolism study, there is no reasonable expectation of finding
quantifiable residues of pyrasulfotole and pyrasulfotole-desmethyl in
eggs and poultry muscle and fat; thus, the current tolerances of 0.02
ppm for residues of pyrasulfotole and pyrasulfotole-desmethyl in fat,
meat, and meat byproducts of poultry are adequate.  There is reasonable
expectation of residues of pyrasulfotole and pyrasulfotole-desmethyl in
poultry meat byproducts.  Therefore, a tolerance of 0.20 ppm for
residues of pyrasulfotole and pyrasulfotole desmethyl in poultry
byproducts is necessary.  A revised Section F should be submitted to
include the above tolerances and correct tolerance expression for
livestock commodities.

The available grain sorghum and grass residue data are classified as
scientifically acceptable for determination of the magnitude of residue
for and the metabolite pyrasulfotole-desmethyl when treated with the end
use products Huskie™ Herbicide.  As the number and geographical
representation of the grain sorghum and grass trials are appropriate,
the residue data are adequate to support the proposed uses.

The grain sorghum crop field trial data support a maximum seasonal
application rate of 0.078 pound (lb) ai/acre (A) (~1x the maximum
proposed application rate) on sorghum forage, grain, and stover
[preharvest interval (PHI) of 5-7 days for forage, 60 days for grain and
stover].  With these use patterns, total residues of pyrasulfotole and
pyrasulfotole-desmethyl are not expected to exceed 0.902 ppm (forage,
7-day PHI), 0.325 ppm (grain), and 0.420 ppm (stover).  Using the North
American Free Trade Agreement (NAFTA) Maximum Residue Limit
(MRL)/Tolerance Harmonization Workgroup methodology for forage, grain,
and stover; the available grain sorghum crop field trial data indicate
that the appropriate tolerances for residues of pyrasulfotole and
pyrasulfotole-desmethyl in/on grain sorghum commodities are 1.5 ppm for
sorghum, grain, forage; 0.70 ppm for sorghum, grain, grain; and 0.80 ppm
for sorghum, grain, stover.  Section F of the petition should be revised
to include the aforementioned HED-recommended tolerances and the correct
commodity definitions for grain sorghum RACs.

The grass crop field trial data support a maximum seasonal application
rate of 0.076-0.091 lb ai/A (~1x the maximum proposed application rate)
on grass forage and hay (PHI of 7 days for forage, and 30 days hay). 
With these use patterns, total pyrasulfotole and pyrasulfotole-desmethyl
residue levels are not expected to exceed 6.52 ppm (forage, 7-day PHI)
and 2.31 ppm (hay).  Using the NAFTA MRL/Tolerance Harmonization
Workgroup methodology for forage (7-day PHI) and hay, the available
grass crop field trial data indicate that the appropriate tolerances for
residues of pyrasulfotole and pyrasulfotole-desmethyl in/on grass
commodities are 25 ppm for grass, forage; and 3.5 ppm for grass, hay. 
Section F of the petition should be revised to include the
aforementioned HED-recommended tolerances.

™ Herbicide (EPA Reg. No. 264-1023).  The submitted confined and
limited field trial data support the proposed PBIs.

HED Conclusion/Recommendations

Provided 1) Section B is revised to include a prohibition on the use of
adjuvants on grain sorghum and grass grown for seed and instructions of
application equipment and spray volume for grass grown for seed; 2)
Section F is revised to the HED-recommended tolerances, as well as
correct commodity definitions and tolerance expressions; and 3)
analytical reference standards for pyrasulfotole-desmethyl and labeled
internal standards are submitted to the EPA National Pesticide Standards
Repository, the residue chemistry database supports the establishment of
an unconditional registration and permanent tolerances as listed below.

Tolerances are established for residues of the herbicide pyrasulfotole,
including its metabolites and degradates, in or on the commodities in
the table below.  Compliance with the tolerance levels specified below
is to be determined by measuring only the sum of pyrasulfotole
((5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl)[2-(methylsulfonyl)-4-(trifluor
omethyl)phenyl]methanone) and its desmethyl metabolite
(5-hydroxy-3-methyl-1H-pyrazol-4-yl)[2-(methylsulfonyl)-4-(trifluorometh
yl)phenyl]methanone), calculated as the stoichiometric equivalent of
pyrasulfotole, in or on the following commodities:

Sorghum, grain, grain	0.70 ppm	Hog, fat*	0.02 ppm

Sorghum, grain, forage	1.5 ppm	Hog, liver	0.30 ppm

Sorghum, grain, stover	0.80 ppm	Hog, meat byproducts, except liver	0.05
ppm

Grass, forage	25 ppm	Sheep, meat*	0.02 ppm

Grass, hay	3.5 ppm	Sheep, fat	0.03 ppm

Milk	0.03 ppm	Sheep, liver	3.0 ppm

Cattle, meat*	0.02 ppm	Sheep, meat byproducts, except liver	0.70 ppm

Cattle, fat	0.03 ppm	Horse, meat*	0.02 ppm

Cattle, liver	3.0 ppm	Horse, fat	0.03 ppm

Cattle, meat byproducts, except liver	0.70 ppm	Horse, liver	3.0 ppm

Goat, meat*	0.02 ppm	Horse, meat byproducts, except liver	0.70 ppm

Goat, fat	0.03 ppm	Poultry, meat*	0.02 ppm

Goat, liver	3.0 ppm	Poultry, fat*	0.02 ppm

Goat, meat byproducts, except liver	1.0 ppm	Poultry, meat byproducts
0.20 ppm

Hog, meat*	0.02 ppm	Eggs*	0.02 ppm

* The recommended tolerances for these commodities are at the same level
as the current tolerances under 40 CFR 180.631.

A human-health risk assessment will be prepared as a separate document.

Background

Pyrasulfotole is a postemergence dicot herbicide currently registered
for use on small cereal grains, including wheat, barley, oat and
triticale.  Pyrasulfotole is an effective inhibitor of the enzyme
4-hydroxyphenylpyruvate dioxygenase (HPPDase) and consequently blocks
the pathway of prenylquinone biosynthesis in plants.  The end-use
products are applied to the target weeds and act primarily through leaf
uptake and translocation to the target site.  The first symptoms appear
three to five days after application.  Bleaching and discoloration
appear initially and symptoms progress to tissue necrosis and plant
death within two weeks. 

Huskie™ Herbicide is an EC mixture containing pyrasulfotole,
bromoxynil, and mefenpyr-diethyl safener.  The nomenclature and
physicochemical properties of pyrasulfotole are presented below in
Tables 1 and 2.



Table 1.  Test Compound and Metabolite Nomenclature.

Compound	Chemical Structure



Common name	Pyrasulfotole

Company Experimental name	AE 0317309

IUPAC name	5-hydroxy-1,3-dimethylpyrazol-4-yl
2-mesyl-4-(trifluoromethyl)phenyl ketone

CAS name
(5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl)[2-(methylsulfonyl)-4-(trifluoro
methyl)phenyl]methanone

CAS #	365400-11-9

End-use products (EPs)	AE 0317309 SE06 Herbicide and AE 0317309 +Bromo
Herbicide

Compound	Chemical Structure



Common name	Pyrasulfotole-desmethyl

Company Experimental name	AE 1073910

CAS name
(5-hydroxy-1H-pyrazol-4-yl)[2-mesyl-4-(trifluoromethyl)phenyl]methanone



Table 2.  Physicochemical Properties of the Technical Grade Test
Compound.

