Document ID: EPA-HQ-OPP-2006-0333-0004
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-08-28T04:00Z

Page
1
of
24
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
MEMORANDUM
DATE:
26­
JUL­
2006
SUBJECT:
Kresoxim­
Methyl
on
Cucurbit
Vegetables
(
PP#
3E6594).
Health
Effects
Division
(
HED)
Human­
Health
Risk
Assessment.
DP#:
313836.
PC
Code
129111.
Decision#:
354442.
40
CFR:
180.554.

FROM:
Sarah
J.
Levy,
M.
S.,
Chemist
George
F.
Kramer,
Ph.
D.,
Senior
Chemist
P.
V.
Shah,
Ph.
D.,
Toxicologist,
Branch
Senior
Scientist
Mark
I.
Dow,
Ph.
D.,
Biologist
Registration
Action
Branch
1
(
RAB1)/
HED
(
7509P)

Susan
Stanton,
Environmental
Scientist
Reregistration
Branch
3
(
RRB3)/
HED
(
7509P)

THROUGH:
Felecia
Fort,
RAB1
Acting
Branch
Chief
RAB1/
HED
(
7509C)

TO:
Barbara
Madden/
Dan
Rosenblatt,
PM
Team
05
Registration
Division
(
RD;
7505P)

The
HED
of
the
Office
of
Pesticide
Programs
(
OPP)
is
charged
with
estimating
the
risk
to
human
health
from
exposure
to
pesticides.
The
RD
of
OPP
has
requested
that
HED
evaluate
hazard
and
exposure
data
and
conduct
dietary,
occupational/
residential,
and
aggregate
exposure
assessments,
as
needed,
to
estimate
the
risk
to
human
health
that
will
result
from
the
registered
and
proposed
uses
of
the
fungicide
kresoxim­
methyl
[
methyl
(
 E)­
 ­(
methoxyimino)­
2­[(
2­
methylphenoxy)
methyl]
benzeneacetate].

A
summary
of
the
findings
and
an
assessment
of
human­
health
risk
resulting
from
the
registered
and
proposed
uses
of
kresoxim­
methyl
are
provided
in
this
document.
The
risk
assessment
was
provided
by
Sarah
Levy
(
RAB1),
the
residue
chemistry
data
review
by
George
Kramer
(
RAB1),
the
occupational/
residential
exposure
assessment
by
Mark
Dow
(
RAB1),
the
dietary
exposure
assessment
by
Susan
Stanton
(
RRB3)
and
Sarah
Levy
(
RAB1),
the
hazard
characterization
by
P.
V.
Shah
(
RAB1),
and
the
drinking
water
assessment
by
Roxolana
Kashuba
of
the
Environmental
Fate
and
Effects
Division
(
EFED).
OFFICE
OF
PREVENTION,
PESTICIDES,
AND
TOXIC
SUBSTANCES
Page
2
of
24
NOTE:
The
last
kresoxim­
methyl
risk
assessment
HED
completed
was
for
the
use
on
pome
fruits,
grapes,
and
pecans
(
Memo,
T.
Bloem,
12­
APR­
1999;
D255097).
This
document
contains
only
those
aspects
of
the
risk
assessment
which
are
affected
by
the
addition
of
these
new
uses
of
kresoxim­
methyl
on
cucurbit
vegetables.

1.0
EXECUTIVE
SUMMARY
Kresoxim­
methyl
belongs
to
the
Quinone
Outside
Inhibitor
(
QoI)
class
of
fungicides.
It
inhibits
mitochondrial
respiration
by
blocking
electron
transfer
at
the
bc1
complex
in
fungi.
The
protective
effect
is
due
to
the
inhibition
of
both
spore
germination
and
host
infection.
The
curative
and
eradicative
effects
are
the
result
of
kresoxim­
methyl's
inhibition
of
mycelial
growth
and
sporulation.
This
is
the
second
food­
use
application
for
kresoxim­
methyl.
The
first
food­
use
registration
for
this
active
ingredient
(
ai)
on
pome
fruits,
grapes,
and
pecans
was
conditionally
approved
through
PP#
7F04880
(
Memo,
T.
Bloem,
12­
APR­
1999;
D255097).

The
Interregional
Research
Project
No.
4
(
IR­
4)
has
proposed
to
amend
the
Sovran
®

Fungicide
water­
dispersible
granule
(
WDG)
fungicide
label
for
use
on
cucurbit
vegetables.
In
conjunction
with
this
amendment,
the
petitioner
requests
the
establishment
of
a
permanent
tolerance
for
the
combined
residues
of
kresoxim­
methyl
[
methyl
(
 E)­
 ­
(
methoxyimino)­
2­[(
2­
methylphenoxy)
methyl]
benzeneacetate]
and
its
metabolites
BF
490­
2
[
2­[
o­(
o­
hydroxymethylphenoxymethyl)
phenyl]­
2­(
methoxyimino)
acetic
acid]
and
BF
490­
9
[
2­[
o­(
p­
hydroxymethylphenoxymethyl)
phenyl]­
2­(
methoxyimino)
acetic
acid]
as
follows:

Crop
Group
9,
Cucurbit
Vegetables
Group
 .   
0.5
ppm
There
are
no
registered
or
proposed
uses
of
kresoxim­
methyl
that
would
result
in
residential
exposures.

Hazard
Assessment
Kresoxim­
methyl
is
toxicity
category
III
or
IV
for
acute
oral,
dermal
and
inhalation
toxicity.
It
is
a
non­
irritant
and
is
not
a
skin
sensitizer.
For
subchronic
toxicity,
the
primary
effects
of
concern
in
the
rat
were
increased
levels
of
serum
gamma
glutamyl
transferase
(
SGGT)
and
decreased
body
weights
and
body
weight
gains.
In
the
chronic
studies,
SGGT
levels
were
also
elevated,
accompanied
by
liver
weight
changes
and
liver
histopathological
changes.
Liver
and
biliary
carcinomas
were
observed
in
male
and
female
rats
in
more
than
one
study.
Kresoxim­
methyl
was
not
associated
with
tumors
in
mice.
The
developmental
toxicity
studies
in
the
rat
and
rabbit
produced
no
toxicity
in
mothers
and
offspring
at
the
limit­
dose
level.
The
reproductive
toxicity
study
indicated
systemic
and
postnatal
developmental
toxicity
in
the
form
of
reduced
body
weight
and
body
weight
gain
in
F0
and
F1
parental
animals,
and
delayed
growth
and
maturation.
Since
parental
and
developmental
effects
were
observed
at
the
same
dose
levels,
there
is
no
evidence
of
increased
susceptibility
in
offspring.
No
treatment­
related
effects
were
observed
on
the
reproductive
performances
of
either
generation
at
any
dose
level.
Page
3
of
24
There
is
no
concern
for
mutagenic
activity
based
on
the
submitted
guideline
studies.
At
a
meeting
held
17­
MAR­
1999,
kresoxim­
methyl
was
classified
as
likely
to
be
carcinogenic
to
humans
according
to
the
EPA
Proposed
Guidelines
for
Carcinogen
Risk
Assessment
by
the
HED
Cancer
Assessment
Review
Committee
(
CARC;
19­
AUG­
1999;
HED
Doc.
No.
013685).
The
HED
CARC
requested
more
detailed
data
(
mechanistic
hepatic
turmorigenesis
in
the
rat)
in
order
to
complete
a
weight­
of­
the­
evidence
evaluation.
In
the
interim,
the
Committee
has
authorized
the
use
of
the
unit
risk,
Q1
*,
(
mg/
kg/
day)­
1
for
kresoxim­
methyl
based
on
female
rat
combined
(
adenomas
and/
or
carcinomas)
liver
tumor
rates
at
2.9
x
10­
3
(
mg/
kg/
day)­
1
in
human
equivalents
(
Memo,
L.
Brunsman,
20­
MAY­
1999;
HED
Doc.
No.
013383).
(
Q1
*
is
a
quantitative
estimate
of
cancer
risk
or
cancer
potency
factor.)

Dose­
Response
Assessment
The
HED
Hazard
Identification
Assessment
Review
Committee
(
HIARC)
met
on
02­
FEB­
1999
to
select
endpoints
for
risk
assessment
and
to
evaluate
the
potential
for
increased
susceptibility
of
infants
and
children
from
exposure
to
kresoxim­
methyl
(
Memo,
13­
APR­
1999;
TXR#:
0013316).
The
RAB1
risk
assessment
team
re­
evaluated
the
potential
for
increased
susceptibility
of
infants
and
children
according
to
the
2002
OPP
10X
guidance
document.
The
HIARC
and
the
risk
assessment
team
recommended
that
the
Food
Quality
Protection
Act
(
FQPA)
safety
factor
(
SF)
be
reduced
to
1X
in
assessing
the
potential
risk
posed
by
kresoxim­
methyl
because
the
toxicological
database
is
complete;
there
is
no
evidence
for
increased
susceptibility
due
to
pre­/
post­
natal
toxicity,
and
there
are
no
residual
uncertainties
in
the
exposure
database.

An
acute
reference
dose
(
RfD)
was
not
established.
No
appropriate
toxicological
endpoint
attributable
to
a
single
exposure
was
identified
in
the
available
toxicity
studies.
Specifically,
no
adverse
effects
were
seen
at
2000
mg/
kg/
day
in
the
acute
neurotoxicity
study
in
rats.
No
maternal
or
developmental
toxicity
was
observed
at
the
limit
dose
(
1000
mg/
kg/
day)
in
the
rat
or
rabbit
developmental
toxicity
studies.

The
chronic
RfD
of
0.36
mg/
kg/
day
was
established,
based
on
the
no­
observed­
adverse­
effectlevel
(
NOAEL)
of
800
ppm
(
36
and
48
mg/
kg/
day
in
males
and
females,
respectively),
in
the
2­
year
chronic
toxicity
in
rats
and
using
an
uncertainty
factor
of
100
(
10x
for
inter­
species
extrapolation,
10x
for
intra­
species
variability).
The
lowest­
observed­
adverse­
effect­
level
(
LOAEL)
in
this
study,
8000
ppm
(
370
and
503
mg/
kg/
day
in
males
and
females,
respectively),
was
based
on
minor
decreases
in
body
weight
gain
and
increases
in
gross
and
microscopic
liver
(
and
biliary)
lesions
in
males;
and
lowered
body
weights
and
body
weight
gains
and
increased
incidence
of
liver
masses
and
increased
SGGT
levels
in
females.

