Document ID: EPA-HQ-OPP-2006-0522-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-07-05T04:00Z

EPA
Registration
Division
contact:
Barbara
Madden,
703­
305­
6463
Interregional
Research
Project
Number
4
and
BASF
Corporation
PP#
5E7014
and
5F7002
EPA
has
received
a
pesticide
petition
(
PP#
5E7014)
from
Interregional
Research
Project
Number
4
(
IR­
4),
681
U.
S.
Highway
#
1
South,
North
Brunswick,
NJ
08902­
3390,
proposing
pursuant
to
section
408(
d)
of
the
Federal
Food,
Drug
and
Cosmetic
Act
(
FFDCA),
21
U.
S.
C
section
346a
(
d),
to
amend
40
CFR
part
180.582
by
establishing
tolerances
for
the
combined
residues
of
the
fungicide
pyraclostrobin,
carbamic
acid,
[
2­[[[
1­(
4­
chlorophenyl)­
1Hpyrazol
3­
yl]
oxy]
methyl]
phenyl]
methoxy­,
methyl
ester
and
its
metabolite
methyl­
N­[[[
1­(
4­
chlorophenyl)
pyrazol­
3­
yl]
oxy]
o­
tolyl]
carbamate
(
BF
500­
3);
expressed
as
parent
compound
in
or
on
the
raw
agricultural
commodities
endive,
belgian,
at
11
ppm,
fruit,
pome,
group,
at
6.5
ppm,
and
fruit,
stone,
group
at
11
ppm.
EPA
has
also
received
a
pesticide
petition
(
PP
5F7002)
from
BASF
Corporation,
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
180.582
by
establishing
a
tolerance
for
residues
of
pyraclostrobin
in
or
on
the
raw
agricultural
commodities
berry
group
at
4
parts
per
million
(
ppm),
cotton
undelinted
seed
at
0.4
ppm,
and
cotton
gin
byproducts
at
30
ppm.
EPA
has
determined
that
the
petitions
contain
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
petitions.
Additional
data
may
be
needed
before
EPA
rules
on
the
petitions.

A.
Residue
Chemistry
1.
.
Plant
and
animal
metabolism.
Nature
of
the
residue
studies
(
OPPTS
860.1300)
were
conducted
in
grape,
potato
and
wheat
as
representative
crops
in
order
to
characterize
the
fate
of
pyraclostrobin
in
all
crop
matrices.
Pyraclostrobin
demonstrated
a
similar
pathway
and
fate
in
all
three
crops.
In
all
three
crops
the
pyraclostrobin
Residues
of
Concern
(
ROC)
of
were
characterized
as
parent
(
pyraclostrobin)
and
BAS
500­
3),
methyl­
N[[[
1­(
4­
chlorophenyl)
pyrazol­
3yl]
oxy]
o­
tolyl]
carbamate.
In
hens
the
residues
of
concern
were
determined
to
be
parent
compound
and
a
hydroxlated
metabolite,
BAS
500­
16.
In
goats
the
residues
of
concern
were
determined
to
be
parent
and
a
hydroxylated
metabolite
BAS
500­
10.

2.
Analytical
method.
In
plants
the
method
of
analysis
is
aqueous
organic
solvent
extraction,
column
clean
up
and
quantitation
by
LC/
MS/
MS.
In
animals
the
method
of
analysis
involves
base
hydrolysis,
organic
extraction,
column
clean
up
and
quantitation
by
LC/
MS/
MS
or
derivatization
(
methylation)
followed
by
quantitation
by
GC/
MS..

3.
Magnitude
of
residues.
Field
trials
were
carried
out
in
order
to
determine
the
magnitude
of
the
residue
in
berry
group,
cotton
undelinted
seed,
cotton
gin
byproducts,
endive,
belgian,
fruit,
pome,
group,
and
fruit,
stone,
group
to
satisfy
the
requirements
for
a
tolerance
of
pyraclostrobin
in
these
commodities.
Field
trials
were
carried
out
using
the
maximum
label
rate,
the
maximum
number
of
applications,
and
the
minimum
preharvest
interval
for
berry
group,
cotton
undelinted
seed,
cotton
gin
byproducts,
and
endive,
belgian.
Post­
harvest
treatments
were
utilized
for
fruit,
pome,
group,
and
fruit,
stone,
group.