Parameter	Value	Reference

Melting point	Pure: 201°C

No boiling point, decomposition starts at 245°C	MRID 46801701

pH at 22.9°C	3.03

	Density	1.53

	Water solubility (g/L at 20(C)	2.3

4.2 

69.1 

49.0

	pH 3.0 (distilled water)

pH 3.9 (buffer pH 4.0)

pH 5.4 (buffer pH 7.0)*

pH 5.2 (buffer pH 9.0)*

* exceeded buffer capacity

	Solvent solubility (g/L at 20(C)	Ethanol 

n-Hexane

Tolune

Dichloromethane

Ac瑥湯൥瑅票⁬捡瑥瑡൥楄敭桴汹猠汵潦楸敤㈇⸱ശ⸰
㌰സ⸶㘸ㄍ〲ㄭ〵㠍⸹ല㜳㈮

≥ 600

	Vapor pressure at 20(C	2.7 X 10-7 Pa

	Dissociation constant (pKa)	4.2

	n-octanol-water partition coefficient Log(KOW) at 23°C	0.276

-1.362

-1.580 	pH 4.0

pH 7.0

pH 9.0

	UV/visible absorption spectrum	max= 264, 241, 216 nm in water, 0.1M
HCl, 0.1M NaOH respectively.

	

860.1200 Directions for Use

Pyrasulfotole will be formulated as Huskie™ Herbicide, an EC
formulation containing 0.31 lb ai/gal pyrasulfotole, bromoxynil (present
as the mixed heptanoate and octanoate esters), and the safener
mefenpyr-diethyl for use on grain sorghum and grass grown for seed.  The
following rotational crop restrictions are listed on the proposed label:
 1 month for wheat, barley, oats, rye and triticale; 4 months for
alfalfa, millet, sorghum (grain), and soybeans; and 9 months for canola,
canaryseed, chickpeas, corn, dry beans, flax, field peas, green beans,
green peas, lentils (for all states except 18 months in MN, MT, ND, and
SD), mustards, potatoes, safflower, sunflowers, and sugar beets.  Where
not specified, the label requires a field bioassay be conducted in order
to determine if crop can be successfully rotated with pyrasulfotole.  A
minimum 30-day PBI is required for all crops.  Table 3 is a summary of
the proposed use patterns.  

Table 3.  Summary of Proposed Use Patterns.

Crops	Product

(EPA Reg. No.)	Application Timing; Type; and Equip.	# App.	Application
Rate

(lb ai/A)	RTI1 (days)	PHI1

Huskie™ Herbicide (EPA Reg. No. 264-1023)	Crop application – apply
between 3-leaf stage of growth up to 12 inches.

Ground equipment as a foliar spray.	2	0.039	0.078	11	Forage – 7 days;
grains or stover – 60 days	Apply in 10-15 gal of water/A.



Grass grown for seed	Huskie™ Herbicide (EPA Reg. No. 264-1023)	Crop
application – apply to actively growing grass between 3-leaf stage up
to 12 inches.	2	0.036	0.073	30	forage – 7 days; hay – 30 days

	1 RTI = retreatment interval; PHI = preharvest interval; NA = not
applicable.

HED Conclusions:  The use directions provided by the petitioner are
adequate to allow evaluation of the residue data relative to the
proposed uses on grain sorghum and grass grown for seed, with the
exception of instructions for the use of adjuvants and the proposed
application type/equipment or spray volume for grass grown for seed. 
The submitted magnitude of residue studies were performed without the
use of adjuvants.  Therefore, the label should be amended to prohibit
the use of adjuvants on grain sorghum and grass grown for seed.  In
addition, the available magnitude of residue data support broadcast
foliar spray applications, and a spray volume of 10-24 gal/A.  The
proposed label should be revised to specify instructions of application
equipment and spray volume for grass grown for seed. 

860.1300 Nature of the Residue - Plants

Data concerning the metabolism of pyrasulfotole in spring wheat were
submitted and reviewed in conjunction with PP#6F7509 (Memo, J. Tyler,
6/8/07; D333412).  A total of three studies were submitted, including a
phenyl-labeled study (MRID 46801749), a pyrazole-labeled study (MRID
46801748), and a phenyl-labeled study comparing the nature of the
residue in spring wheat with and without the safener (MRID 46801801). 
The available wheat metabolism studies are adequate, and indicate that
the metabolism of pyrasulfotole in spring wheat involves the
demethylation and subsequent glucosylation of the parent compound,
yielding pyrasulfotole-desmethyl-O-glucoside.  There was also cleavage
of the complete pyrazole moiety resulting in the pyrasulfotole-benzoic
acid metabolite as detected by the phenyl-label study and polar fraction
(p1) formed from the pyrazole-label study.  Fraction p1 was
characterized as being natural or incorporated into the matrix.  Based
on the results of the wheat metabolism studies, parent and
pyrasulfotole-desmethyl are the residues of concern for tolerances and
risk assessment purposes (Memo, J. Tyler et al., 06/08/07; D328640). 
This conclusion applies to the use of pyrasulfotole on grain sorghum and
grass grown for seed.  However, any future uses on other crops, such as
leafy vegetables, or legumes, may require the submission of additional
metabolism data.

860.1300 Nature of the Residue - Livestock

Data concerning the metabolism of pyrasulfotole in ruminants (lactating
goat) and poultry (laying hen) were submitted and reviewed in
conjunction with PP#6F7509 (Memo, J. Tyler, 6/8/07; D333412).  The
nature of the pyrasulfotole residues in livestock is understood based on
the acceptable phenyl- and pyrazole-labeled lactating goat and laying
hen metabolism studies.  The goat study indicates that the metabolism of
pyrasulfotole in lactating goats involved either N-demethylation of
pyrasulfotole to form pyrasulfotole-desmethyl, or oxidation of
pyrasulfotole to form pyrasulfotole-hydroxymethyl.  The hen study
indicates that the metabolism of pyrasulfotole in laying hens involved
the N-demethylation of pyrasulfotole to yield the
pyrasulfotole-desmethyl metabolite.  The residues of concern in
livestock for tolerance and risk assessment purposes are parent and the
desmethyl metabolite (Memo, J. Tyler, 06/08/07; D328640).

860.1340 Residue Analytical Method – Plants

In the grain sorghum and grass grown for seed magnitude of residue
studies, residues of pyrasulfotole and its metabolite
pyrasulfotole-desmethyl quantitated using Bayer Method AI-001-P04-01, an
LC-MS/MS using the stable isotopically labeled analytes as internal
standards.  The lowest limit of method validation (LLMV) for each
analyte was 0.01 ppm in all matrices.  The method is acceptable based on
concurrent recoveries.  All residues were reported in parent
equivalents.

Bayer Method AI-001-P04-01, an HPLC-MS/MS method, has been adequately
radiovalidated and has undergone a successful ILV trial.  The proposed
method was forwarded to ACB/BEAD for a PMV (Memo, J. Tyler, 1/30/07;
D335558).  ACB reviewed the proposed enforcement method data without a
laboratory validation, but recommended the petitioner provide
information for a second MS/MS ion transition to provide a confirmation
of analyte identities (Memo, C. Stafford, 6/7/07; D335559).  In
response, the company submitted Bayer Method AI-001-P04-02 (MRID
47806401), which includes the requested information for a second MS/MS
ion transition.  HED reviewed this method, and determined it suitable
for determination of pyrasulfotole and pyrasulfotole-desmethyl in crop
matrices (Memo, G. Kramer, 12/18/09; D367796).