The
FQPA
SF
was
reduced
to
1x
for
chronic
dietary
exposure.
Therefore,
the
chronic
population
adjusted
dose
(
cPAD)
and
the
chronic
RfD
are
equivalent.

Short­
and
intermediate­
term
dermal
risk
assessments
are
not
required
since
no
dermal
or
systemic
toxicity
was
seen
at
the
limit
dose
of
1000
mg/
kg/
day
in
the
21­
day
dermal
study.
Inhalation
(
any
time
frame)
risk
assessments
are
not
required
based
on
low
inhalation
toxicity,
and
a
particle
size
which
is
not
in
the
respirable
range.
Page
4
of
24
However,
long­
term
dermal
and
inhalation
cancer
risk
assessment
is
required
since
the
Q1
*

approach
for
kresoxim­
methyl
has
been
recommended
by
the
HED
CARC
(
based
on
female
rat
combined
(
adenomas
and/
or
carcinomas)
liver
tumor
rates
at
2.9
x
10­
3
(
mg/
kg/
day)­
1
in
human
equivalents
(
Memo,
L.
Brunsman,
20­
MAY­
1999;
HED
Doc.
No.
013383)).

Residential
Exposure
Estimates
Currently,
there
are
no
registered
or
proposed
uses
of
kresoxim­
methyl
that
would
result
in
residential
exposures.

Occupational
Exposure
and
Risk
Assessment
Regarding
occupational
pesticide
handler
exposure,
based
on
the
proposed
use
pattern
HED
believes
that
the
most
highly­
exposed
occupational
pesticide
handlers
(
i.
e.,
mixers,
loaders,
applicators)
will
be:
1)
mixer/
loader
using
open
pour
of
granules
and
2)
applicator
using
opencab
ground­
boom
equipment.

No
chemical­
specific
data
were
available
with
which
to
assess
potential
exposure
to
pesticide
handlers.
The
estimates
of
exposure
to
pesticide
handlers
are
based
on
surrogate
study
data
available
in
the
Pesticide
Handler's
Exposure
Database
(
PHED)
(
v.
1.1,
1998).
For
pesticide
handlers,
it
is
HED
standard
practice
to
present
estimates
of
dermal
exposure
for
"
baseline;"
i.
e.,
for
workers
wearing
a
single
layer
of
work
clothing
consisting
of
a
long­
sleeved
shirt,
long
pants,
shoes
plus
socks
and
no
protective
gloves
as
well
as
for
baseline
plus
the
use
of
protective
gloves
or
other
personal­
protective
equipment
(
PPE)
as
might
be
necessary.
The
Sovran
®

Fungicide
label
instructs
applicators
and
other
handlers
must
wear:
long­
sleeved
shirt,
long
pants,
waterproof
gloves
and
shoes
plus
socks.

Occupational
pesticide
handler
risk
is
based
on
the
findings
of
HED's
HIARC.
The
HIARC
determined
that
there
were
no
applicable
dermal
or
inhalation
toxicological
endpoints
on
which
to
base
risk
assessments.
There
was
no
dermal
or
systemic
toxicity
noted
in
the
21­
day
dermal
toxicity
study
in
the
rat.
Kresoxim­
methyl
is
classified
as
acute
toxicity
category
IV
for
inhalation
and
the
HIARC
determined
that
particle
size
was
not
in
the
respirable
range.
Therefore,
neither
dermal
or
inhalation
acute
risks
were
assessed.

However,
the
HED
CARC
determined
that
kresoxim­
methyl
is
likely
to
be
carcinogenic
to
humans
and
recommended
the
linear
low­
dose
approach
to
risk
assessment;
therefore,
cancer
risks
to
occupational
pesticide
handlers
and
to
agricultural
workers
were
estimated.
Agricultural
workers
experience
post­
application
exposures
to
pesticides
as
a
result
of
typical
agricultural
practices.
Cancer
risks
ranged
from
1.0
x
10­
7
to
7.3
x
10­
6
and
therefore
do
not
exceed
HED's
levels
of
concern
for
pesticide
handlers
or
for
agricultural
workers
(
i.
e.,
less
than
10­
4).
Page
5
of
24
Dietary
Risk
Estimates
(
Food
+
Water)
A
partially­
refined,
Tier
3
chronic/
cancer
dietary
risk
assessment
was
conducted
using
the
Dietary
Exposure
Evaluation
Model
software
with
the
Food
Commodity
Intake
Database
(
DEEMFCID
 
,
Version
2.03),
which
uses
food
consumption
data
from
the
U.
S.
Department
of
Agriculture's
(
USDA's)
Continuing
Surveys
of
Food
Intakes
by
Individuals
(
CSFII)
from
1994­
1996
and
1998.
The
analysis
incorporated
average
field­
trial
residues
for
all
food
commodities,
available
processing
data
for
grapes
and
apples
and
screening­
level
percent
crop
treated
(%
CT)
data
for
most
of
the
registered
commodities.

Drinking
water
exposure
was
assessed
directly
in
the
DEEM­
FCID
 
analysis
using
estimated
drinking
water
concentrations
(
EDWCs)
of
kresoxim­
methyl
and
its
BF
490­
1
metabolite
in
surface
water
that
were
generated
by
the
screening
level
Pesticide
Root
Zone
Model/
Exposure
Analysis
Modeling
System
(
PRZM/
EXAMS)
model.

The
resulting
chronic
dietary
exposure
estimates
for
food
and
water
combined
are
well
below
HED's
level
of
concern
(
i.
e.,
<
100%
of
the
cPAD)
for
the
overall
U.
S.
population
and
all
population
subgroups.
Using
the
DEEM­
FCID
 
software,
chronic
dietary
exposure
is
estimated
at
0.000326
mg/
kg/
day
for
the
U.
S.
population
(<
1.0%
of
the
cPAD)
and
0.000953
mg/
kg/
day
(<
1.0%
of
the
cPAD)
for
infants
less
than
1
year
old,
the
population
subgroup
with
the
highest
estimated
chronic
dietary
exposure
to
kresoxim­
methyl.

HED
is
generally
concerned
when
estimated
cancer
risk
from
dietary
exposure
exceeds
approximately
one
in
one
million
(
i.
e.,
10­
6).
For
kresoxim­
methyl,
estimated
exposure
from
food
and
drinking
water
results
in
a
lifetime
cancer
risk
of
5.91
x
10­
7.
HED
considers
cancer
risk
estimates
between
1
x
10­
6
and
3
x
10­
6
to
fall
within
the
acceptable
range
of
cancer
risk;
therefore,
the
cancer
risk
estimate
for
kresoxim­
methyl
is
below
HED's
level
of
concern.
Although
the
cancer
risk
is
at
the
upper
end
of
the
acceptable
range,
actual
cancer
risk
is
likely
significantly
lower
due
to
conservative
assumptions/
inputs
into
the
models.

Aggregate­
Risk
Estimates
Aggregate
exposure
risk
assessments
were
assessed
by
incorporating
the
drinking
water
estimates
directly
into
the
dietary
exposure
assessment
for
the
following
scenarios:
chronic
and
cancer
aggregate
exposure
(
food
+
drinking
water).
Short­,
intermediate­
and
long­
term
aggregate­
risk
assessments
were
not
performed
because
there
are
no
registered
or
proposed
uses
of
kresoximmethyl
which
result
in
residential
exposures.
An
acute
aggregate­
risk
assessment
was
not
performed
because
no
appropriate
endpoint
was
available
to
determine
the
aRfD
for
the
general
population
or
any
population
subgroup.
Therefore,
the
chronic
and
cancer
exposure
estimates
provided
in
the
previous
section
represent
aggregate
exposure.
Page
6
of
24
Recommendations
for
Tolerances/
Registration
Provided
revised
Sections
B
and
F
are
submitted,
HED
concludes
there
are
no
residue
chemistry
or
toxicology
data
requirements
that
would
preclude
establishing
conditional
registrations
and
permanent
tolerances
for
residues
of
kresoxim­
methyl
and
its
metabolites
BF
490­
2
and
BF
490­
9
in/
on
the
following
raw
agricultural
commodities
(
RACs):

Vegetable,
cucurbit,
group
9....................................................................
0.40
ppm
Registration
should
be
made
conditional
pending
resolutions
of
deficiencies
regarding
the
confined
rotational
crop
study
and
the
submission
of
reference
analytical
standards
for
kresoximmethyl
metabolites.

2.0
PHYSICAL/
CHEMICAL
PROPERTIES
CHARACTERIZATION
2.1
Identification
of
Active
Ingredient
Table
2.1.1.
Kresoxim­
Methyl
Nomenclature.