B.
Toxicological
Profile
1.
Acute
toxicity.
Pyraclostrobin
and
its
formulated
products
have
favorable
acute
toxicity.
The
acute
toxicity
studies
place
technical
pyraclostrobin
in
toxicity
category
IV
for
acute
oral
and
acute
inhalation
and
category
III
for
acute
dermal.
Pyraclostrobin
is
category
III
for
both
eye
and
skin
irritation,
and
it
is
not
a
dermal
sensitizer.
Two
formulated
end
use
products
are
proposed,
an
Emulsifiable
Concentrate
(
EC)
and
an
Extruded
Granule
(
EG).
The
EC
has
an
acute
oral
toxicity
category
of
II,
acute
dermal
of
III,
acute
inhalation
of
IV,
eye
and
skin
irritation
categories
of
III,
and
is
not
a
dermal
sensitizer.
The
EG
has
acute
oral
and
dermal
toxicity
categories
of
III,
acute
inhalation
of
IV,
eye
irritation
of
III,
skin
irritation
of
IV
and
is
not
a
dermal
sensitizer.

2.
Genotoxicty.
Pyraclostrobin
was
negative
for
inducing
mutations
in
both
an
in
vitro
Ames
test
and
an
in
vitro
CHO/
HGPRT
Locus
Mammalian
Cell
Mutation
Assay.
Pyraclostrobin
also
demonstrated
no
chromosomal
effects
in
an
in
vitro
V79
Cells
CHO
Cytogenetic
Assay
and
an
in
vivo
Mouse
Micronucleus
test.
An
additional
in
vitro
study
investigating
DNA
damage
and
repair
also
showed
no
effects.
Pyraclostrobin
has
been
tested
in
a
total
of
5
genetic
toxicology
assays
consisting
of
in
vitro
and
in
vivo
studies.
It
can
be
stated
that
pyraclostrobin
did
not
show
any
mutagenic,
clastogenic
or
other
genotoxic
activity
when
tested
under
the
conditions
of
the
studies
mentioned
above.
Therefore,
pyraclostrobin
does
not
pose
a
genotoxic
hazard
to
humans.

3.
Reproductive
and
developmental
toxicity.
The
reproductive
and
developmental
toxicity
of
pyraclostrobin
was
investigated
in
a
2­
generation
rat
reproduction
study
as
well
as
in
rat
and
rabbit
teratology
studies.
There
were
no
adverse
effects
on
reproduction,
systemic
toxicity
to
adults
or
developmental
toxicity
in
the
two­
generation
study
so
the
NOAEL
is
the
highest
dose
tested
of
300
ppm
(
approximately
32.6
mg/
kg
bw/
day).

No
teratogenic
effects
were
noted
in
either
the
rat
or
rabbit
developmental
studies.
In
the
rat
study,
maternal
toxicity
observed
at
the
mid
and
high
dose
consisted
of
decreased
food
consumption
and
body
weight
gain.
Developmental
changes
noted
at
the
high
dose
were
increased
incidences
of
dilated
renal
pelvis
and
cervical
ribs
with
no
cartilage.
The
maternal
NOAEL
was
10
mg/
kg
bw
and
the
developmental
NOAEL
was
25
mg/
kg
bw.

In
the
rabbit
teratology
study,
maternal
toxicity
observed
at
the
mid
and
high
doses
consisted
of
decreased
food
consumption
and
body
weight
gain
(
severe
at
the
high
dose).
An
increased
postimplantation
loss
was
also
observed
at
the
mid
and
high
doses
due
to
an
increase
in
early
resorptions.
In
rabbits,
these
types
of
effects
are
often
observed
with
significant
stress
on
the
mothers
(
as
seen
by
the
body
weight
gain
decrease
in
this
study)
and
not
indicative
of
frank
developmental
toxicity.
The
NOAEL
for
both
maternal
and
developmental
toxicity
was
5
mg/
kg
bw.

4.
Subchronic
toxicity.
The
subchronic
toxicity
of
pyraclostrobin
was
investigated
in
90­
day
feeding
studies
with
rats,
mice
and
dogs,
and
in
a
28­
day
dermal
administration
study
in
rats.
A
90­
day
neurotoxicity
study
in
rats
was
also
performed.
Generally,
mild
toxicity
was
observed.
At
high
dose
levels
in
feeding
studies,
general
findings
in
all
three
species
were
decreased
food
consumption
and
body
weight
gain
and
a
thickening
of
the
duodenum.
Anemia
occurred
at
high
dose
levels
in
both
rats
and
mice
with
accompanying
extramedullary
hematopoiesis
of
the
spleen
in
rats.
In
rats
only,
a
finding
of
liver
cell
hypertrophy
was
indicative
of
a
physiological
response
to
the
handling
of
the
chemical.
The
lowest
NOAEL
in
the
90­
day
feeding
studies
was
from
the
dog
study
and
determined
to
be
5.8
mg/
kg
bw/
day.

In
the
28­
day
repeat
dose
dermal
study,
no
systemic
effects
were
noted
up
to
the
highest
dose
tested
of
250
mg/
kg
bw/
day.

In
a
90­
day
rat
neurotoxicity
study,
a
direct
neurotoxic
effect
was
not
observed.

