in the developmental neurotoxicity study] and are used as endpoints for
appropriate risk assessments.

There are also no additional residual uncertainties with respect to the
exposure data base.  The exposure data are complete or are estimated
based on data that reasonably account for potential exposures.  The
dietary food exposure assessment utilized empirical processing factors,
100% crop treated (acute assessment), average residue levels, and
livestock maximum residues.  Results from ruminant feeding studies and
poultry metabolism studies were used to determine the maximum residue
levels for livestock commodities.  The dietary drinking water assessment
utilized health protective high-end model estimates of drinking water
concentrations (EDWCs).  EDWCs were further refined by applying regional
percent cropped area (PCA) factors for canola, beans, peanuts, and rice.
 There is no potential for residential exposure.  Based on these data
and conclusions, the 10X FQPA Safety Factor is subsumed in the form of a
database uncertainty factor (UFDB ) for lack of data to establish a
NOAEL and a LOAEL for neurotoxicity (brain morphometry and peripheral
nerve lesions) observed in the rat developmental neurotoxicity study.

3.5	Hazard Identification and Toxicity Endpoint Selection  TC \l2 "3.5
Hazard Identification and Toxicity Endpoint Selection

3.5.1.	Acute Reference Dose (aRfD) - Females age 13 – 49  TC \l3
"3.5.1	Acute Reference Dose (aRfD) Females age 13-49

Study Selected: Developmental Toxicity in Rabbits	OPPTS 870.6300  (83-6

MRID No.: 46246327  (Prothioconazole-desthio)

Executive Summary:   In a developmental toxicity study (MRID 46246327)
prothioconazole-desthio (94%) was administered to groups of 15 female
Himalayan rabbits by oral gavage at 0, 2, 10, or 50 mg/kg bw/d from post
coitum (pc) day 6 to 18.  The animals were sacrificed on pc day 29.

There were no effects on clinical signs, water intake, or mortality.
Food intake was marginally lowered in high-dose dams.  Body weight of
high-dose animals was adversely affected during gestation, presumably as
a result of elevated resorption rate.  At terminal sacrifice, there was
no significant gross pathological observation.  Treatment-related
histopathological findings were evident in the liver of mid- and
high-dose dams.  The liver findings included increased destruction of
individual hepatocytes and low glycogen mobilization.  Examination of
fetal parameters revealed no treatment-related findings on fetal weight
and sex, or on skeletal system development.  The placentas were normal.
Due to an elevated resorption rate, the gestation rate and the number of
fetuses were lower at 50 mg/kg bw/d group.  Malformation was observed at
10 and 50 mg/kg bw/d groups.  At 10 mg/kg bw/d, alterations included
malformed vertebral body and ribs, arthrogryposis, and multiple
malformations.  These malformations could arise spontaneously in
Himalayan rabbits.  At 50 mg/kg bw/d, malformed alterations included
cleft plates.

The maternal LOAEL is 50 mg/kg bw/d, based on decreased food
consumption, body weight gain, elevated resorption rate (including total
litter loss) and decreased number of fetuses per dam at this dose.  The
maternal NOAEL is 10 mg/kg bw/d.

The developmental LOAEL is 10 mg/kg bw/d, based on arthrogryposis and
multiple malformations at this dose.  The developmental NOAEL is 2 mg/kg
bw/d.  Prothioconazole-desthio was teratogenic in the Himalayan rabbit
at maternally non-toxic doses.

The developmental toxicity study in the rabbit is acceptable and
satisfies the guideline requirement for a developmental toxicity study
(OPPTS 870.3700; OECD 414) in rabbits.

Dose and Endpoint for Establishing aRfD: Developmental toxicity LOAEL =
10 mg/kg/day, based on multiple malformations including malformed
vertebral body and ribs, arthrogryposis .  The NOAEL is 2.0 mg/kg/day.

Uncertainty Factor (UF): 1000 (10X for interspecies extrapolation and
10X for intraspecies variations, 10X for database uncertainty.  See
Sections 3.1.3, 3.1.4)

Comments about Study/Endpoint   Please refer to the summary table in
Section 3.1.3. There is a co-critical study which reported developmental
effects in the fetus and neonate following exposure to prothioconazole
desthio, using a developmental neurotoxicity protocol (MRID 46246418).
Deviated snout and malocclusion were observed at 15.1 mg/kg/day (NOAEL =
3.6 mg/kg/day).  Also, brain morphometrics changes and an increased
incidence of peripheral nerve lesions were observed at 43.3 mg/kg/day
(NOAEL not reported).  If the NOAEL of 3.6 mg/kg/day were used as the
endpoint, with 100X UF, the Acute RfD would be 0.036 mg/kg.  Since the
endpoint derived from the developmental neurotoxicity study is not as
low as the endpoint from the rabbit developmental study, it is not used
for this risk assessment.  Another study (MRIDs 46246321, 46246322)
showing increased incidence of supernumerary ribs and incomplete/delayed
ossifications using an oral developmental toxicity protocol in the rat,
was also considered for this endpoint.  However, the rabbit study
provided more robust endpoint on which to base a risk assessment, while
occurring at dose levels very similar to the rat study.  Therefore the
rat study was not used.

Acute RfD (females 13-49 years old)  =  2.0 mg/kg/day  = 0.002 mg/kg

					           1000 (UF)

3.5.2	Acute Reference Dose (aRfD) - General Population, including
Infants & Children  TC \l3 "3.5.2	Acute Reference Dose (aRfD) –
General Population, including Infants & Children

An endpoint of concern attributed to a single dose effect was not
identified in the database; therefore, acute risk to the general
population including infants and children was not quantified.  An
acceptable acute neurotoxicity study using prothioconazole is available,
which showed reduce levels of motor and locomotor activity at a
relatively high single dose (NOAEL = 200 mg/kg/day).  However, these
effects were transient and reversible; and occurred at a dose which is
two orders of magnitude higher than the levels where toxicity is
observed in the chronic studies.  Therefore; the Chronic RfD provides
more than adequate protection from these transient and reversible acute
effects.

3.5.3	Chronic Reference Dose (cRfD) - All Populations  TC \l3 "3.5.3
Chronic Reference Dose (cRfD) - All Populations

Study Selected: Chronic/Oncogenicity Study in Rats	OPPTS 870.6300  (83-6

MRID No. 46246342  (Prothioconazole-desthio)

Executive Summary:   See Executive Summary in Section 3.3.2.

Uncertainty Factor (UF): 1000 (10X for interspecies extrapolation, 10X
for intraspecies variations, 10X for database uncertainty. See Sections
3.1.3 and 3.1.4)

Dose and Endpoint for Establishing cRfD: Chronic toxicity LOAEL = 8.0,
based on liver histopathology in males and females [hepatocellular
vacuolation and fatty change (single cell, centrilobular, and
periportal)].  The NOAEL was 1.1 mg/kg/day.

Comments about Study/Endpoint: This study showed significant effects at
dose levels lower than any other appropriate study in the database.  It
is also of an appropriate duration (chronic), and the NOAEL is expected
to be protective against the uncertainties surrounding the brain
morphometric and peripheral nerve degeneration observations in the
developmental neurotoxicity study, the number for risk assessment there
being 0.043 mg/kg/day (43.4 mg/kg/day/1000 UF).

Chronic RfD (general population)  =  1.1 mg/kg/day (LOAEL) = 0.001 mg/kg

						               1000 (UF)

3.5.4	Incidental Oral Exposure (Short- and Intermediate-Term)   TC \l3
"3.5.4	Incidental Oral Exposure (Short- and Intermediate-Term)

Dose and Endpoint for Risk Assessment: None.  Residential exposure is
not anticipated..

3.5.5	Dermal Absorption  TC \l3 "3.5.5	Dermal Absorption

The dermal absorption factor is based on a dermal penetration study on
prothioconazole-desthio.  In a dermal absorption study (Guideline OPPTS
870.7600 [(85-2], MRID 46246425), five male rhesus monkeys received a
dermal dose of 144 µg (6 µg/cm2) prothioconazole-desthio containing
14C prothioconazole-desthio for 8 hours.

Observed was a mean recovery of 18.61% of the dose in excreta (10.25 %
in urine, 5.79 % in feces, 1.50 % in cage debris/rinse samples, and 1.07
% in the pan wash/wipe and chair wipe) through 144 hours.  The majority
of the administered dermal dose was recovered from the application site
(mean = 73.54 %) from the washings.  The overall mean recovery of
radioactivity from the dermally dosed animals was 92.15 %.

The dermal absorption rate was 18.6%.

3.5.6	Dermal Exposure (Short-, and Intermediate-Term)   TC \l3 "3.5.6
Dermal Exposure (Short-, and Intermediate-Term)

Study Selected: Dermal Developmental Toxicity in Rats	OPPTS 870.6300
(83-6

MRID No.: 46246325 (Prothioconazole-desthio)

Executive Summary: In a developmental toxicity study (MRID 46246325,
46246326) SXX 0665 technical (93.7% a.i.) was administered by topical
application as a suspension in 1% aqueous Cremophor EL to four groups of
25 mated female Wistar rats (Bor/WISW [SPF Cpb]) at dose levels of 0,
10, 30, 100, 300 or 1000 mg/kg bw/day from day 6 to 15 post coitum.  The
applications were made for 6 hours/day, under occlusive dressings, to a
5 x 5 cm area of clipped dorsal area.

≥300 mg/kg, which persisted up to 4 days.  There was also very slight
swelling in one animal at 1000 mg/kg for one day.  There were no
treatment-related clinical findings.  There were no treatment-related
effects on body weight, body weight gain or food intake.  There were no
treatment-related findings at necropsy or in liver weight.  The maternal
NOAEL was 1000 mg/kg.  The maternal LOAEL was > 1000 mg/kg, based on
lack of adverse systemic effects in dams at doses tested.

There were no treatment-related differences in pregnancy rate, number of
corpora lutea, implantations, live fetuses, pre- or post- implantation
loss, fetal weight, sex ratio, the total number of resorptions, late
resorptions, and mean fetal weights.

There was an increased incidence of supernumerary 14th rib in all
treatment groups (> 100 mg/kg). There was an increased incidence of
microphthalmia at 300 and 1000 mg/kg compared with concurrent and
historical controls.  There was an increased incidence of the following
malformations at 1000 mg/kg:  macroglosia, hydrocephaly and
hydronephrosis compared to concurrent and historical controls. Cleft
palate occurred in only one fetus and litter, at 1000 mg/kg, as well as
in the historical control data and is not considered treatment-related.
There was an increased incidence of tubular bone dysplasia at 1000 mg/kg
and an increased incidence of 15th rib at >300 mg/kg relative to
concurrent controls.  The developmental NOAEL was 30 mg/kg.  The
developmental LOAEL was 100 mg/kg, based on an increased incidence of
supernumerary rib (14th rib) at this dose.  There was a quantitative
increase in pup sensitivity, with malformations occurring at
non-maternally toxic doses.

Dose and Endpoint for Risk Assessment:  Developmental toxicity NOAEL =
30 mg/kg/day. LOAEL = 100 mg/kg/day, based on increased incidence of
supernumerary rib.  Also, because this study showed effects in the
fetus, a female-specific body weight of 60 kg should be used for dermal
exposure estimates.

Comments about Study/Endpoint:  This study is an acceptable repeated
exposure, route-specific dermal study, therefore it is deemed to be the
most appropriate study for this risk assessment.

<IP_ADDRESS>. Dermal Exposure Long Term:

Dose and Endpoint for Risk Assessment: None; long term exposure is not
expected.

3.5.7	Inhalation Exposure (Short-, and Intermediate-Term)   TC \l3
"3.5.6	Inhalation Exposure (Short-, and Intermediate-Term)

Study Selected: Developmental Toxicity in Rabbits	OPPTS 870.6300  (83-6

MRID No.: 46246327 (Prothioconazole-desthio)

	Executive Summary:   See Section <IP_ADDRESS>.

Dose and Endpoint for Risk Assessment: Developmental toxicity LOAEL = 10
mg/kg/day, based on multiple malformations including malformed vertebral
body and ribs, arthrogryposis.  The NOAEL is 2.0 mg/kg/day.

Uncertainty Factor (UF): 1000 (10X for interspecies extrapolation and
10X for intraspecies variations, 10X for database uncertainty.)

Comments about Study/Endpoint   Please refer to the summary table in
Section 3.1.3. There is a co-critical study which reported developmental
effects in the fetus and neonate following exposure to prothioconazole
desthio, using a developmental neurotoxicity protocol (MRID 46246418).
Deviated snout and malocclusion were observed at 15.1 mg/kg/day (NOAEL =
3.6 mg/kg/day).  Also, brain morphometrics changes and an increased
incidence of peripheral nerve lesions were observed at 43.3 mg/kg/day
(NOAEL not reported).  If the NOAEL of 3.6 mg/kg/day were used as the
endpoint, with 100X UF, the Acute RfD would be 0.036 mg/kg.  Since the
endpoint derived from the developmental neurotoxicity study is not as
low as the endpoint from the rabbit developmental study, it is not used
for this risk assessment.  Another study (MRIDs 46246321, 46246322)
showing increased incidence of supernumerary ribs and incomplete/delayed
ossifications using an oral developmental toxicity protocol in the rat,
was also considered for this endpoint.  However, the rabbit study
provided more robust endpoint on which to base a risk assessment, while
occurring at dose levels very similar to the rat study.  Therefore the
rat study was not used.

<IP_ADDRESS>. Inhalation Exposure Long Term:

Dose and Endpoint for Risk Assessment: None; a long-term inhalation
exposure scenario has not been identified

3.5.8	Level of Concern for Margin of Exposure  TC \l3 "3.5.8	Level of
Concern for Margin of Exposure

A summary of the level of concern margins of exposure (MOEs) for risk
assessment purposes are presented below:

Table 3.5.8 Summary of Levels of Concern for Risk Assessment.

Route

Short-Term

(1 - 30 Days)

Intermediate-Term

(1 - 6 Months)

 Long-Term

(> 6 Months)

Occupational (Worker) Exposure

Dermal

1000

1000

None

Inhalation

1000

1000

None

Residential Exposure

Dermal or Inhalation

None

None

None

Occupational exposure:  Dermal and Inhalation: Based on the conventional
uncertainty factor of 1000X (10X for interspecies extrapolation, 10X for
intraspecies variation and 10X FQPA for database uncertainty).

Based on the conventional uncertainty factor of 100X (10X for
interspecies extrapolation and 10X for intraspecies variation), plus 10X
for lack of a NOAEL for brain morphometry and peripheral nerve lesions
in the oral developmental neurotoxicity study.

Residential exposure:  None expected.

3.5.9	Recommendation for Aggregate Exposure Risk Assessments  TC \l3
"3.5.9	Recommendation for Aggregate Exposure Risk Assessments

For this assessment all dietary exposures, i.e., food and drinking
water, are aggregated.  For the proposed crops, the estimated
concentrations of prothioconazole and its degradates in drinking water,
provided by EFED, were incorporated directly into the acute and chronic
dietary assessments.

For exposures to mixers, loaders, and applicators, risk estimates for
short- and intermediate-term exposures from both inhalation and dermal
routes are added together, because the hazard/endpoint is the same.
Because the MOEs for dermal and inhalation exposures are calculated
using different NOAELs, a total MOE approach [1/((1/MOE dermal) +
(1/MOEinhalation))] should be used to combine dermal and inhalation
risks.

3.5.10	Classification of Carcinogenic Potential  TC \l3 "3.5.10
Classification of Carcinogenic Potential

The available studies in the mouse and rat show no increase in tumor
incidence.  Therefore, HED has concluded prothioconazole or its
metabolites are not carcinogenic, and are classified “Not likely to be
Carcinogenic to Humans” according to the 2005 Cancer Guidelines.