Compound
O
CH
3
N
O
CH
3
O
O
C
H
3
Common
name
Kresoxim­
methyl
Company
experimental
name
BAS
490
F
IUPAC
name
methyl
(
E)­
2­
methoxyimino­
2­[
2­(
o­
tolyloxymethyl)
phenyl]
acetate
CAS
name
methyl
(
 E)­
 ­(
methoxyimino)­
2­[(
2­
methylphenoxy)
methyl]
benzeneacetate
CAS
registry
number
143390­
89­
0
End­
use
product
(
EP)
Sovran
®
Fungicide
(
EPA
Reg.
No.
7969­
154)
Page
7
of
24
2.2
Physical
and
Chemical
Properties
Table
2.2.1.
Physicochemical
Properties
of
the
Technical
Grade
Kresoxim­
Methyl.
1
Parameter
Value
Reference
Melting
range
PAI:
97.2­
101.7
°
C
TGAI:
98­
100
°
C
PMRA
Document
PRDD2003­
05
pH
5.8
USEPA;
Pesticide
Fact
Sheet
for
Kresoxim­
Methyl
(
143390­
89­
0)

Density
PAI:
1.258
g/
cm3
at
20
°
C
PMRA
Document
PRDD2003­
05
Water
solubility
PAI:
2.00
±
0.08
mg/
L
(
20
°
C)
PMRA
Document
PRDD2003­
05
Solvent
solubility
(
g/
100
mL
@
20
°
C)
n­
heptane
0.172
toluene
11.1
dichloromethane
93.9
methanol
1.46
acetone
2.17
ethyl
acetate
12.3
acetonitrile
16.6
i­
propanol
0.480
PMRA
Document
PRDD2003­
05
Vapor
pressure
2.3
x
10­
6
Pa
at
20
°
C
PMRA
Document
PRDD2003­
05
Dissociation
constant,
pKa
No
pKa
value
at
pH
2­
12
PMRA
Document
PRDD2003­
05
Octanol/
water
partition
coefficient,
Log(
KOW)
3.4
±
0.02
PMRA
Document
PRDD2003­
05
UV/
visible
absorption
spectrum
at
26
°
C
 max
at
204
nm,
no
absorption
at
 >
350
nm
PMRA
Document
PRDD2003­
05
1
PAI
=
Pure
Active
Ingredient;
TGAI
=
Technical
Grade
Active
Ingredient;
PMRA
=
Canadian
Pest
Management
Regulatory
Agency.

3.0
HAZARD
CHARACTERIZATION
The
existing
toxicological
database
for
kresoxim­
methyl
is
adequate
to
support
the
establishment
of
permanent
tolerances
for
residues
of
kresoxim­
methyl
in/
on
the
RACs
resulting
from
the
proposed
uses
on
cucurbit
vegetables.
There
are
no
toxicology
data
gaps
in
terms
of
guideline
studies.

3.1
Hazard
Profile
Kresoxim­
methyl
is
classified
in
toxicity
category
III
or
IV
for
acute
oral,
dermal
and
inhalation
toxicities.
It
is
a
non­
irritant
and
is
not
a
skin
sensitizer.
For
subchronic
toxicity,
the
primary
effects
of
concern
in
the
rat
were
increased
levels
of
SGGT
at
the
LOAEL
(
577
mg/
kg/
day);
the
NOAEL
was
146
mg/
kg/
day).
Decreased
body
weights
and
body­
weight
gains
were
observed
at
1267
mg/
kg/
day
in
the
rat
13­
week
neurotoxicity
study.
The
NOAEL
was
314
mg/
kg/
day.
Significant
toxicity
was
not
demonstrated
in
the
mouse
in
a
subchronic
toxicity
study
at
dose
levels
up
to
1937
and
2583
mg/
kg/
day
in
males
and
females,
respectively.

In
the
rat
chronic
studies,
SGGT
levels
were
elevated
in
both
sexes
accompanied
by
liver
weight
changes
and
liver
histopathological
changes.
Both
males
and
females
showed
changes
in
body
weights
and
body­
weight
gains.
The
rat
LOAEL
and
NOAEL
for
these
effects
was
370
and
36
mg/
kg/
day,
respectively.
In
the
dog,
decreases
in
body
weight
and
body­
weight
gain
and
food
Page
8
of
24
efficiency
were
observed
at
714
mg/
kg/
day,
with
a
NOAEL
of
138
mg/
kg/
day.
In
the
mouse,
decreased
body­
weight
gain
was
seen
in
females
at
400
mg/
kg/
day,
and
in
males
at
1305
mg/
kg/
day.
Liver
amyloidosis
was
also
observed
in
males
at
1305
mg/
kg/
day.
The
NOAEL
was
304/
81
mg/
kg/
day
(
M/
F).
Liver
and
biliary
carcinomas
were
observed
in
male
and
female
rats
in
more
than
one
study.

The
developmental
toxicity
studies
in
the
rat
and
rabbit
produced
no
toxicity
in
mothers
and
offspring
at
the
limit
dose
level
(
1000
mg/
kg/
day).

The
reproductive
toxicity
study
indicated
systemic
and
postnatal
developmental
toxicity
at
4000
ppm
(
437.2
mg/
kg/
day)
in
the
form
of
reduced
body
weight
and
body
weight
gain
in
F0
and
F1
parental
animals,
and
delayed
growth
and
maturation
in
F1
and
F2
pups.
The
NOAELs
for
parents
and
offspring
were
95
mg/
kg/
day
in
males
and
105
mg/
kg/
day
in
females.
Since
parental
and
developmental
effects
were
observed
at
the
same
dose
levels,
there
is
no
evidence
of
increased
susceptibility
in
offspring.
No
treatment­
related
effects
were
observed
on
the
reproductive
performances
of
either
generation
at
any
dose
level.

There
is
no
concern
for
mutagenic
activity
in
several
studies
including:
Salmonella
typhimurium,
E.
coli,
in
vitro
mammalian­
cell
gene­
mutation
assays,
mammalian­
cell
chromosome­
aberration
assays,
in
vivo
mouse
bone
marrow
micronucleus
assays,
and
unscheduled
DNA
synthesis
assays.

A
rat
metabolism
study
indicated
that
about
63%
of
the
given
radioactivity
was
excreted
48
hours
after
a
single
50
mg/
kg
oral
dose
in
both
sexes.
At
500
mg/
kg
(
orally),
however,
rats
excreted
only
about
8­
13%
of
the
given
dose
in
the
urine
and
14­
15%
in
the
bile
(
total
of
about
23­
27%
of
dose)
after
48
hours.
This
was
due
to
absorption
saturation;
where
the
absorption
mechanism
is
overwhelmed
and
the
absorption
rate
curve
flattens
out.
Consistent
with
absorption
saturation,
relatively
more
radioactivity
was
observed
in
the
feces
of
this
group.
There
were
some
sex­,
dose­,
route­,
and
label­
dependent
differences
in
the
metabolite
profiles.
M9
or
M1
(
also
called
BF
490­
9
or
BF
490­
1)
were
the
most
abundant
metabolites
in
the
urine
and
feces
of
all
groups.

Overall,
the
quality
of
the
toxicology
database
is
good,
and
the
confidence
in
the
hazard
and
dose
responses
is
high.
There
are
no
toxicology
data
gaps
in
terms
of
guideline
studies.
However,
special
studies
were
submitted
in
summary
form
on
possible
mechanism
of
hepatic
turmorigenesis
observed
in
the
rat.
The
Agency
has
requested
more
complete
data
submission
on
these
studies,
as
an
aid
to
its
cancer
assessment
process.

3.2
Dose­
Response
Assessment
The
doses
and
toxicological
endpoints
selected
for
various
exposure
scenarios
are
summarized
in
Table
3.2.1.
Page
9
of
24
Table
3.2.1.
Summary
of
Toxicological
Dose
and
Endpoints
for
Kresoxim­
methyl
for
Use
in
Human
Risk
Assessment1.

Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Hazard
and
Exposure
Based
FQPA
Safety
Factor
Study
and
Toxicological
Effects
Acute
Dietary
Not
applicable.
An
endpoint
attributable
to
a
single
exposure
was
not
identified
for
the
U.
S.
population
or
any
population
subgroup.

Chronic
Dietary
all
populations
NOAEL=
36
mg/
kg/
day
UF
=
100
cRfD
=
0.36
mg/
kg/
day
FQPA
SF
=
1X
cPAD
=
cRfD
FQPA
SF
=
0.36
mg/
kg/
day
Combined
Oral
Chronic
Toxicity/
Carcinogenicity
Study
 
Rat.
LOAEL
=
375/
497
mg/
kg/
day
in
males/
females,
based
on
decreased
body
weights
and
body
weight
gains
and
increased
gross
and
microscopic
liver
and
biliary
lesions,
and
(
in
females)
increased
incidences
of
liver
masses.

Cancer
(
oral,
dermal,
inhalation)
Kresoxim­
methyl
has
been
classified
as
"
likely
to
be
carcinogenic
to
humans"
by
the
HED
CARC
(
Meeting,
17­
Mar­
1999).
The
Q1*
for
kresoxim­
methyl
is
0.0029
(
mg/
kg/
day)­
1
(
3/
4
scaling
factor;
Memo,
L.
Brunsman,
20­
MAY­
1999;
HED
Doc.
No.
013383).

1
UF
=
uncertainty
factor,
FQPA
SF
=
FQPA
safety
factor,
NOAEL
=
no­
observed­
adverse­
effect­
level,
LOAEL
=
lowest­
observed­
adverse­
effect­
level,
PAD
=
population­
adjusted
dose
(
a
=
acute,
c
=
chronic)
RfD
=
reference
dose,
MOE
=
margin
of
exposure,
LOC
=
level
of
concern
4.0
EXPOSURE
ASSESSMENT
AND
CHARACTERIZATION
4.1
Summary
of
Registered/
Proposed
Uses
There
is
currently
one
kresoxim­
methyl
end­
use
product
(
EP)
registered
to
BASF
Corporation
for
use
on
pome
fruits,
grapes,
and
pecans:
Sovran
®
Fungicide,
a
50%
WDG
(
EPA
Reg.
No.
7969­
154).
There
are
no
registered
or
proposed
uses
of
kresoxim­
methyl
that
would
result
in
residential
exposures.
IR­
4
is
supporting
the
use
of
Sovran
®
Fungicide
on
cucurbit
vegetables.
The
target
organisms
are
powdery
mildew
and
gummy
stem
blight.
Optimal
disease
control
is
achieved
when
kresoxim­
methyl
is
used
as
a
preventative
treatment.
An
example
label
was
provided
and
the
proposed
use
directions
are
summarized
below
in
Table
4.1.1.
Page
10
of
24
Table
4.1.1.
Summary
of
Proposed
Directions
for
Use
of
Kresoxim­
methyl.
1
Application
Timing,
Type
and
Equipment
Formulation
[
EPA
Reg.
No.]
Single
rate
(
lb
ai/
A)
Max.
Number
Applications
per
Season
Max.
Seasonal
Application
Rate
(
lb
ai/
A)
PHI
(
days)
Use
Directions
and
Limitations
Cucurbit
Vegetables:
EPA
Crop
Group
9:
Cantaloupe;
Citron
melon;
Muskmelon;
Watermelon;
Chayote;
Chinese
waxgourd;
Cucumber;
Gherkin;
Gourd,
edible;
Momordica
spp.;
Pumpkin;
Squash,
summer;
Squash,
winter;
zucchini
Foliar
applications
Sovran
®

Fungicide
[
7969­
154]
0.1­
0.15
4
0.6
0
Applications
may
be
made
using
ground
or
aerial
equipment.

