FILE
NAME:
company.
wpt
(
7/
1/
2003)
(
xml)

COMPANY
FEDERAL
REGISTER
DOCUMENT
SUBMISSION
TEMPLATE
(
7/
1/
2003)

EPA
Registration
Division
contact:
[
Lana
Coppolino,
703­
305­
0086]

[
Bayer
CropScience]

[
PP
4F6830]
EPA
has
received
a
pesticide
petition
([
4F6830])
from
Bayer
CropScience,
2
T.
W.
Alexander
Drive,
Research
Triangle
Park,
NC
27709
proposing,
pursuant
to
section
408(
d)
of
the
Federal
Food,
Drug,
and
Cosmetic
Act
(
FFDCA),
21
U.
S.
C.
346a(
d),
to
amend
40
CFR
part
180
by
establishing
tolerances
for
residue
of
prothioconazole
and
its
desthio
metabolite
in
or
on
the
raw
agricultural
commodities
and
processed
commodities
barley,
grain
at
0.2
parts
per
million
(
ppm);
barley,
hay
at
7.0
ppm;
barley,
straw
at
2.0
ppm;
barley,
pearled
barley
at
0.2
ppm;
barley,
bran
at
0.4
ppm;
black
mustard,
seed
at
0.1
ppm;
borage,
seed
at
0.1
ppm;
canola,
seed
at
0.1
ppm;
crambe,
seed
at
0.1
ppm;
mustard
seed,
field
at
0.1
ppm;
flax,
seed
at
0.1
ppm;
grain,
aspirated
fractions
at
13.0
ppm;
Indian
mustard,
seed
at
0.1
ppm;
Indian
rapeseed
at
0.1
ppm;
pea
and
bean,
dried
shelled,
except
soybean,
subgroup
at
0.8
ppm;
peanut,
nutmeat
at
0.02
ppm;
peanut,
hay
at
5.0
ppm;
peanut,
meal
at
0.3
ppm;
rapeseed,
seed
at
0.1
ppm;
rice,
grain
at
0.25
ppm;
rice,
straw
at
1.5
ppm;
rice,
hulls
at
1.0
ppm;
wheat,
grain
at
0.06
ppm;
wheat,
forage
at
7.0
ppm;
wheat,
hay
at
4.0
ppm;
wheat,
straw
at
2.3
ppm;
wheat,
bran
at
1.5
ppm;
and
wheat,
germ
at
0.15
ppm;
as
well
as
tolerances
for
residues
of
prothioconazole,
its
desthio
metabolite,
and
4­
hydroxy
metabolite
and
conjugates
of
each
in
meat,
cattle
at
0.01
ppm;
meat
by­
products,
cattle
at
1.2
ppm;
fat,
cattle
at
0.1
ppm
and
milk
at
0.006
ppm.
EPA
has
determined
that
the
petition
contains
data
or
information
regarding
the
elements
set
forth
in
section
408(
d)(
2)
of
the
FFDCA;
however,
EPA
has
not
fully
evaluated
the
sufficiency
of
the
submitted
data
at
this
time
or
whether
the
data
supports
granting
of
the
petition.
Additional
data
may
be
needed
before
EPA
rules
on
the
petition.
EPA
has
determined
that
the
petition
contains
data
or
information
regarding
the
elements
set
forth
in
section
408(
d)(
2)
of
the
FFDCA;
however,
EPA
has
not
fully
evaluated
the
sufficiency
of
the
submitted
data
at
this
time
or
whether
the
data
supports
granting
of
the
petition.
Additional
data
may
be
needed
before
EPA
rules
on
the
petition.
A.
Residue
Chemistry
1.
Plant
and
large
animal
metabolism.
[
In
plants,
the
metabolism
of
prothioconazole
is
adequately
understood
for
purposes
of
establishing
these
proposed
tolerances.
Prothioconazole
was
extensively
metabolized
in
plants
with
the
major
residue
found
in
all
crops
(
wheat,
peanuts
and
sugar
beets)
being
JAU6476­
desthio
with
smaller
amounts
of
various
isomers
of
JAU6476­
hydroxy­
desthio,
and
their
conjugates
also
being
found.
Triazolylalanine,
triazolylhydroxypropionic
acid,
and
triazolylacetic
acid,
metabolites
common
to
the
triazolederivative
class
of
fungicides,
were
also
found.
Based
on
the
above
data
the
residues
of
concern
in
plants
are
prothioconazole
and
its
metabolite
JAU6476­
desthio.
The
risk
assessment
for
the
common
metabolites
arising
from
the
triazole­
derivative
fungicides
is
being
addressed
by
the
US
Triazole
Task
Force.
In
large
animals,
the
nature
of
residues
is
also
adequately
understood
for
Page
2
of
8
purposes
of
establishing
the
proposed
tolerances.
The
residues
of
concern
in
edible
tissues
and
milk
are
prothioconazole,
its
metabolites
JAU6476­
desthio,
JAU6476­
4­
hydroxy,
and
their
conjugates
that
can
be
converted
to
these
three
compounds
by
acid
hydrolysis.
]