3.5.10	Summary of Toxicological Doses and Endpoints for Prothioconazole
for Use in Human Risk Assessments  TC \l3 "3.5.10	Summary of
Toxicological Doses and Endpoints for Prothioconazole for Use in Human
Risk Assessments

Table <IP_ADDRESS>  Summary of Toxicological Doses and Endpoints for
Prothioconazole desthio for Use in Dietary and Non-Occupational Human
Health Risk Assessments

Exposure/

Scenario	Point of Departure	Uncertainty/FQPA Safety Factors	RfD, PAD,
Level of Concern for Risk Assessment	Study and Toxicological Effects

Acute Dietary (Females 13 – 49)	NOAEL = 2.0 mg/kg/day	UFA=10x

UFH=10x

FQPA SF=10x (UFDB)	Acute RfD = 0.002 mg/kg/day

aPAD = 0.002 mg/kg/day	Developmental Toxicity study in rabbits

LOAEL = 10 mg/kg/day, based on structural alterations including
malformed vertebral body and ribs, arthrogryposis, and multiple
malformations.

Acute Dietary (General Population, including infants and 	None	None	None
An appropriate study was not identified

Chronic Dietary (All Populations)	NOAEL=1.1 mg/kg/day	UFA=10x

UFH=10x

FQPA SF=10x (UFDB)	Chronic RfD =

0.001 mg/kg/day

cPAD = 0.001 mg/kg/day	Chronic/Oncogenicity study in rats

LOAEL = 8.0 mg/kg/day based on liver histopathology (hepatocellular
vacuolation and fatty change (single cell, centrilobular, and
periportal)).

Incidental Oral Short- and Intermediate-Term (1-30 days and 1-6 months)
N/A	N/A	N/A	Incidental oral exposure endpoint not identified because
residential exposure is not anticipated.

Dermal Short- and Intermediate-Term (1-30 days and 1-6 months)	N/A	N/A
N/A

	Dermal endpoints are not applicable because residential exposure is not
anticipated.

Inhalation Short- and Intermediate-term (1-30 days and 1-6 months)	N/A
N/A	N/A

	Inhalation endpoints are not applicable because residential exposure is
not anticipated

Cancer (oral, dermal, inhalation)	Classification:  “Not likely to be
Carcinogenic to Humans” based on the absence of significant tumor
increases in two adequate rodent carcinogenicity studies.

For acute and chronic dietary (food and water) risk assessments, the 10x
FQPA SF has been retained in the form of a UFdb (10x) for the lack of
NOAEL and a LOAEL from the developmental neurotoxicity study, regarding
some neurotoxic endpoint (peripheral nerve lesions and brain
morphometrics).

Point of Departure (POD) = A data point or an estimated point that is
derived from observed dose-response data and  used to mark the beginning
of extrapolation to determine risk associated with lower environmentally
relevant human exposures.  NOAEL = no observed adverse effect level.
LOAEL = lowest observed adverse effect level.  UF = uncertainty factor.
UFA = extrapolation from animal to human (intraspecies).  UFH =
potential variation in sensitivity among members of the human population
(interspecies).  UFL = use of a LOAEL to extrapolate a NOAEL.  UFS = use
of a short-term study for long-term risk assessment.  UFDB = to account
for the absence of key data (i.e., lack of a critical study).  FQPA SF =
FQPA Safety Factor.  PAD = population adjusted dose (a = acute, c =
chronic).  RfD = reference dose.  MOE = margin of exposure.  LOC = level
of concern.  N/A = not applicable.

Table <IP_ADDRESS>  Summary of Toxicological Doses and Endpoints for
Prothioconazole desthio for Use in Occupational Human Health Risk
Assessments

Exposure/

Scenario	Point of Departure	Uncertainty Factors	Level of Concern for
Risk Assessment	Study and Toxicological Effects

Dermal Short- and Intermediate-Term (1-30 days and 1-6 months)	NOAEL=30
mg/kg/day

	UFA=10x

UFH=10x

UFDB = 10x 	Occupational LOC for MOE = 1000	Dermal developmental study
in rats

LOAEL = 100 mg/kg/day based on an increased incidence of supernumerary
rib (14th rib).

Inhalation Short- and Intermediate-term (1-30 days and 1-6 months)
NOAEL=2.0 mg/kg/day

Inhalation absorption are assumed to be 100%	UFA=10x

UFH=10x

UFDB = 10x	Occupational LOC for MOE = 1000	Developmental Toxicity study
in rabbits

LOAEL = 10 mg/kg/day, based on structural alterations including
malformed vertebral body and ribs, arthrogryposis, and multiple
malformations.

Cancer (oral, dermal, inhalation)	Classification:  “Not likely to be
Carcinogenic to Humans” based on the absence of significant tumor
increases in two adequate rodent carcinogenicity studies.

The LOC for occupational exposure to prothioconazole desthio is based on
the conventional uncertainty factor of 100x (UFA = 10x and UFH = 10x)
and an additional UFDB (10x) for the lack of NOAEL and a LOAEL from the
developmental neurotoxicity study, regarding some neurotoxic endpoint
(peripheral nerve lesions and brain morphometrics).

Point of Departure (POD) = A data point or an estimated point that is
derived from observed dose-response data and  used to mark the beginning
of extrapolation to determine risk associated with lower environmentally
relevant human exposures.  NOAEL = no observed adverse effect level.
LOAEL = lowest observed adverse effect level.  UF = uncertainty factor.
UFA = extrapolation from animal to human (intraspecies).  UFH =
potential variation in sensitivity among members of the human population
(interspecies).  UFL = use of a LOAEL to extrapolate a NOAEL.  UFS = use
of a short-term study for long-term risk assessment.  UFDB = to account
for the absence of key date (i.e., lack of a critical study).  MOE =
margin of exposure.  LOC = level of concern.  N/A = not applicable.

3.6	Endocrine disruption  TC \l2 "3.6	Endocrine disruption

EPA is required under the FFDCA, as amended by FQPA, to develop a
screening program to determine whether certain substances (including all
pesticide active and other ingredients) may have an effect in humans
that is similar to an effect produced by a naturally occurring estrogen,
or other such endocrine effects as the Administrator may designate.
Following recommendations of its Endocrine Disruptor and Testing
Advisory Committee (EDSTAC), EPA determined that there was a scientific
basis for including, as part of the program, the androgen and thyroid
hormone systems, in addition to the estrogen hormone system.  EPA also
adopted EDSTAC’s recommendation that the Program include evaluations
of potential effects in wildlife.  For pesticide chemicals, EPA will use
FIFRA and, to the extent that effects in wildlife may help determine
whether a substance may have an effect in humans, FFDCA authority to
require the wildlife evaluations.  As the science develops and resources
allow, screening of additional hormone systems may be added to the
Endocrine Disruptor Screening Program (EDSP).

The submitted data on the toxicity of prothioconazole and its desthio,
deschloro, and sulfonic acid K salt metabolites do not suggest a concern
for endocrine disruption at this time.

4.0	Public Health and Pesticide Epidemiology Data  TC \l1 "4.0	Public
Health and Pesticide Epidemiology Data

Prothioconazole is an unregistered, new active ingredient, and
therefore, no public health, epidemiologic data, and/or incident reports
are available.

5.0	Dietary Exposure/Risk Characterization  TC \l1 "5.0	Dietary
Exposure/Risk Characterization

The potential for dietary exposure to prothioconazole and its
metabolites and/or degradates includes consumption of food and drinking
water.  Acute and chronic dietary (food plus drinking water) exposure
analyses were conducted.

5.1	Pesticide Metabolism and Environmental Degradation  TC \l2 "5.1
Pesticide Metabolism and Environmental Degradation

5.1.1	Metabolism in Primary Crops  TC \l3 "5.1.1	Metabolism in Primary
Crops

The applicant has submitted metabolism studies on three dissimilar
crops, wheat, peanut, and sugar beet.  The crops selected for the
studies are sufficiently representative of the crops for which the
applicant is requesting registration:  barley, peanut, rice, wheat, the
dried shell and bean subgroup, and the oilseed crop group.  The
application patterns used in the studies are similar to those the
applicant is proposing (foliar applications), and bracket the preharvest
intervals that are being proposed.  The applicant submitted studies
reflecting labeling in both rings for all three crops.  Detailed
discussions are presented in the residue chemistry summary document
(Prothioconazole.  Petition for Establishment of Tolerances for Use on
Barley, Oilseed (Except Sunflower and Safflower) Crop Group, Dried
Shelled Pea and Bean (Except Soybean) Crop Subgroup, Peanut, Rice, and
Wheat. Summary of Analytical Chemistry and Residue Data. PP#4F6830.
D303508; S. Funk, 08/21/06).

The metabolism of prothioconazole was investigated in plants following
foliar spray applications of [triazole-UL-14C] prothioconazole or
[phenyl-UL-14C] prothioconazole to wheat, peanuts, and sugar beet and
seed treatment application of [phenyl-UL-14C] prothioconazole to wheat.

Bayer CropScience submitted   SEQ CHAPTER \h \r 1 eight plant metabolism
studies to support the proposed uses, seven of which were reviewed:  (1)
a wheat metabolism study reflecting foliar application of
[phenyl-14C]-prothioconazole (MRID 46246141); (2) a wheat metabolism
study reflecting seed treatment with [phenyl-14C]-prothioconazole (MRID
46246142); (3) a wheat metabolism study reflecting foliar application of
[triazole-14C]-prothioconazole (MRID 46246143); (4) a peanut metabolism
study reflecting foliar application of [phenyl-14C]-prothioconazole
(MRID 46246145); (5) a peanut metabolism study reflecting foliar
application of [triazole-14C]-prothioconazole (MRID 46246146); (6) a
sugar beet metabolism study reflecting foliar application of
[triazole-14C]-prothioconazole (MRID 46246147); and (7) a sugar beet
metabolism study reflecting foliar application of
[phenyl-14C]-prothioconazole (MRID 46246148).    SEQ CHAPTER \h \r 1 A
wheat metabolism study reflecting application of
[triazole-14C]-prothioconazole-desthio (metabolite) (MRID 46246144) was
not reviewed, because it did not provide any additional relevant
information.

The results of the plant studies showed that prothioconazole (JAU6476)
was extensively metabolized after the foliar (wheat, peanut, and sugar
beet) and seed treatment application (wheat) of [triazole-UL-14C]
prothioconazole or [phenyl-UL-14C] prothioconazole.  The parent compound
represented only <1 to 7% of the residues in all matrices.  The proposed
metabolic profile for prothioconazole in sugar beet, wheat and peanut is
presented in Appendix B., Figures B.1. and B.2.

In the phenyl label studies, the major residue found in wheat, peanut,
and sugar beet was prothioconazole-desthio (6% to 58% of the total
radioactive residue (TRRs) in wheat, peanuts, and sugar beet).  A second
major metabolic process involved hydroxylation followed by conjugation.
Since prothioconazole has multiple positions that could potentially
undergo hydroxylation, the majority of the remaining metabolites were
simply multiple isomers of monohydroxylated prothioconazole-desthio and
their corresponding glucosides along with prothioconazole-hydroxy-diene,
dihydroxy-diene, dihydroxy-olefin, and their conjugates.  Collectively,
these conjugated and/or hydroxylated metabolites represented a major
portion (18 to 37%) of the TRRs in the crop matrices and contained both
the phenyl and the triazole rings in the molecule.  However, none of
these hydroxylated metabolites individually reached or exceeded 10% of
the TRRs in any target crop matrix.  Cleavage of the triazole moiety
occurred resulting in the formation of the label-specific metabolite
prothioconazole-benzylpropyldiol and its glucoside, which represented a
minor portion of the TRRs.

A total of 60% to 74% of the residues from the phenyl label foliar
studies were identified.  An additional 20% to 48% of the TRRs were
characterized by extraction and/or chromatographic behaviors.  Only 1 to
8% of the residues remained unextracted.  The unextracted residues from
the wheat seed treatment study ranged from 8% to 26% of the TRRs in the
wheat forage, hay, and straw.  However, the actual ppm residue levels of
unextractable residues ranged from only 0.01 ppm to 0.02 ppm.

The triazole label plant studies showed three major metabolic processes
(desulfuration, hydroxylation, and cleavage of the triazole moiety).
Prothioconazole-desthio (6% to 25% maximum levels in wheat, peanuts, and
sugar beet) and the label-specific triazole conjugates, triazolylalanine
(TA), triazolylacetic acid (TAA), and triazolylhydroxypropionic acid
(THP) (collectively representing a maximum of 29% to 90% of the TRRs in
wheat, peanuts, and sugar beet) were the major residues found in the
triazole label studies.  Although the triazole label studies showed
greater cleavage of the triazole moiety (compared to the phenyl label),
no free triazole was detected in any crop matrix.  As was found in the
phenyl label studies, numerous minor hydroxylated metabolites and their
conjugates comprised the majority of the remainder of the residues.
Triazolyl-ethanol and its glucoside and triazolyethanol sulfonic acid
glucoside were minor metabolites arising from cleavage of the benzylic
group.

A total of 61% to 94% of the residues from the triazole label studies
were identified.  An additional 6% to 33% of the TRRs were characterized
by extraction and/or chromatographic behaviors.  The unextractable
residues ranged from only <1% to 6% of the TRRs in the plant matrices.

With the exception of the label-specific metabolites, the metabolic
profiles were very similar for the target crop studies with both labels.
 The triazole and phenyl label studies clearly elucidated the metabolic
fate of the prothioconazole molecule in target crops and were very much
complementary to each other.  Irrespective of the mode of application
(foliar or seed treatment) and the target crop (wheat, peanuts, or sugar
beet), the major residues found in all crops were
prothioconazole-desthio, TA, THP acid, and TAA.  The metabolic profiles
for the target crops were also similar to the profiles found in the
rotational crops.  However, the levels of the triazole-based conjugates
were much higher in the rotational crops, a finding which was consistent
with that expected for confined rotational crop studies with a
triazole-based fungicide.

Following the initial metabolism of prothioconazole to
prothioconazole-desthio (through oxidation of the sulfur to the
corresponding sulfonic acid with subsequent elimination of the sulfonic
acid group), two major metabolic processes were observed.  One major
pathway involved the hydroxylation of the phenyl ring and/or benzylic
carbon to form multiple isomers of prothioconazole-hydroxy-desthio,
prothioconazole-dihydroxy-desthio, and
prothioconazole-α-hydroxy-desthio followed by conjugation to form the
corresponding glucosides or acetate.  The other major pathway involved
the cleavage of the H2C-N bond to release the triazole moiety (and
benzylpropyldiol) leading to the formation of TA and THPA and further
metabolism of the triazole conjugates to TAA.  The fact that no free
triazole was found in any target crop matrix suggests an immediate or
very rapid conjugation of the released triazole to form the triazole
conjugates.

Minor metabolic processes involved the successive reductions of the
phenyl ring to form dienes and olefins; formation of
prothioconazole-triazolinone; and cleavage of the chlorobenzylic group
to form triazolyl-ethanol and its glucoside.

Wheat Metabolism Summary:  The submitted wheat metabolism data are
adequate to satisfy data requirements.  Based on the results of the
wheat metabolism studies, the applicant concluded that prothioconazole
is initially metabolized in wheat by oxidation and loss of sulfur to
form prothioconazole-desthio, after which two major metabolic processes
occur:  (1) hydroxylation of the phenyl ring and/or benzylic carbon to
form isomers of prothioconazole-OH-desthio, prothioconazole-diOH
desthio, and prothioconazole-α-OH-desthio, followed by conjugation to
form the corresponding glucosides, malonyl-glucosides and acetate; and
(2) release of the triazole moiety to form triazolylalanine and THPA and
further metabolism of the triazole conjugates to form triazolylacetic
acid.  The applicant noted that the absence of free triazole in any
wheat matrix suggested that immediate or very rapid conjugation of
released triazole occurred.  The following minor metabolic pathways were
reported:  formation of prothioconazole-triazolinone and
prothioconazole-desthio-phenyl-cysteine; conjugation of
prothioconazole-desthio with glucose and malonic acid; oxidation of the
sulfur atom of prothioconazole to form prothioconazole sulfonic acid;
and cleavage of the benzylic group to form triazolyl-ethanol and its
glucoside.

A similar metabolic pathway is proposed for the metabolism of
prothioconazole in wheat following application as a seed treatment.