Application
through
any
type
of
irrigation
system
is
prohibited.

RTI
=
7­
10
days
REI
=
12
hours
1
lb
ai/
A
=
pounds
of
active
ingredient
per
acre;
PHI
=
Preharvest
interval;
RTI
=
Retreatment
interval;
REI
=
Restricted­
entry
interval.

Conclusions.
The
submitted
product
label
for
Sovran
®
Fungicide
(
EPA
Reg.
No.
7969­
154)
is
adequate
to
allow
evaluation
of
the
residue
data
relative
to
the
proposed
use
on
cucurbit
vegetables.
However,
based
on
the
results
of
the
limited
field
rotational
crop
study,
the
label
should
be
amended
to
specify
a
plant­
back
interval
(
PBI)
interval
of
14
days
for
all
crops
not
included
on
the
label.
Also,
a
statement
should
be
added
to
the
label
prohibiting
ultra­
low
volume
(<
2
gallons
of
spray
per
acre)
aerial
applications.
A
revised
Section
B
should
be
submitted.

4.2
Dietary
Exposure/
Risk
Pathway
The
residue
chemistry
data
submitted
in
support
of
the
proposed
petition
were
evaluated
by
HED
on
26­
MAY­
2006
(
Memo,
G.
Kramer;
D328725).
The
drinking
water
assessment
was
completed
by
EFED
(
electronic
correspondence,
R.
Kashuba,
17­
JUL2006;
DP#
330783).
The
dietary
exposure
assessment
was
completed
by
HED
(
Memo,
S.
Stanton,
31­
MAY­
2006;
S.
Stanton;
and
Memo,
S.
Levy,
26­
JUL­
2006;
D331118).

4.2.1
Residue
Profile
Background
Kresoxim­
methyl
belongs
to
the
QoI
class
of
fungicides.
It
inhibits
mitochondrial
respiration
by
blocking
electron
transfer
at
the
bc1
complex
in
fungi.
The
protective
effect
is
due
to
the
inhibition
of
both
spore
germination
and
host
infection.
The
curative
and
eradicative
effects
are
the
result
of
kresoxim­
methyl's
inhibition
of
mycelial
growth
and
sporulation.
This
is
the
second
food­
use
application
for
kresoxim­
methyl.
The
first
food­
use
registration
for
this
ai
on
pome
fruits,
grapes,
and
pecans
was
conditionally
approved
through
PP#
7F04880
(
Memo,
T.
Bloem,
12­
APR­
1999;
D255097).
Kresoxim­
methyl
tolerances
are
established
in
40
CFR
§
180.554
for
apple
pomace,
pome
fruit,
grape,
raisin,
pecans,
and
the
meat
byproducts
of
cattle,
goat,
and
Page
11
of
24
sheep.

The
IR­
4,
on
behalf
of
the
Agricultural
Experiment
Stations
of
AZ,
CA,
MI,
NC,
NY,
OK,
OR,
SC,
TN,
and
WI,
has
submitted
a
petition
for
an
amended
Section
3
registration
of
Sovran
®

Fungicide
(
EPA
Reg.
No.
7969­
154),
a
50%
kresoxim­
methyl
WDG
formulation,
for
use
on
cucurbit
vegetables.
The
petitioner
requests
the
establishment
of
a
permanent
tolerance
for
the
combined
residues
of
kresoxim­
methyl
and
its
metabolites
BF
490­
2
and
BF
490­
9
as
follows:

Crop
Group
9,
Cucurbit
Vegetables
Group
 .   
0.5
ppm
Note
that
the
requirements
for
livestock
metabolism
data,
analytical
enforcement
methodology
for
livestock
commodities,
storage
stability
data
for
livestock
commodities,
and
magnitude
of
the
residue
data
in
meat,
milk,
poultry
and
eggs
are
not
relevant
to
this
petition
because
there
are
no
feedstuffs
associated
with
the
proposed
use
on
cucurbit
vegetables.
Therefore,
a
discussion
of
these
requirements
are
not
presented
herein.

Nature
of
the
Residue
in
Plants
The
nature
of
the
residues
in
pome
fruits,
grapes
and
wheat
is
adequately
understood.
The
major
metabolic
pathway
for
kresoxim­
methyl
in
the
above
crops
is
the
isomerization
to
its
Z­
isomer
(
a
minor
component)
or
hydrolysis
of
the
ester
to
the
acid
(
BF
490­
1).
This
acid
metabolite
oxidizes
at
one
of
the
three
positions
on
the
cresyl
ring
to
yield
BF
490­
2,
BF
490­
9,
and/
or
BF
490­
15.
All
of
the
hydroxylated
metabolites
undergo
conjugation
with
glucose.
There
is
no
apparent
cleavage
of
the
two
rings.

The
Metabolism
Assessment
Review
Committee
(
MARC)
previously
determined
that
the
available
plant
metabolism
studies
are
sufficient
for
the
registration
of
kresoxim­
methyl
on
pome
fruits,
grapes,
pecans,
and
related
crops
(
fruit
or
fruiting
vegetables).
Based
on
these
data,
the
nature
of
the
residue
in
cucurbit
vegetables
is
considered
to
be
understood.
The
MARC
also
determined
that
the
tolerance
expression
for
kresoxim­
methyl
in/
on
pome
fruits,
grapes
and
pecans
will
include
kresoxim­
methyl,
BF
490­
1,
BF
490­
2
(
free
and
glucose
conjugated)
and
BF
490­
9
(
free
and
glucose
conjugated)
(
Memo,
T.
Bloem,
05­
APR­
1999;
D254643).
The
kresoxim­
methyl
tolerances
established
in
40
CFR
§
180.554
for
apple
pomace,
pome
fruit,
grape,
raisin,
and
pecans
are
expressed
as
such.
It
is
noted
that
the
metabolite
BF
490­
1
is
included
in
the
tolerance
expression
because
the
analytical
methods
do
not
distinguish
between
kresoximmethyl
and
BF
490­
1.
Chemical
names
and
structures
for
these
metabolites
are
presented
in
Attachment
1.

Residue
Analytical
Methods
There
is
an
adequate
analytical
methodology
for
tolerance
enforcement
of
regulated
residues
in/
on
plant
commodities.
BASF
Methods
350/
3­
US
and
D9611A
are
high­
performance
liquid
chromatography
(
HPLC)/
column­
switching
methods
with
ultraviolet
(
UV)
detection
(
270
nm)
which
have
been
determined
to
meet
Agency
guidelines
for
the
enforcement
of
kresoxim­
methyl
tolerances
on
plant
commodities.
BASF
Method
350/
3­
US
converts
glucose
conjugates
of
BF
490­
B
and
BF
490­
C
to
their
unconjugated
forms
BF
490­
2
and
BF
490­
9,
respectively,
following
enzyme
hydrolysis.
The
parent,
kresoxim­
methyl,
is
converted
to
the
acid
metabolite
BF
490­
1
Page
12
of
24
following
enzymatic
cleavage
and
base
hydrolysis.
The
metabolite
BF
490­
1
is
measured
as
kresoxim­
methyl
equivalents.

The
methods
have
been
forwarded
to
the
U.
S.
Food
and
Drug
Administration
(
FDA)
for
publication
as
Roman
numeral
methods
in
the
Pesticide
Analytical
Manual
(
PAM)
Volume
II.
BASF
Method
350/
3­
US
will
be
designated
as
Method
I
and
has
been
determined
to
be
applicable
for
pome
fruits,
apple
pomace,
grapes,
and
raisins.
This
method
will
also
be
suitable
for
cucurbit
vegetables.
BASF
Method
D9611A
will
be
designated
as
Method
II
and
is
applicable
for
pecans.
The
limit
of
quantitation
(
LOQ)
is
0.05
ppm
for
each
analyte
(
BF
490­
1,
BF
490­
2,
and
BF
490­
9).
The
limit
of
detection
(
LOD)
is
described
as
about
0.025
ppm
for
each
analyte.

Samples
collected
from
the
submitted
field
trials,
storage
stability,
and
field
rotational
crop
studies
were
analyzed
for
residues
of
kresoxim­
methyl
and
its
metabolites
BF
490­
2
and
BF
490­
9
using
BASF
Method
350/
3­
US
or
a
slightly
modified
version
of
the
method.
Concurrent
method
recoveries
were
well
within
the
acceptable
range
of
70­
120%.

Analytical
standards
for
kresoxim­
methyl
are
currently
available
in
the
National
Pesticide
Standards
Repository.
However,
standards
for
the
regulated
metabolites
(
BF
490­
1,
BF
490­
2,
and
BF
490­
9)
are
not
available
and
should
be
submitted
to
the
Repository.

Multiresidue
Method
(
MRM)
The
data
requirements
for
MRMs
are
fulfilled.
It
was
reported
in
PP#
7F04880
(
Memo,
T.
Bloem
12­
APR­
1999;
D255097)
that
acceptable
recoveries
and
standard
deviations
were
achieved
with
protocols
D,
E,
and
F
for
kresoxim­
methyl.
Recoveries
for
BF
490­
2
and
BF
490­
9
were
low
or
variable.
BF
490­
9
was
recovered
well
through
protocols
B
and
D
in
a
non­
fatty
matrix
(
grapes).
BF
490­
1
was
recovered
adequately
through
protocols
E
and
F.
No
single
protocol
recovered
all
of
the
compounds
efficiently.
Additionally,
none
of
the
protocols
incorporate
enzymatic
release
of
the
conjugated
residues.
The
MRMs
are
thus
not
suitable
for
enforcement
of
the
proposed
tolerances.