2.
Analytical
method.
[
The
analytical
method
for
determining
residues
of
concern
in
plants
extracts
residues
of
prothioconazole
and
JAU6476­
desthio
and
converts
the
prothioconazole
to
JAU6476­
desthio
and
JAU6476­
sulfonic
acid.
Following
addition
of
internal
standards
the
sample
extracts
are
analyzed
by
LC/
MS/
MS.
Radiovalidation
and
independent
laboratory
validation
have
shown
that
the
method
adequately
quantifies
prothioconazole
residues
in
treated
commodities.
The
analytical
method
for
analysis
of
large
animal
tissues
includes
extraction
of
the
residues
of
concern,
followed
by
addition
of
an
internal
standard
to
the
extract.
The
extract
is
then
hydrolyzed
to
release
conjugates,
partitioned
and
analyzed
by
LC/
MS/
MS
as
prothioconazole,
JAU6476­
desthio
and
JAU6476­
4­
hydroxy.
The
method
for
analysis
of
milk
eliminated
the
initial
extraction
step
in
the
tissue
method.]

3.
Magnitude
of
residues.
[
Field
trials
were
conducted
for
the
various
crops
according
to
label
use
directions.
Results
of
analysis
of
the
various
crop
samples
are
given
below.
i
Barley:
A
total
of
25
field
trials
(
23
harvest
and
2
decline)
were
conducted
as
part
of
the
supervised
crop
field
trial
study
to
measure
the
prothioconazole
derived
residues
in/
on
barley
following
two
foliar
spray
applications
of
JAU6476
480
SC
at
a
target
rate
of
0.11
lb
ai/
acre
(
0.123
kg
ai/
ha)
for
the
first
application
and
0.18
lb
ai/
acre
(
0.202
kg
ai/
ha)
for
the
second
application,
equivalent
to
1X
the
maximum
proposed
rate.
Ten
sites
were
in
the
United
States
and
15
sites
were
in
Canada.
Barley
hay
was
collected
14
(
±
2)
days
after
the
second
application,
and
barley
grain
and
straw
were
collected
at
earliest
commercial
harvest
(
ECH).
Pre­
harvest
intervals
(
PHIs)
ranged
from
12
to
16
days
for
hay,
and
from
30
to
71
days
for
grain
and
straw.
The
total
prothioconazole
highest
average
field
trial
(
HAFT)
residue
was
0.15
ppm
in/
on
barley
grain
at
ECH
of
32
days
after
treatment
(
DAT)
with
a
maximum
residue
of
0.16
ppm.
In
barley
hay
the
HAFT
total
prothioconazole
derived
residue
was
5.95
ppm
found
at
ECH
of
13
DAT
with
a
maximum
residue
of
6.59
ppm.
In
barley
straw
the
HAFT
total
prothioconazole
derived
residue
was
1.65
ppm
found
at
ECH
of
36
DAT
with
a
maximum
residue
of
1.87
ppm.
In
decline
trials
the
total
prothioconazole
derived
residue
decreased
slightly
with
time
in
hay
and
straw,
but
not
in
grain.