Peanut Metabolism Summary:  The submitted peanut metabolism data are
adequate to satisfy data requirements.  Based on the results of the
peanut metabolism studies, the applicant concluded that prothioconazole
is initially metabolized in peanut by:  (1) oxidation and loss of sulfur
to form prothioconazole-desthio; (2) hydroxylation of the chlorobenzyl
ring of prothioconazole-desthio at positions 3 and 4 to form the hydroxy
desthio metabolites; (3) conjugation of the hydroxylated metabolites;
(4) exchange of oxygen for sulfur; and (5) release of the triazole
moiety to form triazolylalanine and THPA.  Free triazole was not
detected in any peanut matrix.

Sugar beet metabolism summary:  The sugar beet metabolism data are
adequate to satisfy data requirements. Based on the results of the sugar
beet metabolism studies, the applicant concluded that prothioconazole is
extensively metabolized in sugar beet via:  (1) oxidation of the sulfur
of the triazolinethione ring to the corresponding sulfonic acid and
subsequent elimination of the sulfonic acid group to form desthio
prothioconazole; (2) hydroxylation of the phenyl ring or the benzyl
carbon to form multiple isomers, with subsequent conjugation with
glucose or further reaction to produce
prothioconazole-desthio-hydroxy-dieneyl-cysteine; (3) release of the
triazole moiety to form triazolylalanine and THPA; and (4) elimination
of the phenyl ring.  The applicant noted that free triazole was not
identified.

Based on these considerations, HED concludes that the submitted studies
are adequate to delineate the nature of prothioconazole residues in
plants.

The residues of concern for both enforcement purposes (tolerance) and
for risk assessment in plant commodities are parent prothioconazole and
its metabolite prothioconazole-desthio, expressed as prothioconazole.

5.1.2	Metabolism in Rotational Crops  TC \l3 "5.1.2	Metabolism in
Rotational Crops

Bayer CropScience submitted t  SEQ CHAPTER \h \r 1 wo confined
rotational crop studies to support the proposed uses, one conducted
using [phenyl-14C]-prothioconazole (MRID 46246225) and one conducted
using [triazole-14C]-prothioconazole (MRID 46246226).  Additionally, a
limited field rotational crop study (MRID 46246227) on the
representative crops mustard greens (leafy vegetable), turnip (root
vegetable), and wheat (cereal grain) was submitted.  Detailed
discussions of the results of these studies are presented below in
section 5.1.10 and in the residue chemistry summary document (D303508;
S. Funk, 08/21/06).

The metabolism in rotational crops was found to be qualitatively similar
to that in the primary crops peanut, sugar beet and wheat, as the same
major metabolites were detected.  The presence of minor unknown polar
compounds indicated that composition of metabolites in rotational crops
was influenced by the metabolism of prothioconazole in soil.  In
addition, it appeared that conjugation was more prevalent in rotational
crop metabolism than in primary crop metabolism.

The confined study did show the potential for accumulation of residue in
rotated crops.

5.1.3	Metabolism in Livestock  TC \l3 "5.1.3	Metabolism in Livestock

The metabolic pathway for prothioconazole was evaluated in livestock
following three consecutive daily oral doses of [phenyl-UL-14C]
prothioconazole or [triazole-UL-14C] prothioconazole to lactating goats
and laying hens.  Some qualitative and quantitative differences between
goats and laying hens were observed.  These differences were:

cleavage of prothioconazole and prothioconazole-desthio to release
1,2,4-triazole and triazolylethanol occurred in poultry, but these
metabolites were not found in goats (1,2,4-triazole was also found in
rats following an oral dose of [triazole-UL-14C] prothioconazole),

methylation of the sulfur atom of the parent compound was a major
metabolic process in poultry, but was only a minor pathway in goats,

cleavage of the triazolinthione ring to yield thiocyanate was a major
metabolic process in goats, but was only a minor pathway in poultry, and

conjugation of prothioconazole with lactose occurred only in goats.

With the exception of the above-mentioned differences, the metabolism of
prothioconazole was very similar in all livestock. Conjugation of the
unchanged parent compound with glucuronic acid forming an S-glucuronide
and desulfuration of prothioconazole yielding prothioconazole-desthio
were major metabolic processes in both poultry and goats.  However, the
majority of the metabolites found in poultry and goats were products of
hydroxylations of prothioconazole and its desthio metabolite (probably
through epoxide intermediates) leading to the formation of the
corresponding dihydroxy and dihydroxy-dienes.  Detailed discussions of
the results of the livestock metabolism studies are presented below and
in the residue chemistry summary document (D303508; S. Funk, 08/21/06).
The proposed metabolic profile for prothioconazole in livestock is
presented in Appendix B., Figures B.3 through B.6.

In goats, the di-hydroxylated metabolites (prothioconazole-dihydroxy and
prothioconazole-desthio-dihydroxy-diene) were further conjugated with
glucuronic acid; in poultry, the sulfate and glucuronic acid conjugates
of the di-hydroxylated prothioconazole-desthio metabolites were formed.
Sulfate and glucuronic acid conjugation of prothioconazole-3/4-hydroxy
and methylation of prothioconazole-dihydroxy-desthio occurred in both
poultry and goats.

Five livestock metabolism studies were supplied to support the proposed
uses:  (1) a goat metabolism study reflecting dosing with
[triazole-14C]-prothioconazole (MRID 46246149); (2) a goat metabolism
study reflecting dosing with [phenyl-14C]-prothioconazole (MRID
46246150); (3) a goat metabolism study reflecting dosing with
[phenyl-14C] prothioconazole-desthio (MRID 46246201), which was not
considered; (4) a hen metabolism study reflecting dosing with
[phenyl-14C]-prothioconazole (MRID 46246202); and (5) a hen metabolism
study reflecting dosing with [triazole-14C]-prothioconazole (MRID
46246203).

Goat Metabolism Summary:  The goat metabolism data are adequate to
satisfy data requirements. Based on the results of the goat metabolism
studies, it is concluded that prothioconazole is metabolized in goats
via several steps:  conjugation of the unchanged parent compound with
glucuronic acid resulting in an S- or O-glucuronide; additional
glucuronidation of the triazole-thione nitrogen atom of the parent
compound to form prothioconazole-N-glucuronide; hydroxylation of the
parent compound to form prothioconazole-4-hydroxy and a further hydroxy
isomer, followed by conjugation with glucuronic acid; oxidation of the
phenyl ring of the parent compound to form
prothioconazole-dihydroxy-diene; elimination of sulfur to form
prothioconazole-desthio; further hydroxylation of the chlorophenyl
moiety to form prothioconazole-3-hydroxy-desthio and
prothioconazole-4-hydroxy-desthio, followed by conjugation with
glucuronic acid; oxidation of the chlorophenyl moiety of
prothioconazole-desthio to form prothioconazole-desthio-dihydroxy-diene;
conjugation of the triazolinethione moiety of the parent compound with
lactose; conjugation of hydroxylated metabolites of prothioconazole with
sulfate; methylation of the triazolinethione moiety of prothioconazole
to form prothioconazole-S-methyl; and cleavage of the parent compound to
form thiocyanate.  The presence of
prothioconazole-dihydroxy-desthio-glucuronides indicated that isomers of
prothioconazole-dihydroxy-desthio were formed as intermediates.
Methylation of prothioconazole-hydroxy-desthio-glucuronides to form
prothioconazole-hydroxymethoxy-desthio-glucuronides occurred to a small
extent, as did the glucuronidation of prothioconazole-desthio.

Hen Metabolism Summary:  The hen metabolism data are adequate to satisfy
data requirements.

Based on the study results, the applicant concluded that prothioconazole
is metabolized in hens via several steps:  conjugation of the unchanged
parent compound with glucuronic acid to form an S- (more likely) or an
O-glucuronide; methylation of the triazolinethione moiety to form
prothioconazole-S-methyl; elimination of sulfur to form the metabolite
prothioconazole-desthio; hydroxylation of the chlorophenyl moiety of the
metabolite prothioconazole-desthio to form
prothioconazole-4-hydroxy-desthio and possibly
prothioconazole-3-hydroxy-desthio, followed by conjugation with sulfate;
oxidation of the chlorophenyl moiety of prothioconazole-desthio,
followed by conjugation with glucuronic acid, to form
prothioconazole-desthio-3,4-dihydroxy-dienyl-glucuronide; cleavage of
the aliphatic carbon chain to form 1,2,4-triazole and
prothioconazole-triazolylethanol; cleavage of the triazolinethione
moiety to form thiocyanate; hydroxylation of the parent compound to form
prothioconazole-4-hydroxy; glucuronidation of a triazolinethione
nitrogen atom of the parent compound to form
prothioconazole-N-glucuronide; and, to a small extent, methylation of
prothioconazole-hydroxy-desthio to form
prothioconazole-hydroxymethoxy-desthio-glucuronides.  The presence of
sulfate conjugates of prothioconazole-dihydroxy-desthio and
prothioconazole-hydroxymethoxy-desthio indicated that
prothioconazole-dihydroxy-desthio and
prothioconazole-hydroxymethoxy-desthio were formed as intermediates.

The residue of concern for tolerance enforcement in livestock
commodities is prothioconazole and prothioconazole-desthio and
conjugates that are converted to prothioconazole or
prothioconazole-desthio by acid hydrolysis, expressed as
prothioconazole.  The residue of concern for risk assessment in
livestock commodities is prothioconazole, prothioconazole-desthio,
prothioconazole-4-hydroxy and conjugates that are converted to
prothioconazole, prothioconazole-desthio, or prothioconazole-4-hydroxy
by acid hydrolysis, expressed as prothioconazole.

5.1.4	Analytical Methodology  TC \l3 "5.1.4	Analytical Methodology

PP#4F6830.  New Chemical – Prothioconazole in/on Plant and Livestock
Commodities.  Tolerance Method Validation Report. (MRID #’s 462462-04,
462462-06, 462462-07, and 462462-09) Chemical # 113961.  Decision
Number:  318440.  ACB # B05-39.  DP Barcode 318440. P. Schermerhorn.
08/04/06.

Adequate analytical methods exist for the determination of the residue
as defined for both tolerance enforcement and for determination of the
residues of concern for risk assessment for both plant and livestock
commodities.

Enforcement Method for Plant Commodities

An HPLC-MS/MS method was developed and proposed for data gathering and
enforcement purposes for plant matrices.  An oxidative extraction
procedure converts prothioconazole residues to a mixture of
prothioconazole-desthio and prothioconazole sulfonic acid. The desthio
prothioconazole metabolite remains unchanged after extraction.  The
cooled extract is spiked with an isotopically labeled internal standard,
cleaned up by C18 solid-phase extraction (SPE), and mixed with either
0.1% formic acid or 1% acetic acid for analysis by LC-MS/MS.  The
results for prothioconazole sulfonic acid and prothioconazole-desthio
are reported in prothioconazole equivalents and then totaled to yield
“total prothioconazole derived residues.”  The validated LOQs
reported for each of the two analytes in the method are 0.02 ppm for
canola seed, peanut nutmeat, and wheat grain; and 0.05 ppm for dried
peas, wheat forage, wheat hay, and wheat straw.  Adequate extraction
efficiencies were demonstrated using radiolabeled wheat forage, and
sugar beet tops analyzed with the enforcement method.  The method was
sent to the analytical chemistry laboratory (ACL) for validation.  The
Analytical Chemistry Branch (ACB) found the method meets the requirement
of the Residue Chemistry Test Guidelines, OPPTS 860.1340, for acceptable
tolerance enforcement methods.

The registrant has submitted a high performance liquid chromatography
(with electrospray ionization) and tandem mass spectrometry (LC-MS/MS)
data gathering method for the determination of residues of
1H-1,2,4-triazole and the triazole conjugates triazolylalanine (TA) and
triazolylacetic acid (TAA) in plant commodities.  Validated LOQs range
from 0.01-0.05 ppm for 1H-1,2,4-triazole and 0.01-1.5 ppm for TA and
TAA.

Enforcement Method for Livestock Commodities

The livestock analytical method (HPLC-MS/MS), similar for both data
collection and enforcement, is capable of determining prothioconazole,
prothioconazole-desthio, prothioconazole-4-hydroxy, and conjugates that
can be converted to one of these compounds via acid hydrolysis.  Samples
of bovine liver, kidney, and muscle are extracted with acetonitrile
(ACN)/water and 25% aqueous L-cysteine HCl.  An internal standard
solution is added to the extract.  The internal standard solution
consists of a mixture of [triazole-15N3-13C2]-prothioconazole,
[triazole-15N3-13C2]-prothioconazole-desthio, and
[triazole-15N3-13C2]-prothioconazole-4-hydroxy in ACN containing 50
µg/mL L-cysteine HCl.  Fat samples are extracted with n-hexane and then
with a mixture of ACN, 25% aqueous L-cysteine HCl, and acetone; the
combined extracts are allowed to separate, and internal standard
solution is added to the aqueous phase.  Samples of milk and cream are
mixed with internal standard solution directly.  For all matrices, the
extract/sample is hydrolyzed using aqueous HCl, and the hydrolysate is
partitioned with methylene chloride and acetone.  The organic phase is
concentrated to aqueous, mixed with ACN and water, and analyzed by
LC-MS/MS.  Adequate extraction efficiencies were demonstrated using
radiolabeled goat milk, goat liver, goat muscle and goat fat analyzed
with the enforcement method.  The method has been validated by an
independent laboratory for ruminant commodities only.  The limits of
quantitation (LOQ) are as follows for each of the three analytes: 0.005
ppm for milk; 0.010 ppm for skim milk, cream, and muscle; 0.010 ppm for
liver; 0.010 ppm for kidney; and 0.050 ppm for fat.

The method was sent to the analytical chemistry laboratory (ACL) for
validation.  The Analytical Chemistry Branch (ACB) found the method
meets the requirement of the Residue Chemistry Test Guidelines, OPPTS
860.1340, for acceptable tolerance enforcement methods.

Recommendations for Methods for Plant and Livestock Commodities

ACB finds that both methods (plant and livestock) which use liquid
chromatography with tandem mass spectrometry using electrospray
ionization in both the positive and negative modes meets the
requirements of the Residue Chemistry Test Guidelines, OPPTS 860.1340,
for acceptable tolerance enforcement methods.

ACB recommends that the petitioner include a confirmatory procedure for
each method submitted. The OPP guidelines require either a confirmatory
method or an interference study to eliminate the possibility of false
positives while using the primary enforcement method.  When mass
spectrometry is used for detection in the primary enforcement method a
confirmatory method is waived as long as the detector provides enough
selectivity to eliminate false positives.  While we fully agree that
MS/MS provides excellent selectivity, expert opinion has changed over
the past several years as mass spectrometrists have gained more
experience with the instrumentation.  A single MS/MS ion transition used
to be considered sufficient for positive confirmation of analyte
residue.  However, instances of false positive interferences have led
towards consensus that two ion transitions are needed to provide
“confirmation” of residues.  The ACB recommends that future
revisions of these methods include at least two multiple reaction
monitoring (MRM) transitions.  References include the following:

a) Commission Decision 2002/657/EC, Official Journal of the European
Communities, August 12, 2002.

b) Guidance for Industry:  Mass Spectrometry for Confirmation of the
Identity of Animal Drug Residues, US FDA Center for Veterinary Medicine,
May 1, 2003.

c) Bethem, et al, Establishing the Fitness for Purpose of Mass
Spectrometric Methods, J Am Soc Mass Spectrom 2003, 14, 523-541.

ACB reviewed the Independent Laboratory Validation (ILV) reports for
both the plant and livestock methods (MRID #’s 462462-09 and
462462-07, respectively).  ACB recommends that there were successful
ILV’s.

a) However, the first ILV trial of the plant method failed due to
incomplete mixing following the addition of internal standard and prior
to the removal of an aliquot for the C-18 SPE cartridge cleanup.  This
step may require a precautionary note in any future revisions of the
method.

b) The ILV performing the livestock method found that a quadratic
regression calibration curve with 1/x2 weighting gave the best fit for
the milk.  ACB was able to use a linear regression of y = mx + b for the
milk.  Both the ILV and ACB used a 1/x weighted least square regression
fit for the liver.  A 1/x weighted linear regression was recommended and
used by the petitioner.