860.1340 Residue Analytical Method – Livestock

A HPLC-MS/MS method (Method AI-004-A05-01) for collecting data on
pyrasulfotole in livestock tissues, including milk, matrices was
previously submitted and reviewed by HED (Memo, J. Tyler, 06/08/07;
D333412).  However, based on the results of the livestock metabolism
studies, the residues of concern in livestock are pyrasulfotole and
pyrasulfotole-desmethyl for tolerance and risk assessment purposes
(Memo, J. Tyler et al., 6/8/07; D328640).  Therefore, HED requested the
petitioner submit a ruminant analytical enforcement method to determine
residues of pyrasulfotole and pyrasulfotole-desmethyl as well as
adequate radiovalidation and ILV data.  In response, the company
submitted a new HPLC-MS/MS (Method AI-006-A08-01) for collecting
pyrasulfotole and pyrasulfotole-desmethyl in livestock tissues and milk
(MRID 47860002), as well as ILV data (MRID 47860003).  HED reviewed
these submissions; and, based on validation data provided by the
petitioner and the successful ILV, determined that Method AI-006-A08-01
is suitable as an enforcement method for livestock commodities as
defined in SOP No. ACB-019 (9/15/08) (Memo, G. Kramer, 12/18/09;
D367796).  HED also determined that radiovalidation data are not
necessary as the extraction procedures are identical to the previous
version of the method (for which adequate extraction efficiency data
were provided).

860.1360 Multiresidue Methods (MRM)

Bayer CropScience previously submitted adequate MRM recovery data for
pyrasulfotole and the metabolite pyrasulfotole-desmethyl through FDA
Protocols A through E (Memo, J. Tyler, 06/08/07; D328640). 
Pyrasulfotole and the metabolite pyrasulfotole-desmethyl were subjected
to analysis by selected Protocols of the FDA PAM I, third edition. 
Pyrasulfotole and pyrasulfotole-desmethyl were tested according to
Protocols A, B, and C of the FDA PAM I testing procedures.  The results
of the MRM analysis indicate that pyrasulfotole is partially recovered
through Protocol B, and completely recovered through Protocol C module
DG-17.  Pyrasulfotole-desmethyl was not recovered through any of the
Protocols.  The report has been forwarded to FDA for inclusion in PAM I
(Memo, J. Tyler, 1/30/07; D335562). 

860.1380 Storage Stability

No storage stability data were submitted in conjunction with the
proposed uses.  The results of a study to determine freezer storage
stability of pyrasulfotole, pyrasulfotole-desmethyl, and
pyrasulfotole-benzoic acid in soybean and wheat matrices have been
submitted and reviewed by HED (Memo, J. Tyler, 06/08/07; D328640).  The
data are acceptable and indicate that residues of pyrasulfotole and
pyrasulfotole-benzoic acid are stable in soybean seed and wheat matrices
for up to 11 months, and residues of pyrasulfotole-desmethyl decline in
wheat forage and hay (ca. 0.12% per day) in frozen storage.  The storage
stability data support the sample storage intervals and conditions in
the submitted crop field trials.

Sorghum:  In the grain sorghum magnitude of residue studies, the maximum
frozen storage interval from sampling to extraction of pyrasulfotole was
398 days for forage and 309 days for grain and stover.  For sorghum
forage, some samples from the crop field trial were stored for
approximately 13 months, which is 2 months longer than the storage
duration used in the wheat storage stability study.  However, it is
unlikely that a 13-month storage stability study within the same cereal
grain crop group would differ significantly from the currently available
11-month wheat study.  Residues of the metabolite,
pyrasulfotole-desmethyl, were stable in wheat grain.  Pyrasulfotole
desmethyl residues were found to decline in wheat forage and hay at
approximately 0.12% per day.  Therefore, pyrasulfotole-desmethyl residue
values in grain sorghum forage samples were corrected for 46.3% decline
based on wheat forage data and pyrasulfotole-desmethyl residue values in
grain sorghum stover were corrected for 46.5% decline based on wheat hay
data.

Grass:  In the grass magnitude of residue study, the maximum frozen
storage interval from sampling to extraction prior to analysis of
pyrasulfotole was 349 days for grass forage and 312 days for grass hay. 
It should be noted that some grass forage samples were stored for
approximately 2 weeks longer than the length of the storage stability
wheat study.  However, it is unlikely that storage stability study
extended by 2 weeks would differ significantly from the currently
available 11-month wheat study.  Residues of the metabolite,
pyrasulfotole-desmethyl, however, were found to decline in wheat forage
and wheat hay at approximately 0.12% per day. Therefore,
pyrasulfotole-desmethyl residue values in grass forage samples were
corrected for 46.3% decline based on wheat forage data and
pyrasulfotole-desmethyl residue values in grass hay were corrected for
46.5% decline based on wheat hay data.

860.1480 Meat, Milk, Poultry, and Eggs

Table 4.  Calculation of MRDB of Cattle for Pyrasulfotole.

Feed Commodity	Feedstuff Type1	% Dry Matter2	% Diet2	Proposed or
Recommended Tolerances (ppm)	MRDB (ppm)3

Beef/Dairy Cattle (R=15/45%; CC=80/45%; PC=5/10%)

Barley grain	CC	88	35/0	0.02	0.0080/0

Aspirated grain fractions	CC	85	5/0	0.40	0.023/0

Sorghum grain	CC	86	40/45	0.70	0.33/0.37

Sorghum forage	R	35	15/0	1.5	0.64/0

Grass forage	R	25	0/45	25	0/45

Untreated	PC	NA	5/10	NA	-0-

Total	1.0/45

Poultry (CC=75-80%; PC=20-25%)

Sorghum grain	CC	-	75	0.70	0.52

Oat grain	CC	-	5	0.08	0.004

Untreated	PC	-	20	NA	-0-

Total	0.52

Hogs (CC=80-85%; PC=15-20%)

Sorghum grain	CC	-	80	0.70	0.56

Wheat milled byproducts	CC	-	5	0.02	0.0005

Untreated	PC	-	15	NA	-0-

Total	0.56

1	CC = carbohydrate concentrate; R = roughage; PC = protein concentrate.

2	Table 1 (860.1000 OPPTS Test Guidelines; June 2008  Revisions of
Livestock Diets Percents Reasonable Balanced Diets.

3	Contribution = [tolerance /% DM (if cattle)] X % diet.

Ruminants:  No ruminant feeding study was submitted with the subject
petition.  Permanent tolerances have been established for residues of
pyrasulfotole and its metabolite pyrasulfotole-desmethyl in/on the
following livestock commodities:  fat and meat of cattle, goats, hogs,
horses and sheep at 0.02 ppm; liver of cattle, goats, hogs, horses and
sheep at 0.35 ppm; meat byproducts, except liver, of cattle, goats,
hogs, horses and sheep at 0.06 ppm; and milk at 0.01 ppm (Memo, J.
Tyler, 06/08/07; D328640).  The results of a ruminant feeding study was
submitted and reviewed by HED in the 06/08/07 memo.  From the results of
that study, HED estimated the MRDB using HED-recommended pyrasulfotole
tolerances.  HED calculated that the total dietary burden from the
worst-case diet calculated for dairy cattle was approximately 0.39 ppm
and consisted of 20% wheat hay (dietary burden = 0.18 ppm), 25% wheat
forage (dietary burden = 0.20 ppm), 45% barley grain (dietary burden =
0.01 ppm), 10% untreated.  The total dietary burden from the worst case
diet for beef cattle was approximately 0.18 ppm and consisted of 15%
wheat forage (dietary burden = 0.14 ppm), 50% barley grain (dietary
burden = 0.01 ppm), 25% wheat grain (dietary burden = 0.006 ppm); 5%
aspirated grain fractions (dietary burden = 0.02 ppm); and 5% untreated.
 Based on these results, and in order to harmonize with PMRA, the
aforementioned tolerances were established.