ii.
Wheat.
A
total
of
54
field
trials
(
52
harvest
and
2
decline)
at
33
sites
were
conducted
as
part
of
the
supervised
crop
field
trial
study
for
wheat
to
measure
the
prothioconazole
derived
residues
in/
on
wheat
following
two
foliar
spray
applications
of
JAU6476
480
SC
at
a
target
rate
of
0.113
lb
ai/
acre
(
0.127
kg
ai/
ha)
for
the
first
application
and
0.18
lb
ai/
acre
(
0.202
kg
ai/
ha)
for
the
second
application,
equivalent
to
1X
the
maximum
proposed
rate.
Seventeen
sites
were
in
the
United
States
and
16
sites
were
in
Canada.
Wheat
forage
was
collected
at
7
days
after
the
second
application
(
DAT),
wheat
hay
14(
±
2)
DAT,
and
wheat
grain
and
straw
were
collected
at
ECH.
PHIs
were
7
days
for
forage,
and
ranged
from
12
to
17
days
for
hay,
and
from
10
to
57
days
for
grain
and
straw.
The
prothioconazole
derived
HAFT
residue
in/
on
wheat
grain
were
0.05
ppm
with
a
maximum
residue
of
0.06
ppm.
For
wheat
forage,
hay
and
straw
the
HAFT
was
5.84
ppm,
3.54
ppm
and
1.90
ppm,
respectively.
The
corresponding
Page
3
of
8
maximum
residues
were
6.99ppm,
3.57
ppm
and
1.96
ppm.
The
total
prothioconazole
derived
residues
declined
rapidly
over
time
in
wheat
forage
and
hay
samples,
but
not
in
wheat
straw.
Since
wheat
grain
had
very
low
or
non­
detectable
residues,
residue
decline
could
not
be
measured.
Results
of
the
wheat
processing
study
indicated
that
prothioconazole
residues
concentrated
in
bran
(
2.4X)
and
germ
(
2.0X),
but
not
in
flour,
middlings
or
shorts.
A
concentration
factor
of
250X
was
determined
for
aspirated
grain
fractions.

iii.
Rice.
A
total
of
16
field
trials
(
14
harvest
and
2
decline)
were
conducted
as
part
of
the
supervised
crop
field
trial
study
for
wheat
to
measure
the
prothioconazole
derived
residues
in/
on
rice
following
two
foliar
spray
applications
of
JAU6476
480
SC
at
a
target
rate
of
0.18
lb
ai/
acre/
application
(
0.20
kg
ai/
ha/
application),
equivalent
to
1.25X
the
maximum
proposed
rate.
All
16
sites
were
in
the
United
States.
Rice
grain
and
rice
straw
were
collected
at
ECH
from
each
treated
plot
with
PHIs
ranging
from
40
to
67
days
for
rice
grain
and
straw.
The
HAFT
total
prothioconazole
derived
residue
was
0.19
ppm
in/
on
rice
grain
at
an
ECH
of
40
DAT
with
a
maximum
residue
of
0.22
ppm.
In
rice
straw
the
HAFT
total
prothioconazole
derived
residue
was
1.33
ppm
with
a
maximum
of
1.58
ppm.
Results
of
the
rice
processing
study
indicated
that
prothioconazole
residues
concentrated
in
rice
hulls
(
4.4X),
but
not
in
polished
grain
or
bran.