Multiresidue Methods

Bayer CropScience has submitted multiresidue method data (MRID 46246210)
for prothioconazole, the metabolites prothioconazole-desthio and
prothioconazole-4-hydroxy, and the triazole-related compounds triazole,
triazolylalanine, and triazolylacetic acid.  The test substances were
analyzed according to the FDA Multi-Residue Method Test guidelines in
PAM, Vol. I (dated 1/94).  Prothioconazole, prothioconazole-desthio,
prothioconazole-4-hydroxy, triazole and triazolylacetic acid were tested
through Protocols A and C.  As a result of Protocol C testing,
prothioconazole, prothioconazole-desthio, and prothioconazole-4-hydroxy
were tested through Protocol F.  Prothioconazole-4-hydroxy and
triazolylacetic acid were tested through Protocol B.  Based on the
results of the Protocol F testing, testing under Protocols D and E was
not required for prothioconazole, and testing under Protocol E was not
required for prothioconazole-4-hydroxy.  Because the test substances are
not substituted ureas, no testing under Protocol G was required.  A
suitable solvent for triazolylalanine could not be found; therefore,
testing of this compound could not be conducted.

Sensitivity for triazolylacetic acid was poor using Protocol A, and no
response was obtained for the other test compounds.  Protocol C testing
indicated that further testing using Protocols D, E, and F was not
required for triazolylacetic acid and triazole.  Triazolylacetic acid
and prothioconazole-4-hydroxy could not be adequately recovered under
Protocol B.  Prothioconazole and prothioconazole-4-hydroxy were not
adequately recovered using the Florisil column cleanup steps of Protocol
F, and prothioconazole-4-hydroxy did not yield adequate chromatography
using Protocol D; thus, no further testing of these compounds was
conducted.  Prothioconazole-desthio could not be adequately recovered
under Protocols D or E, using wheat hay.  Recovery of
prothioconazole-desthio was variable (66-100%) under Protocol F, using
ground beef.

Conclusions:  The multiresidue test data will be forwarded to FDA for
further evaluation.  Based on the results of the testing, the
multiresidue methods are not appropriate for determining prothioconazole
residues of concern, or for determining residues of triazole,
triazolylalanine, or triazolylacetic acid.

5.1.5	Environmental Degradation TC \l3 "5.1.5	Environmental Degradation

A detailed characterization of the environmental fate and transport of
prothioconazole and its degradates is provided in the following
document: “Prothioconazole Section 3: Environmental Fate and
Ecological Risk Assessment”, DP Barcode: 324660, Decision #: 341716,
C. Salice and R. Kashuba, 06/01/06.

Based on environmental fate data submitted by the registrant,
prothioconazole is expected to degrade rapidly in the environment.  The
major transformation products (created in amounts greater than or equal
to 10% of applied radioactivity) resulting from degradation processes of
prothioconazole include: prothioconazole-desthio,
prothioconazole-S-methyl, prothioconazole-thiazocine, and
1,2,4-triazole.  The identified minor transformation products (created
in amounts less than 10% of applied radioactivity) resulting from
degradation processes of prothioconazole include:  SEQ CHAPTER \h \r 1
prothioconazole-sulfonic acid, prothioconazole-triazolinone,
prothioconazole-3, 4, 5, and 6-hydroxy-desthio, 2-chlorobenzoic acid,
and prothioconazole-triazolylketone.

The predominant means of degradation of prothioconazole combined
residues of concern in the environment is likely to be aerobic aquatic
metabolism, with loss of prothioconazole, prothioconazole-desthio, and
prothioconazole-S-methyl attributed to the formation of 1,2,4-triazole,
prothioconazole-triazolinone, other minor unidentified degradates and
CO2.

The predominant degradate is prothioconazole-desthio, which is formed
quickly and in large amounts from all degradation processes evaluated
(maximum of 5.7% of applied in hydrolysis, 55.7% in aqueous photolysis,
39.0% in soil photolysis, 49.4% in aerobic soil metabolism, and 54.6 %
in aerobic aquatic metabolism total system).  It is the result of
desulfonation of prothioconazole parent.  Prothioconazole-S-methyl is
also formed in large amounts from anaerobic aquatic metabolism (78.2% of
applied in total system) and in lesser amounts from aerobic soil
metabolism (14.6% of applied) and aerobic aquatic metabolism (12.7 % of
applied in total system).  It is the result of methylation of the sulfur
of prothioconazole parent.  Both of these identified major
transformation products are expected to form in large concentrations in
both terrestrial and aquatic environment compartments.

Prothioconazole-desthio is expected to be persistent with moderate
mobility in the soil.  Since prothioconazole and prothioconazole-desthio
are both stable to hydrolysis, together very slowly degraded by aerobic
soil metabolism, anaerobic aquatic metabolism and aqueous photolysis,
and together moderately degraded by aerobic aquatic metabolism,
transport to surface water of the relatively persistent prothioconazole
and prothioconazole-desthio combination will occur.  Due to this
persistence and moderate mobility of prothioconazole-desthio in some
soils, transport to ground water is also likely, particularly in areas
with porous soil of low organic carbon content.

Prothioconazole-thiazocine is formed at a maximum of 14.1% of applied
radioactivity from aqueous photolysis only.  This mode of degradation is
only likely to be influential in clear, shallow water, under clear
atmospheric conditions.  In actual environmental systems, aqueous
photolysis is likely to proceed at a much slower rate due to the
attenuation of light due to increasing depth of water bodies, light
adsorption by suspended solids, and natural obstruction of sunlight.
Therefore, since it is likely to form only in very small amounts under
very specific circumstances in the environment, and HED has very low
concern regarding the hazard associated with this environmental
metabolite, prothioconazole-thiazocine is not considered in this
assessment.

The 1,2,4-triazole degradate was only tracked in aerobic soil
metabolism, aerobic aquatic metabolism, and aqueous photolysis studies.
It formed in large amounts (maximum of 41.8% of applied radioactivity)
as a result of aerobic aquatic metabolism, at medium amounts (maximum of
11.9% of applied radioactivity) as a result of aqueous photolysis and at
very small, practically non-detectable amounts (maximum of <2.0% of
applied radioactivity) as a result of aerobic soil metabolism.  The
1,2,4-triazole degradate is being characterized in a separate,
cumulative triazole assessment and is, therefore, not considered
separately in this assessment.

5.1.6	Comparative Metabolic Profile TC \l3 "5.1.6	Comparative Metabolic
Profile

The metabolism of prothioconazole was similar in all livestock (hens and
goats).  Conjugation of the unchanged parent compound with glucuronic
acid forming an S-glucuronide and desulfuration of prothioconazole
yielding prothioconazole-desthio were major metabolic processes in both
poultry and goats.  However, the majority of the metabolites found in
poultry and goats were products of hydroxylations of prothioconazole and
its desthio metabolite (probably through epoxide intermediates) leading
to the formation of the corresponding dihydroxy and dihydroxy-dienes.

Some qualitative and quantitative differences between goats and laying
hens were observed.  These differences were:

cleavage of prothioconazole and prothioconazole-desthio to release
1,2,4-triazole and triazolylethanol occurred in poultry, but these
metabolites were not found in goats (1,2,4-triazole was also found in
rats following an oral dose of [triazole-UL-14C] prothioconazole),

methylation of the sulfur atom of the parent compound was a major
metabolic process in poultry, but was only a minor pathway in goats,

cleavage of the triazolinthione ring to yield thiocyanate was a major
metabolic process in goats, but was only a minor pathway in poultry, and

conjugation of prothioconazole with lactose occurred only in goats.

The metabolism observed in livestock was similar to that observed in the
rat.  Prothioconazole and/or the O- or S-glucuronide were/was a major
component of the residue in all species.  Prothioconazole-desthio was
likewise found in the rat (bile, urine) and in livestock commodities.
The metabolite prothioconazole-4-hydroxy and/or it glucuronide was found
in livestock and in the rat (feces).  The metabolite
prothioconazole-3-hydroxy desthio was tentatively identified as a
component in goat matrices and was a minor constituent in rat feces, but
was absent in poultry.  The metabolite prothioconazole-4-hydroxy desthio
was found in all species.  Prothioconazole triazolinone was found in rat
feces, but not in goat or poultry commodities.  Prothioconazole-S-methyl
was a major metabolite found in hen fat and rat feces, but not in goat
commodities.  Finally, desthio prothioconazole 3,4-dihydroxy dienyl
glucuronide was found in hen commodities and in rat urine.

-α-hydroxy-desthio followed by conjugation to form the corresponding
glucosides or acetate.  The other major pathway involved the cleavage of
the H2C-N bond to release the triazole moiety (and benzylpropyldiol)
leading to the formation of TA and THPA and further metabolism of the
triazole conjugates to TAA.  The fact that no free triazole was found in
any target crop matrix suggests an immediate or very rapid conjugation
of the released triazole to form the triazole conjugates.

5.1.7	Toxicity Profile of Major Metabolites and Degradates TC \l3 "5.1.7
Toxicity Profile of Major Metabolites and Degradates

As explained in detail previously in this document, prothioconazole is
rapidly metabolized by plants, livestock, and laboratory animals, and is
rapidly degraded in the environmental.  The predominant metabolite and
degradate is prothioconazole-desthio.  Prothioconazole-desthio is more
toxic than parent prothioconazole by nearly an order of magnitude.  As
explained in detail throughout section 3 of this document, the toxicity
findings for the metabolite/degradate prothioconazole-desthio are of
paramount importance to the risk assessment of prothioconazole.  In
addition to the full toxicology database for prothioconazole, there is a
second nearly complete database of studies for the major
metabolite/degradate prothioconazole-desthio (also known as SXX0665).  A
few additional toxicity studies were also submitted on other minor
metabolites/degradates, i.e. prothioconazole-deschloro and
prothioconazole sulfonic acid K salt.  The toxicity profiles for
prothioconazole and prothioconazole-desthio are available in Appendixes
A.2. and A.3. below.

5.1.8	Pesticide Metabolites and Degradates of Concern TC \l3 "5.1.8
Pesticide Metabolites and Degradates of Concern

The major constituents of the TRR in plant foliar and seed treatment
studies and in limited field rotational crop studies were
prothioconazole and prothioconazole-desthio, totaling 20–30%.   Minor
components (each <10% TRR) were hydroxylated and dihydroxylated
derivatives of these two compounds.  Limited rotational crop field
studies revealed no quantifiable residues of prothioconazole or
prothioconazole-desthio at a 30 day PBI.  Because the analytical method
converts prothioconazole to a mixture of prothioconazole sulfonic acid
and prothioconazole-desthio, it is not possible to estimate the relative
amounts of prothioconazole and prothioconazole-desthio in the numerous
field trial studies.

It is estimated that the various minor hydroxy metabolites are of no
greater toxicological concern than the parent.  Therefore, for risk
assessment purposes, the residue of concern is defined as the sum of
parent prothioconazole and the prothioconazole-desthio metabolite.

Prothioconazole underwent extensive metabolism in both ruminants and
poultry, and the pathways were generally similar.  Parent (or
glucoronide conjugate) was significant (>10% TRR) in ruminant liver,
kidney, muscle, milk, and fat and in hen liver, egg, muscle, and fat.
The desthio-prothioconazole metabolite was present in all commodities,
but >10% only in fat (goat and hen) and eggs.  The
prothioconazole-4-hydroxy (or its glucuronide conjugate) was >10% TRR in
goat liver, goat fat, and goat kidney and was present (minor) in several
poultry commodities.

Conjugation of the unchanged parent compound with glucuronic acid
forming an S-glucuronide and desulfuration of prothioconazole yielding
prothioconazole-desthio were major metabolic processes in both poultry
and goats.  However, the majority of the metabolites found in poultry
and goats were products of hydroxylations of prothioconazole and its
desthio metabolite (probably through epoxide intermediates) leading to
the formation of the corresponding dihydroxy and dihydroxy-dienes.  In
goats, the di-hydroxylated metabolites (prothioconazole-dihydroxy and
prothioconazole-desthio-dihydroxy-diene) were further conjugated with
glucuronic acid; in poultry, the sulfate and glucuronic acid conjugates
of the di-hydroxylated prothioconazole-desthio metabolites were formed.
Sulfate and glucuronic acid conjugation of prothioconazole-3/4-hydroxy
and methylation of prothioconazole-dihydroxy-desthio occurred in both
poultry and goats.

It is estimated that the various hydroxy and dihydroxy metabolites and
conjugates thereof of both prothioconazole and prothioconazole-desthio
are of no greater toxicological concern than the parent.  For tolerance
enforcement purposes, the residue is defined as the sum prothioconazole
and prothioconazole-desthio and conjugates that can be converted to
these two compounds by acid hydrolysis, expressed as prothioconazole.
As the prothioconazole-4-hydroxy and its conjugates were significant
(>10% TRR) in several ruminant commodities, they will be included in the
residue of concern for dietary risk assessment.  The residue of concern
for dietary risk assessment purposes is defined as the sum of
prothioconazole, prothioconazole-desthio, prothioconazole-4-hydroxy and
conjugates that can be converted to one of these three compounds by acid
hydrolysis, expressed as prothioconazole.

Not considered in the degradates/metabolites for risk assessment and
tolerance expression are prothioconazole-S-methyl, 20–28% TRR in hen
fat and minor amounts (<10%) in hen egg, liver, and muscle; thiocyanate
ion, 12–40% TRR in goat commodities; and prothioconazole-6-hydroxy
sulfate, 10% in goat liver.  These metabolites are of no special
toxicological concern relative to the parent prothioconazole.

Table 5.1.8	Summary of Metabolites and Degradates to be included in the
Risk Assessment and 			Tolerance Expression

Matrix	Residues included in Risk Assessment	Residues included in
Tolerance Expression

Plants

	Primary Crop	Prothioconazole

Desthio-prothioconazole	Prothioconazole

Desthio-prothioconazole

	Rotational Crop	Not necessary	Not necessary

Livestock

	Ruminant	Prothioconazole

Prothioconazole-Desthio

Prothioconazole-4-Hydroxy

Acid hydrolyzable conjugates of the above three	Prothioconazole

Prothioconazole-Desthio

Acid hydrolyzable conjugates of the above two

	Poultry	Prothioconazole

Prothioconazole-Desthio

Prothioconazole-4-Hydroxy

Acid hydrolyzable conjugates of the above three	Prothioconazole

Prothioconazole-Desthio

Acid hydrolyzable conjugates of the above two

Drinking Water

	Prothioconazole

Prothioconazole-Desthio

Prothioconazole-S-Methyl	Not Applicable

5.1.9	Drinking Water Residue Profile TC \l3 "5.1.9	Drinking Water
Residue Profile

Prothioconazole has the potential to reach surface water via runoff,
erosion, and spray drift.  Prothioconazole appears to degrade relatively
quickly in the environment.  Its major degradates are
prothioconazole-desthio and prothioconazole-S-methyl.  These degradates
are detected in major amounts in almost all fate laboratory studies, and
therefore, it is assumed that these degradates are likely to result in
significant environmental concentrations.  Estimated environmental
concentrations are based on total toxic residues, i.e., the parent
prothioconazole compound plus prothioconazole-desthio and
prothioconazole-S-methyl.  Two other major degradates were not included
in this assessment:  prothioconazole-thiazocine (not considered a
degradate of concern) and 1,2,4-triazole (since it is assessed
separately as a common degradate in the conazole aggregate risk
assessment).  The prothioconazole-desthio and prothioconazole-S-methyl
degradates are persistent, moderately to slightly mobile, and may reach
ground water; because of this and their toxicity they have been included
in the drinking water exposure estimates.