5.
Chronic
toxicity.
Pyraclostrobin
was
administered
to
groups
of
5
male
and
5
female
purebred
Beagle
dogs
in
the
diet
at
concentrations
of
0,
100,
200
and
400
ppm
over
a
period
of
12
months.
Signs
of
toxicity
were
observed
at
the
high
dose.
Diarrhea
was
observed
throughout
the
study
period
for
both
sexes.
High
dose
males
and
females
initially
lost
weight
and
body
weight
gain
was
decreased
for
the
entire
study
period
for
females.
Hematological
changes
observed
were
an
increase
in
white
blood
cells
in
males,
and
an
increase
in
platelets
in
both
sexes
at
the
high
dose.
Clinical
chemistry
demonstrated
a
decrease
in
serum
total
protein,
albumin,
globulins
and
cholesterol
in
high
dose
animals
of
both
sexes
possibly
due
to
the
diarrhea
and
reduced
nutritional
status
of
the
animals.
The
NOAEL
was
200
ppm
(
ca.
5.5
mg/
kg
bw/
day
males;
5.4
mg/
kg
bw/
day
females).

In
an
oncogenicity
study,
pyraclostrobin
was
administered
to
groups
of
50
male
and
50
female
Wistar
rats
at
dietary
concentrations
of
0;
25;
75,
and
200
ppm
for
24
months.
In
a
companion
chronic
toxicity
study,
20
rats/
sex
were
used
at
the
same
dose
levels
as
in
the
oncogenicity
study.
A
body
weight
gain
depression
of
10­
11%
in
males
and
14­
22%
in
females
with
an
accompanying
decrease
in
food
efficiency
was
observed
at
the
high
dose.
There
was
no
evidence
that
pyraclostrobin
produced
a
carcinogenic
effect
in
rats.
The
NOAEL
for
the
chronic
rat
and
the
cancer
rat
study
is
75
ppm
(
ca.
3.4
mg/
kg
bw/
day
males;
4.7
mg/
kg
bw/
day
females).

Pyraclostrobin
was
administered
to
groups
of
50
male
and
50
female
B6C3F1
mice
at
dietary
concentrations
of
0,
10,
30,
120
and
180
ppm
(
females
only)
for
18
months.
Body
weights
were
reduced
at
the
highest
doses
tested
in
both
males
and
females.
At
the
high
dose,
body
weight
gain
decreases
of
27%
in
females
and
29%
in
males
with
an
accompanying
decrease
in
food
efficiency
were
observed.
No
other
signs
of
toxicity
were
noted
at
any
dose
level.
The
NOAEL
was
found
to
be
30
ppm
(
ca.
4.1
mg/
kg
bw/
day)
for
males.
The
Agency
determined
that
the
body
weight
effect
at
the
high
dose
in
females
was
not
sufficient
to
determine
an
MTD.
Therefore
the
NOAEL
for
females
is
considered
greater
than
the
highest
dose
tested
of
32.8
mg/
kg
bw/
day.
There
was
no
evidence
that
pyraclostrobin
produced
a
carcinogenic
effect
in
mice.

6.
Animal
metabolism.
In
a
rat
metabolism
study
with
pyraclostrobin,
10­
13%
of
the
administered
dose
was
excreted
in
the
urine
and
74­
91%
in
the
feces
within
48
hours.
Excretion
via
bile
was
significant
accounting
for
35­
38%
of
the
administered
dose.
By
120
hours
after
dosing,
very
little
radioactivity
remained
in
tissues.
Pyraclostrobin
was
rapidly
and
almost
completely
metabolized.
Very
little
unchanged
parent
was
detected.
The
phase
one
biotransformation
is
characterized
by
N­
demethoxylation,
various
hydroxylations,
cleavage
of
the
ether
bond
and
further
oxidation
of
the
two
resulting
molecule
parts.
Conjugation
of
the
formed
hydroxyl
groups
by
glucuronic
acid
or
sulfate
also
occurred.
In
summary,
pyraclostrobin
is
extensively
metabolized
and
rapidly
eliminated
primarily
via
the
bile,
with
no
evidence
of
accumulation
in
tissues.

7.
Metabolite
toxicology.
A
comparison
of
the
rat
metabolism
results
with
the
plant
metabolism/
residue
results
indicates
that
toxicology
studies
performed
with
the
parent
pyraclostrobin
are
sufficient
to
cover
dietary
exposure.
Plant
residues
are
primarily
the
parent
compound
with
a
fraction
(
up
to
10­
20%
at
most)
being
the
demethoxylated
parent.
This
metabolite
is
referred
to
as
BF
500­
3
in
the
plant
studies
and
as
500M07
in
the
rat
study.
This
metabolite
in
the
rat
is
the
first
step
in
the
major
biotransformation
process
leading
to
the
majority
of
the
metabolites
determined
in
the
major
excretion
pathway.