Magnitude
of
Residues
in
Plants
IR­
4
has
submitted
crop
field
trials
on
cantaloupe,
cucumber,
and
summer
squash,
which
are
the
representative
crops
of
cucurbit
vegetables
(
Crop
group
9).
The
results
from
these
studies
are
discussed
below
and
summarized
in
Table
4.2.1.1.

Table
4.2.1.1.
Summary
of
Residue
Data
from
Crop
Field
Trials
with
Kresoxim­
Methyl.

Residue
Levels
(
ppm)
1
Commodity
Total
Applic.
Rate
(
lb
ai/
A)
PHI
(
days)
Analyte
N
Min.
Max.
HAFT2
Median
Mean
Std.
Dev.

Kresoximmethyl
12
<
0.05
0.220
0.210
0.088
0.101
0.057
BF
490­
2
12
<
0.05
<
0.05
<
0.05
0.025
0.025
0.0
BF
490­
9
12
<
0.05
<
0.05
<
0.05
0.025
0.025
0.0
Cantaloupe
1.044­
1.0552
0
Combined
12
<
0.15
<
0.320
<
0.310
0.138
0.151
0.057
Page
13
of
24
Table
4.2.1.1.
Summary
of
Residue
Data
from
Crop
Field
Trials
with
Kresoxim­
Methyl.

Residue
Levels
(
ppm)
1
Commodity
Total
Applic.
Rate
(
lb
ai/
A)
PHI
(
days)
Analyte
N
Min.
Max.
HAFT2
Median
Mean
Std.
Dev.

Kresoximmethyl
16
<
0.05
0.120
0.106
0.025
0.037
0.030
BF
490­
2
16
<
0.05
<
0.05
<
0.05
0.025
0.025
0.0
BF
490­
9
16
<
0.05
<
0.05
<
0.05
0.025
0.025
0.0
Cucumber
1.0462­
1.0695
0
Combined
16
<
0.15
<
0.220
<
0.206
0.075
0.087
0.030
Kresoximmethyl
10
<
0.05
0.240
0.219
0.025
0.066
0.081
BF
490­
2
10
<
0.05
<
0.05
<
0.05
0.025
0.025
0.0
BF
490­
9
10
<
0.05
<
0.05
<
0.05
0.025
0.025
0.0
Squash,
summer
1.049­
1.0742
0
Combined
10
<
0.15
<
0.340
<
0.319
0.075
0.116
0.081
1
The
LOQ
was
0.05
ppm
for
kresoxim­
methyl,
BF
490­
2,
and
BF
490­
9.
The
LOD
was
0.025
ppm
for
each
analyte.
The
minimum,
maximum,
and
HAFT
values
are
based
on
the
LOQ.
For
calculating
the
median,
mean,
and
standard
deviation,
half
the
LOQ
was
used
for
residues
reported
below
the
LOQ.
2
HAFT
=
Highest­
Average
Field
Trial.

Adequate
field
trial
data
are
available
for
cantaloupes,
cucumbers,
and
summer
squash,
which
are
the
representative
crops
of
cucurbit
vegetables
(
Crop
group
9).
The
maximum
combined
residues
of
kresoxim­
methyl
and
its
metabolites
BF
490­
2
and
BF
490­
9
in/
on
cucurbit
vegetables
harvested
0
days
following
the
last
of
six
broadcast
foliar
applications
of
the
50%
WDG
formulation
for
a
total
seasonal
rate
of
~
1.0
lb
ai/
A
(~
1.1x)
were
<
0.320
ppm
in/
on
cantaloupe,
<
0.220
ppm
in/
on
cucumber,
and
<
0.340
ppm
in/
on
summer
squash.
The
parent
accounted
for
the
majority
of
the
combined
residues;
maximum
individual
residues
of
kresoxim­
methyl
in/
on
treated
samples
were
0.220
ppm
for
cantaloupe,
0.120
ppm
for
cucumbers,
and
0.240
ppm
for
squash.
Individual
residues
of
metabolites
BF
490­
2
and
BF
490­
9
were
each
below
the
method
LOQ
(<
0.05
ppm)
in/
on
all
treated
samples
collected
at
a
0­
day
PHI.

The
proposed
tolerance
expression,
listed
in
the
petition's
Section
F,
is
expressed
in
terms
of
the
combined
residues
of
the
fungicide
kresoxim­
methyl;
i.
e.,
methyl
(
E)­
2­
methoxyimino­
2­[
2­(
otolyloxmethyl
phenyl]
acetate
and
its
metabolites
2­[
o­(
o­
hydroxymethylphenoxymethyl)
phenyl]­
2­
(
methoxyimino)
acetic
acid
and
2­[
o­(
p­
hydroxymethylphenoxymethyl)
phenyl]­
2
(
methoxyimino)
acetic
acid.

The
HED
MARC
has
determined
that
the
tolerance
expression
for
kresoxim­
methyl
on
pome
fruits,
grapes,
pecans,
and
related
crops
(
fruit
or
fruiting
vegetables)
will
include
kresoxim­
methyl,
BF
490­
1,
BF
490­
2
(
free
and
glucose
conjugated)
and
BF
490­
9
(
free
and
glucose
conjugated).
The
petitioner
should
thus
submit
a
revised
Section
F
to
reflect
all
the
residues
of
concern
[
kresoxim­
methyl,
BF
490­
1,
BF
490­
2
(
free
and
glucose
conjugated)
and
BF
490­
9
(
free
and
glucose
conjugated)]
in
the
tolerance
expression
as
specified
in
40
CFR
§
180.554(
a)(
1):
"
combined
residues
of
the
fungicide
kresoxim­
methyl
(
methyl
(
E)­
2­[
2­(
2­
methylphenoxy)­
methyl]
phenyl­
2­(
methoxyimido)
acetate)
and
its
metabolites
as
follows:
(
E)­
2­[
2­(
2­
methylphenoxy)
methyl]­
phenyl­
2­(
methoxyimido)
acetic
acid;
(
E)­
2­[
2­(
2­
hydroxymethylphenoxy)
methyl]­
phenyl­
2­(
methoxyimido)
acetic
acid
(
free
and
glucose
Page
14
of
24
conjugated);
and
(
E)­
2­[
2­(
4­
hydroxy­
2­
methylphenoxy)­
methyl]
phenyl­
2­(
methoxyimido)
acetic
acid
(
free
and
glucose
conjugated)."

The
residue
field
trial
data
for
cantaloupes,
cucumbers,
and
summer
squash,
which
reflect
the
proposed
use
pattern
on
cucurbit
vegetables,
were
entered
into
a
tolerance
spreadsheet
as
specified
by
the
Guidance
for
Setting
Pesticide
Tolerances
Based
on
Field
Trial
Data
SOP;
see
Appendix
II.
The
recommended
tolerance
level
for
kresoxim­
methyl
on
"
Vegetable,
cucurbit,
group
9"
is
0.40
ppm.
The
petitioner
should
submit
a
revised
Section
F
to
specify
the
HEDassessed
tolerance
of
0.40
ppm
and
to
revise
commodity
definition
from
"
Crop
Group
9,
Cucurbit
Vegetables
Group"
to
"
Vegetable,
cucurbit,
group
9."
A
tolerance
summary
assessment
for
this
petition
is
listed
in
Table
4.2.1.2.

Codex,
Canada,
and
Mexico
have
established
maximum
residue
limits
(
MRLs)
for
kresoximmethyl
on
various
crop
commodities.
The
Codex
and
Mexico
residue
definitions
for
kresoximmethyl
in
plant
commodities
are
in
terms
of
the
parent,
and
a
Codex
MRL
is
established
for
cucumber
at
0.05
ppm.
The
U.
S.
and
Codex
tolerances/
MRLs
are
not
compatible
with
regard
to
tolerance
expression
and
the
levels
can
not
be
harmonized
as
the
recommended
tolerance
(
0.40
ppm)
is
significantly
higher
than
the
Codex
MRL
(
0.05
ppm).

Table
4.2.1.2.
Tolerance
Summary
for
Kresoxim­
Methyl.

Commodity
Proposed
Tolerance
(
ppm)
Recommended
Tolerance
(
ppm)
Comments;
Correct
Commodity
Definition
Crop
Group
9,
Cucurbit
Vegetables
Group
0.5
0.40
Vegetable,
cucurbit,
group
9
Confined
and
Field
Accumulation
in
Rotational
Crops
Confined:
The
nature
of
the
residues
in
rotational
crops
is
adequate
pending
submission
of
supporting
sample
storage
stability
information/
data.
In
the
submitted
confined
rotational
crop
study,
total
radioactive
residues
accumulated
at
 
0.01
ppm
in
all
rotated
crops
(
radish,
Swiss
chard,
and
sorghum)
planted
14/
28,
91,
or
210/
245
days
following
four
applications
of
[
14C]
kresoxim­
methyl
for
a
total
rate
of
1.2
lb
ai/
A
(
1.3x).
The
parent,
kresoxim­
methyl,
was
not
detected
in/
on
any
rotational
crop
commodity
at
any
PBI.
The
major
residue
components
identified
in
rotational
crop
commodities
were
the
glucosides
of
490
M2
and
490
M9.
These
conjugated
metabolites,
490
M2
and
490
M9,
are
converted
to
their
unconjugated
metabolites
BF
490­
2
and
BF
490­
9
following
enzyme
hydrolysis.