The ruminant feed items associated with the subject petition are sorghum
grain, forage, and stover; and grass forage and hay.  HED recalculated
the MRDB for beef and dairy cattle to include these new uses (see Table
4).  The results of a dairy cattle feeding study for pyrasulfotole have
been submitted and reviewed by HED (Memo, J. Tyler, 6/8/07; D333412).  

Based on the results of the livestock metabolism studies, the residues
of concern in livestock are pyrasulfotole and pyrasulfotole-desmethyl
for tolerance and risk assessment purposes (Memo, J. Tyler, 06/08/07;
D328640).  However, only pyrasulfotole was analyzed for in the available
dairy cattle feeding study.  HED previously assumed the transfer of
pyrasulfotole-desmethyl from plants to livestock to be equivalent to
that of the parent pyrasulfotole based on the structure similarity and
concluded that the available dairy cattle feeding study was thus
adequate for tolerance-setting purposes.  As the doses used in the dairy
cattle feeding study still bracket the MRDB and pyrasulfotole-desmethyl
comprised only ~15% of the total residue, HED concludes that this
feeding study is still adequate for tolerance-setting purposes. 
However, for any new uses which significantly increase the MRDB of
pyrasulfotole-desmethyl, the petitioner may be required to submit a
feeding study in with the desmethyl metabolite.

In that study, dosing was conducted at 0 (control), 3, 9, or 30 ppm/day
in the feed (dry weight basis); these levels were at 0.067x, 0.2x, and
0.67x the MRDB to dairy cattle.  The 0.67x feeding level is closest to
the actual feeding level of 1x; therefore, it will be used to determined
appropriate tolerances for ruminant commodities (see Table 5).

Table 5.  Determination of Appropriate Tolerance for Ruminant
Commodities.

Matrix	Feeding Level

(ppm/day)

[exaggeration]1	Residues (ppm)



	Max Residues in Feeding Study	Residues When Extrapolated to 1x
Recommended Tolerance (ppm)

Milk	30 [0.67x]	0.0134	0.0200	0.03

Milk Fat	30 [0.67x]	0.0085	0.0127	0.02

Fat	30 [0.67x]	0.0143	0.0213	0.03

Kidney	30 [0.67x]	0.4144	0.618	0.70

Liver	30 [0.67x]	1.939	2.89	3.0

Muscle	30 [0.67x]	0.0039	0.00582	0.02

1  From previously reviewed lactating dairy cattle feeding study
(46801824.der.doc; Memo, J. Tyler, 6/8/07; D333412).  

≤0.0134 ppm in milk and≤0.0085 (<LOQ) in milk fat, resulting in
residues of 0.0200 ppm and 0.0127 ppm, respectively, when extrapolated
to 1x.  Residues of pyrasulfotole in were ≤0.0010 ppm (<LOQ) muscle
and ≤0.0062 ppm (<LOQ) in fat, resulting in residues of 0.00582 ppm
and 0.0213 ppm, respectively, when extrapolated to 1x.  Residues of
pyrasulfotole were ≤1.939 ppm in liver and ≤0.4144 ppm in kidney,
resulting in residues of 2.89 ppm and 0.618 ppm, respectively, when
extrapolated to 1x.  Based on these residues, the current tolerances of
0.02 ppm for meat of cattle, goat, horse and sheep are adequate to
support the proposed uses.  However, tolerances should be established
for residues of pyrasulfotole and pyrasulfotole-desmethyl in/on milk at
0.03 ppm; fat of cattle, goat, horse and sheep at 0.03 ppm; liver of
cattle, goat, horse, and sheep at 3.0 ppm; and meat byproducts, except
liver, of cattle, goat, horse, and sheep at 0.70 ppm.  A revised Section
F should be submitted to include the above tolerances, as well as
correct commodity definitions and tolerance expression.

Based upon a MRDB of 0.56 ppm for hogs, the 3-ppm feeding level in the
ruminant feeding study is equivalent to 5.3x the MRDB for hogs.  At the
5.3x feeding level, the maximum pyrasulfotole residues were 0.0010 ppm
in muscle, 0.2224 ppm in kidney, 1.230 ppm in liver, and 0.0062 ppm in
fat.  Residues at the 1x feeding level would be 0.00019 ppm in muscle,
0.042 ppm in kidney, 0.23 ppm in liver, and 0.0012 ppm in fat.  There is
no reasonable expectation of finding quantifiable residues of
pyrasulfotole and pyrasulfotole-desmethyl in hog muscle and fat; thus,
the current tolerances of 0.02 ppm are adequate.  There is reasonable
expectation of residues of pyrasulfotole and pyrasulfotole-desmethyl in
hog liver and kidney.  Therefore, the following tolerances for residues
of pyrasulfotole and pyrasulfotole-desmethyl are necessary:  hog, meat
byproducts, except liver at 0.05 ppm; and hog, liver at 0.30 ppm.  A
revised Section F should be submitted to include the above tolerances,
as well as correct commodity definitions and tolerance expression.

Poultry:  No poultry feeding study was submitted with the subject
petition.  Permanent tolerances have been previously established for
residues of pyrasulfotole per se in/on meat, fat and meat byproducts of
poultry at 0.02 ppm; and egg at 0.02 ppm (Memo, J. Tyler, 06/08/07;
D328640).  The calculated MRDB for poultry was approximately 0.058 ppm
and consisted of 70% oat grain (dietary burden = 0.056 ppm), 10% wheat
milled byproducts (dietary burden = 0.002 ppm), 5% barley, and 10%
untreated.  Based on these results, the aforementioned tolerances were
established.

The only poultry feed item associated with the subject petition is
sorghum grain.  HED recalculated the MRDB for poultry to include this
new use (see Table 4).  The results of a poultry feeding study for
pyrasulfotole have been submitted and reviewed by HED (Memo, J. Tyler,
6/8/07; D333412).  The results of the study are inadequate to determine
the need for poultry tolerances as only residues of
pyrasulfotole-benzoic acid were measured in the study.  However, because
the poultry metabolism studies were conducted for 14 days, the results
of the these studies can be used to determine the need for a new poultry
feeding study and/or poultry tolerances.  Based on the MRDB of 0.52 ppm
for poultry, the phenyl-labeled (8.6 ppm) and pyrazole-labeled (10.5
ppm) poultry metabolism studies were conducted at 16x and 20x the MRDB
for poultry, respectively.