8.
Endocrine
disruption.
Endocrine
effects.
No
specific
tests
have
been
conducted
with
pyraclostrobin
to
determine
whether
the
chemical
may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen
or
other
endocrine
effects.
However,
there
were
no
significant
findings
in
other
relevant
toxicity
studies
(
i.
e.,
subchronic
and
chronic
toxicity,
teratology
and
multi­
generation
reproductive
studies)
which
would
suggest
that
pyraclostrobin
produces
endocrine
related
effects.

C.
Aggregate
Exposure
1.
Dietary
exposure.
Exposure
assessments
were
conducted
to
evaluate
the
potential
risk
due
to
acute
and
chronic
dietary
exposure
of
the
U.
S.
population
to
residues
of
pyraclostrobin.
This
fungicide
and
its
desmethoxy
metabolite,
in
or
on
raw
agricultural
commodities,
and
metabolites
in
or
on
animal
fat,
liver,
meat
and
meat
byproducts
were
expressed
as
the
parent
compound.
The
tolerance
values
previously
established
for
various
cereals,
vegetables,
fruits,
and
animal
products
are
listed
in
the
U.
S.
EPA
final
rule
published
in
the
Federal
Register
October
29,
2004
(
Vol
69,
No.
209,
p
63083
 
63100)
and
U.
S.
40
CFR
§
180.582.
This
analysis
included
all
current
and
proposed
tolerance
values
for
berry
group
at
4
parts
per
million
(
ppm),
cotton
undelinted
seed
at
0.4
ppm,
cotton
gin
byproducts
at
30
ppm,
endive,
belgian,
at
11
ppm,
fruit,
pome,
group,
at
6.5
ppm,
and
fruit,
stone,
group
at
11
ppm.

The
pyraclostrobin
chronic
reference
dose
(
cRfD)
is
0.034
mg/
kg
bw/
day
based
on
the
NOAEL
of
3.4
mg/
kg
bw/
day
in
the
rat
chronic
toxicity
study
and
a
100X
safety
factor.
The
acute
reference
dose
(
aRfD)
is
3
mg/
kg
b.
w./
day
for
the
general
population
based
on
a
NOAEL
from
the
acute
neurotoxicity
study
of
300
mg/
kg
bw/
day
and
a
100X
safety
factor.
For
females
of
child
bearing
years
(
13­
49
years),
the
aRfD
is
0.05
mg/
kg
b.
w./
day
based
on
the
NOAEL
of
5
mg/
kg
bw/
day
from
the
rabbit
teratology
study
and
a
100X
safety
factor.
The
EPA
determined
that
the
FQPA
safety
factor
should
be
1X
for
all
exposure
scenarios.
Therefore,
the
acute
Population
Adjusted
Dose
(
aPAD)
and
the
chronic
Population
Adjusted
Dose
(
cPAD)
are
the
same
as
the
aRfD
and
cRfD,
respectively.

i.
Food.
Acute
Dietary
Exposure
Assessment
The
acute
dietary
exposure
estimates
were
based
on
tolerance
values,
default
process
factors,
100%
crop
treated
values
for
all
commodities
except
for
leafy
vegetables,
pome
fruit
and
stone
fruit
crop
groups
where
the
percent
crop
treated
(%
CT)
values
listed
in
the
Federal
Register
October
29,
2004
(
Vol
69,
No.
209,
p
63083
 
63100)
were
utilized.
The
consumption
data
was
from
the
USDA
Continuing
Survey
of
Food
Intake
by
Individuals
(
CSFII
1994
­
1996,
1998)
and
the
EPA
Food
Commodity
Ingredient
Database
(
FCID)
using
Exponent's
Dietary
Exposure
Evaluation
Module
(
DEEM­
FCID)
software.

The
acute
population
adjusted
dose
(
aPAD)
used
for
females
13­
49
years
of
age
was
0.05
mg/
kg
bw/
day
and
3.0
mg/
kg
bw/
day
for
all
other
sub­
populations.
Considering
the
exposure
assumptions
discussed
above,
pyraclostrobin
acute
dietary
exposure
from
food
is
less
than
5
%
aPAD
for
the
U.
S.
population
and
all
sub­
populations
except
females
13­
49
years
of
age
that
occupies
49.9
%
of
the
aPAD.
The
results
of
the
acute
dietary
assessment
are
presented
in
Table
1.