Field:
An
acceptable
limited
field
rotational
crop
study
with
kresoxim­
methyl
is
available.
Representative
rotational
crops
of
cabbage
(
leafy
vegetable),
radish
(
root
vegetable),
and
wheat
(
cereal
grain)
were
planted
at
intervals
of
~
14,
30,
and
45
days
after
the
primary
crop
(
cucumbers)
was
treated
at
~
1.2x
and
harvested
at
maturity.
Only
residues
of
the
glycoside
metabolites
(
BF
490­
2
and
BF
490­
9)
were
measured
in
this
limited
study
since
these
glycoside
metabolites
were
the
predominant
residues
identified
in
the
confined
rotational
crop
study.
The
results
indicate
that
at
a
PBI
of
14
days,
residues
of
BF
490­
2
and
BF
490­
9
were
each
below
the
Page
15
of
24
LOQ
(<
0.05
ppm)
in/
on
cabbage
(
with
and
without
wrapper
leaves),
radish
roots
and
tops,
and
wheat
forage,
hay,
straw,
and
grain.
Because
residues
were
below
the
LOQ
in
all
samples
of
rotated
crop
commodities
from
the
14­
day
PBI,
samples
from
later
PBIs
were
not
analyzed.
Based
on
these
data,
HED
concludes
that
tolerances
for
rotational
crop
commodities
are
not
required
for
the
purpose
of
this
petition
provided
the
label
for
Sovran
®
Fungicide
(
EPA
Reg.
No.
7969­
154)
is
amended
to
specify
a
PBI
of
14
days
for
all
crops
not
included
on
the
label.

4.2.2
Dietary
Exposure
Analyses
A
kresoxim­
methyl
chronic
dietary
exposure
assessment
was
conducted
using
DEEM­
FCID
 
Version
2.03,
which
incorporates
consumption
data
from
USDA's
CSFII,
1994­
1996
and
1998.
The
1994­
96,
98
data
are
based
on
the
reported
consumption
of
more
than
20,000
individuals
over
two
non­
consecutive
survey
days.
Foods
"
as
consumed"
(
e.
g.,
apple
pie)
are
linked
to
EPAdefined
food
commodities
(
e.
g.
apples,
peeled
fruit
­
cooked;
fresh
or
N/
S;
baked;
or
wheat
flour
­
cooked;
fresh
or
N/
S,
baked)
using
publicly
available
recipe
translation
files
developed
jointly
by
USDA/
ARS
and
EPA.
For
chronic
exposure
assessment,
consumption
data
are
averaged
for
the
entire
U.
S.
population
and
within
population
subgroups,
but
for
acute
exposure
assessment
are
retained
as
individual
consumption
events.
Based
on
analysis
of
the
1994­
96,
98
CSFII
consumption
data,
which
took
into
account
dietary
patterns
and
survey
respondents,
HED
concluded
that
it
is
most
appropriate
to
report
risk
for
the
following
population
subgroups:
the
general
U.
S.
population,
all
infants
(<
1
year
old),
children
1­
2,
children
3­
5,
children
6­
12,
youth
13­
19,
adults
20­
49,
females
13­
49,
and
adults
50+
years
old.

For
chronic
dietary
exposure
assessments,
an
estimate
of
the
residue
level
in
each
food
or
foodform
(
e.
g.,
orange
or
orange
juice)
on
the
food
commodity
residue
list
is
multiplied
by
the
average
daily
consumption
estimate
for
that
food/
food
form
to
produce
a
residue
intake
estimate.
The
resulting
residue
intake
estimate
for
each
food/
food
form
is
summed
with
the
residue
intake
estimates
for
all
other
food/
food
forms
on
the
commodity
residue
list
to
arrive
at
the
total
average
estimated
exposure.
Exposure
is
expressed
in
mg/
kg
body
weight/
day
and
as
a
percent
of
the
cPAD.
This
procedure
is
performed
for
each
population
subgroup.

4.2.2.1
Acute­
Dietary
Exposure
Analysis
An
acute­
dietary
exposure
assessment
was
not
performed
because
there
were
no
toxic
effects
attributable
to
a
single
dose.
Thus,
an
endpoint
of
concern
was
not
identified
to
quantitate
acutedietary
risk
to
the
general
population
or
to
any
population
subgroup.

4.2.2.2
Chronic
(
Non­
Cancer)­
Dietary
Exposure
Analysis
Kresoxim­
methyl
chronic
dietary
(
food
+
water)
exposure
estimates
using
the
DEEM­
FCID
 
software
are
below
HED's
level
of
concern
for
the
U.
S.
population
and
each
of
the
population
subgroups.
The
1­
in
10­
year
annual
mean
concentration
value
was
used
to
estimate
water
exposure.
Dietary
exposure
was
estimated
at
0.000326
mg/
kg/
day
for
the
U.
S.
population
(<
1.0%
of
the
cPAD)
and
0.000953
mg/
kg/
day
(<
1.0%
of
the
cPAD)
for
the
most
highly
exposed
population
subgroup
(
all
infants,
<
1
year
old).
The
estimated
exposures/
risks
from
food
and
Page
16
of
24
water
are
summarized
in
Table
4.2.2.2.1
for
all
populations.

Table
4.2.2.2.1.
Summary
of
Chronic
(
Non­
Cancer)­
Dietary
Exposure
and
Risk
for
Kresoxim­
methyl.
1
Population
Subgroup
cPAD
(
mg/
kg/
day)
Exposure
(
mg/
kg/
day
%
cPAD
General
U.
S.
Population
0.000326
<
1.0
All
Infants
(<
1
year
old)
0.000953
<
1.0
Children
1­
2
years
old
0.000566
<
1.0
Children
3­
5
years
old
0.000529
<
1.0
Children
6­
12
years
old
0.000342
<
1.0
Youth
13­
19
years
old
0.000235
<
1.0
Adults
20­
49
years
old
0.000286
<
1.0
Adults
50+
years
old
0.000321
<
1.0
Females
13­
49
years
old
0.36
0.000291
<
1.0
1The
population
subgroup
with
the
highest
estimated
chronic
dietary
(
food
+
drinking
water)
exposure
and
risk
is
indicated
by
bold
text.

4.2.2.3
Chronic
(
Cancer)­
Dietary
Exposure
Analysis
The
estimated
exposure
of
the
general
U.
S.
population
to
kresoxim­
methyl
is
0.000204
mg/
kg/
day.
Applying
the
Q1*
of
0.0029
(
mg/
kg/
day)­
1
to
the
exposure
value
results
in
a
lifetime
cancer
risk
estimate
of
5.91
x
10­
7.
HED
considers
cancer
risk
estimates
between
1
x
10­
6
and
3
x
10­
6
to
fall
within
the
acceptable
range
of
cancer
risk
(
i.
e.,
less
than
10­
6);
therefore,
the
cancer
risk
estimate
for
kresoxim­
methyl
is
below
HED's
level
of
concern.

4.3
Water
Exposure/
Risk
Pathway
The
residues
of
concern
in
drinking
water
are
kresoxim­
methyl
and
its
major
acid
degradate/
metabolite,
BF
490­
1.
Based
on
the
environmental
fate
properties
of
kresoxim­
methyl,
EFED
believes
that
the
parent
compound
is
relatively
short­
lived
and,
therefore,
unlikely
to
leach
to
ground
water
or
move
offsite
to
surface
water
in
significant
concentrations
(
electronic
correspondence,
R.
Kashuba,
17­
JUL2006;
DP#
330783).
However,
BF
490­
1
has
the
physical/
chemical
characteristics
of
pesticides
that
are
known
to
leach
to
ground
water
or
to
move
offsite
to
surface
water
and
may
pose
a
risk
of
ground
or
surface
water
contamination,
particularly
when
kresoxim­
methyl
is
applied
to
fields
with
one
or
more
of
the
following
characteristics:
alkaline
soils,
low
organic
matter,
high
sand
content,
shallow
groundwater
table
or
nearby
bodies
of
water.

There
are
no
drinking
water
monitoring
data
available
for
kresoxim­
methyl
or
its
metabolite.
Estimated
ground
water
and
surface
water
concentrations
were
generated
using
the
Screening
Concentration
in
Ground
Water
(
SCI­
GROW)
and
PRZM­
EXAMS
models,
respectively.
EDWCs
were
provided
for
both
kresoxim­
methyl
and
BF
490­
1.
The
PRZM­
EXAMS
surface
water
modeling
estimates
were
based
on
a
Florida
cucurbits
crop
scenario.
The
modeled
EDWCs
for
ground
and
surface
water
are
summarized
in
Table
4.3.1.
Page
17
of
24
Table
4.3.1.
Ground
and
Surface
Water
EDWCs
for
Kresoxim­
methyl
and
BF
490­
1.
Surface
Water
Ground
Water
Concentration
(
ppb)
1­
in
10­
Year
Annual
Mean
Concentration
(
ppb)
30­
Year
Mean
Concentration
(
ppb)
Kresoxim­
methyl
0.000385
0.11
0.07
BF
490­
1
6.27
12.1
6.36
Combined
Residues
of
Concern
6.27
12.21
6.43
4.4
Residential
Exposure/
Risk
Pathway
There
are
no
products
containing
kresoxim­
methyl
proposed
or
registered
that
would
result
in
residential
exposure.
Therefore,
a
residential
exposure
assessment
was
not
performed.

Spray
drift
is
always
a
potential
source
of
exposure
to
residents
nearby
to
spraying
operations.
This
is
particularly
the
case
with
aerial
application,
but,
to
a
lesser
extent,
could
also
be
a
potential
source
of
exposure
from
groundboom
application
methods.
The
Agency
has
been
working
with
the
Spray
Drift
Task
Force,
EPA
Regional
Offices
and
State
Lead
Agencies
for
pesticide
regulation
and
other
parties
to
develop
the
best
spray
drift
management
practices.
The
Agency
is
now
requiring
interim
mitigation
measures
for
aerial
applications
that
must
be
placed
on
product
labels/
labeling.
The
Agency
has
completed
its
evaluation
of
the
new
database
submitted
by
the
Spray
Drift
Task
Force,
a
membership
of
U.
S.
pesticide
registrants,
and
is
developing
a
policy
on
how
to
appropriately
apply
the
data
and
the
AgDRIFT
®
computer
model
to
its
risk
assessments
for
pesticides
applied
by
air,
orchard
airblast,
and
ground
hydraulic
methods.
After
the
policy
is
in
place,
the
Agency
may
impose
further
refinements
in
spray
drift
management
practices
to
reduce
off­
target
drift
and
risks
associated
with
aerial
as
well
as
other
application
types
where
appropriate.