The quick degradation of prothioconazole in concert with poor extraction
methods in soil and sediment metabolism studies leads to great
uncertainty in the composition and bioavailability of large amounts of
unextracted material.  It cannot be determined which portions of the
unextracted material are composed of potentially bioavailable parent
prothioconazole, which are composed of potentially bioavailable
prothioconazole-desthio or other degradates, and which are composed of
legitimately unextractable, non-bioavailable material.  Due to this
uncertainty, biotic degradation rates are unable to be calculated for
prothioconazole alone.  Therefore, a total toxic residues method,
including unextracted material, is utilized for higher bound
environmental exposure estimate modeling.  For lower bound estimate
modeling, it is assumed that unextracted material is non-bioavailable
and non-toxic.  There is evidence that the prothioconazole-desthio
degradate is moderately mobile (Kds of 4.13 to 13.38 mL/g in four soils,
stability to hydrolysis, long half-lives to other environmental
degradation processes and multiple detections at 15-30 cm and one
detection at 30-45 cm in terrestrial field dissipation studies).

Additionally, the Agency does have concern about the potential toxicity
of 1,2,4-triazole and two conjugates, triazolylalanine (TA) and
triazolylacetic acid (TAA); these metabolites are common to most of the
triazole fungicides.  To support the extension of existing tolerances
and the granting of new parent triazole-derivative fungicide tolerances,
EPA has conducted a human health risk assessment for aggregate exposure
to 1,2,4-triazole and triazole conjugates (1,2,4-Triazole, Triazole
Alanine, Triazole Acetic Acid: Human Health Aggregate Risk Assessment in
Support of Reregistration and Registration Actions for
Triazole-derivative Fungicide Compounds. M. Doherty et. al., 12/22/05).

The estimated drinking water concentration (EDWC) values used in the
dietary risk assessment were provided by the Environmental Fate and
Effects Division (EFED) in the following memo: Prothioconazole Tier II
Estimated Drinking Water Concentrations (EDWCs) for Use in the Human
Health Risk Assessment [Second Revision] (DP Barcode 330265, R. Kashuba,
6/21/06).  The EDWCs for prothioconazole and its degradates in drinking
water from the proposed uses were incorporated directly into the acute
and chronic dietary risk assessments.  Water residues were incorporated
in the DEEM-FCID( in the food categories “water, direct, all
sources” and “water, indirect, all sources.”  Ground water sources
were not included in the dietary risk assessment because the EDWCs for
this water source are minimal in comparison to surface water.

EDWCs and time series values for surface water sources were determined
using the PRZM-EXAMS screening models, with the exception of rice.
SEQ CHAPTER \h \r 1 EDWCs for rice paddies  SEQ CHAPTER \h \r 1  were
determined using the Interim Rice Model, 10/29/2002.  The Interim Rice
Model is capable of calculating EDWCs for acute exposures only, and is
used to generate screening level rice paddy water concentrations
resulting from pesticide use on rice.  This model is intended to be an
interim measure until a more complete rice modeling method becomes
available.

Because of the uncertainties with unextracted residues and KOC, EFED has
provided HED with upper and lower bound Tier II EDWCs in order to
characterize how this uncertainty affects the EDWCs.  Generally, upper
and lower EDWCs differed by a factor of 1.3 to 2.6 as a result of these
bounding assumptions.  Inclusion or exclusion of unextracted residues
made a larger difference in concentrations than use of a high or low
KOC.

EDWCs and time series values were submitted for both lower and upper
bounds for each crop scenario to account for two major uncertainties in
the drinking water modeling.  First, some prothioconazole residues
remained in the bound phase in EFED studies used to characterize
persistence.  To address this uncertainty, modeling was bound based on
inclusion and exclusion of unextracted residues in half-life
calculations.  Secondly, the two, major water degradates of
prothioconazole formed rapidly after application and have different
mobility.  To address this uncertainty, modeling was conducted using
KOCs (soil organic carbon-water partitioning coefficients) for
prothioconazole-desthio and prothioconazole-S-methyl.  The lower bound
EDWC and time series values represent the exclusion of unextracted
residues and the use of the higher Koc.  Conversely, the higher bound
estimates represent the inclusion of unextracted residues and the use of
the lower Koc.  Any concern about the uncertainties of any bound
residues or differences in Koc values are adequately addressed by
regulating and relying upon the upper bound EDWCs in the dietary risk
assessment.

To further refine EDWCs for canola, beans, peanuts, and rice, regional
default Percent Cropped Area factors (PCA) have been applied to
estimated concentrations.  Because wheat is grown across the country,
and a crop-specific national PCA is available, wheat EDWCs are not
further refined with regional PCAs.  Canola is grown within a single
regional basin, and therefore, only one default regional PCA was used in
canola refinement.  Alternately, most beans and peanuts are grown in two
regional basins each and, therefore, two default regional PCAs were used
in bean and peanut refinement.  Similarly, EDWCs for rice are reported
with two (lower and higher end) regional PCAs.

Surface water EDWCs are summarized in Table 5.1.9 below.  DEEM analyses
were performed for both the upper and lower bound estimates for the rice
and bean crop scenarios, since these EDWC values (in bold) were the
highest values reported.  The EDWC values for rice were only used in the
acute assessment.

Table 5.1.9.  Ranges of Tier II EDWCs for Surface Water Based on Aerial
Application of

Prothioconazole

DRINKING WATER SOURCE    (MODEL USED)	USE SCENARIO       (rate modeled)
ESTIMATED DRINKING WATER CONCENTRATION  (EDWC)  ( ppb)

Acute 	Chronic

Surface water  (PRZM/EXAMS)	NATIONAL PERCENT CROPPED AREA (PCA)

	Wheat1     	5.4 – 11	2.6 – 6.0

	Canola1           	7.5 – 14	3.5 – 9.1

	Bean1               	14 – 23	6.7 – 12

	Peanut1            	21 – 29	6.2 – 10.

	Rice2	45 - 115	N/A

	REGIONAL PERCENT CROPPED AREA (PCA)

	Canola1           	7.2 – 13	3.3 – 8.7

	Bean3               	10. – 22	4.9 – 11

	Peanut3            	9.3 – 22	2.7 – 8.1

	Rice4	21 - 112	N/A

1Represents ranges in input parameters (aerobic soil, aerobic aquatic,
and anaerobic aquatic metabolism half-lives and KOC).

2Represents range in Kd input parameter.

3Represents ranges in input parameters (aerobic soil, aerobic aquatic,
and anaerobic aquatic metabolism half-lives and KOC) as well as ranges
in regional PCAs.

4Represents range in Kd input parameter as well as ranges in regional
PCAs.

5.1.10	Food Residue Profile  TC \l3 "5.1.10	Food Residue Profile

Based on the current prothioconazole feed items, residues of concern are
anticipated in ruminant commodities at or about the limit of
quantitation of the analytical method for all commodities, except liver
and kidney.  Finite residues are anticipated for these commodities.

Based on the current prothioconazole feed items, residues of concern are
not anticipated in poultry commodities at or about the limit of
quantitation of the analytical method for all commodities, except liver.
 Residues at the limit of quantitation may be anticipated in poultry
liver.

In general, prothioconazole/prothioconazole-desthio residues did not
concentrate appreciably in the processed fractions of grain, oil seeds,
or peanuts.  The exceptions are aspirated grain fractions (wheat) (245X)
and rice hulls (4.4X), suggesting that the residue may be concentrated
in the surface of commodities.

Magnitude of Residues in Plants

Crop field trial data were submitted for barley, canola, dried peas and
beans, peanut, rice, and wheat reflecting the proposed use pattern for
the 4 lb/gal FlC formulation.  The residue data provided is summarized
in Table <IP_ADDRESS>, including total prothioconazole derived residues, and
residue data for 1,2,4-triazole and triazole conjugates triazolylalanine
and triazolylacetic acid.  Detailed discussions of the results of the
crop field trial studies are presented in the residue chemistry summary
document (D303508; S. Funk, 08/21/06).  Confirmatory storage stability
data will be submitted to support all crop field trials.  Adequate
processing data have been submitted for canola, peanut, rice, and wheat,
which indicate that a tolerance is needed for rice hulls; additional
storage stability data are required to support the processing studies.
The available rotational crop data indicate that the proposed rotational
crop restrictions are appropriate; no rotational crop tolerances are
needed to support this petition.

The petitioner included residue data for 1,2,4-triazole and triazole
conjugates triazolylalanine and triazolylacetic acid with the crop field
trial, processing, and field rotational crop studies submitted with this
petition.  The data indicate that quantifiable residues of the triazole
conjugates will occur in primary, processed, and field rotational crop
commodities following treatment of primary crops with prothioconazole.
Radiovalidation data for the method used to collect these data and
completion of the ongoing storage stability study with these compounds
are needed to support these residue data.

Table <IP_ADDRESS> Summary of Residues from Crop Field Trials with
Prothioconazole.

Crop Matrix	Applic.Rate

(lb ai/A)

[kg ai/ha]	PHI (days)	Residues (ppm)

	n	Min.	Max.	HAFT1	Median	Mean	Std. Dev.

BARLEY (proposed use = 0.293 lb ai/A [0.328 kg ai/ha] total application
rate, 30-day PHI)

Total Prothioconazole-Derived Residues

Barley grain	0.286-0.309

[0.321-0.348]	30-71	49	<0.02	0.158	0.151	0.022	0.040	0.041

Barley hay	0.286-0.309

[0.321-0.348]	12-16	49	0.317	6.59	5.95	1.22	1.72	1.39

Barley straw	0.286-0.309

[0.321-0.348]	30-71	50	<0.05	1.871	1.65	0.304	0.554	0.510

1,2,4-Triazole Residues

Barley grain	0.286-0.309

[0.321-0.348]	30-71	50	<0.01	<0.01	<0.01	0.005	0.005	0.0

Barley hay	0.286-0.309

[0.321-0.348]	12-16	49	<0.01	<0.01	<0.01	0.005	0.005	0.0

Barley straw	0.286-0.309

[0.321-0.348]	30-71	50	<0.01	<0.01	<0.01	0.005	0.005	0.0

Triazole Conjugate Residues

Barley grain	0.286-0.309

[0.321-0.348]	30-71	50	<0.10	0.915	0.909	0.239	0.300	0.215

Barley hay	0.286-0.309

[0.321-0.348]	12-16	49	<0.05	0.547	0.445	0.135	0.134	0.104

Barley straw	0.286-0.309

[0.321-0.348]	30-71	50	<0.1	0.385	0.359	0.05	0.090	0.093

CANOLA (proposed use = 0.356 lb ai/A [0.400 kg ai/ha] total application
rate, 36-day PHI)

Total Prothioconazole-Derived Residues

Canola seed	0.35-0.37 [0.39-0.42]	36-83	44	<0.020	0.097	0.086	0.010
0.015	0.0169

1,2,4-Triazole Residues

Canola seed	0.35-0.37 [0.39-0.42]	36-83	44	<0.020	<0.020	<0.020	0.010
0.010	0

Triazole Conjugate Residues

Canola seed	0.35-0.37 [0.39-0.42]	36-83	44	0.064	0.848	0.716	0.311	0.321
0.124

DRIED PEA AND BEAN (proposed use = 0.534 lb ai/A [0.600 kg ai/ha] total
application rate, 7-day PHI)

Total Prothioconazole-Derived Residues

Pea, dried shelled	0.530-0.549

[0.595-0.615]	7-8	26	<0.05	0.684	0.661	0.025	0.156	0.219

Bean, dried shelled	0.534-0.580

[0.598-0.650]	7-8	20	<0.05	0.288	0.243	0.025	0.062	0.072

1,2,4-Triazole Residues

Pea, dried shelled	0.530-0.549

[0.595-0.615]	7-8	26	<0.01	0.011	0.01	0.005	0.005	0.001

Bean, dried shelled	0.534-0.580

[0.598-0.650]	7-8	20	<0.01	<0.01	<0.01	0.005	0.005	0.0

Triazole Conjugate Residues

Pea, dried shelled	0.530-0.549

[0.595-0.615]	7-8	26	<0.05	0.789	0.775	0.085	0.177	0.213

Bean, dried shelled	0.534-0.580

[0.598-0.650]	7-8	20	<0.02	0.311	0.249	0.045	0.080	0.093

PEANUT (proposed use = 0.713 lb ai/A [0.800 kg ai/ha] total application
rate, 14-day PHI)

Total Prothioconazole-Derived Residues

Peanut nutmeat	0.707-0.734

[0.792-0.823]	13-15	24	<0.02	<0.02	<0.02	0.01	0.01	0.0

Peanut hay	0.707-0.734

[0.792-0.823]	13-15	24	0.989	4.458	3.630	2.657	2.612	0.884

1,2,4-Triazole Residues

Peanut nutmeat	0.707-0.734

[0.792-0.823]	13-15	24	<0.02	0.02	<0.02	0.01	0.01	0.0

Peanut hay	0.707-0.734

[0.792-0.823]	13-15	24	<0.02	<0.02	<0.02	0.01	0.01	0.0

Triazole Conjugate Residues

Peanut nutmeat	0.707-0.734

[0.792-0.823]	13-15	24	0.162	3.903	3.390	0.827	1.158	1.127

Peanut hay	0.707-0.734

[0.792-0.823]	13-15	24	<0.10	1.278	1.244	0.176	0.323	0.361

RICE (proposed use = 0.285 lb ai/A [0.320 kg ai/ha] total application
rate, 40-day PHI)

Total Prothioconazole-Derived Residues

Rice, grain	0.34-0.37

[0.38-0.41]	40-67	32	<0.02	0.222	0.191	0.01	0.031	0.048

Rice, straw	0.34-0.37

[0.38-0.41]	40-67	32	<0.05	1.277	1.189	0.432	0.464	0.319

1,2,4-Triazole Residues

Rice, grain	0.34-0.37

[0.38-0.41]	40-67	32	<0.01	<0.01	<0.01	0.005	0.005	0.0

Rice, straw	0.34-0.37

[0.38-0.41]	40-67	32	<0.01	<0.01	<0.01	0.005	0.005	0.0

Triazole Conjugate Residues

Rice, grain	0.34-0.37

[0.38-0.41]	40-67	32	<0.05	0.571	0.553	0.025	0.103	0.148

Rice, straw	0.34-0.37

[0.38-0.41]	40-67	32	<0.05	0.506	0.478	0.025	0.088	0.122

WHEAT (proposed use = 0.293 lb ai/A [0.328 kg ai/ha] total application
rate, 30-day PHI)

Total Prothioconazole-derived Residues

Wheat hay	0.281-0.313 2

[0.315-0.350]	12-17	66	0.288	3.571	3.543	1.269	1.420	0.970

Wheat grain	0.281-0.313 2

[0.315-0.350]	10; 30-57	66	<0.02	0.061	0.045	0.010	0.014	0.011

Wheat straw	0.281-0.313 2

[0.315-0.350]	10; 30-57	64	0.106	1.96	1.899	0.350	0.577	0.471

Wheat forage	0.286-0.299

[0.320-0.336]	7	46	0.061	6.987	5.842	1.352	1.401	1.268

1,2,4-Triazole Residues

Wheat hay	0.281-0.313 2

[0.315-0.350]	12-17	66	<0.01	<0.01	<0.01	0.005	0.005	0.0

Wheat grain	0.281-0.313 2

[0.315-0.350]	10; 30-57	66	<0.01	<0.01	<0.01	0.005	0.005	0.0

Wheat straw	0.281-0.313 2

[0.315-0.350]	10; 30-57	66	<0.01	<0.01	<0.01	0.005	0.005	0.0

Wheat forage	0.286-0.299

[0.320-0.336]	7	46	<0.01	<0.01	<0.01	0.005	0.005	0.0

Triazole Conjugate Residues

Wheat hay	0.281-0.313 2

[0.315-0.350]	12-17	66	0.018	0.665	0.631	0.204	0.220	0.124

Wheat grain	0.281-0.313 2

[0.315-0.350]	10; 30-57	66	0.098	1.76	1.76	0.460	0.534	0.320

Wheat straw	0.281-0.313 2

[0.315-0.350]	10; 30-57	64	<0.025	0.495	0.449	0.063	0.095	0.104

Wheat forage	0.286-0.299

[0.320-0.336]	7	46	<0.01	0.175	0.173	0.038	0.050	0.042

1  HAFT = Highest Average Field Trial.

2  In one field trial, the total application rate was 0.375 lb ai/A
(0.420 kg ai/ha); we note that this trial did not include maximum
residues for any of the metabolites.