In the phenyl-labeled study, total residues of pyrasulfotole and
pyrasulfotole-desmethyl were 0.037 ppm in muscle, 0.065 ppm in fat, and
1.557 ppm in liver.  Residues of pyrasulfotole and
pyrasulfotole-desmethyl at a 1x feeding level would be 0.0023 ppm in
muscle, 0.0064 ppm in fat, and 0.097 ppm in liver.  In the
pyrazole-labeled study, total residues of pyrasulfotole and
pyrasulfotole-desmethyl were 0.018 ppm in muscle, 0.014 ppm in fat, and
1.277 ppm in liver.  Residues of pyrasulfotole and
pyrasulfotole-desmethyl at a 1x feeding level would be 0.00090 ppm in
muscle, 0.00070 ppm in fat, and 0.064 ppm in liver.  In both
radiolabeled studies, as the total extractable residues in eggs were <
0.01 ppm; the samples were not analyzed further for identification
purposes.  Based on the results of the poultry metabolism study, there
is no reasonable expectation of finding quantifiable residues of
pyrasulfotole and pyrasulfotole-desmethyl in eggs and poultry muscle and
fat.  Thus, the established tolerances of 0.02 ppm for residues of
pyrasulfotole and pyrasulfotole-desmethyl in fat, meat, and meat
byproducts of poultry are adequate.  There is reasonable expectation of
residues of pyrasulfotole and pyrasulfotole-desmethyl in poultry meat
byproducts.  Therefore, a tolerance of 0.20 ppm for residues of
pyrasulfotole and pyrasulfotole desmethyl in poultry byproducts is
necessary.  A revised Section F should be submitted to include the above
tolerances and correct tolerance expression.

860.1500 Crop Field Trials

47815001.der.doc (grass grown for seed); Memo, T. Goodlow, 8/17/10,
D380769

47815002.der.doc (grain sorghum) ; Memo, T. Goodlow, 8/17/10, D380769

Grain Sorghum

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

Matrix	Total Applic. Rate (lb a.i./A)	PHI1 (days)	Residue Levels2,3
(ppm)



	N	Min.	Max.	HAFT4	Median	Mean	Std. Dev. 

Pyrasulfotole

Sorghum Forage	0.077 - 0.080

(~1x)	0	24	1.097	5.741	5.080	2.167	2.286	1.062



5 to 8	24	0.014	0.462	0.454	0.069	0.133	0.145



ECH (32 to 82)	28	<0.01	0.124	0.123	<0.01	0.026	0.034

Sorghum Grain

56 to 60	24	<0.01	0.151	0.143	0.028	0.041	0.037

Sorghum Stover

56 to 60	24	<0.01	0.035	0.030	0.011	0.015	0.007

Pyrasulfotole-desmethyl

Sorghum Forage	0.077 - 0.080

(~1x)	0	24	0.029	0.346	0.343	0.137	0.164	0.266



5 to 8	24	0.074	0.499	0.479	0.199	0.231	0.359



ECH (32 to 82)	28	<0.01	0.380	0.371	0.050	0.108	0.236

Sorghum Grain

56 to 60	24	<0.01	0.185	0.180	0.056	0.076	0.058

Sorghum Stover

56 to 60	24	<0.01	0.390	0.351	0.129	0.152	0.098

Total Pyrasulfotole

Sorghum Forage	0.077 - 0.080

(~1x)	0	24	1.184	6.021	5.356	2.419	2.449	1.10



5 to 8	24	0.097	0.902	0.881	0.300	0.364	0.241



ECH (32 to 82)	28	<0.02	0.504	0.494	0.043	0.135	0.160

Sorghum Grain

56 to 60	24	<0.02	0.325	0.322	0.089	0.117	0.092

Sorghum Stover

56 to 60	24	<0.02	0.420	0.383	0.142	0.166	0.103

1 ECH = earliest commercial harvest

2 LLMV = 0.01 ppm for each analyte.  LOD for pyrasulfotole = 0.0009 ppm
for forage, 0.0019 ppm for grain, 0.0033 ppm for stover.  LOD for
pyrasulfotole-desmethyl = 0.0011 ppm for forage, 0.0025 ppm for grain,
and 0.0014 ppm for stover.  Residues in parentheses are between the LOD
and LLMV.

3 Total (ppm) = sum of pyrasulfotole (ppm) and pyrasulfotole-desmethyl
(ppm).  LLMV (0.01 ppm) was used when values were <LLMV.

4HAFT = highest-average field trial. 

™ Herbicide on grain sorghum.  Twelve trials were conducted in the
United States during the 2008 growing season.  The trials encompassed
NAFTA Growing Zones 2 (1 trial in GA), 4 (1 trial in MS), 5 (1 trial
each in IN, IA, OH, MN), 6 (1 trial each in OK, TX), 7 (1 trial in ND),
and 8 (l trial each in CO, OK, TX).  Each site consisted of one control
plot and two treatment plots, with one treatment plot for sampling
forage and one for sampling grain and stover.  The treatment plots each
received two applications of the formulated product at a target rate of
0.039 lb pyrasulfotole/A/ application (1x the maximum proposed single
application rate).  Actual total application rates ranged from 0.077 to
0.080 lb ai/A/season (1x the maximum proposed seasonal rate).  The
retreatment interval (RTI) ranged from 11 to 16 days and the spray
volumes ranged from 12 to 20 gal/A.  An adjuvant was not used in the
spray applications.  Sorghum forage samples were collected at target
PHIs of 0 and 7 days and also at earliest commercial harvest (ECH) (BBCH
81, beginning of ripening, to BBCH 87, hard dough), which corresponded
to PHIs of 32 to 82 days.  Sorghum grain and stover samples were
collected at a target PHI of 60 days.  A residue decline trial was also
conducted at one site, in which forage samples were collected at PHIs of
0, 1, 3, 7, 10, and 14 days with additional samples collected at five
intervals before, at, and after earliest commercial harvest  (ECH-14,
ECH-7, ECH, ECH+7, and ECH+14 days; actual PHIs were 18, 25, 32, 39, and
46 days).  Grain and stover samples were collected at five intervals
corresponding to target PHIs of 47, 53, 60, 67, and 74 days.

™ Herbicide to grain sorghum at a total rate of 0.077 to 0.080 lb ai/A
(~1x the maximum proposed seasonal rate) for pyrasulfotole, residues of
total pyrasulfotole (sum of pyrasulfotole and pyrasulfotole-desmethyl)
in the forage samples ranged from 1.18 ppm to 6.02 ppm at a PHI of 0
days, from 0.097 ppm to 0.902 ppm at a PHI of 5 to 8 days, and from
<LLMV (0.02 ppm) to 0.504 ppm at ECH (PHI of 32 to 82 days).  Residues
in grain and stover samples collected at a PHI of 56 to 60 days from
plots treated at a total rate of 0.077 to 0.080 lb ai/A ranged from
below the LLMV (0.02 ppm) to 0.325 ppm and from <0.02 to 0.420 ppm,
respectively.

  

Residue decline data showed that residues of pyrasulfotole,
pyrasulfotole-desmethyl decreased with time in/on grain sorghum early
forage.  The residues also generally decreased with time in/on sorghum
forage collected around earliest commercial harvest (ECH -14 day to ECH
+14 day), however, a spike in residues was observed at the ECH -7 day
interval.  In/on sorghum stover, the residues increased with time. 
In/on sorghum grain, residues of pyrasulfotole and
pyrasulfotole-desmethyl decreased with time.

