Bifenazate
(
000586)
Human­
Health
Risk
Assessment
D323893
Page
1
of
24
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
MEMORANDUM
Date:
26­
July­
2006
Subject:
Bifenazate
(
PC
Code
000586).
Application
of
Bifenazate
to
Tuberous
and
Corm
Vegetables,
Succulent
Peas
and
Stone
Fruit.
HED
Human­
Health
Risk
Assessment.
DP
Nos.:
323893
and
330737.
Registration:
5E6992
and
400­
503
Acramite
50
WS.
Decision
Nos.:
360901
and
362741.
40
CFR
180.572.

From:
Thomas
Bloem,
Chemist
Lisa
Austin,
Ph.
D.,
Toxicologist
Mark
Dow,
Ph.
D.,
Biologist
Registration
Action
Branch
1
(
RAB1)
Health
Effects
Division
(
HED)
(
7509P)

Through:
Felicia
Fort,
Branch
Chief
PV
Shah,
Ph.
D.,
Senior
Toxicologist
RAB1/
HED
(
7509P)

To:
Daniel
Rosenblatt/
Sidney
Jackson;
RM
05
Daniel
Kenny/
Rita
Kumar;
RM
01
Registration
Division
(
RD)
(
7505P)

RD
of
the
Office
of
Pesticide
Programs
(
OPP)
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
all
registered
and
proposed
uses
of
bifenazate.
A
summary
of
these
findings
is
provided
in
this
document.
The
risk
assessment,
residue
chemistry
review,
and
dietary
exposure
assessment
were
provided
by
Tom
Bloem
of
RAB1;
the
hazard
characterization
was
provided
by
Lisa
Austin
of
RAB1;
the
occupational/
residential
exposure
and
risk
assessment
was
provided
by
Mark
Dow
of
RAB1;
and
the
drinking
water
assessment
was
provided
by
Thuy
Nguyen,
of
the
Environmental
Fate
and
Effects
Division
(
EFED).

NOTE:
In
2002,
HED
completed
a
Section
3
risk
assessment
for
the
application
of
bifenazate
to
fruiting
vegetables,
cucurbit
vegetables,
tree
nuts
pistachio,
okra,
and
mint
(
D286170,
T.
Bloem
et
al.,
30­
May­
2003).
The
current
document
contains
only
those
aspects
of
the
risk
assessment
which
are
affected
by
the
addition
of
the
proposed
bifenazate
uses.
OFFICE
OF
PREVENTION,
PESTICIDES,
AND
TOXIC
SUBSTANCES
Bifenazate
(
000586)
Human­
Health
Risk
Assessment
D323893
Page
2
of
24
Table
of
Contents
1.0
EXECUTIVE
SUMMARY.........................................................................................................
3
3.0
HAZARD
CHARACTERIZATION............................................................................................
8
3.1
Endocrine
Disruption.............................................................................................................
9
3.2
Residues
of
Concern
for
Dietary
Risk
Assessment..................................................................
9
4.0
EXPOSURE
ASSESSMENT
AND
CHARACTERIZATION...................................................
10
4.1
Summary
of
Registered
Uses
...............................................................................................
10
4.2
Summary
of
Proposed
Uses
.................................................................................................
10
4.3
Dietary
Exposure/
Risk
Pathway...........................................................................................
11
4.5
Dietary
Exposure
Analysis
...................................................................................................
15
4.6
Residential
Exposure
and
Risk
Assessment
..........................................................................
16
4.7
Non­
occupational
Off­
Target
Exposure
...............................................................................
16
6.0
CUMULATIVE
RISK
..............................................................................................................
18
7.0
OCCUPATIONAL
EXPOSURE
AND
RISK
ASSESSMENT
..................................................
18
7.1
Handler
Exposure
and
Risk
Assessment
...............................................................................
18
7.2
Post­
Application
Exposure
and
Risk
Assessment
.................................................................
21
7.3
REIs....................................................................................................................................
23
8.0
DEFICIENCIES
.......................................................................................................................
23
8.1
Toxicology..........................................................................................................................
23
8.2
Residue
Chemistry...............................................................................................................
23
8.3
Occupational/
Residential......................................................................................................
23
Attachment
1:
chemical
structures
....................................................................................................
24
Bifenazate
(
000586)
Human­
Health
Risk
Assessment
D323893
Page
3
of
24
1.0
EXECUTIVE
SUMMARY
Bifenazate
(
1­
methylethyl
2­(
4­
methoxy[
1,1'­
biphenyl]­
3­
yl)
hydrazinecarboxylate;
see
attachment
1
for
structures)
is
a
selective
miticide
which
controls
the
motile
stage
of
mites
either
by
direct
contact
or
through
contact
with
foliar
residues.
The
petitioner
indicated
that
bifenazate
blocks
or
closes
the
gamma­
aminobutyric
acid
(
GABA)
activated
chloride
channels
of
susceptible
pests
resulting
in
over­
excitation
of
the
peripheral
nervous
system.
Bifenazate
is
currently
registered
for
application
to
pome
fruit,
fruiting
vegetable,
cucurbit
vegetable,
tree
nut,
nectarine,
peach,
plum,
grape,
strawberry,
cotton,
hops,
okra,
peppermint,
and
spearmint
and
for
with
tolerances
ranging
from
0.1
­
35
ppm
(
40
CFR
180.572(
a)(
1)).
Section
18
registrations
have
also
been
established
for
application
of
bifenazate
to
cherry,
tomato,
soybean,
potato,
and
timothy
with
tolerances
ranging
from
0.05­
150
ppm
(
40
CFR
180.572(
b)).
Tolerances,
as
a
result
of
secondary
residues,
are
established
in
milk,
ruminant
meat,
ruminant
fat,
and
ruminant
meat
byproducts
at
0.02­
0.10
ppm
(
40
CFR
180.572(
a)(
1)
and
(
a)(
2)).
Bifenazate
is
also
registered
for
application
by
homeowners
to
ornamentals.