Table
1.
Results
for
Pyraclostrobin
Acute
Dietary
Exposure
Analysis
Considering
all
Current
and
Proposed
Tolerances
Including
Berry
group,
Cotton
Undelinted
Seed,
Cotton
Gin
Byproducts,
Endive,
Belgian,
Fruit,
Pome,
Group,
and
Fruit,
Stone,
Fruit
using
DEEM­
FCID
at
the
95th
Percentile
Population
Exposure
Estimate
%
aPAD
Subgroups
(
mg/
kg
b.
w./
day)*

U.
S.
Population
0.034804
1.16
All
Infants
(<
1
year
old)
0.056964
1.90
Children
(
1­
2
years
old)
0.093888
3.13
Children
(
3­
5
years
old)
0.06993
2.33
Children
(
6­
12
years
old)
0.043257
1.44
Youth
(
13­
19
years
old)
0.028396
0.95
Females
(
13­
49
years
old)
0.024956
49.91
Adults
(
20­
49
years
old)
0.024346
0.81
Adults
(
50+
years
old)
0.025516
0.85
aPAD
=
acute
population
adjusted
dose
*
Exposure
Estimate
(
95th
percentile)
was
based
on
tolerance
values,
default
processing
factors,
and
considering
100%
crop
treated
for
all
commodities
except
for
leafy
vegetables,
pome
and
stone
fruit
which
included
the
percent
crop
treated
values
listed
in
the
Federal
Register
Vol
69,
No.
209,
October
29,
2004
(
95%
percentile)

The
results
of
the
analysis
show
that
for
all
sub­
populations,
the
exposures
are
below
the
Agency's
level
of
concern
(<
100%
aPAD).
Additional
refinements
in
the
dietary
risk
assessment
(
i.
e.
utilizing
anticipated
residue
values,
process
factors,
percent
crop
treated
values
for
all
crops)
would
further
reduce
the
estimated
exposure
values.

Chronic
Dietary
Exposure
Assessment
The
chronic
dietary
exposure
estimates
were
based
on
tolerance
values,
default
process
factors,
%
crop
treated
values
for
all
commodities
listed
in
the
Federal
Register
October
29,
2004
(
Vol
69,
No.
209,
p
63083
 
63100),
and
100%
crop
treated
values
for
banana,
cotton,
endive,
Belgian,
mango,
and
papaya.
The
consumption
data
was
from
the
USDA
Continuing
Survey
of
Food
Intake
by
Individuals
(
CSFII
1994
­
1996,
1998)
and
the
EPA
Food
Commodity
Ingredient
Database
(
FCID)
using
Exponent's
Dietary
Exposure
Evaluation
Module
(
DEEM­
FCID)
software.
The
tolerance
values
included
the
proposed
berry
group
at
4
parts
per
million
(
ppm),
cotton
undelinted
seed
at
0.4
ppm,
cotton
gin
byproducts
at
30
ppm,
endive,
belgian,
at
11
ppm,
fruit,
pome,
group,
at
6.5
ppm,
and
fruit,
stone,
group
at
11
ppm.

The
chronic
population
adjusted
dose
(
cPAD)
used
for
U.
S.
population
and
all
sub­
populations
is
0.034
mg/
kg
bw/
day.
Considering
the
exposure
assumptions
discussed
above,
pyraclostobin
chronic
dietary
exposure
from
food
for
the
U.
S.
population
was
10.4%
of
the
cPAD.
The
most
highly
exposure
population
sub
group
was
children
1­
2
years
of
age
at
40.6%
cPAD.
The
results
of
the
chronic
dietary
assessment
are
presented
in
Table
2.

Table
2.
Results
for
Pyraclostrobin
Chronic
Dietary
Exposure
Analysis
Considering
all
Current
and
Proposed
Tolerances
Including
Berry
group,
Cotton
Undelinted
Seed,
Cotton
Gin
Byproducts,
Endive,
Belgian,
Fruit,
Pome,
Group,
and
Fruit,
Stone,
using
DEEM­
FCID
Population
Exposure
Estimate
%
cPAD
Subgroups
(
mg/
kg
b.
w./
day)
U.
S.
Population
0.003545
10.4
All
Infants
(<
1
year
old)
0.010022
29.5
Children
(
1­
2
years
old)
0.013814
40.6
Children
(
3­
5
years
old)
0.00944
27.8
Children
(
6­
12
years
old)
0.005168
15.2
Youth
(
13­
19
years
old)
0.002611
7.7
Females
(
13­
49
years
old)
0.002461
7.2
Adults
(
20­
49
years
old)
0.002324
6.8
Adults
(
50+
years
old)
0.002676
7.9
cPAD
=
chronic
population
adjusted
dose
*
Exposure
estimates
based
on
tolerance
values,
default
processing
factor,
and
considering
%
crop
treated
listed
in
the
Federal
Register
Vol
69,
No.
209,
October
29,
2004
and
100%
crop
treated
values
for
banana,
cotton,
endive,
belgian,
mango,
and
papaya.