HED Conclusions:  The submitted grain sorghum residue data are
classified as scientifically acceptable for determination of the
magnitude of residue of pyrasulfotole and pyrasulfotole-desmethyl in
grain sorghum.  As the number and geographical representation of the
trials are the same as the number and geographical locations recommended
in OPPTS Guideline 860.1500, the residue data are adequate to support
the proposed uses.

™ Herbicide on grain sorghum.  In the trials, two applications of
Huskie™ Herbicide were applied to each treatment plot at a total
seasonal rate of 0.078 lb pyrasulfotole/A/season (1x the proposed rate).
 Forage samples were collected at a target 0- and 7- day PHIs, as well
as at ECH (PHI of 32 to 82 days).  Grain and stover samples were
collected at a target 60-day PHI.  A residue decline trial was also
conducted at one site, in which forage samples were collected at PHIs of
0, 3, 7, 10, and 14 days with additional samples collected at five
intervals of ECH-14, ECH-7, ECH, ECH+7, and ECH+14 days (actual PHIs
were 18, 25, 32, 39, and 46 days).  Grain and stover samples were
collected at five intervals corresponding to target PHIs of 47, 53, 60,
67, and 74 days.  Based on concurrent recoveries, acceptable analytical
methods were used.  Adequate storage stability data are available;
however, residues of pyrasulfotole-desmethyl were found to decline in
wheat forage and hay at approximately 0.12% per day.  Therefore,
pyrasulfotole-desmethyl residue values in grain sorghum forage samples
were corrected for 46.3% decline based on wheat forage data and
pyrasulfotole-desmethyl residue values in grain sorghum stover were
corrected for 46.5% decline based on wheat hay data. 

With the use pattern in this study, total residues of pyrasulfotole
in/on grain sorghum forage are not expected to exceed 6.02 ppm (0-day
PHI), 0.902 ppm (7-day PHI), or 0.504 ppm (ECH).  In/on sorghum grain
and stover (60-day PHI), total residues of pyrasulfotole is not expected
to exceed 0.325 ppm or 0.420 ppm, respectively.  Using the NAFTA
MRL/Tolerance Harmonization Workgroup methodology for forage (7-day
PHI), grain, and stover, the available grain sorghum crop field trial
data indicate that the appropriate tolerances for residues of
pyrasulfotole and pyrasulfotole-desmethyl in/on grain sorghum grain
commodities are 1.5 ppm for sorghum, grain, forage; 0.70 ppm for
sorghum, grain, grain; and 0.80 ppm for sorghum, grain, stover (see
Section 860.1550 Proposed Tolerances).  Section F of the petition should
be revised to include the aforementioned HED-recommended tolerances and
the correct commodity definitions for grain sorghum RACs.

Grass Grown for Seed

Table 7.  Summary of Residue Data from Crop Field Trials with
Pyrasulfotole.

Matrix	Total Applic. Rate

(lb a.i./A)	PHI (days)	Residue Levels1,2 (ppm)



	N	Min.	Max.	HAFT3	Median	Mean	Std. Dev.

Pyrasulfotole

Grass Forage	0.076 - 0.091

(~1x)	0	24	0.055	6.51	6.39	1.83	2.54	2.11



7-11	26	<0.01	6.32	6.21	0.079	1.33	2.09

Grass Hay	0.077 - 0.080

(~1x)	28-31	24	<0.01	1.71	1.69	0.0183	0.202	0.472

Pyrasulfotole-desmethyl

Grass Forage	0.076 - 0.091

(~1x)	0	24	0.045	0.631	0.619	0.182	0.234	0.181



7-11	26	0.041	0.544	0.512	0.205	0.234	0.146

Grass Hay	0.077 - 0.080

(~1x)	28-31	24	<0.01	0.607	0.574	0.112	0.186	0.172

Total Pyrasulfotole

Grass Forage	0.076 - 0.091

(~1x)	0	24	0.132	6.77	6.75	2.49	3.14	2.20



7-11	26	0.062	6.52	6.40	0.317	1.56	2.09

Grass Hay	0.077 - 0.080

(~1x)	28-31	24	<0.02	2.31	2.27	0.157	0.390	0.611

1 LLMV = 0.01 ppm for each analyte.  LOD for pyrasulfotole = 0.00353 ppm
for forage and 0.00162 for hay.  LOD for pyrasulfotole-desmethyl =
0.00521 ppm for forage and 0.00132 ppm for hay.  Residues in parentheses
are between the LOD and LLMV.

2 Total (ppm) = sum of pyrasulfotole (ppm) and pyrasulfotole-desmethyl
(ppm).  LLMV (0.05 ppm) was used when values were <LLMV.

3HAFT = highest-average field trial.

Bayer CropScience has submitted field trial data for the product
Huskie™ Herbicide on grass grown for seed (Bermuda, bluegrass, and
fescue).  Twelve trials were conducted in the United States and Canada
during the 2008 growing season.  The trials encompassed NAFTA Growing
Zones 1 (1 trial in Atlantic Provinces, Canada), 2 (1 trial in GA), 3 (1
trial in FL), 4 (1 trial in AR), 5 (1 trial in WI; 1 trial in NE), 9 (1
trial in ID), 10 (1 trial in CA), 11 (1 trial in ID; 1 trial in WA), and
12 (1 trial in British Columbia, Canada; 1 trial in OR).  Each site
consisted of one control plot and two treatment plots, with one
treatment plot for sampling forage and one for sampling hay.  The
treatment plots each received two broadcast foliar applications of the
formulated product at a target rate of 0.039 lb
pyrasulfotole/A/application (~1x the maximum proposed single application
rate).  Actual total application rates ranged from 0.076 to 0.091 lb
ai/A/season (~1x the maximum proposed seasonal application rate) with a
27- to 30-day RTI.  Spray volumes ranged from 10 to 24 gal/A.  An
adjuvant was not used in the spray applications.  Grass forage samples
were collected at target PHI of 0 days and 7 days.  Grass hay samples
were collected at a target PHI of 30 days.  A residue decline trial was
also conducted at one site, in which forage samples were collected at
PHIs of 0, 1, 3, 7, 10, and 14 days and hay samples were collected at
PHIs of 20, 25, 30, 36, and 40 days.

™ Herbicide a total rate of 0.076 - 0.091 lb ai/A, ranged from below
the LLMV to 1.71 ppm.  Residues of pyrasulfotole-desmethyl in/on the
grass hay samples ranged from below the LLMV to 0.607 ppm and total
pyrasulfotole residues ranged from below the LLMV (<0.02 ppm) to 2.31
ppm.  

Residue decline data showed that residues of pyrasulfotole and
metabolites decreased with time in grass forage and hay.  A slight
increase in pyrasulfotole residues was observed in grass hay between the
30 and 35 day PHI interval.

HED Conclusions:  The submitted grass residue data are classified as
scientifically acceptable for determination of the magnitude of residue
of pyrasulfotole and pyrasulfotole-desmethyl in grass grown for seed.