The
Interregional
Research
Project
Number
4
(
IR­
4)
requested
a
Section
3
registration
for
the
application
of
bifenazate
to
succulent
pea
and
the
tuberous
and
corm
vegetables
(
subgroup
1c).
Crompton
Corporation
(
Bethany,
CT)
also
requested
a
label
ammendment
for
application
of
bifenqazate
to
stone
fruit.
The
following
tolerances
for
the
combined
residues
of
bifenazate
and
D3598
were
proposed:

pea,
garden.......................................................................................................................
0.2
ppm
pea,
edible
podded............................................................................................................
4.0
ppm
vegetable,
tuberous
and
corm,
subgroup
1c
....................................................................
0.01
ppm
fruit,
stone,
crop
12,
except
plum........................................................................................
2
ppm
Hazard
Assessment:
The
acute
toxicity
data
for
bifenazate
show
that
this
chemical
is
not
acutely
toxic
by
the
oral,
inhalation,
or
dermal
routes
of
exposure
(
Toxicity
Categories
IV).
It
is
minimally
irritating
to
the
eye
(
Toxicity
Category
IV)
and
slightly­
irritating
to
the
skin
(
Toxicity
Category
IV).
Bifenazate
is
a
dermal
sensitizer
by
the
Magnusson/
Kligman
method,
but
not
the
Buehler
method.