The
results
of
the
analysis
show
that
for
all
sub­
populations,
the
exposures
are
below
a
level
of
concern
(<
100%
cPAD).
Additional
refinements
in
the
chronic
dietary
risk
assessment
(
i.
e.
utilizing
anticipated
residue
values,
process
factors)
would
further
reduce
the
estimated
exposure
values.

ii.
Drinking
water.
Based
on
the
PRZM/
EXAMS
and
SCIGROW
models,
the
peak
EDWCs
of
pyraclostrobin
for
acute
exposure
are
estimated
to
be
22.6
ug/
L
(
ppb)
in
surface
water
and
0.02
ug/
L
in
shallow
ground
water.
The
peak
EDWCs
for
chronic
exposure
are
estimated
to
be
1.9
ug/
L
in
surface
water
and
0.02
ug/
L
in
shallow
ground
water.
These
concentrations
are
based
on
maximum
applications
to
turf,
which
have
the
highest
labeled
application
rate
of
any
pyraclostrobin
use.

Drinking
water
contributions
were
assessed
based
on
the
maximum
estimated
pyraclostrobin
water
concentrations
(
acute
­
22.6
ug/
L,
chronic
1.9
ug/
L),
and
water
consumption
and
body
weights
reported
in
CSFII,
using
DEEM­
FCID
software.
The
acute
and
chronic
estimated
water
exposure
values
are
summarized
in
Tables
3
and
4,
respectively.
Minimal
exposure
of
pyraclostrobin
occurs
through
drinking
water
with
<
0.5%
the
aPAD
and
cPAD
for
all
subpopulations
with
the
exception
of
females
13­
49
years
of
age
with
a
2.2%
aPAD.

Table
3.
Results
for
Pyraclostrobin
Acute
Water
Exposure
Analysis
Considering
the
Maximum
Estimated
Acute
Drinking
Water
Concentration
using
DEEM­
FCID
Population
Water
Exposure
Estimate
%
aPAD
Subgroups
(
mg/
kg
b.
w./
day)
U.
S.
Population
0.001181
0.04
All
Infants
(<
1
year
old)
0.004451
0.15
Children
(
1­
2
years
old)
0.001852
0.06
Children
(
3­
5
years
old)
0.001692
0.06
Children
(
6­
12
years
old)
0.001178
0.04
Youth
(
13­
19
years
old)
0.000958
0.03
Females
(
13­
49
years
old)
0.0011
2.20
Adults
(
20­
49
years
old)
0.001094
0.04
Adults
(
50+
years
old)
0.000988
0.03
aPAD
=
acute
population
adjusted
dose
Based
on
estimated
acute
surface
water
value
of
22.6
ug/
L
Table
4.
Results
for
Pyraclostrobin
Chronic
Water
Exposure
Analysis
Considering
the
Maximum
Estimated
Chronic
Drinking
Water
Concentration
using
DEEM­
FCID
Population
Water
Exposure
Estimate
%
cPAD
Subgroups
(
mg/
kg
b.
w./
day)

U.
S.
Population
0.00004
0.1
All
Infants
(<
1
year
old)
0.000131
0.4
Children
(
1­
2
years
old)
0.000059
0.2
Children
(
3­
5
years
old)
0.000056
0.2
Children
(
6­
12
years
old)
0.000038
0.1
Youth
(
13­
19
years
old)
0.000029
0.1
Females
(
13­
49
years
old)
0.000037
0.1
Adults
(
20­
49
years
old)
0.000037
0.1
Adults
(
50+
years
old)
0.000039
0.1
cPAD
=
chronic
population
adjusted
dose
Based
on
estimated
chronic
surface
water
value
of
1.9
ug/
L
Acute
Aggregate
Exposure
and
Risk
(
Food
and
water)

The
aggregate
acute
risk
includes
residues
of
pyraclostrobin
from
food
and
water
(
Table
5).
Exposures
from
residential
uses
are
not
included
in
the
acute
aggregate
assessment.
The
results
demonstrate
that
there
are
no
safety
concerns
for
any
subpopulation
based
on
established
and
new
uses,
and
that
the
results
clearly
meet
the
FQPA
standard
of
reasonable
certainty
of
no
harm.

Table
5.
Estimated
Acute
Aggregate
Exposure
and
Risk
of
Pyraclostrobin
Population
Subgroup
aPAD
(
mg/
kg/
day)
Food
Exposure
(
mg/
kg/
day)
Water
Exposure
(
mg/
kg/
day)
Total
Exposure
(
mg/
kg/
day)
%
aPAD
U.
S.
Population
3
0.034804
0.001181
0.035985
1.20
All
Infants
(<
1
yr
old)
3
0.056964
0.004451
0.061415
2.05
Children
1­
2
years
3
0.093888
0.001852
0.09574
3.19
Children
3­
5
years
3
0.06993
0.001692
0.071622
2.39
Children
6
 