iv.
Peanuts.
A
total
of
12
field
trials
(
11
harvest
and
1
decline
trial)
were
conducted
as
part
of
the
supervised
crop
field
trial
study
for
peanuts
to
measure
the
prothioconazole
derived
residues
in/
on
peanuts
following
four
foliar
spray
applications
of
JAU6476
480
SC
at
a
target
rate
of
0.18
lb
ai/
acre/
application
(
0.20
kg
ai/
ha/
application),
equivalent
to
1X
the
maximum
proposed
rate.
All
twelve
sites
were
in
the
United
States.
Peanuts
(
nutmeats
with
shells)
and
peanut
hay
were
each
collected
at
full
maturity
at
14
(
±
1)
DAT.
The
total
prothioconazole
derived
residue
was
less
than
the
LOQ
(<
0.02
ppm)
in
all
peanut
nutmeat
samples
at
full
maturity
(
14
(
±
1)
DAT).
The
HAFT
total
prothioconazole
derived
residue
was
3.63
ppm
in/
on
peanut
hay
at
a
PHI
of
14
days
with
a
maximum
residue
of
4.46
ppm.
No
decline
in
total
prothioconazole
derived
residue
was
observed
in
peanut
hay
with
time.
Results
of
the
peanut
processing
study
indicated
that
prothioconazole
residues
concentrated
in
the
peanut
meal
(
13.3X),
but
not
in
dry
roasted
peanuts,
peanut
butter
or
refined
oil.

v.
Canola.
A
total
of
22
field
trials
(
20
harvest
and
2
decline)
were
conducted
as
part
of
the
supervised
crop
field
trial
study
for
canola
to
measure
the
prothioconazole
derived
residues
in/
on
canola
following
two
foliar
spray
applications
of
JAU6476
480
SC
at
a
target
rate
of
0.18
lb
ai/
acre/
application
(
0.20
kg
ai/
ha/
application),
equivalent
to
1X
the
maximum
proposed
rate.
Six
sites
were
in
the
United
States
and
16
sites
were
in
Canada.
Canola
seed
was
collected
at
ECH.
PHIs
ranged
from
36
to
83
days
for
canola
seed.
The
HAFT
total
prothioconazole
derived
residue
was
0.09
ppm
in/
on
canola
seed
at
ECH
of
37
DAT
with
a
maximum
residue
of
0.10
ppm.
The
prothioconazole
total
residue
in
all
decline
study
samples
was
less
than
the
LOQ.
Results
from
a
processing
study
indicated
that
prothioconazole
residues
did
not
concentrate
in
canola
meal
or
refined
oil.

vi.
Dried
Shelled
Peas
and
Beans
(
Crop
Subgroup
6C):
A
total
of
23
field
trials
(
11
harvest
and
2
decline
trials
for
dried
pea,
and
9
harvest
and
1
decline
trial
for
dried
beans)
were
conducted
Page
4
of
8
as
part
of
the
supervised
crop
field
trial
studies
for
dried
peas
and
dried
beans
to
measure
the
prothioconazole
derived
residues
in/
on
peas
and
beans
following
three
foliar
spray
applications
of
JAU6476
480
SC
at
a
target
rate
of
0.180
lb
ai/
acre/
application
(
0.200
kg
ai/
ha/
application),
equivalent
to
1X
the
maximum
proposed
rate.
For
the
dried
pea
trials,
6
sites
were
in
the
United
States
and
7
sites
were
in
Canada.
For
the
dried
bean
trials,
8
sites
were
in
the
United
States
and
2
sites
were
in
Canada.
Seed
was
collected
at
full
maturity.
PHIs
ranged
from
7
to
8
days
for
both
dried
peas
and
dried
beans.
The
HAFT
total
prothioconazole
derived
residue
was
0.66
ppm
in/
on
dried
peas
at
full
maturity
at
a
pre­
harvest
interval
(
PHI)
of
8
days
with
a
maximum
residue
of
0.68
ppm.
In
dried
beans,
the
HAFT
total
prothioconazole
derived
residue
was
0.24
ppm
at
full
maturity
at
a
PHI
of
7
days
with
a
maximum
residue
of
0.29
ppm.
The
total
prothioconazole
derived
residue
decreased
with
time
in
dried
bean
decline
trial
and
one
of
the
dried
pea
decline
trials
but
not
in
the
second
dried
pea
decline
trial
.]