5.0
AGGREGATE­
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATION
Aggregate
exposure
risk
assessments
were
assessed
by
incorporating
the
drinking
water
directly
into
the
dietary
exposure
assessment
for
the
following
scenarios:
chronic
and
cancer
aggregate
exposure
(
food
+
drinking
water).
Short­,
intermediate­
and
long­
term
aggregate­
risk
assessments
were
not
performed
because
there
are
no
registered
or
proposed
uses
of
kresoximmethyl
which
result
in
residential
exposures.
An
acute
aggregate­
risk
assessment
was
not
performed
because
no
appropriate
endpoint
was
available
to
determine
the
aRfD
for
the
general
population
or
any
population
subgroup.
Therefore,
the
chronic
and
cancer
dietary
exposure
estimates
provided
in
Sections
4.2.2.2
and
4.2.2.3,
respectively,
of
this
document
represent
chronic
and
cancer
aggregate
exposure.
Page
18
of
24
6.0
CUMULATIVE
RISK
Section
408(
b)(
2)(
D)(
v)
of
the
FFDCA
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."

EPA
does
not
have,
at
this
time,
available
data
to
determine
whether
kresoxim­
methyl
has
a
common
mechanism
of
toxicity
with
other
substances.
Unlike
other
pesticides
for
which
EPA
has
followed
a
cumulative
risk
approach
based
on
a
common
mechanism
of
toxicity,
EPA
has
not
made
a
common
mechanism
of
toxicity
finding
as
to
kresoxim­
methyl
and
any
other
substances
and
kresoxim­
methyl
does
not
appear
to
produce
a
toxic
metabolite
produced
by
other
substances.
For
the
purposes
of
this
tolerance
action,
therefore,
EPA
has
not
assumed
that
kresoxim­
methyl
has
a
common
mechanism
of
toxicity
with
other
substances.
For
information
regarding
EPA's
efforts
to
determine
which
chemicals
have
a
common
mechanism
of
toxicity
and
to
evaluate
the
cumulative
effects
of
such
chemicals,
see
the
policy
statements
released
by
EPA's
Office
of
Pesticide
Programs
concerning
common
mechanism
determinations
and
procedures
for
cumulating
effects
from
substances
found
to
have
a
common
mechanism
on
EPA's
website
at
http://
www.
epa.
gov/
pesticides/
cumulative/.

7.0
OCCUPATIONAL
EXPOSURE
In
support
of
the
proposed
petition,
the
occupational
exposure
was
assessed
by
HED
on
26­
APR­
2005
(
Memo,
M.
Dow;
D313913).

7.1
Occupational
Handler
Based
on
the
proposed
use
pattern,
HED
believes
that
the
most
highly­
exposed
occupational
pesticide
handlers
(
i.
e.,
mixers,
loaders,
applicators)
will
be:
1)
mixer/
loader
using
open
pour
of
granules
and
2)
applicator
using
open­
cab
ground­
boom
equipment.

HED
believes
most
handlers,
in
this
cropping
situation,
are
likely
to
be
private
(
i.
e.,
"
grower")
handlers
who
will
most
likely
be
exposed
to
short­
term
duration
exposures
(
1­
30
days).
However
the
HED
Science
Advisory
Council
for
Exposure
(
ExpoSAC)
maintains
it
is
possible
for
commercial
handlers
to
experience
intermediate­
term
duration
exposures
(
1­
6
months).
It
is
expected
that
some
private
(
i.
e.,
grower)
applicators
may
perform
all
tasks,
that
is
mix,
load
and
apply
the
material.
However,
HED
ExpoSAC
draft
Standard
Operating
Procedure
(
SOP)
(
29­
MAR­
2000)
directs
that
although
the
same
individual
may
perform
all
tasks,
in
some
cases
they
shall
be
assessed
separately.

The
available
exposure
data
for
combined
mixer/
loader/
applicator
scenarios
are
limited
in
comparison
to
the
data
available
for
monitoring
of
these
two
activities
separately.
These
exposure
scenarios
are
outlined
in
the
PHED
Surrogate
Exposure
Guide
(
AUG­
1998).
HED
has
adopted
a
methodology
to
present
the
exposure
and
risk
estimates
separately
for
the
job
functions
in
some
scenarios
and
to
present
them
as
combined
in
other
cases.
Most
exposure
scenarios
for
Page
19
of
24
hand­
held
equipment
(
such
as
hand
wands,
backpack
sprayers,
and
push­
type
granular
spreaders)
are
assessed
as
a
combined
job
function.
With
these
types
of
hand­
held
operations,
all
handling
activities
are
assumed
to
be
conducted
by
the
same
individual.
The
available
monitoring
data
support
this
and
HED
presents
them
in
this
way.
Conversely,
for
equipment
types
such
as
fixedwing
aircraft,
groundboom
tractors,
or
air­
blast
sprayers,
the
applicator
exposures
are
assessed
and
presented
separately
from
those
of
the
mixers
and
loaders.
By
separating
the
two
job
functions,
HED
determines
the
most
appropriate
levels
of
PPE
for
each
aspect
of
the
job
without
requiring
an
applicator
to
wear
unnecessary
PPE
that
might
be
required
for
a
mixer/
loader
(
i.
e.,
chemical­
resistant
gloves
may
only
be
necessary
during
the
pouring
of
a
liquid
formulation).

No
chemical­
specific
data
were
available
with
which
to
assess
potential
exposure
to
pesticide
handlers.
The
estimates
of
exposure
to
pesticide
handlers
are
based
on
surrogate
study
data
available
in
the
PHED
(
v.
1.1,
1998).
For
pesticide
handlers,
it
is
HED
standard
practice
to
present
estimates
of
dermal
exposure
for
"
baseline;"
i.
e.,
for
workers
wearing
a
single
layer
of
work
clothing
consisting
of
a
long­
sleeved
shirt,
long
pants,
shoes
plus
socks
and
no
protective
gloves
as
well
as
for
baseline
and
the
use
of
protective
gloves
or
other
PPE
as
might
be
necessary.
The
Sovran
®
Fungicide
label
instructs
applicators
and
other
handlers
must
wear:
longsleeved
shirt,
long
pants,
waterproof
gloves
and
shoes
plus
socks.

See
Table
7.1.1
for
a
summary
of
estimated
occupational
handler
exposures.
See
Table
7.3.1
for
a
summary
of
cancer
risks.
Page
20
of
24
Table
7.1.1.
Estimated
Exposures
to
Pesticide
Handlers
Applying
Kresoxim­
Methyl.

Unit
Exposure1
mg
ai/
lb
ai
handled
Applic.
Rate2
lb
ai
handled/
A
Units
Treated3
Avg.
Daily
Dose4
mg
ai/
kg
bw/
day
Mixer/
Loader
­
Granular
­
Open
Pour
DermNG
0.0084
LC
DermNG
0.00227
DermWG
0.0069
MC
DermWG
0.00186
INHAL.
0.0017
HC
0.15
200
A/
day
Inhalation
0.000729
Applicator
­
Groundboom
­
Open
Cab
DermNG
0.014
HC
DermNG
0.00378
DermWG
0.014
MC
DermWG
0.00378
INHAL.
0.00074
HC
0.15
200
A/
day
Inhalation
0.000317
1.
Unit
Exposure
=
mg
ai/
lb
ai
handled;
taken
from
PHED
Surrogate
Exposure
Guide
version
1.1;
AUG­
1998;
DermNG
=
Dermal
Single
Layer
of
Work
Clothing
No
Gloves;
DermWG
=
Dermal
Single
Layer
Work
Clothing
WITH
Gloves;
Inhal.
=
Inhalation.
HC
=
high
confidence
data;
MC
=
medium
confidence
data;
LC
=
low
confidence
data
2.
Application
Rate
from
proposed
amendments
to
EPA
Reg
No.
7969­
154
3.
Acres
Treated
are
derived
from
ExpoSAC
SOP.
No.
9.1
Rev.
25
Sept.
2001
4.
Average
Daily
Dose
(
ADD)
=
Unit
Exposure
*
Application
Rate
*
Units
Treated
*
Absorption
factor
(
63%
dermal;
100%
inhalation)
÷
70
kg
body
weight.

7.2
Occupational
Post­
Application
Exposure
There
is
a
potential
for
agricultural
workers
to
experience
post­
application
exposure
to
pesticides
during
the
course
of
typical
agricultural
activities.
HED,
in
conjunction
with
the
Agricultural
Reentry
Task
Force
(
ARTF),
has
identified
a
number
of
post­
application
agricultural
activities
that
may
occur.
HED
has
also
identified
transfer
coefficients
(
TC)
(
cm
²
/
hr)
relative
to
the
various
activities
which
express
the
amount
of
foliar
contact
over
time,
during
each
of
the
activities.

For
cucurbits,
the
post­
application
activity
with
the
highest
TC
is
for
hand­
harvesting
and
the
TC
is
2,500
cm
²
/
hr.

The
TC
used
in
this
assessment
is
from
an
interim
transfer
coefficient
SOP
developed
by
HED's
ExpoSAC
using
proprietary
data
from
the
ARTF
database
(
SOP
#
3.1).
It
is
the
intention
of
HED's
ExpoSAC
that
this
SOP
will
be
periodically
updated
to
incorporate
additional
information
about
agricultural
practices
in
crops
and
new
data
on
TC.
Much
of
this
information
will
originate
from
exposure
studies
currently
being
conducted
by
the
ARTF,
from
further
analysis
of
studies
already
submitted
to
the
Agency,
and
from
studies
in
the
published
scientific
literature.
Page
21
of
24
Compound­
specific
dislodgeable
foliar
residue
(
DFR)
data
were
not
available
for
cucurbits.
Therefore,
HED
assumes
20%
of
the
application
rate
is
available
as
DFR
on
day
zero
after
application.
This
is
adapted
from
the
ExpoSAC
SOP
No.
003
(
07­
MAY­
1998
­
Revised
07­
AUG­
2000).
HED
considers
this
practice
to
be
conservative,
that
is
to
say,
protective.