Barley: Bayer CropScience has submitted field trial data on barley from
field trials conducted in the U.S. and Canada.  A total of 25 five
trials were conducted in Regions 1 (PA; 1 trial), 5 (ND; 2 trials, ON; 1
trial), 5B (QC; 1 trial), 7 (ND; 3 trials, and SK; 1 trial), 9 (AZ; 1
trial), 10 (AZ; 1 trial), 11 (ID and OR; 2 trials) and 14 (AB; 4 trials,
MB; 4 trials, and SK; 4 trials) during the 2000-2001 growing season.
The number and locations of field trials are in accordance with OPPTS
Guideline 860.1500 and Directive 98-02; Section 9.

At each test location, two broadcast foliar applications of the 4 lb/gal
(480 g/L) suspension concentrate formulation (flowable concentrate; FlC)
were made to barley at ~0.11-0.18 lb a.i./A (~0.123-0.202 kg a.i./ha) at
an average 12-day retreatment interval, for a total seasonal application
rate of ~0.29 lb a.i./A (~0.33 kg a.i./ha).  Applications were made in
~5-43 gal/A (~45-407 L/ha) of water using ground equipment.  An adjuvant
was not added to the spray mixture for any applications.  Barley hay was
cut at 23 test sites, 12-16 days after treatment, and was left in the
field for 1-14 days prior to collection of barley hay.  Samples of
barley grain and straw were harvested at 23 test sites 30-71 days after
the last application.  At two locations, additional samples were
collected to determine residue decline.  In the decline trial performed
in Region 7 (Northwood, ND), samples were harvested 8, 13, 22, and 28
days after treatment for barley hay and 32, 37, 44, and 47 days after
treatment for barley grain and straw.  In the decline trial performed in
Region 5 (Branchton, ON), samples were harvested  9, 14, 21, and 29 days
after treatment for barley hay and 36, 39, 45, and 49 days after
treatment for barley grain and straw.

Samples were analyzed for total prothioconazole-derived residues
(prothioconazole and the metabolite prothioconazole-desthio) using
LC-MS/MS method RPA JA/03/01.  The validated LOQs for the total
prothioconazole-derived residues were 0.02 ppm for barley grain and 0.05
ppm for barley hay and straw.  The method is adequate for data
collection for barley grain, hay and straw based on acceptable
concurrent method recovery data and method validation data. Samples were
analyzed for residues of 1H-1,2,4-triazole and the triazole conjugates
triazolylalanine and triazolylacetic acid using an LC-MS/MS method
(Bayer Report No. G200598).  The validated LOQ for 1H-1,2,4-triazole was
0.01 ppm for barley grain, hay and straw, and the validated LOQs for the
triazole conjugates were 0.10 ppm for barley grain and straw, and 0.05
ppm for hay.  The methods are adequate for data collection for barley
matrices based on acceptable concurrent method recovery data.

In barley matrices harvested 30-71 days (12-16 days for hay), total
prothioconazole-derived residues were 0.158 ppm, 6.59 ppm and 1.87 ppm,
respectively, in/on barley grain, hay, and straw.  Residues of
1H-1,2,4-triazole were less than the LOQ (<0.01 ppm) in/on barley grain,
hay, and straw; and 0.915 ppm, 0.547 ppm and 0.385 ppm, respectively,
in/on barley grain, hay, and straw for the triazole conjugates. Total
prothioconazole-derived residues did not increase with increasing
sampling intervals in barley grain, hay, and straw, and residues of the
triazole conjugates did not increase in grain, but increased slightly
with increasing sampling intervals in samples from one trial each for
hay and straw.

The maximum storage intervals of crop samples from harvest to analysis
for total prothioconazole-derived residues were 1234 days (40.6 months)
for barley grain and 1269 days (41.7 months) for barley hay and straw.
The degree of loss of prothioconazole-derived residues and
prothioconazole-desthio residues is not expected to exceed 30% after
41.7 months in barley grain, hay and straw.

Canola: Bayer CropScience has submitted field trial data on canola from
field trials conducted in the U.S. and Canada.  A total of 22 trials
were conducted in Regions 2 (GA; 1 trial), 5 (ND; 1 trial, and ON; 1
trial), 7 (ND; 1 trial, and SK; 1 trial), 11 (ID; 3 trials), and 14 (AB;
4 trials, MB; 5 trials, and SK; 5 trials) during the 2000 growing
season.  The number and locations of field trials were in accordance
with OPPTS Guideline 860.1500 and Directive 98-02; Section 9.

At each test location, two broadcast foliar applications of the 4 lb/gal
(480 g/L) suspension concentrate formulation (flowable concentrate; FlC)
were made to canola at 0.17-0.19 lb a.i./A (0.19-0.21 kg a.i./ha) at an
average 16-day retreatment interval (7-44 days), for a total seasonal
application rate of 0.35-0.37 lb a.i./A (0.39-0.42 kg a.i./ha).
Applications were made in ~11-42 gal/A (106-395 L/ha) of water using
ground equipment.  An adjuvant was not added to the spray mixture for
any applications.  Samples of canola were harvested at 20 test sites,
36-83 days after the last application.  Two locations (Ashton, ID and
Branchton, ON) were designated for residue decline studies.  Samples
were harvested 50, 54, 59, and 64 days after treatment in the decline
trial performed in ID (region 11).  In the ON trial (region 5), all
samples were cut inadvertently on day 41.  Seed samples from this site
were collected on the day of harvest, and 5, 10, and 15 days after
harvest.

Samples were analyzed for total prothioconazole-derived residues
(prothioconazole and the metabolite prothioconazole-desthio) using
LC-MS/MS method RPA JA/03/01.  The validated LOQ for total
prothioconazole-derived residues was 0.02 ppm for canola seed.  Samples
were analyzed for residues of 1H-1,2,4-triazole, and the triazole
conjugates triazolylalanine and triazolylacetic acid using an LC-MS/MS
method (Bayer Report No. G200598).  The validated LOQs were 0.02 ppm for
1H-1,2,4-triazole and 0.025 ppm for the triazole conjugates for canola
seed.  The methods were adequate for data collection based on acceptable
concurrent method recovery data.

The results from the canola field trials indicated that the maximum
residues of prothioconazole in/on canola seed harvested 36-83 days
following the last of two broadcast foliar applications were 0.097 ppm
for total prothioconazole-derived residues, <0.02 ppm for
1H-1,2,4-triazole, and 0.848 ppm for the triazole conjugates.

In the residue decline trial conducted in ID, total
prothioconazole-derived residues and residues of 1H-1,2,4-triazole were
less than the LOQ (<0.02 ppm each) at all sampling intervals.  Residues
of the triazole conjugates did not increase with increasing sampling
intervals.

The maximum storage interval of canola seed samples from harvest to
analysis for total prothioconazole-derived residues was 1265 days (41.6
months).  Prothioconazole-derived residues and prothioconazole-desthio
residues are stable up to 12.7 months (interim report) in canola
matrices. The degree of loss of prothioconazole-derived residues and
prothioconazole-desthio residues is not expected to exceed 30% after
41.6 months.

Dried shelled pea and bean, group 6C: Bayer CropScience has submitted
field trial data on dried peas and beans. A total of 23 field trials
were conducted during the 2002 growing season in the U.S. and Canada.
Thirteen trials were conducted on dried peas in Regions 5 (MN and ON; 2
trials), 11 (ID; 1 trial, OR; 3 trials, and WA; 1 trial), and 14 (AB; 2
trials, MB; 1 trial, and SK; 3 trials), and 10 trials were conducted on
dried beans in Regions 5 (IL, IN, KS, and ON; 4 trials), 7 (ND;1 trial),
7A (AB; 1 trial), 8 (TX; 1 trial), 9 (MT; 1 trial), 10 (CA; 1 trial),
and 11 (WA; 1 trial).  The number and locations of field trials are in
accordance with OPPTS Guideline 860.1500 and Directive 98-02; Section 9.

At each test location, three broadcast foliar applications of the 4
lb/gal (480 g/L) suspension concentrate formulation (flowable
concentrate; FlC) were made at ~0.180 lb a.i./A (~ 0.200 kg a.i./ha) at
9- to 15-day retreatment intervals, for a total seasonal application
rate of ~0.54 lb a.i./A (~0.60 kg a.i./ha).  Applications were made in
~10-33 gal/A of water using ground equipment.  A non-ionic surfactant
was added to the spray mixture for all applications.  An additional plot
at each trial was treated with three applications at a target rate of
~0.134 lb a.i./A (~ 0.150 kg a.i./ha); however, the applicant stated
that the results from this application were not used because they did
not support the desired product label application rate.  Samples of
dried shelled peas and beans were harvested 7-8 days after the last
application from all test sites.  It should be noted that in three of
the pea field trials and five of the bean field trials, the pea and bean
plants were cut and allowed to dry in the field for 2-8 days prior to
collection.  At two locations for dried peas and one location for dried
beans, additional samples were collected to determine residue decline.
Samples were harvested, at both locations, 0, 3-4, 7, 14-15, and 21-22
days after treatment for dried peas and 0, 7, 14, and 21 days after
treatment for dried beans.

Samples were analyzed for total prothioconazole-derived residues
(prothioconazole and the metabolite prothioconazole-desthio) using
LC-MS/MS method RPA JA/03/01.  The validated LOQ for total
prothioconazole-derived residues was 0.05 ppm for dried peas and dried
beans.  Samples were analyzed for residues of 1H-1,2,4-triazole and the
triazole conjugates triazolylalanine and triazolylacetic acid using an
LC-MS/MS method (Bayer Report No. G200598).  The validated LOQs were
0.01 ppm for 1H-1,2,4-triazole for dried peas and beans, 0.02 ppm for
the triazole conjugates for dried beans, and 0.05 ppm for the triazole
conjugates for dried peas.  The methods are adequate for data collection
based on acceptable concurrent method recovery data.

The results from the pea and bean field trials show that the maximum
residues of prothioconazole in/on dried peas and beans harvested 7-8
days following the last of three broadcast foliar applications at a
total seasonal rate of 0.530-0.580 lb a.i./A (0.595-0.650 kg a.i./ha)
were 0.684 ppm in/on dried peas and 0.288 ppm in/on dried beans for
total prothioconazole-derived residues; 0.011 ppm in/on dried peas and
less than the LOQ (<0.01 ppm) in/on dried beans for 1H-1,2,4-triazole;
and 0.789 ppm in/on dried peas and 0.311 ppm in/on dried beans for the
triazole conjugates.

In the residue decline trials, residues of 1H-1,2,4-triazole were less
than the method LOQ (<0.01 ppm) at all sampling intervals in dried peas
and beans.  Total prothioconazole-derived residues did not increase with
increasing sampling intervals in the dried bean trial and in one dried
pea trial; in the other dried pea trial, residues increased slightly
with increasing sampling intervals (from an average of 0.31 ppm at the
7-day PHI to an average of 0.34 ppm at the 21-day PHI).  Residues of the
triazole conjugates did not increase with increasing sampling intervals
in dried peas, but increased slightly in dried beans with increasing
sampling intervals.

The maximum storage interval of crop samples from harvest to analysis
for total prothioconazole-derived residues was 542 days (17.8 months)
for dried beans and peas.  The degree of loss of prothioconazole-derived
residues and prothioconazole-desthio residues is not expected to exceed
30% after 17.8 months in dried beans and peas.

Peanut: Bayer CropScience has submitted field trial data on peanuts.
Twelve trials were conducted in Regions 2 (AL; 1 trial, GA; 3 trials,
NC; 3 trials, and VA; 1 trial), 3 (FL; 1 trial), 6 (TX; 2 trials), and 8
(OK; 1 trial) during the 2000 growing season.  The number and locations
of field trials are in accordance with OPPTS Guideline 860.1500 and
Directive 98-02; Section 9.

At each test location, four broadcast foliar applications of the 4
lb/gal (480 g/L) suspension concentrate formulation (flowable
concentrate; FlC) were made to peanuts at  ~0.18 lb a.i./A (~0.20 kg
a.i./ha) at 12- to 14-day retreatment intervals, for a total seasonal
application rate of ~0.72 lb a.i./A (~0.80 kg a.i./ha).  Applications
were made in ~13-37 gal/A (~119-349 L/ha) of water using ground
equipment.  An adjuvant was not added to the spray mixture for any
applications.  Peanut plants were dug up at all test sites 13-15 days
after treatment, and were left in the field for 2-8 days prior to
collection of peanuts and peanut hay.  In one field trial (GA),
additional samples were dug up at 7, 14, 21, and 28 days following the
last application to evaluate residue decline.

Samples were analyzed for total prothioconazole-derived residues
(prothioconazole and the metabolite prothioconazole-desthio) using
LC-MS/MS method RPA JA/03/01.  The validated LOQs for total
prothioconazole-derived residues were 0.02 ppm for peanut nutmeat and
0.05 ppm for hay.  Samples were analyzed for residues of
1H-1,2,4-triazole and the triazole conjugates triazolylalanine and
triazolylacetic acid using an LC-MS/MS method (Bayer Report No.
G200598).  The validated LOQ for 1H-1,2,4-triazole was 0.02 ppm for
peanut nutmeat and hay, and the validated LOQs for the triazole
conjugates were 0.125 ppm for peanut nutmeat and 0.10 ppm for hay.  The
methods were adequate for data collection based on acceptable concurrent
method recovery data.

The results from the peanut field trials indicated that the maximum
residues of prothioconazole in/on peanut matrices harvested 13-15 days
following the last of four broadcast foliar applications at a total
seasonal rate of 0.707-0.734 lb a.i./A (0.792-0.823 kg a.i./ha) were
<0.02 ppm in/on nutmeat and 4.458 ppm in/on hay for total
prothioconazole-derived residues; 0.02 ppm in/on nutmeat and less than
the LOQ (<0.02 ppm) in/on hay for 1H-1,2,4-triazole; and 3.903 ppm in/on
nutmeat and 1.278 ppm in/on hay for the triazole conjugates.

In the residue decline trial, residues of 1H-1,2,4-triazole were less
than the method LOQ (<0.02 ppm) at all sampling intervals for peanut
nutmeat and hay, and total prothioconazole-derived residues were less
than the method LOQ (<0.02 ppm) at all sampling intervals for nutmeat.
The average total prothioconazole-derived residues in hay increased
slightly from the 7-day sampling interval to the 14-day sampling
interval and then decreased by the 28-day sampling interval.  Residues
of the triazole conjugates increased slightly in nutmeat (from an
average of 0.868 ppm to an average of 0.964 ppm) with increasing
sampling intervals; a greater increase was observed in peanut hay (from
an average of 0.117 ppm to an average of 0.355 ppm).

The maximum storage interval of crop samples from harvest to analysis
for total prothioconazole-derived residues was 1214 days (39.9 months)
for peanut nutmeat and hay.

Prothioconazole-derived residues and prothioconazole-desthio residues
are stable up to 12.7 months (interim report).  The degree of loss of
prothioconazole-derived residues and prothioconazole-desthio residues is
not expected to exceed 30% after 39.9 months.

Rice: Bayer CropScience has submitted field trial data on rice.  A total
of 16 trials were conducted in Regions 4 (LA; 6 trials, AR; 4 trials,
and MS; 1 trial), 5 (MI; 1 trial), 6 (TX; 2 trials), and 10 (CA; 2
trials) during the 2000 growing season.  The number and locations of
field trials are in accordance with OPPTS Guideline 860.1500 and
Directive 98-02; Section 9.