B.
Toxicological
Profile
1.
Acute
toxicity.
[
Prothioconazole
exhibits
very
low
acute
oral,
dermal
and
inhalation
toxicity.
The
acute
oral
LD50
for
prothioconazole
in
rats
was
>
6200
mg/
kg/
day
while
the
dermal
LD50
was
>
2000
mg/
kg/
day
and
the
four­
hour
rat
inhalation
LC50
>
4990
mg/
m3.
Prothioconazole
was
not
irritating
to
the
eye
or
skin
of
rabbits
and
did
not
cause
skin
sensitization
in
guinea
pigs.]
2.
Genotoxicty.
[
Prothioconazole
is
not
mutagenic.
Slightly
positive
and
equivocal
responses
seen
in
in
vitro
cytogenetic
and
UDS
assays
were
negative
in
in
vivo
tests.]
3.
Reproductive
and
developmental
toxicity.
[
Prothioconazole
is
not
considered
a
primary
reproductive
toxicant
in
a
two­
Generation
rat
reproduction
study.
The
NOAEL
for
parental
toxicity
is
9.7
mg/
kg
bw/
day
and
the
NOAEL
for
reproductive
and
neonatal
effects
is
95.6
mg/
kg
bw/
day.
In
the
rat
oral
developmental
toxicity
study
the
fetal
NOAEL
was
500
mg/
kg
bw/
day
and
the
maternal
NOAEL
was
80
mg/
kg
bw/
day.
A
dose
level
of
1000
mg/
kg
bw/
day
administered
to
the
rat
by
the
dermal
route
does
not
elicit
developmental
toxicity.
In
the
rabbit,
prothioconazole
does
not
produce
developmental
toxicity
at
dose
levels
exceeding
the
maximum
tolerated
dose.
Thus,
prothioconazole
is
not
teratogenic
in
either
the
rat
or
rabbit.]
4.
Subchronic
toxicity.
[
90­
day
feeding
studies
conducted
in
rats,
mice,
and
dogs
showed
the
liver
and/
or
kidney
to
be
the
target
organs.
In
these
subchronic
studies
NOAELs
were
established
at
100
mg/
kg/
day
for
the
rat
and
25
mg/
kg/
day
for
the
mouse
and
dog.]
5.
Chronic
toxicity.
[
Prothioconazole
is
not
carcinogenic
in
either
the
rat
or
the
mouse
even
at
dose
levels
in
the
rat
exceeding
the
maximum
tolerated
dose.
The
liver
and
kidney
are
target
organs
of
prothioconazole
for
non­
neoplastic
toxicity
in
the
rat,
mouse
and
dog.
The
lowest
NOAEL
established
on
the
basis
of
long­
term
toxicity
studies
is
5
mg/
kg
bw/
day
in
the
rat
chronic
toxicity/
carcinogenicity
study
and
the
dog
52­
week
toxicity
study.]
6.
Animal
metabolism.
[
Metabolism
and
pharmacokinetic
studies
in
the
rat
demonstrate
that
prothioconazole
is
rapidly
absorbed,
metabolized
and
eliminated.
The
primary
metabolites
included
JAU6476­
desthio,
as
well
as
S­
and
O­
glucuronides
of
prothioconazole.]
Page
5
of
8
7.
Metabolite
toxicology.
[
The
major
metabolite
of
prothioconazole
in
the
rat,
plants
and
large
animals
is
JAU6476­
desthio.
Therefore,
a
comprehensive
evaluation
of
the
mammalian
toxicity
of
JAU6476­
desthio
has
been
performed.