12
years
3
0.043257
0.001178
0.044435
1.48
Youth
13­
19
years
3
0.028396
0.000958
0.029354
0.98
Females
13­
49
years
0.05
0.024956
0.0011
0.026056
52.11
Adults
20­
49
years
3
0.024346
0.001094
0.02544
0.85
Adults
+
50
3
0.025516
0.000988
0.026504
0.88
Short­
and
Intermediate
Term
Aggregate
Exposure
and
Risk
(
food,
water,
and
residential)
Short­
term
aggregate
risk
from
pyraclostrobin
takes
into
account
exposures
from
dietary
consumption
(
food
and
water)
and
residential
exposure
from
turf
use.
Post
application
exposure
from
the
turf
use
is
considered
short­
term.
The
aggregate
MOE
from
food,
water,
and
residential
exposure
are
115
and
257
for
the
children
1­
2
years
old
and
the
US
population,
respectively.
These
MOE
are
greater
than
the
target
MOE
of
100
which
indicates
there
is
no
safety
concern.
The
results
of
the
analysis
are
shown
in
Table
6.

Table
6.
Estimated
Short/
Intermediate
Term
Aggregate
Exposure
and
Risk
of
Pyraclostrobin
Population
NOAEL
(
mg/
kg/
day)
Target
MOE1
Food
Exposure
(
mg/
kg/
day)
Water
Exposure
(
mg/
kg/
day)
Residential
Exposure2
(
mg/
kg/
day)
Total
Exposure
(
mg/
kg/
day)
MOE3
US
5.8
100
0.003545
0.00004
0.019
0.022585
257
Child
1­
2
yr
old
5.8
100
0.013814
0.000059
0.036425
0.050298
115
1
Target
MOE
is
100.
2
Residential
Exposure
=
Exposure
to
adult
while
playing
golf.
3
Aggregate
MOE
=
(
NOAEL
/
(
Food
+
Water
+
Residential
Exposure)

Chronic
Aggregate
Exposure
and
Risk
(
food
and
water)
The
aggregate
chronic
risk
includes
residues
of
pyraclostrobin
from
food
and
water
(
Table
7).
Exposures
from
residential
uses
are
not
included
in
the
chronic
aggregate
assessment.
The
results
demonstrate
there
are
no
safety
concerns
for
any
subpopulation
based
on
established
and
new
uses,
and
that
the
results
clearly
meet
the
FQPA
standard
of
reasonable
certainty
of
no
harm.

Table
7.
Estimated
Chronic
Aggregate
Exposure
and
Risk
of
Pyraclostrobin
Population
Subgroup
cPAD
(
mg/
kg/
day)
Food
Exposure
(
mg/
kg/
day)
Water
Exposure
(
mg/
kg/
day)
Total
Exposure
(
mg/
kg/
day)
%
cPAD
U.
S.
Population
0.034
0.003545
0.00004
0.003585
10.54
All
Infants
(<
1
yr
old)
0.034
0.010022
0.000131
0.010153
29.86
Children
1­
2
years
0.034
0.013814
0.000059
0.013873
40.80
Children
3­
5
years
0.034
0.00944
0.000056
0.009496
27.93
Children
6
 
12
years
0.034
0.005168
0.000038
0.005206
15.31
Youth
13­
19
years
0.034
0.002611
0.000029
0.00264
7.76
Females
13­
49
years
0.034
0.002461
0.000037
0.002498
7.35
Adults
20­
49
years
0.034
0.002324
0.000037
0.002361
6.94
Adults
+
50
0.034
0.002676
0.000039
0.002715
7.99
Aggregate
Cancer
Risk
for
U.
S.
Population
The
aggregate
MOE
value
(
considering
food
and
drinking
water)
was
calculated
for
pyraclostrobin
and
is
shown
in
Table
8.
The
36­
year
average
of
pyraclostrobin
in
surface
water
that
was
estimated
by
PRZM/
EXAMS
for
use
in
the
chronic/
cancer
risk
assessment
is
1.2
ug/
L.
The
results
demonstrate
there
are
no
safety
concerns
for
US
population
based
on
established
and
new
uses,
and
that
the
results
clearly
meet
the
FQPA
standard
of
reasonable
certainty
of
no
harm.