The submitted field trial data reflect the use of Huskie™ Herbicide on
grass grown for seed.  In the trials, two applications of Huskie™
Herbicide was applied to each treatment plot at a total seasonal rate of
0.076 to 0.091 lb ai/A.  Forage samples were collected at a target 0-
and 7- day PHI and hay samples were collected at a target 30-day PHI. 
Decline trials were also conducted in which sample collection occurred
at PHIs of 0, 1, 3, 7, 10 and 14 days for forage and 20, 25, 30, 35, and
40 days for hay.  Based on concurrent recoveries, acceptable analytical
methods were used.  Storage stability data from grass, wheat, and/or
barley demonstrate that residues of pyrasulfotole is stable in grass
forage and hay under the storage conditions used in this study; however,
residues of pyrasulfotole-desmethyl were found to decline in wheat
forage and hay at approximately 0.12% per day.  Therefore,
pyrasulfotole-desmethyl residue values in grass forage samples were
corrected for 46.3% decline based on wheat forage data and
pyrasulfotole-desmethyl residue values in grass hay samples were
corrected for 46.5% decline based on wheat hay data.

With the use pattern in this study, total residues of pyrasulfotole, are
not expected to exceed 6.73 ppm (0-day PHI) or 6.52 ppm (7-day PHI)
in/on grass forage and 2.31 ppm in grass hay (30-day PHI).  Using the
NAFTA MRL/Tolerance Harmonization Workgroup methodology for grass forage
(7-day PHI) and hay, the available grass crop field trial data indicate
that the appropriate tolerances for residues of pyrasulfotole and
pyrasulfotole-desmethyl in/on are 25 ppm for grass, forage; and 3.5 ppm
for grass, hay (see Section 860.1550 Proposed Tolerances).  Section F of
the petition should be revised to include the aforementioned
HED-recommended tolerances.

In addition, the proposed label does not specify application equipment
or a minimum spray volume for application to grass grown for seed.  The
submitted data support ground foliar applications made in spray volumes
of 10-24 gal/A.  A revised label should be submitted to include these
use directions.

860.1520 Processed Food and Feed

As there are no processed commodities associated with the proposed uses,
processing studies are not required.

860.1650 Submittal of Analytical Reference Standards

Analytical reference standards for pyrasulfotole have been received by
the EPA National Pesticide Standard Repository for distribution to State
and Federal regulatory labs (personal communication between J. Tyler and
T. Cole, 9/15/10).  However, the Repository has not received reference
standard for the desmethyl metabolite and labeled internal standards. 
These standards should be sent to the Analytical Chemistry Lab to the
attention of either Theresa Cole or Dallas Wright at the following
address:

USEPA

National Pesticide Standards Repository/Analytical Chemistry Branch/OPP

701 Mapes Road

Fort George G. Meade, MD 20755-5350

The extended zip code must be used or the mail will be returned.

860.1850 and 860.1900 Confined/Field Accumulation in Rotational Crops

No rotational crop data were submitted in conjunction with the proposed
uses.  According to the current guidance, grain sorghum and grass grown
for seed are considered to be rotated crops.  The following rotational
crop restrictions are currently on the proposed label:

Wheat, barley, oats, rye and triticale	1 month

Alfalfa*, millet, sorghum (grain), and soybeans	4 months

Canola, canaryseed, chickpeas, corn, dry beans, flax, field peas, green
beans, green peas, lentils**, mustards, potatoes, safflower, sunflowers,
and sugar beets	9 months

All other crops	30 days***

*Thorough tillage prior to planting alfalfa and a minimum of 12 inches
of rainfall, overhead, furrow or flood irrigation or any combination of
these water source totaling 12 inches is required between the time
following a Huskie™ Herbicide application and the time of alfalfa
seeding.

**Lentils:  9 months for all states except 18 months in MN, MT, ND, and
SD.

***Where a crop is not specified, conduct a field bioassay as described
in “FIELD BIOASSAY” section of proposed label.

Adequate confined and field rotational crop data have been submitted by
the petitioner and reviewed by HED in conjunction with PP#6F7509 (Memo,
J. Tyler, 6/8/07, D366490).  The results of the submitted confined and
limited field rotational crop studies together are adequate to determine
appropriate PBIs for rotational crops.  In the confined rotational crop
study, following application of either phenyl- or pyrazole-labeled
pyrasulfotole, the TRR in the 122-days after treatment (DAT) Swiss
chard, turnip tops, and turnip roots were <0.01 (<LOQ).  In the limited
field rotational crop study, maximum residue levels of pyrasulfotole and
pyrasulfotole-desmethyl were <LOD in all corn and soybean RACs at PBIs
of 114-123 days.  Maximum residues levels for pyrasulfotole-benzoic acid
were 0.0018 ppm in corn forage, 0.0027 ppm in soybean forage, 0.0126 ppm
in soybean hay and <LOD in corn grain, corn stover and soybean seed. 
However, it was determined that residues of pyrasulfotole-benzoic acid
are not of concern for both tolerance and risk assessment purposes
(Memo, J. Tyler et al., 06/08/07; D328640).

In addition, HED approved a requested to revise the Crop Rotation
Guidelines on the currently approved Huskie™ Herbicide (EPA Reg. No.
264-1023) label as follows:  1) an increased PBI from 7 days to 1 month
for wheat, barley, oats, rye, and triticale; 2) an addition of green
beans and green peas to the 9-month PBI; and 3) a decreased PBI for
alfalfa from 9 months to 4 months.  Therefore, the submitted confined
and limited field trial data support the proposed PBIs.

860.1550 Proposed Tolerances

A summary of the recommended tolerances and the correct commodity
definitions for the proposed uses are listed in Table 8.  

The available crop field trial data on grain sorghum and grass grown for
seed are adequate to support the proposed uses of pyrasulfotole.  For
purposes of determining appropriate tolerance levels for the proposed
uses, individual pyrasulfotole and pyrasulfotole-desmethyl residues were
summed to yield a total residue value.  Appropriate tolerances where
determined using the methodology formulated by the NAFTA MRL/Tolerance
Harmonization Workgroup for calculating statistically-based pesticide
tolerances for plant commodities based on field trial residue data.

Using the 0.67x data from the adequate cattle feeding study and a
calculated MRDB of 45 ppm for pyrasulfotole and pyrasulfotole-desmethyl
residues in dairy cattle diets, estimated pyrasulfotole and
pyrasulfotole-desmethyl residues in ruminants at a 1x dose level are
0.0200 ppm in milk; 0.00127 ppm in milk fat; 0.0213 ppm in fat; 0.00582
ppm in muscle; 2.89 ppm in liver; and 0.618 ppm in kidney.  Based on the
quantifiable residues, tolerances should be established for residues of
pyrasulfotole and pyrasulfotole-desmethyl in/on milk at 0.03 ppm; fat of
cattle, goat, horse and sheep at 0.03 ppm; liver of cattle, goat, horse,
and sheep at 3.0 ppm; and meat byproducts, except liver, of cattle,
goat, horse, and sheep at 0.70 ppm.  Although, there is no reasonable
expectation of finding quantifiable residues of pyrasulfotole and
pyrasulfotole-desmethyl in muscle of cattle, goat, horse and sheep, the
current tolerances for these commodities (established in order to
harmonize with PMRA) are adequate to support the proposed uses on grain
sorghum and grass grown for seed.