The
following
convention
may
be
used
to
estimate
post­
application
exposure:

Average
Daily
Dose
(
ADD)
(
mg
ai/
kg
bw/
day)
=
DFR
µ
g/
cm2
*
TC
cm2/
hr
*
hr/
day
*
0.001
mg/
µ
g
*
1/
70
kg
bw
and
Surrogate
DFR
=
application
rate
*
20%
available
as
dislodgeable
residue
*
(
1­
D)
t
*
4.54
x
108
µ
g
/
lb
*
2.47
x
10­
8
A/
cm2
when
compound
specific
DFR
data
are
not
available.

DFR
=
0.15
lb
ai/
A
*
0.20
*
4.54
x
108
µ
g/
lb
*
2.47
x
10­
8
A/
cm2
=
0.34
µ
g/
cm
²
and
0.34
µ
g/
cm
²
*
2,500
cm
²
/
hr
*
8
hr/
day
*
0.001
mg/
µ
g
*
63%
(
dermal
absorption)
*
1/
70kg
bw
=
0.061
mg
ai/
kg
bw/
day.

7.3
Cancer
Risk
Assessment
As
was
noted
earlier,
kresoxim­
methyl
is
classified
as
likely
to
be
carcinogenic
to
humans
with
a
potency
factor
(
Q1
*)
of
2.9
x
10­
3
mg
ai/
kg
bw/
day.
Cancer
risk
to
handlers
is
calculated
as
Q1
*

(
mg
ai/
kg
bw/
day)
*
Lifetime
Average
Daily
Dose
(
LADD)
(
mg
ai/
kg
bw/
day).
There
are
no
definitive
data
regarding
numbers
of
exposures
per
year
or
numbers
of
years
"
worked"
by
pesticide
handlers.
Therefore
the
HED
ExpoSAC
utilizes
the
assumptions
of
10
days
per
year
of
exposure
over
a
35­
year
"
working"
lifetime
and
a
70­
year
expected
lifespan
for
private
growers
who
might
apply/
handle
a
compound
or
perform
agricultural
functions.
HED
assumes
30
days
per
year
of
exposures
for
commercial
occupational
pesticide
handlers
and
agricultural
workers
who
might
"
follow"
crops
as
opposed
to
occasional
exposure
from
work
on
one
or
few
farms
by
"
private"
individuals
(
Pers.
Comm.
J.
Dawson,
HED/
OPP,
04­
APR­
2005).

LADD
=
Average
Daily
Dose
*
10
(
or
30)
working
days
exposed/
yr
*
35
year
working
life
span
365
days/
yr
70
year
expected
life
span
The
ADD
is
taken
from
Table
7.1.1
above
and
from
the
calculation
of
post­
application
exposure.
The
ADD
equals
dermal
exposure
+
inhalation
exposure.
Since
the
label
requires
the
use
of
protective
gloves
by
occupational
pesticide
handlers,
only
exposures
with
the
use
of
gloves
are
presented
below.
See
Table
7.3.1
for
a
summary
of
estimated
cancer
risks
from
the
proposed
use
of
kresoxim­
methyl.
Page
22
of
24
Table
7.3.1.
Summary
of
Estimated
Cancer
Risk
from
Proposed
Use.

ADD
mg
ai/
kg
bw/
day
LADD
mg
ai/
kg
bw/
day
Q1
*

mg
ai/
kg
bw/
day
Cancer
Risk
Estimated
Cancer
Risks
at
10
Days
Exposure/
Year
Mixer/
Loader
0.00259
3.55
x
10­
5
1.0
x
10­
7
Groundboom
Appl.
0.0041
5.62
x
10­
5
1.6
x
10­
7
Post­
Appl.
Hand
Harvest
0.061
8.36
x
10­
4
2.9
x
10­
3
2.4
x
10­
6
Estimated
Cancer
Risks
at
30
Days
Exposure/
Year
Mixer/
Loader
0.00259
1.06
x
10­
4
3.1
x
10­
7
Groundboom
Appl.
0.0041
1.68
x
10­
4
4.9
x
10­
7
Post­
Appl.
Hand
Harvest
0.061
2.51
x
10­
3
2.9
x
10­
3
7.3
x
10­
6
Since
all
estimated
cancer
risks
are
less
than
7.30
x
10­
6,
the
proposed
use
does
not
exceed
HED's
level
of
concern.

REI
Kresoxim­
methyl
is
classified
in
acute
toxicity
category
III
for
acute
dermal
toxicity
and
primary
eye
irritation.
It
is
classified
in
category
IV
for
acute
inhalation
toxicity
and
primary
skin
irritation.
It
is
not
a
skin
sensitizer.
The
interim
worker­
protection
standard
(
WPS)
REI
(
as
listed
on
the
proposed
label)
of
12
hours
is
adequate
to
protect
occupational
handlers
and
agricultural
workers
from
exposures
to
kresoxim­
methyl.

8.0
DEFICIENCIES/
DATA
NEEDS
8.1
Chemistry
 
Revised
Section
B.
The
label
for
Sovran
®
Fungicide
(
EPA
Reg.
No.
7969­
154)
should
be
amended
to
specify
a
PBI
interval
of
14
days
for
all
crops
not
included
on
the
label.
Also,
a
statement
should
be
added
to
the
label
prohibiting
ultra­
low
volume
(<
2
gallons
of
spray
per
acre)
aerial
applications.
 
Revised
Section
F.
The
Section
F
should
reflect
all
the
residues
of
concern
[
kresoximmethyl
BF
490­
1,
BF
490­
2
(
free
and
glucose
conjugated)
and
BF
490­
9
(
free
and
glucose
conjugated)]
in
the
tolerance
expression
as
specified
in
40
CFR
§
180.554(
a)(
1):
"
for
the
combined
residues
of
the
fungicide
kresoxim­
methyl
(
methyl
(
E)­
2­[
2­(
2­
methylphenoxy)­
methyl]
phenyl­
2­(
methoxyimido)
acetate)
and
its
metabolites
as
follows:
Page
23
of
24
(
E)­
2­[
2­(
2­
methylphenoxy)
methyl]­
phenyl­
2­(
methoxyimido)
acetic
acid;
(
E)­
2­[
2­(
2­
hydroxymethylphenoxy)
methyl]­
phenyl­
2­(
methoxyimido)
acetic
acid
(
free
and
glucose
conjugated);
and
(
E)­
2­[
2­(
4­
hydroxy­
2­
methylphenoxy)­
methyl]
phenyl­
2­
(
methoxyimido)
acetic
acid
(
free
and
glucose
conjugated)."
In
addition,
the
petitioner
should
revise
the
commodity
definition
and
tolerance
level
to
"
Vegetable,
cucurbit,
group
9
at
0.40
ppm."
 
Upgraded
confined
rotational
crop
study.
The
petitioner
should
provide
dates
of
analysis
for
all
sample
extracts
and
hydrolysates.
In
addition,
if
final
analyses
of
samples
and
extracts
were
not
completed
within
18
months
of
sample
collection
for
any
rotated
crop,
the
petitioner
should
provide
data
demonstrating
that
the
metabolite
profile
in
the
rotated
crop
was
stable
during
the
storage
interval
of
the
study.
 
Submission
of
analytical
standards
for
the
regulated
metabolites.
Standards
of
BF
490­
1,
BF
490­
2,
and
BF
490­
9
are
not
available,
and
should
be
submitted,
to
the
National
Pesticide
Standards
Repository,
located
at
Fort
Meade,
MD.

8.2
Toxicology
 
Special
studies
were
previously
submitted
in
summary
form
only
on
the
possible
mechanism
of
hepatic
turmorigenesis
observed
in
the
rat.
HED
previously
requested
a
more
complete
data
submission
on
these
studies
as
an
aid
to
its
cancer
assessment
process
(
for
example,
Gamer
et
al.,
1995,
BASF
Reg.
#
95/
10567
and
Polloth
et
al.,
1994,
BASF
Reg.
#
94
10867).

8.3
Occupational
Exposure
 
None.

cc:
S.
Levy
(
RAB1),
G.
Kramer
(
RAB1),
P.
V.
Shah
(
RAB1),
M.
Dow
(
RAB1),
S.
Stanton
(
RRB3)
RDI:
Branch
(
21­
JUN­
2006);
RAB1
Chemists
(
24­
MAY­
2006)
S.
Levy:
S­
10953:
PY1:(
703)
305­
0783:
7509P:
RAB1
Page
24
of
24
Attachment
1:
Chemical
Name
and
Structures
of
Regulated
Metabolites.

Common
Name/
Company
Code
Structure
BF
490­
1
(
acid)

(
E)­
2­[
2­(
2­
methylphenoxy)
methyl]­
phenyl­
2­
(
methoxyimido)
acetic
acid
O
N
O
CH
3
O
O
H
CH
3
BF
490­
2
(
hydroxymethyl
metabolite)

(
E)­
2­[
2­(
2­
hydroxymethylphenoxy)
methyl]­
phenyl­
2­
(
methoxyimido)
acetic
acid
O
N
O
CH
3
O
O
H
OH
BF
490­
9
(
para
hydroxy
metabolite)

(
E)­
2­[
2­(
4­
hydroxy­
2­
methylphenoxy)­
methyl]
phenyl­
2­(
methoxyimido)
acetic
acid
O
N
O
CH
3
O
O
H
CH
3
O
H
BF
490­
B
490
M2
Glucoside
O
N
O
CH
3
O
O
H
Glu­
O
BF
490­
C
490
M9
Glucoside
O
N
O
CH
3
O
O
H
Glu­
O
CH
3
Glycine
conjugate
of
a
dihydroxylated
metabolite
of
kresoxim­
methyl1
No
structure
provided
1
Proposed
identification
based
on
LC/
MS/
MS.