Table
8.
Aggregate
Cancer
Risk
of
Pyraclostrobin
to
the
U.
S.
Population
Population
NOAEL
(
mg/
kg/
day)
Food
Exposure
(
mg/
kg/
day)
Water
Exposure
(
mg/
kg/
day)
Total
Exposure
(
mg/
kg/
day)
Total
MOE
U.
S.
Population
32.80
0.003545
0.000025
0.00357
9188
2.
Non­
dietary
exposure.
Pyraclostrobin
is
registered
for
use
on
residential
and
recreational
turf.
The
applications
to
turf
will
be
made
only
by
professional
pest
control
operators.
Therefore,
residential
handler
exposure
was
not
evaluated.
The
exposure
assessment
cited
in
this
notice
of
filing
was
transcribed
from
the
most
recent
Federal
Register
Notice
on
pyraclostrobin
(
U.
S.
EPA
final
rule
published
in
the
Federal
Register
October
29,
2004
[
Vol
69,
No.
209,
p
63083
 
63100).
The
EPA
evaluated
the
following
post­
application
exposure
scenarios
1)
adults
and
toddler
post­
application
dermal
exposure
2)
toddlers'
incidental
ingestion
of
pesticide
residues
on
lawns
form
hand­
to­
mouth
transfer,
3)
toddlers'
object­
to­
mouth
transfer
from
mouthing
pesticide­
treated
turfgrass,
and
4)
toddlers'
incidental
ingestion
of
soil
from
pesticide­
treated
residential
areas.
The
post­
application
exposure
assessment
was
based
on
generic
assumptions
specified
in
the
Recommended
Revisions
to
the
Residential
Standard
Operating
Procedures
and
recommended
approaches
by
an
EPA
science
advisory
council.
A
dermal
absorption
value
of
14%
was
used
in
the
assessment
of
pyraclostrobin.
The
exposure
and
risk
estimates
for
the
residential
exposure
scenarios
are
assessed
for
the
day
of
application
because
adults
and
toddlers
could
contact
treated
turf
immediately
after
application.
All
short­
/
intermediate
term
MOE
were
greater
than
100
which
indicates
that
exposure
from
all
residential
scenarios
result
in
exposures
below
a
level
of
concern.

D.
Cumulative
Effects
Section
408(
b)(
2)(
D)(
v)
requires
that,
when
considering
whether
to
establish,
modify,
or
revoke
a
tolerance,
the
Agency
consider
  
available
information''
concerning
the
cumulative
effects
of
a
particular
pesticide's
residues
and
  
other
substances
that
have
a
common
mechanism
of
toxicity.'
Pyraclostrobin
is
a
foliar
fungicide
which
belongs
to
the
new
class
of
strobilurin
chemistry.
It
is
a
synthetic
analog
of
strobilurin
A,
a
naturally
occurring
antifungal
metabolite
of
the
mushroom
Strobillurus
tenacellus
(
Anke
et.
al.,
1977).
The
active
ingredient
acts
in
the
fungal
cell
through
inhibition
of
electron
transport
in
the
mitochondrial
respiratory
chain
at
the
position
of
the
cytochrome­
bc1
complex.
The
protective
effect
is
due
to
the
resultant
death
of
the
fungal
cells
by
disorganization
of
the
fungal
membrane
system.
Pyraclostrobin
also
acts
curatively
to
prevent
the
increase
and
spread
of
fungal
infections
by
inhibiting
mycelial
growth
and
sporulation
on
the
leaf
surface.
BAS
500F
inhibits
spore
germination,
germ
tube
growth
and
penetration
into
the
host
tissues
The
EPA
is
currently
developing
methodology
to
perform
cumulative
risk
assessments.
At
this
time,
there
is
no
available
data
to
determine
whether
BAS
500
F
has
a
common
mechanism
of
toxicity
with
other
substances
or
how
to
include
this
pesticide
in
a
cumulative
risk
assessment.
Unlike
other
pesticides
for
which
EPA
has
followed
a
cumulative
risk
approach
based
on
a
common
mechanism
of
toxicity,
pyraclostrobin
does
not
appear
to
produce
a
toxic
metabolite
common
to
other
substances.

E.
Safety
Determination
1.
U.
S.
population.
Based
on
this
risk
assessment,
BASF
concludes
that
there
is
a
reasonable
certainty
that
no
harm
will
result
to
the
general
population
from
the
aggregate
exposure
to
pyraclostrobin
residues.
2.
Infants
and
children.
Based
on
this
risk
assessment,
BASF
concludes
that
there
is
a
reasonable
certainty
that
no
harm
will
result
to
infants
or
children
from
the
aggregate
exposure
to
pyraclostrobin
residues.

F.
International
Tolerances
No
Codex
or
Mexican
maximum
residue
levels
(
MRLs)
have
been
proposed
or
are
established
for
residues
of
pyraclostrobin.
Therefore,
no
tolerance
discrepancies
exist
between
countries
for
this
chemical.
Since
the
application
for
registration
of
pyraclostrobin
was
reviewed
jointly
with
the
Pest
Management
Regulatory
Agency
(
PMRA)
of
Canada,
several
Canadian
MRLs
for
pyraclostrobin
are
proposed
and
are
expected
to
be
published
soon.
However,
the
joint
review
is
expected
to
have
eliminated
the
potential
for
discrepancies
between
U.
S.
tolerances
and
Canadian
MRLs.