At each test location, two broadcast foliar applications of the 4 lb/gal
(480 g/L) suspension concentrate formulation (flowable concentrate; FlC)
were made to rice at  ~0.18 lb a.i./A (~0.20 kg a.i./ha) at 13- to
16-day retreatment intervals, for a total seasonal application rate of
~0.36 lb a.i./A (~0.40 kg a.i./ha).  Applications were made in ~12-23
gal/A of water using ground equipment.  An adjuvant was not added to the
spray mixture for any applications.  Samples of rice were harvested at
14 test sites 40-67 days after the last application.  At two locations,
additional samples were collected to determine residue decline.  Samples
were harvested 49, 55, 58, and 65 days after treatment for the decline
trial conducted in Benoit, MS (Region 4), and 64, 69, 74, and 80 days
after treatment for the decline trial conducted in Glen, CA (Region 10).

Samples were analyzed for total prothioconazole-derived residues
(prothioconazole and the metabolite prothioconazole-desthio) using
LC-MS/MS method RPA JA/03/01.  The validated LOQs for total
prothioconazole-derived residues were 0.02 ppm for rice grain and 0.05
ppm for rice straw.  Samples were analyzed for residues of
1H-1,2,4-triazole and the triazole conjugates triazolylalanine and
triazolylacetic acid using an LC-MS/MS method (Bayer Report No.
G200598).  The validated LOQs were 0.01 ppm for 1H-1,2,4-triazole and
0.05 ppm for the triazole conjugates for rice grain and straw.  The
methods are adequate for data collection based on acceptable concurrent
method recovery data.

The results from the rice field trials showed that the total
prothioconazole-derived residues in/on rice matrices harvested 40-67
days following the last of two broadcast foliar applications were 0.222
ppm in/on rice grain and 1.277 ppm in/on rice straw.  Residues of
1H-1,2,4-triazole were less than the LOQ (<0.01 ppm) in/on rice grain
and straw.  Maximum residues of the triazole conjugates were 0.571 ppm
(rice grain) and 0.506 ppm (rice straw).

In the residue decline trials, total prothioconazole-derived residues
in/on rice grain were <LOQ (0.02 ppm) in one trial, and did not increase
with increasing sampling intervals in/on rice grain in the other trial.
For rice straw, total prothioconazole-derived residues increased
slightly with increasing sampling intervals in one trial.  In the other
trial, residues in/on straw increased slightly at the middle sampling
intervals, and then decreased at the final sampling interval.  Residues
of the triazole conjugates in/on rice grain were <LOQ (<0.05 ppm) for
one trial, and increased slightly in rice grain with increasing sampling
intervals in the other trial.  For rice straw, residues increased
slightly with increasing sampling intervals in one trial, while residues
did not increase in the other trial.  Residues of 1H-1,2,4-triazole
in/on rice grain and straw from both trials were less than the method
LOQs (<0.02 ppm for total prothioconazole-derived residues, <0.05 ppm
for the triazole conjugates, and <0.01 ppm for 1H-1,2,4-triazole) at all
sampling intervals.

The maximum storage interval of crop samples from harvest to analysis
for total prothioconazole-derived residues was 1240 days (40.8 months)
for rice grain and straw.  The degree of loss of prothioconazole-derived
residues and prothioconazole-desthio residues is not expected to exceed
30% after 40.8 months in rice grain and straw.

Wheat: Bayer CropScience has submitted field trial data on wheat from
trials conducted in the U.S. and Canada.  A total of 54 trials were
conducted in Regions 2 (GA and NC; 2 trials), 4 (MS; 2 trials), 5 (IN; 1
trial, KS; 2 trials, NE; 2 trials, and ON; 2 trials), 6 (TX; 2 trials),
7 (AB; 1 trial, ND; 5 trials, SD; 2 trials, and SK; 3 trials), 7A (AB; 2
trials), 8 (OK; 3 trials and TX; 7 trials), 11 (OR; 2 trials), and 14
(AB; 6 trials, MB; 6 trials, and SK; 4 trials) during the 2000 growing
season.  The number and locations of field trials are in accordance with
OPPTS Guideline 860.1500 and Directive 98-02; Section 9.

At each test location, two broadcast foliar applications of the 4 lb/gal
(480 g/L) suspension concentrate formulation (flowable concentrate; FlC)
were made to wheat.  The first application was made at 0.108-0.120 lb
a.i./A (0.122-0.135 kg a.i./ha) followed by a second application at
0.170-0.199 lb a.i./A (0.190-0.223 kg a.i./ha) with a 5- to 18-day
retreatment interval, for a total seasonal application rate of ~0.29 lb
a.i./A (~0.33 kg a.i./ha).  In one field trial conducted in IN, the
first application was made at 0.185 lb a.i./A (0.207 kg a.i./ha)
followed by a second application at 0.190 lb a.i./A (0.213 kg a.i./ha)
with a 14-day retreatment interval, for a total seasonal application
rate of 0.375 lb a.i./A (0.420 kg a.i./ha).  Applications were made in
11-45 gal/A of water using ground equipment.  An adjuvant was not added
to the spray mixture for any applications.

For 33 trials, including two decline trials, two treatment plots
(designated as FORAG and HGRST) were used.  The timing of the
application varied for the two treatment plots.  In the FORAG plot the
second application was made 1 day prior to the first cutting of forage
and in the HGRST plot the second application was made at full flowering.
 Wheat forage from the FORAG plots was harvested one day after
treatment, but these samples were never analyzed or reported.  Wheat hay
from the HGRST plots was cut 12-17 days after treatment and was left in
the field for 0-14 days prior to collection of wheat hay.  Samples of
wheat grain and straw from the HGRST plots were harvested at earliest
commercial harvest, 30-57 days after the last application, except in one
trial in which samples were harvested 10 days after second application.

For 21 trials, one treatment plot (designated as TRTD) was used; the
second application was made 7 days prior to the first cutting of the
forage.  Only wheat forage was harvested from these trials.

At two locations (ND and NE), additional samples were collected to
determine residue decline. The samples were harvested at both locations
0, 1, 7, and 14 days after treatment for wheat forage at 6 or 7, 14, 20
or 21, and 28 days after treatment for wheat hay, and at 35 or 36, 39 or
40, 44 or 46, and 49 or 50 days after treatment for wheat grain and
straw.

Samples were analyzed for total prothioconazole-derived residues
(prothioconazole and the metabolite prothioconazole-desthio) using
LC-MS/MS method RPA JA/03/01.  The validated LOQs for the total
prothioconazole-derived residues were 0.02 ppm for wheat grain and 0.05
ppm for wheat forage, hay, and straw.  The method is adequate for data
collection for wheat grain hay, forage and straw based on acceptable
concurrent method recovery data and method validation data. Samples were
analyzed for residues of 1H-1,2,4-triazole and the triazole conjugates
triazolylalanine and triazolylacetic acid using an LC-MS/MS method
(Bayer Report No. G200598).  The validated LOQ for 1H-1,2,4-triazole and
triazolylalanine was 0.01 ppm for wheat forage, hay, grain, and straw;
and the validated LOQs for triazolylacetic acid were 0.01 ppm for wheat
forage, hay, and grain and 0.025 ppm for wheat straw.  The method is
adequate for data collection in wheat matrices based on acceptable
concurrent method recovery data.

The results from the wheat field trials show that in wheat matrices
harvested 10-57 days (12-17 days for hay) following the last of two
broadcast foliar applications at a total seasonal rate of 0.281-0.375 lb
a.i./A (0.315-0.420 kg a.i./ha), the maximum residues of prothioconazole
were 0.061 ppm, 1.96 ppm, and 3.571 ppm, respectively, in/on wheat
grain, straw, and hay for the total prothioconazole-derived residues;
less than the LOQ (<0.01 ppm) in/on wheat grain, straw, and hay for
1H-1,2,4-triazole; and 0.495 ppm, 0.665 ppm, and 1.76 ppm, respectively,
in/on wheat straw, hay, and grain for the triazole conjugates.  In wheat
forage harvested 7 days following the last of two broadcast foliar
applications at a total seasonal rate of 0.286-0.299 lb a.i./A
(0.320-0.336 kg a.i./ha), the maximum residues were 6.987 ppm for the
total prothioconazole-derived residues, less than the LOQ (<0.01 ppm)
for 1H-1,2,4-triazole, and 0.175 ppm for the triazole conjugates.

In the residue decline trials, residues of 1H-1,2,4-triazole at all
sampling intervals were less than the method LOQ (<0.01 ppm) in/on wheat
hay, grain, straw, and forage for both trials (NE and ND).  Total
prothioconazole-derived residues did not increase in any wheat matrix
with increasing sampling intervals, and residues of the triazole
conjugates increased slightly in samples of wheat forage from both
trials and in wheat straw from one trial but did not increase in wheat
hay or grain with increasing sampling intervals.

The maximum storage intervals of crop samples from harvest to analysis
for total prothioconazole-derived residues were 469 days (15.4 months)
for wheat forage, 1214 days (39.9 months) for wheat grain, 1221 days
(40.1 months) for wheat hay, and 1203 days (39.5 months) for wheat
straw.  Prothioconazole-derived residues are relatively stable up to 1
year (interim report) in wheat matrices.  Corrections due to apparent
dissipation of prothioconazole-derived residues in samples stored beyond
a year are not necessary due to the low absolute (ppm) and % residue
levels in wheat matrices.  Residues of prothioconazole-desthio are
stable for up to 1 year and the degree of loss is not expected to exceed
30% after 40.1 months.

Conclusions:  The submitted crop field trial residue data are adequate
to satisfy data requirements.  As stated under Directions for Use
(860.1200), the applicant has proposed use on an “Oilseed Crop
Subgroup” which consists of the members of the Oilseed Crop Group 20
with the exception of safflower seed and sunflower seed.  The
representative crops of Crop Group 20 are canola and sunflower.
Currently, no crop subgroups have been defined by HED for Crop Group 20.
 The applicant has submitted crop field trial data for canola but not
for sunflower.  The available crop field trial data will support use of
prothioconazole on the following oilseed commodities:  rapeseed, canola,
Indian rapeseed, field mustard seed, and crambe.

The submitted crop field trial data support the following tolerances for
the combined residues

of prothioconazole and its desthio metabolite:  barley grain at 0.35ppm;
barley hay at 7.0 ppm;

barley straw at 4.0 ppm; dried shelled pea and bean, except soybean,
subgroup 6C, at 0.90

ppm; peanut at 0.02 ppm; peanut hay at 6.0 ppm, rapeseed seed at 0.15
ppm; rice grain at 0.20

ppm; rice straw at 1.4 ppm; wheat grain at 0.07 ppm; wheat forage at 6.0
ppm; wheat hay at 4.5

ppm; and wheat straw 5.0 ppm.  The tolerance values were determined
using a statistical

calculation with the available field trial data.

Residue data for wheat aspirated grain fractions were included with the
processing study (see 860.1520).  The residue data indicate that total
prothioconazole-derived residues concentrate in aspirated grain
fractions.  Based on a processing factor of 245x and a HAFT residue of
0.045 ppm for wheat grain, the expected residues in wheat aspirated
grain fractions following treatment at 1x would be 11.0 ppm.  Therefore,
a tolerance for aspirated grain fractions is needed to support the
proposed uses.  Because the applicant is not proposing use of
prothioconazole on field corn, sorghum, or soybeans, the residue data
from wheat are used to determine the tolerance level for aspirated grain
fractions; these data indicate that a tolerance of 11 ppm would be
appropriate.

The residue data for aspirated grain fractions indicate that residues of
1,2,4-triazole and the triazole conjugates do not concentrate in wheat
aspirated grain fractions.

Magnitude of the Residue in Processed Commodities

Conclusions:  The submitted processing data for canola, peanut, rice,
and wheat are adequate to satisfy data requirements.  A summary of the
processing factors for prothioconazole residues is provided in Table
<IP_ADDRESS>.  The processing data indicate that total
prothioconazole-derived residues concentrate >7.9x in peanut meal, 4.4x
in rice hulls, 2.4x in wheat bran, and 2.0x in wheat germ.  Because
total prothioconazole-derived residues were below the LOQ in/on all
peanut nutmeat samples from the crop field trials, the actual residues
observed in peanut meal in the processing study will be used to
determine expected residues.  Total prothioconazole-derived residues
averaged 0.159 ppm in peanut meal in the processing study.  When this
value is corrected for the exaggerated rate of the study (5x) expected
residues in peanut meal following treatment at 1x are calculated to be
0.032 ppm.  Because the tolerance for peanut nutmeat will be established
at the LOQ (0.02 ppm) and because expected residues in peanut meal are
less than 2x the LOQ for peanut nutmeat, a tolerance for peanut meal is
not needed.

Based on a processing factor of 4.4x for rice hulls and a HAFT residue
of 0.191 ppm for rice grain, the expected residues in rice hulls
following treatment at 1x would be 0.840 ppm.  Because the expected
residues are greater than the proposed tolerance of 0.60 ppm for rice
grain, a tolerance for rice hulls is needed; a tolerance of 0.90 ppm is
appropriate.

Based on processing factors of 2.4x for wheat bran and 2.0x for wheat
germ and a HAFT residue of 0.045 ppm for wheat grain, the expected
residues in wheat bran and germ following treatment at 1x would be 0.11
and 0.09 ppm, respectively.  Because the germ residue is less than the
recommended tolerance of 0.10 ppm for wheat grain and because the bran
residue is only slightly greater than the recommended tolerance for
wheat grain, tolerances are not appropriate for germ and bran.

The HAFT total prothioconazole-derived residues in barley grain are
0.151 ppm.  Based on the 2.4x processing factor for wheat bran, the
expected residues in barley bran following treatment at 1x would be 0.36
ppm.  Because expected residues are not significantly greater than the
proposed tolerance of 0.35 ppm for barley grain, a tolerance for barley
bran is not needed.

The processing data indicate that residues of 1,2,4-triazole may
concentrate in peanut meal (>1.9x), dry roasted peanuts (>12.5x), and
peanut butter (>11.9x).  Because 1,2,4-triazole residues were below the
LOQ in/on all but one peanut nutmeat sample from the crop field trials,
the actual residues observed in peanut meal in the processing study
should be used to determine expected residues.  Residues of
1,2,4-triazole averaged 0.019, 0.125, and 0.119 ppm in peanut meal, dry
roasted peanuts, and peanut butter, respectively.  When these values are
corrected for the exaggeration rate of the study, 5x, expected residues
of 1,2,4-triazole in peanut meal, dry roasted peanuts, and peanut butter
following treatment at 1x are calculated to be 0.004, 0.025, and 0.024
ppm, respectively.

The processing data indicate that residues of the triazole conjugates
may concentrate in canola meal (2.9x), peanut meal (1.9x), rice bran
(6.9x), wheat bran (3.1x), wheat germ (3.6x), and wheat shorts (1.5x).
The processing factor for canola meal exceeds the theoretical
concentration factor of 1.9x; therefore, the theoretical concentration
factor will be used to determine expected residues.  Based on these
processing factors and HAFT residues of 0.716, 3.390, 0.553, and 1.76
ppm for canola seed, peanut, rice grain, and wheat grain, respectively,
the expected residues of triazole conjugates in processed commodities
following treatment at 1x would be:  1.36 ppm in canola meal; 6.44 ppm
in peanut meal; 3.82 ppm in rice bran; 5.46 ppm in wheat bran; 6.34 ppm
in wheat germ; and 2.64 ppm in wheat shorts.

Table <IP_ADDRESS>.	Summary of Processing Factors for Prothioconazole.

RAC	Processed Commodity	Average Processing Factor

Total Prothioconazole-Derived Residues	1,2,4-Triazole	Triazole Conjugate
Residues

Canola	Meal	<0.7x	NC 1	2.9x

	Refined oil	<0.7x	NC	<0.02x

Peanut	Meal	>7.9x	>1.9x	1.9x

	Refined oil	NC	NC	<0.01x

	Dry roasted peanuts	NC	>12.5x	0.5x

	Peanut butter	NC	>11.9x	0.6x

Rice	Polished Grain	<0.1x	NC	0.5x

	Bran	0.6x	NC	6.9x

	Hulls	4.4x	NC	0.3x

Wheat	Aspirated grain fractions	245x	NC	0.3x

	Bran	2.4x	NC	3.1x

	Flour	<0.4x	NC	0.5x

	Germ	2.0x	NC	3.6x

	Middlings	0.6x	NC	0.6x

	Shorts	1.0x	NC	1.5x

1  NC = Not calculated.  The processing factor could not be calculated
because residues were below the LOQ in both the RAC and the processed
fraction.