The
acute
oral,
dermal,
and
inhalation
toxicity
of
JAU6476­
desthio
in
the
rat
is
low
(
LD50
values:
2806
/
2506mg/
kg
[
male/
female],
>
5000mg/
kg,
,
4­
hour
LC50:
>
5077mg/
m3,
respectively).
It
is
non­
irritating
to
skin
and
only
very
slightly
irritating
to
eyes
and
has
no
cutaneous
sensitizing
potential
by
topical
application.

The
short
and
long­
term
oral
toxicity
of
JAU6476­
desthio
has
been
investigated
by
dietary
administration
in
the
rat,
mouse
and
dog.
The
common
target
organ
in
all
3
species
is
the
liver.
Secondary
effects
on
the
thyroid
in
the
rat
and
dog
were
associated
with
increased
hepatic
enzyme
induction.
In
the
long
term
studies,
52
weeks
in
the
rat
and
30
weeks
in
the
dog,
the
NOAEL
for
the
rat
and
the
dog
were
1.1
and
10.1
mg/
kg
bw/
day,
respectively.
JAU6476­
desthio
is
not
carcinogenic
in
either
the
rat
or
the
mouse.
The
NOAEL
selected
for
human
risk
assessment
is
1.1
mg/
kg
bw/
day
established
in
the
combined
chronic
toxicity
and
carcinogenicity
study
in
the
rat.

JAU6476­
desthio
was
negative
for
mutagenicity
and
genotoxicity
in
all
in
vitro
and
in
vivo
studies
both
with
and
without
metabolic
activation
In
a
two­
generation
reproduction
study
the
maternal
NOAEL
was
2.7
mg/
kg
bw/
day
and
the
NOAEL
for
reproductive
and
neonatal
effects
10.0
mg/
kg
bw/
day.
The
main
targets
at
the
highest
dose
were
dystocia
(
probably
secondary
to
hepatic
toxicity),
decreased
pup
viability,
growth
retardation
and
low
incidence
of
cleft
palates.

In
the
developmental
toxicity
studies
cleft
palates
were
seen
in
the
rat
and
rabbit
at
the
highest
dose
levels
and
supernumerary
ribs
in
the
rat
at
lower
dose
levels.
The
oral
NOAEL
is
1
mg/
kg
bw/
day
in
the
rat
and
2
mg/
kg/
day
in
the
rabbit.

A
developmental
neurotoxicity
study
(
DNT)
in
rats
was
conducted
with
JAU6476­
desthio
as
the
anticipated
dietary
exposure
is
mainly
to
JAU6476­
desthio
and
not
the
parent.
No
evidence
of
neurotoxicity
was
seen
in
this
study,
including
no
compound­
related
effects
involving
neurobehavioral
tests
and
neuropathology.
Compound­
related
effects
were
limited
to
overt
toxicity
and
developmental
effects
which
were
consistent
with
effects
seen
in
other
developmental
toxicity
studies.
The
overall
NOAEL
was
3.6
mg/
kg
bw/
day.]
8.
Endocrine
disruption.
[
The
toxicology
database
for
prothioconazole
is
current
and
complete.
Studies
in
this
database
include
evaluation
of
the
potential
effects
on
carcinogenic,
reproduction
and
development
effects
including
an
evaluation
of
the
pathology
of
the
endocrine
organs
following
short­
or
long­
term
exposure.
Prothioconazole
is
considered
not
to
have
primary
endocrine
effects.]
Page
6
of
8
C.
Aggregate
Exposure
1.
Dietary
exposure.
[
Prothioconazole
is
a
new
broad
spectrum
systemic
fungicide
with
efficacy
against
a
range
of
diseases
in
cereals,
vegetables,
canola,
peanuts
and
rice.
An
aggregate
risk
assessment
was
conducted
for
all
pending
uses
on
barley,
dried
beans
and
peas
(
Crop
Group
6C),
canola,
peanuts,
rice
and
wheat.
The
acute
toxicity
endpoint
used
in
the
acute
assessment
was
the
NOAEL
of
1.0
mg/
kg/
day
for
the
rat
developmental
toxicity
study
for
JAU6476­
desthio,
the
major
metabolite
of
prothioconazole
in
plants
and
animal
.
Application
of
a
100x
uncertainty
factor
resulted
in
an
acute
reference
dose
(
aRfD)
of
0.01
mg/
kg/
day.
The
chronic
reference
dose
(
cRfD)
of
0.011
mg/
kg/
day
resulted
from
application
of
a
100x
uncertainty
factor
to
the
NOAEL
of
1.1
mg/
kg/
day
from
the
rat
chronic
toxicity
study
with
JAU6476­
desthio.