Subchronic
and
chronic
studies
in
rats
and
dogs
indicate
that
the
liver
and
hematopoietic
system
(
spleen
and/
or
bone
marrow
with
associated
hematological
findings)
are
the
primary
target
organs
in
these
species,
with
additional
toxicity
in
the
kidney
(
chronic
dog)
and
adrenal
gland
(
male
rats)
also
identified.
Similarly,
the
hematopoietic
system
(
spleen)
was
the
primary
target
organ
in
the
repeatdose
dermal
toxicity
study.
Also
associated
with
this
toxicity
in
several
studies
were
decreased
body
weight,
body­
weight
gain,
and
food
consumption.
No
evidence
of
carcinogenicity
was
seen
in
the
rat
and
mouse
studies
and
the
HED
Hazard
Identification
Assessment
Review
Committee
(
HIARC)
classified
bifenazate
as
"
not
likely"
to
be
a
human
carcinogen
by
any
relevant
route
of
exposure.
A
full
battery
of
mutagenicity
studies
were
negative
for
mutagenic
or
clastogenic
activity.
The
developmental
studies
in
rats
and
rabbits
did
not
demonstrate
increased
sensitivity
of
fetuses
to
bifenazate.
Similarly,
increased
qualitative
or
quantitative
susceptibility
to
offspring
were
not
observed
with
bifenazate
during
pre­
or
postnatal
development
in
the
reproduction
study.
There
was
no
evidence
of
neurotoxicity
(
clinical
signs
or
neuropathology)
in
any
of
the
toxicology
studies
conducted
with
bifenazate,
although
guideline
acute
and
subchronic
neurotoxicity
studies
were
not
conducted.
A
bifenazate
developmental
neurotoxicity
study
was
not
required
by
the
HIARC.
It
should
be
noted
that
bifenazate
contains
hydrazine
as
part
of
its
chemical
structure.
This
side
chain
is
structurally
similar
to
unsymmetrical
dimethyl
hydrazine
(
UDMH),
a
B2
animal
carcinogen
(
possible
human
carcinogen).
Bifenazate
(
000586)
Human­
Health
Risk
Assessment
D323893
Page
4
of
24
Carcinogenicity
studies
performed
with
bifenazate
on
rats
and
mice
did
not
result
in
any
carcinogenic
effects
at
a
maximum
dose
of
10
mg/
kg/
day
and
35
mg/
kg/
day,
respectively.
The
rat,
livestock,
and
plant
metabolism
studies
indicate
that
metabolism
of
bifenazate
proceeds
via
oxidation
of
the
hydrazine
moiety
of
bifenazate
to
form
D3598
(
diazene).
D3598
is
then
metabolized
to
D1989
(
methoxy
biphenyl)
and
to
bound
residues
by
reaction
with
natural
products.
The
petitioner
proposed
that
the
degradation
route
for
D3598
to
D1989
involved
the
formation
of
N2
and
CO2
and
not
biphenyl
hydrazine.
The
HED
Metabolism
Assessment
Review
Committee
(
MARC)
reviewed
the
petitioner's
proposed
degradation
route
and
agreed
that
formation
of
free
biphenyl
hydrazine
or
other
hydrazines
is
unlikely
due
to
oxidation
of
the
parent
to
the
conjugated
diazene.
The
MARC
did
suggest
that
if
a
future
metabolism
study
is
submitted,
the
petitioner
should
monitor
for
biphenyl
hydrazine.
Subsequently,
Crompton
Corporation
submitted
a
radish
metabolism
study
which
did
not
result
in
the
identification
of
biphenyl
hydrazine.
Based
on
the
radish
metabolism
study,
the
lack
of
carcinogenic
effects
in
the
bifenazate
carcinogenic
studies,
and
since
biphenyl
hydrazine
was
not
identified
in
the
excreta
in
the
rat
metabolism
study,
RAB1
concluded
that
issues
concerning
the
formation
of
hydrazine(
s)
in
plants
and
livestock
have
been
addressed.

Dose
Response
Assessment:
The
HIARC
met
on
four
occasions
to
examine
the
toxicology
database
for
bifenazate
and
to
determine
the
appropriate
toxicological
endpoints
for
dietary
and
occupational/
residential
exposure
assessment
(
meeting
dates
­
21­
Aug­
2001
(
TXR
No.
0014658),
24­
Apr­
2001
(
TXR
No.
0014576),
13­
Apr­
1999
(
TXR
No.
0013335),
and
4­
Feb­
1999
(
TXR
No.
0013277)).
The
HIARC
found
the
toxicological
database
to
be
complete
with
the
exception
of
a
28­
day
inhalation
study.
The
HED
Food
Quality
Protection
Act
Safety
Factor
Committee
(
FQPA
SFC)
met
on
27­
August­
2001
to
evaluate
the
bifenazate
toxicological
database
in
reference
to
the
potential
for
enhanced
sensitivity
to
infants
and
children
and
concluded
that
the
FQPA
SF
may
be
reduced
to
1x
(
TXR
No.
0014661);
therefore,
based
on
toxicological
considerations,
the
complete
residue
chemistry
and
environmental
fate
databases,
and
the
conservative
assumptions
used
when
generating
the
dietary
and
residential
exposure
estimates,
HED
concludes
that
the
FQPA
SF
may
be
reduced
to
1x.