Using data from the adequate cattle feeding study and a calculated MRDB
of 0.56 ppm pyrasulfotole and pyrasulfotole-desmethyl in hogs, the
estimated pyrasulfotole and pyrasulfotole-desmethyl residues in hogs
were 0.00019 ppm in muscle, 0.042 ppm in kidney, 0.23 ppm in liver, and
0.0012 ppm in fat.  There is no reasonable expectation of finding
quantifiable residues of pyrasulfotole and pyrasulfotole-desmethyl in
muscle and fat; however, the current tolerances of 0.02 ppm (established
in order to harmonize with PMRA) are adequate to support the proposed
uses on grain sorghum and grass grown for seed.  There is reasonable
expectation of residues of pyrasulfotole and pyrasulfotole-desmethyl in
hog liver and kidney.  Therefore, the following tolerances for residues
of pyrasulfotole and pyrasulfotole desmethyl are necessary:  hog, meat
byproducts, except liver at 0.05 ppm; and hog, liver at 0.30 ppm.

Using the data from the poultry metabolism studies and a calculated MRDB
of 0.52 ppm for poultry, the maximum estimated pyrasulfotole and
pyrasulfotole-desmethyl residues in poultry were 0.0023 ppm in muscle,
0.0070 ppm in fat, and 0.097 ppm in liver.  As the total extractable
residues in eggs were <0.01 ppm; the samples were not analyzed further
for identification purposes.  Based on the results of the poultry
metabolism study, there is no reasonable expectation of finding
quantifiable residues of pyrasulfotole and pyrasulfotole-desmethyl in
eggs and poultry muscle and fat; however, the current tolerances of 0.02
ppm (established in order to harmonize with PMRA) are adequate to
support the proposed uses on grain sorghum and grass grown for seed. 
There is reasonable expectation of residues of pyrasulfotole and
pyrasulfotole-desmethyl in poultry meat byproducts.  Therefore, a
tolerance of 0.20 ppm for residues of pyrasulfotole and pyrasulfotole
desmethyl in poultry byproducts is necessary.

The residue chemistry database supports the establishment of the
permanent tolerances for the combined residues of pyrasulfotole and
pyrasulfotole-desmethyl in/on the RACs and livestock commodities listed
in Table 8.  Section F should be revised to include these recommended
tolerances as well as the correct tolerance expression for livestock
commodities.

Table 8.  Tolerance Summary for Pyrasulfotole.

Commodity	Current Tolerance (ppm)	Proposed Tolerance (ppm)	Recommended
Tolerance (ppm)	Comments

(correct commodity definition)

Sorghum, grain	-	0.8	0.70	Sorghum, grain, grain

Sorghum, forage	-	1.2	1.5	Sorghum, grain, forage

Sorghum, stover	-	0.35	0.80	Sorghum, grain, stover

Grass, forage	-	10	25

	Grass, hay	-	2.5	3.5

	Milk*	0.01	0.01	0.03

	Cattle, meat	0.02	0.04	see current tolerance

	Cattle, fat*	0.02	0.04	0.03

	Cattle, meat byproducts*	0.06	2	0.70	Cattle, meat byproducts, except
liver

Cattle, liver*	0.35	8	3.0

	Goat, meat	0.02	0.04	see current tolerance

	Goat, fat*	0.02	0.04	0.03

	Goat, meat byproducts*	0.06	2	0.70	Goat, meat byproducts, except liver

Goat, liver*	0.35	8	3.0

	Hog, meat	0.02	0.04	see current tolerance

	Hog, fat	0.02	0.04	see current tolerance

	Hog, meat byproducts*	0.06	2	0.05	Hog, meat byproducts, except liver

Hog, liver*	-	8	0.30

	Sheep, meat	0.02	0.04	see current tolerance

	Sheep, fat*	0.02	0.04	0.03

	Sheep, meat byproducts*	0.06	2	0.70	Sheep, meat byproducts, except
liver

Sheep, liver*	0.35	8	3.0

	Horse, meat	0.02	0.04	see current tolerance

	Horse, fat*	0.02	0.04	0.03

	Horse, meat byproducts*	0.06	2	0.70	Horse, meat byproducts, except
liver

Horse, liver*	0.35	8	3.0

	Poultry, meat	0.02	-	see current tolerance

	Poultry, fat*	0.02	-	0.02

	Poultry, meat byproducts*	0.02	-	0.20

	Eggs	0.02	-	see current tolerance

	*  Livestock commodities with tolerances that are not harmonized with
PMRA.

The International Residue Limit Status (IRLS) Sheet is attached as
Attachment 1.  There are no established Mexican or Codex MRLs for the
proposed uses.  There are Canadian MRLs established for livestock
commodities.  However, due to the recommended tolerances on the proposed
uses, there was an increase in MRDB for livestock commodities.  This
resulted in the need for an increase in tolerances for several livestock
commodities (see commodities with asterisk in Table 8).  Therefore,
harmonization is not possible at this time.

Attachments

Attachment 1:  IRLS Sheet.

Attachment 2:  Inputs for calculating statistically-based pesticide
tolerances.

cc:  J. Tyler (RAB1)

RDI:  RAB1 Chemists (9/29/10), G. Kramer (9/27/10)

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Attachment 1.  IRLS Sheet.

International Residue Limits 

Pyrasulfotole (000692; 15-SEP-2010)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US	Canada	Mexico2	Codex

40 CFR 180.631:

Plant/Livestock:  pyrasulfotole and pyrasulfotole-desmethyl,
(5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl)[2-(methylsulfonyl)-4-(trifluoro
methyl)phenyl]methanone, and its metabolite,
5-hydroxy-3-methyl-1H-pyrazol-4-yl)
[2-methylsulfornyl)-4-(trifluoromethyl)phenyl]methanone
(5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl)[2-(methylsulfonyl)-4-(trifluoro
methyl)phenyl]methanone, including the metabolite
(5-hydroxy-3-methyl-1H-pyrazol-4-yl)[2-(methylsulfonyl)-4-(trifluorometh
yl)phenyl]methanone

None

Commodity1	Tolerance (ppm) /Maximum Residue Limit (mg/kg)

	US	Canada	Mexico2	Codex

Sorghum, grain	0.7



	Sorghum, forage	1.5



	Sorghum, stover	0.8



	Grass, forage	10



	Grass, hay	3.5



	Milk	0.1	0.01



Cattle, meat	0.02	0.02



Cattle, fat	0.02	0.02



Cattle, meat byproducts, except liver	1.0	0.06



Cattle, liver	4.0	0.35



Goat, meat	0.02	0.02



Goat, fat	0.02	0.02



Goat, meat byproducts, except liver	1.0	0.06



Goat, liver	4.0	0.35



Hog, meat	0.02	0.02



Hog, fat	0.02	0.02



Hog, meat byproducts, except liver	0.05	Meat byproducts of hogs 0.02



Hog, liver	0.30



	Sheep, meat	0.02	0.02



Sheep, fat	0.02	0.02



Sheep, meat byproducts, except liver	1.0	0.06



Sheep, liver	4.0	0.35



Horse, meat	0.02	0.02



Horse, fat	0.02	0.02



Horse, meat byproducts, except liver	1.0	0.06



Horse, liver	4.0	0.35



Poultry, meat	0.02	0.02



Poultry, fat	0.02	0.02



Poultry, meat byproducts	0.20	0.02



Eggs	0.02	0.02



Completed:  M. Negussie; 09/16/2010

1 Includes only commodities of interest for this action.  Tolerance
values should be the HED recommendations and not those proposed by the
applicant.

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

Attachment 2.  Inputs for calculating statistically-based pesticide
tolerances.

Grass Forage – 7-day PHI

Grass Hay

Sorghum Forage

Sorghum Grain

Sorghum Stover

Pyrasulfotole			Summary of Analytical Chemistry and Residue Data		   
DP# 375391

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