Results
from
the
acute
and
chronic
dietary
exposure
assessment
described
below
demonstrate
a
reasonable
certainty
that
no
harm
to
the
overall
U.
S.
population
or
any
population
subgroup
will
result
from
the
use
of
prothioconazole
on
the
above
crops.]
i.
Food.
[
An
acute,
Tier
2
dietary
(
food)
risk
assessment
was
conducted
using
the
highest
field
trial
(
HAFT)
residue
values
for
non­
blended
commodities
and
average
residue
values
for
blended
commodities
and
assuming
100%
crop
treated
for
all
crops.
The
acute
analysis
indicated
that
the
most
highly
exposed
population
subgroup
was
Children
(
1­
2
yrs)
with
an
exposure
equal
to
1.9%
of
the
acute
reference
dose.
The
U.
S.
population
had
an
exposure
of
1.1%
of
the
acute
reference
dose.
A
chronic,
Tier
2
dietary
(
food)
risk
assessment
was
conducted
using
average
residues
for
all
crops
and
incorporating
anticipated
percent
crop
treated
data.
The
chronic
assessment
indicated
that
the
most
highly
exposed
population
subgroup
was
Children
(
1­
2
yrs)
with
an
exposure
equal
to
0.2%
of
the
chronic
reference
dose.
Chronic
exposure
to
the
overall
U.
S.
population
was
0.1%
of
the
chronic
reference
dose.]
ii.
Drinking
water.
[
No
monitoring
data
are
available
for
residues
of
prothioconazole
in
drinking
water
and
EPA
has
established
no
health
advisory
levels
or
maximum
contaminant
levels
for
residues
of
prothioconazole
in
drinking
water.
Conservative
surface
water
estimates
of
prothioconazole
and
its
primary
soil
metabolites
(
JAU6476­
desthio
and
S­
methyl
JAU6476)
in
drinking
water
were
determined
using
PRZM/
EXAMS.
Summation
of
these
estimated
concentrations
(
in
JAU6476­
desthio
toxicity
equivalents)
resulted
in
the
acute
and
chronic
drinking
water
concentrations
(
EDWC).
The
maximum
peak
day
(
acute)
EDWC
concentration
was
2.56
ppb
and
the
annual
average
(
chronic)
concentration
was
0.79
ppb
for
untreated
drinking
water
derived
from
surface
water.
The
calculated
acute
drinking
water
level
of
comparison
(
aDWLOC)
is
98
ppb
for
children
and
346
ppb
for
adults.
The
chronic
drinking
water
level
of
comparison
(
cDWLOC)
is
110
ppb
for
children
and
385
ppb
for
adults.
The
acute
and
chronic
estimated
drinking
water
concentrations
are
well
below
calculated
drinking
water
levels
of
comparison
and
demonstrate
that
the
aggregate
exposure
(
food
and
water)
to
prothioconazole
residues
from
the
requested
uses
is
well
below
the
Agency's
level
of
concern.]
2.
Non­
dietary
exposure.
[
Prothioconazole
is
not
registered
for
residential
uses
nor
are
any
registrations
pending
for
such
uses.]