Bifenazate
has
been
classified
as
"
not
likely"
to
be
a
human
carcinogen
by
any
relevant
route
of
exposure
and
an
acute
dietary
endpoint
was
not
identified
for
the
general
population
including
infants
and
children;
therefore,
acute
dietary
and
cancer
exposure
assessments
were
not
conducted.
Since
the
HIARC
did
not
assign
any
additional
uncertainty
factors
to
the
endpoints
selected
for
the
various
routes
of
exposure
assessment
and
since
the
FQPA
SF
has
been
reduced
to
1x,
the
total
uncertainty
factor
for
all
exposure
assessments
is
100x
(
10x
for
interspecies
extrapolation,
and
10x
for
intraspecies
variation).
Oral
studies
were
selected
for
all
durations
of
inhalation
exposure
assessment
and
the
HIARC
determined
that
a
100%
inhalation­
absorption
factor
is
appropriate
for
route­
to­
route
extrapolation.
Since
a
dermal
study
was
selected
for
all
durations
of
dermal
exposure
assessment,
a
dermal­
absorption
factor
is
not
necessary.
Oral,
dermal,
and
inhalation
exposures
can
be
aggregated
based
on
common
endpoints
(
changes
in
body
weights
and
body­
weight
gains,
and
hematological
effects).
Exposure
assessments
were
conducted
for
the
specific
scenarios
listed
below.

Table
1.
Summary
of
Toxicological
Endpoints
used
in
the
Current
Risk
Assessment1
chronic
dietary
NOAEL
=
1.0
mg/
kg/
day
chronic
RfD
and
cPAD
=
0.01
mg/
kg/
day
short­
term
oral
NOAEL
=
10
mg/
kg/
day
LOC
for
MOEs
 
100
short­
term
dermal
dermal
NOAEL
=
6.3
mg/
kg/
day
LOC
for
MOEs
 
100
(
occupational/
residential)
1
short­
term
inhalation
oral
NOAEL
=
10
mg/
kg/
day2
LOC
for
MOEs
 
100
(
occupational/
residential)
1
1
NOAEL
=
no­
observable
adverse­
effect
level;
RfD
=
reference
dose
=
NOAEL
÷
100;
PAD
=
population­
adjusted
dose
=
RfD
÷
FQPA
SF;
LOC
=
level
of
concern;
MOE
=
margins
of
exposure
=
NOAEL
÷
exposure
2
100%
inhalation
absorption
factor
Bifenazate
(
000586)
Human­
Health
Risk
Assessment
D323893
Page
5
of
24
Exposure
Assessment
Residential
Exposure:
HED
reviewed
and
approved
homeowner
application
of
FloramiteTM
SC
(
EPA
Reg.
No.
400­
508)
to
ornamentals
and
non­
bearing
fruit
trees.
Based
on
the
proposed
use
patterns,
only
short­
term
dermal
and
short­
term
inhalation
exposure
are
expected
for
homeowner
applicators
(
exposures
calculated
using
the
18­
Dec­
1999
HED
Draft
Residential
Standard
Operational
Procedures
(
SOPs)).
The
individual
and
aggregate
MOEs
did
not
exceed
HED's
level
of
concern
(
aggregate
MOE
=
4200).
Post­
application
exposure
is
anticipated
to
be
negligible
and
was
not
assessed.