Storage Stability in Plant Commodities

Bayer has submitted the results of three storage stability studies with
prothioconazole and the metabolite prothioconazole-desthio in plant
commodities (MRID 46477701) as well as the results of a storage
stability study with prothioconazole and the desthio metabolite in wheat
commodities (MRID 46246139).

Storage intervals and conditions of samples from the submitted studies:
The storage intervals and conditions of samples from the submitted crop
field trial, processing, and field rotational crop studies are presented
in Table <IP_ADDRESS>.  The reported storage duration represents the
interval from sample collection to analysis.

Table <IP_ADDRESS>.	Summary of Storage Intervals and Conditions.

Matrix	Storage Temp. (°C)	Actual Storage Duration

Total Prothioconazole-Derived Residues

Crop Field Trials; MRIDs 46246215-46246217 and 46246219-46246221

Barley grain	-30.0 to -4.8	824-1234 days (27.1-40.6 months)

Barley hay	-30.0 to -4.8	859-1269 days (28.2-41.7 months)

Barley straw	-30.0 to -4.8	825-1240 days  (27.1-40.8 months

Bean, dried shelled	-24 to -22	490-536 days (16.1-17.6 months)

Canola seed	-30.0 to -4.8	867-1265 days (28.5-41.6 months)

Pea, dried shelled	-24 to -22	494-542 days (16.2-17.8 months)

Peanut nutmeat	-30.0 to -4.8	1175-1214 days (38.6-39.9 months)

Peanut hay	-30.0 to -4.8	1173-1212 days (38.6-39.8 months)

Rice grain	-30.0 to -4.8	1135-1240 days (37.3-40.8 months)

Rice straw	-30.0 to -4.8	1120-1226 days (36.8-40.3 months)

Wheat hay	-30.0 to -4.8	871-1221 days (28.6-40.1 months)

Wheat grain	-30.0 to -4.8	873-1214 days (28.7-39.9 months)

Wheat straw	-30.0 to -4.8	854-1203 days (28.1-39.5 months)

Wheat forage	-30.0 to -4.8	181-469 days (6.0-15.4 months)

Processing Studies; MRIDs 46246218 and 46246222-46246224

Canola seed	-30.0 to -4.8	1261 days (41 months)

Canola meal and refined oil

918 days (30 months)

Peanut nutmeat	-30.0 to -4.8	1090 days (36 months)

Peanut meal, refined oil, dry roasted peanuts, and peanut butter

911 days (31 months)

Rice grain	<-5	1222 days (40 months)

Rice polished grain, bran, and hulls

902 days (30 months)

Wheat grain	<-5	1285 days (42 months)

Wheat aspirated grain fractions, bran, germ, flour, middlings, and
shorts

909 days (30 months)

Field Rotational Crop Study; MRID 46246227

Mustard greens	-30.0 to -4.8	1135-1263 days (37.3-41.5 months)

Turnip tops	-30.0 to -4.8	1136-1243 days (37.3-40.8 months)

Turnip roots	-30.0 to -4.8	1136-1243 days (37.3-40.8 months)

Wheat forage	-30.0 to -4.8	952-1002 days (31.3-32.9 months)

Wheat hay	-30.0 to -4.8	893-943 days (29.3-31.0 months)

Wheat grain	-30.0 to -4.8	869-919 days (28.6-30.2 months)

Wheat straw	-30.0 to -4.8	861-911 days (28.3-29.9 months)

Conclusions:  The available storage stability data are tentatively
adequate to support the storage intervals and conditions of samples from
the submitted crop field trial, processing, and field rotational crop
studies.  The final reports of the ongoing storage stability studies
with prothioconazole and prothioconazole-desthio (interim results for
which were reported in MRID 46477701) will be submitted as confirmatory
data.

For the storage stability data reported in MRID 46477701 for
prothioconazole and prothioconazole-desthio, RAB3 concludes that the
ongoing study (Storage Stability Study 2) will provide the most
information about any actual decline of prothioconazole or
prothioconazole-desthio residues in crop matrices because it includes
more than one sampling interval.  The results of the other two studies
reported in that submission only reflect one sampling interval.  The
applicant chose the tested matrices in Studies 1 and 2 of that
submission to be representative of five diverse crops [an oilseed
(canola), a non-oily grain (wheat), a leafy vegetable (mustard greens),
a root crop (turnip), and a fruiting vegetable (tomato)] as well as the
processed commodities of three crops [an oilseed, a fruiting vegetable,
and a non-oily grain].  Even though prothioconazole appears to be
slightly unstable in two matrices (tomato paste, wheat bran) the overall
impact on the crop residues will not be significant.  However, based on
OPPTS 860.1380, the Agency will consider corrections on a case-by-case
basis, taking into account factors such as the absolute (ppm) and
relative (% ROC) residue levels of the component that is unstable in
storage.  Therefore, correction for dissipation of
prothioconazole-derived residues during freezer storage will not be
necessary at this time.

Because the applicant has reported that Method No. 00598 is not adequate
for determination of weathered residues of prothioconazole, the results
of the storage stability study reported in MRID 46246139 will not be
used to evaluate the stability of prothioconazole residues in wheat
commodities during frozen storage.

Magnitude of Residue in Meat, Milk, Poultry and Eggs (MMPE)

Bayer CropScience submitted two cattle feeding studies with the subject
petition, one in which cattle were dosed with prothioconazole (MRID
46246213) and one in which cattle were dosed with desthio
prothioconazole (MRID 46246214), which was not reviewed for this
petition.

Maximum Theoretical Dietary Burdens

Using the recommended tolerances for prothioconazole residues in/on
livestock feed items, the calculated maximum theoretical dietary burden
(MTDB) of prothioconazole to livestock is presented in Table <IP_ADDRESS>.

Table <IP_ADDRESS>. Calculation of Maximum Dietary Burdens of
Prothioconazole to Livestock.

	Maximum % of Diet

% of Diet Used

Dietary Burden, ppm

Crop	Commodity	Residue

%DM	Beef	Dairy	Poultry	Swine

Beef	Dairy	Poultry	Swine

Beef	Dairy	Poultry	Swine

Grain	Aspirated grain fractions	11.025

85	20	20	--	20

20	20	--	20

2.59	2.59	0.00	2.21

Wheat	forage	6.987

25	25	60	--	--

25	60	--	--

6.99	16.77	0.00	0.00

Barley	Hay	6.59

88	25	60	--	--

25	20	--	--

1.87	1.50	0.00	0.00

Peanut	Hay	4.458

85	25	50	--	--

25	0	--	--

1.31	0.00	0.00	0.00

Wheat	Hay	3.571

88	25	60	--	--

5	0	--	--

0.20	0.00	0.00	0.00

Wheat	Straw	1.96

88	10	10	--	--

0	0	--	--

0.00	0.00	0.00	0.00

Barley	Straw	1.871

89	10	10	--	--

0	0	--	--

0.00	0.00	0.00	0.00

Rice	Straw	1.277

90	10	10	--	--

0	0	--	--

0.00	0.00	0.00	0.00

Rice	Hulls	0.8404

90	10	10	15	--

0	0	15	--

0.00	0.00	0.13	0.00

Cowpea	Seed	0.684

88	20	20	10	50

0	0	10	50

0.00	0.00	0.07	0.34

Pea, field	Seed	0.684

90	20	20	20	20

0	0	20	20

0.00	0.00	0.14	0.14

Rice	Bran	0.222

90	15	15	25	15

0	0	25	10

0.00	0.00	0.06	0.02

Rice	Grain	0.222

88	40	40	60	65

0	0	30	0

0.00	0.00	0.07	0.00

Barley	Grain	0.158

88	50	40	75	80

0	0	0	0

0.00	0.00	0.00	0.00

Peanut	Meal	0.158

85	15	15	25	15

0	0	0	0

0.00	0.00	0.00	0.00

Wheat	Milled byproducts	0.108

88	40	50	50	50

0	0	0	0

0.00	0.00	0.00	0.00

Canola	Meal	0.097

88	15	15	15	15

0	0	0	0

0.00	0.00	0.00	0.00

Wheat	Grain	0.061

89	50	40	80	80

0	0	0	0

0.00	0.00	0.00	0.00

Total

100	100	100	100

12.97	20.86	0.45	2.71

Magnitude of the Residue in Milk, Meat, and Meat Byproducts of Ruminants

Bayer CropScience submitted a dairy cattle feeding study with
prothioconazole (MRID 46246213).  Prothioconazole was administered
orally (via gelatin capsules) to three groups of dairy cattle (3 cows
per group) once daily for 29 consecutive days.  Dosing was made at
levels equivalent to 9.9, 29.5, and 98.4 ppm in the feed.  The dosing
levels correspond to 0.5-fold, 1.4-fold, and 4.7-fold the anticipated
dietary burden.  Milk and tissue samples were analyzed using the
proposed enforcement method for animal commodities, which was an
LC-MS/MS method (Bayer Report No. 200537).  This method determined
residues of prothioconazole, desthio prothioconazole, and
prothioconazole-4-hydroxy, plus any metabolites hydrolyzable to these
compounds.  Tissue samples (except fat) were extracted with acetonitrile
(ACN)/water and aqueous L-cysteine HCl.  Fat samples were first
extracted with n-hexane, then ACN, L-cysteine HCl and acetone.  All
samples (including milk and cream) were hydrolyzed with aqueous HCl,
then partitioned with methylene chloride and acetone before LC-MS/MS
analysis.  The method was adequate for data collection based on
acceptable concurrent method recovery data.  The storage intervals for
all matrices except fat were reported to be <30 days, therefore no
storage stability data is needed for these matrices.  Fat samples from
the lowest feeding level (0.5-fold) were stored frozen for up to 86 days
prior to analysis.  For the 1.4-fold and 4.7-fold feeding levels,
samples were stored for 43 and 37 days, respectively.  A supporting
storage stability study indicated that residues of prothioconazole,
prothioconazole-desthio, and prothioconazole-4-hydroxy were stable for
27 days (<30% decline).  After 89 days in storage, residues of
prothioconazole-4-hydroxy showed a 33% decline.  The 1.4-fold dose group
(29.5 ppm) was closest to the anticipated dietary burden (21 ppm).
Confirmatory data will be generated to confirm the stability of the
prothioconazole-4-hydroxy in fat for a duration of 45 days.

The maximum residues of prothioconazole, prothioconazole-desthio, and
prothioconazole-4-hydroxy in milk and tissues are listed in Table
<IP_ADDRESS> below.  Because low residue levels were observed in samples
from the mid and high dose groups, milk and muscle samples from the low
dose group (9.9 ppm) were not analyzed.

Table <IP_ADDRESS>.	Maximum Residues of Prothioconazole (A),
Prothioconazole-Desthio (B), and Prothioconazole-4 hydroxy (C), as
prothioconazole equivalents, by Feeding Level Following Dosing of Dairy
Cattle with Prothioconazole for 29 Days.

Matrix

	Residues (ppm)

	9.9 ppm	29.5 ppm	98.4 ppm

	A	B	C	A	B	C	A	B	C

Milk	--	--	--	<0.005	<0.005	<0.005	<0.005	<0.005	<0.005

Skim milk	--	--	--	--	--	--

<0.01	<0.01	<0.01

Cream	--	--	--	--	--	--	<0.01	<0.01	<0.01

Fat	<0.05	<0.05	<0.05	<0.05	<0.05	<0.05	0.062	<0.05	<0.05

Kidney	0.062	<0.01	0.017	0.176	<0.01	0.063	0.79	0.011	0.356

Liver	0.063	<0.01	0.127	0.054	0.011	0.181	0.467	0.030	0.518

Muscle	--	--	--	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01

Quantifiable residues (of prothioconazole, 0.005 - 0.006 ppm) were
observed in only two samples of milk from the highest dosing level.
However, detectable residues of prothioconazole were observed in several
samples.  Based on these residues, it appeared that residues had reached
a plateau by within the first week of dosing.

Conclusions:  The submitted cattle study data are adequate to satisfy
livestock feeding study data requirements for ruminants.

The feeding study data indicate that tolerances are needed for the
combined residues of prothioconazole and desthio prothioconazole in
cattle, goat, hog, horse, and sheep commodities.

Using the results of the prothioconazole feeding study and defining the
residue for tolerance purposes as the sum of prothioconazole,
prothioconazole-desthio, and metabolites that can be hydrolyzed to these
compounds, expressed as prothioconazole, we calculate that tolerances
should be set at the combined LOQs for milk (0.02 ppm, using LOQs for
skim milk and cream); at the combined LOQs for the fat (0.10 ppm) and
muscle (0.02 ppm) of cattle, goats, horses, and sheep; at 0.20 ppm for
the meat byproducts of cattle, goats, horses, and sheep; and at 0.05 ppm
for the meat byproducts of hogs.  The available data indicate that a
tolerance is not needed for milk fat or the fat and meat of hogs.

Magnitude of the Residue in Eggs, Meat, and Meat Byproducts of Poultry

The applicant did not submit a poultry feeding study with the subject
petition but submitted a request for a waiver from the requirements for
a poultry feeding study.

The applicant used a value of 0.455 ppm as the maximum theoretical
dietary burden for poultry, based on a diet consisting of 15% rice
hulls, 60% rice grain, and 25% barley grain (and using “anticipated”
tolerance values of 1.5, 0.3, and 0.2 ppm, respectively).  This agrees
with the 0.45 ppm calculated in Table <IP_ADDRESS> above, resulting from the
feeding of rice and pea commodities.   To determine the residues that
would be found by the proposed enforcement method for livestock
commodities, it can be assumed that residues of
prothioconazole-glucuronide (N-, S- or O- glucuronides) would be
converted to prothioconazole.  Under that assumption, the combined
residues from the metabolism studies (171 ppm and 163 ppm in diet, or
about 360X) were: liver, 1.7 and 1.8 ppm; egg, 0.014 and 0.017 ppm;
muscle, 0.031 and 0.018 ppm; fat, 0.29 and 0.14 ppm.  The residues at a
feeding level of 0.455 ppm can be estimated to be: liver, 0.005 ppm;
egg, 0.00005 ppm; muscle, 0.00009 ppm; fat, 0.0008 ppm.  The enforcement
analytical method for livestock commodities has not been validated for
poultry items.  Assuming that the method has a LOQ of 0.01 ppm for each
of the two analytes for poultry commodities (combined LOQ 0.02 ppm,
based on an LOQ of 0.01 ppm for each analyte in cattle liver), no
residue would be anticipated at the defined feeding level in any of the
poultry commodities, except liver.  Residues appeared not to have
obtained a plateau in eggs, as the TRR in the oviduct egg was about 10X
that in the eggs.  Factoring in a 10X increase in residue in the egg
would not lead to a prediction of detectable residues in eggs at a
feeding level of 0.45 ppm prothioconazole in the diet.

Under the currently proposed uses and defining the residue for tolerance
purposes as the sum of prothioconazole, prothioconazole-desthio, and
metabolites that can be hydrolyzed to these compounds, expressed as
prothioconazole, we conclude that residues are unlikely in poultry
commodities except liver and that, therefore, poultry commodity
tolerances are not needed, except for liver.  A tolerance of 0.02 ppm
should be proposed for chicken liver, based on the validated LOQ of 0.01
ppm for each of the analytes in cattle liver.  HED concludes that the
waiver request for a poultry feeding study is denied.  Additionally, a
fully validated analytical method for poultry commodities is required.

The proposed tolerance of 0.02 ppm for chicken liver is adequate.  The
extrapolation is over a very high range.  The extrapolated value for
liver is 0.005, which might have a considerable error.  Thus, it is
prudent to set a tolerance at the limit of quantitation.  Note that
liver is the only commodity with such a “large” predicted
concentration.  The proposed tolerance was derived by taking the residue
levels for the residues of concern in poultry (parent, and the desthio