D.
Cumulative
Effects
[
Prothioconazole
is
a
member
of
the
conazole
family
of
fungicides.
The
cumulative
Page
7
of
8
effects
of
the
primary
common
metabolites
are
being
addressed
by
the
US
Triazole
Task
Force.]

E.
Safety
Determination
1.
U.
S.
population.
[
Based
on
the
conservative
exposure
assumptions
described
above
and
on
the
completeness
of
the
toxicity
data,
it
can
be
concluded
that
total
food
exposure
to
prothioconazole
from
all
proposed
uses
will
utilize
less
than
2%
of
the
acute
RfD
and
less
than
1%
of
the
chronic
RfDs
for
the
overall
U.
S.
population.
EPA
generally
has
no
concerns
for
exposures
below
100%
of
the
RfD,
because
the
RfD
represents
the
level
at
or
below
which
daily
aggregate
exposure
over
a
lifetime
will
not
pose
appreciable
risks
to
human
health.
Drinking
water
levels
of
comparison
based
on
the
dietary
exposure
are
greater
than
highly
conservative
estimated
drinking
water
concentrations.
Thus,
it
can
be
concluded
that
there
is
a
reasonable
certainty
that
no
harm
will
result
from
aggregate
exposure
of
the
U.
S.
population
to
prothioconazole
residues.]
2.
Infants
and
children.
[
For
the
most
highly
exposed
population
subgroups
(
Children
1­
2
years),
total
food
exposure
to
prothioconazole
will
also
utilize
less
than
2%
of
the
acute
RfD
and
less
than
1%
of
the
chronic
RfD.
EPA
generally
has
no
concerns
for
exposures
below
100%
of
the
RfD,
because
the
RfD
represents
the
level
at
or
below
which
daily
aggregate
exposure
over
a
lifetime
will
not
pose
appreciable
risks
to
human
health.
Drinking
water
levels
of
comparison
based
on
the
dietary
exposure
are
greater
than
highly
conservative
estimated
drinking
water
concentrations.
Thus,
it
can
be
concluded
that
there
is
a
reasonable
certainty
that
no
harm
will
result
from
aggregate
exposure
to
prothioconazole
residues.

In
assessing
the
potential
for
additional
sensitivity
of
infants
and
children
to
residues
of
prothioconazole,
the
data
from
developmental
studies
in
both
rat
and
rabbit
and
a
two­
generation
reproduction
study
in
rats
have
been
considered.
The
developmental
toxicity
studies
evaluate
potential
adverse
effects
on
the
developing
animal
resulting
from
pesticide
exposure
of
the
mother
during
prenatal
development.
The
reproduction
study
evaluates
effects
from
exposure
to
the
pesticide
on
the
reproductive
capability
of
mating
animals
through
two
generations,
as
well
as
any
observed
systemic
toxicity.

FFDCA
Section
408
provides
that
EPA
may
apply
an
additional
safety
or
uncertainty
factor
for
infants
and
children
in
the
case
of
threshold
effects
to
account
for
pre­
and
post­
natal
effects
or
the
completeness
of
the
toxicity
database.
Based
on
current
toxicological
data
requirements,
the
toxicology
database
for
prothioconazole
relative
to
pre­
and
post­
natal
effects
is
complete
and
shows
no
developmental
effects
at
maternally
non­
toxic
doses.
For
the
metabolite
JAU6476­
desthio,
although
developmental
effects
were
seen,
the
NOAEL
for
malformation
is
ten
times
higher
than
the
NOAEL
used
for
risk
assessment.
Therefore,
an
additional
uncertainty
factor
is
not
warranted
and
the
cRfD
of
0.011
mg/
kg
bw/
day
is
appropriate
for
assessing
aggregate
risk
to
infants
and
children.]

F.
International
Tolerances
[
No
CODEX
Maximum
Residue
Levels
(
MRL's)
have
been
established
for
residues
of
prothioconazole
on
any
crops
at
this
time.]
Page
8
of
8