Dietary
Food
Exposure:
Chronic
dietary
risk
assessments
were
conducted
using
the
Dietary
Exposure
Evaluation
Model
­
Food
Consumption
Intake
Database
(
DEEM­
FCID
 
,
ver.
2.03).
DEEM­
FCID
 
incorporates
the
food
consumption
data
from
the
USDA's
Continuing
Surveys
of
Food
Intakes
by
Individuals
(
CSFII;
1994­
1996
and
1998).
The
chronic
analyses
incorporated
tolerance­
level
residues
for
all
commodities
excluding
squash,
peach,
tomato,
and
soybean
(
average
field
trial
residues
were
assumed)
and
milk
(
anticipated
residue
was
assumed).
The
chronic
analyses
incorporated
average
percent
crop
treated
information
provided
by
the
Biological
Economic
Analysis
Division
(
BEAD;
J.
Carter,
13­
Jul­
2006).
DEEM
 
(
ver.
7.81)
default
processing
factors
were
assumed
for
all
commodities
excluding
apple
juice,
grape
juice,
wine/
sherry,
tomato
paste,
and
tomato
puree.
The
processing
factors
for
these
commodities
were
reduced
to
0.23,
0.17,
0.17,
5.0,
and
5.0,
respectively,
based
on
data
from
processing
studies.
The
analyses
also
included
the
chronic
surface
water
point
estimate
generated
using
the
Tier
1
model
FIRST
and
the
strawberry
application
scenario
(
2
x
0.50
lb
ai/
acre;
21­
day
retreatment
interval
(
RTI);
highest
registered/
proposed
rate).
The
chronic
exposure
estimates
are
 
94%
cPAD
and
are,
therefore,
less
than
HED's
level
of
concern
(
children
1­
2
years
old
were
the
most
highly
exposed
population).

Occupational
Exposure
Estimates:
Based
on
the
proposed
use
patterns,
commercial
handlers
and
grower/
applicators
are
anticipated
to
have
only
short­
term
dermal
and
short­
term
inhalation
exposures
(
intermediate­
and
long­
term
exposures
are
not
anticipated).
Workers
entering
fields
following
applications
are
anticipated
to
have
only
short­
term
dermal
exposures.
Chemical­
specific
data
were
not
available
to
assess
pesticide
handler
exposure.
Therefore,
surrogate
data
from
studies
in
the
August
1998
Pesticide
Handler
Exposure
Database
(
PHED;
Ver.
1.1)
Surrogate
Exposure
Guide
were
used
to
estimate
mixer/
loader
and
applicator
exposure.
The
mixer
loader
and
applicator
exposure
estimates
were
generated
assuming
baseline
work
clothing
(
long­
sleeved
shirt,
long
pants,
shoes
plus
socks)
and
baseline
plus
gloves.
Standard
HED
methodology
was
used
to
provide
an
estimate
of
postapplication
exposure.
Transfer
coefficients
were
from
an
interim
transfer
coefficient
policy
developed
by
HED's
Exposure
Science
Advisory
Council
(
ExpoSAC;
Policy
No.
3.1;
Revised
7­
Aug­
2000;
amended
by
ExpoSAC
meeting
notes
13­
Aug­
2001).
Provided
the
handlers
applicators
wear
gloves,
the
resulting
individual
and
aggregate
short­
term
MOEs
did
not
exceed
HED's
level
of
concern
(
calculated
MOEs
 
170).

Aggregate
Exposure
Assessment:
In
general,
aggregate
exposures
are
calculated
by
summing
dietary
(
food
and
water)
and
residential
exposures
(
residential
or
other
non­
occupational
exposures).
Based
on
the
anticipated
residential
exposure
scenarios
and
since
acute
and
cancer
risk
assessments
are
not
required,
only
short­
term
(
residential,
food,
and
water)
and
chronic
(
food
and
water)
aggregate
exposure
assessments
were
conducted.
Aggregate
short­
term
(
food,
water,
and
residential)
exposures
resulted
in
MOEs
 
1600
and
aggregate
chronic
(
food
and
water)
exposures
were
 
94%
the
cPAD;
therefore,
aggregate
exposure
to
bifenazate
as
a
result
of
all
registered/
proposed
uses,
is
less
than
HED's
level
of
concern.
Bifenazate
(
000586)
Human­
Health
Risk
Assessment
D323893
Page
6
of
24
Recommendation
for
Tolerances
and
Registration:
Separate
recommendations
are
written
for
the
tuberous
and
corm
vegetable
and
succulent
pea
petition
and
the
stone
fruit
label
amendment.

Tuberous
and
Corm
Vegetable
(
subgroup
1c)
and
Succulent
Pea
(
5E6992):
Provided
the
petitioner
submits
revised
Sections
B
and
F,
HED
concludes
that
the
toxicology,
residue
chemistry,
and
occupational/
residential
databases
are
sufficient
for
a
conditional
registration
and
establishment
of
the
following
permanent
tolerances
for
the
combined
residues
of
bifenazate
and
D3598
(
expressed
as
bifenazate):

pea,
garden,
succulent
.........................................................................................................
0.20
ppm
pea,
edible
podded,
succulent
................................................................................................
4.0
ppm
vegetable,
tuberous
and
corm,
subgroup
1c
.........................................................................
0.02
ppm
An
unconditional
registration
may
be
established
upon
submission
of
data
addressing
the
following
deficiency.

 
succulent­
shelled
pea
(
Regions
1
or
2
(
n=
1),
5
(
n=
3),
11(
n=
1),
and
12
(
n=
1))
and
edible
podded­
pea
(
n=
3;
Regions
at
the
discretion
of
the
petitioner)
field
trial
data
(
storage
stability
data
validating
the
relevant
intervals
should
also
be
submitted)

Stone
Fruit
label
Amendment
(
400­
503
Acramite
50
WS):
The
initial
petition
requested
registration
for
application
of
bifenazate
to
cotton,
grape,
hop,
pome
fruit,
strawberry,
and
stone
fruit;
since
the
petitioner
did
not
submit
cherry
or
apricot
residue
data,
HED
concluded
that
a
tolerance
in/
on
stone
fruit
was
not
appropriate
(
D277089,
T.
Bloem,
16­
Aug­
2001;
D288660,
T.
Bloem,
20­
Mar­
2003).
The
petitioner
has
subsequently
submitted
these
data.
Provided
a
Section
F
is
submitted
specifying
the
tolerance
listed
below,
HED
concludes
the
toxicology,
residue
chemistry,
and
occupational/
residential
databases
are
sufficient
for
a
conditional
registration
and
establishment
of
the
permanent
tolerances
listed
below
for
the
combined
residues
of
bifenazate
and
D3598
(
the
current
plum
tolerance
may
be
replaced
in
favor
of
that
recommended
here;
currently­
established
fat
tolerance
is
0.1
ppm).

fruit,
stone,
group
12
(
except
plum)
......................................................................................
2.5
ppm
plum....................................................................................................................................
0.20
ppm
cattle,
fat
.............................................................................................................................
0.10
ppm
goat,
fat
..............................................................................................................................
0.10
ppm
hog,
fat
...............................................................................................................................
0.10
ppm
horse,
fat
.............................................................................................................................
0.10
ppm
sheep,
fat.............................................................................................................................
0.10
ppm
An
unconditional
registration
may
be
established
upon
submission
of
data
addressing
the
following
deficiencies.

 
storage
stability
data
for
hops
(
175
days;
7­
day
interval
from
homogenization
to
analysis
should
also
be
validated)

 
grape
field
trial
data
(
Region
1
(
n=
1))

 
confirmation
concerning
the
identification
of
D9569
as
the
major
residue
in
milk
(
see
page
13);
conclusions
concerning
the
need
for
a
new
ruminant
feeding
study
will
be
made
upon
submission
of
data
confirming
the
identity
of
the
major
residue
in
milk
Bifenazate
(
000586)
Human­
Health
Risk
Assessment
D323893
Page
7
of
24
2.0
PHYSICAL/
CHEMICAL
PROPERTIES
Bifenazate
is
a
selective
miticide
which
controls
the
motile
stage
of
mites
either
by
direct
contact
or
through
contact
with
foliar
residues.
The
petitioner
indicated
that
bifenazate
blocks
or
closes
the
GABA
activated
chloride
channels
of
susceptible
pests
resulting
in
over­
excitation
of
the
peripheral
nervous
system.

Table
2.
Test
Compound
Nomenclature.

Compound
O
NH
N
H
O
CH
3
O
CH
3
CH
3
Common
name
Bifenazate
Company
experimental
name
D2341
IUPAC
name
isopropyl
2­(
4­
methoxy­
1,1'­
biphenyl­
2­
yl)
hydrazinecarboxylate
CAS
name
hydrazine
carboxylic
acid,
2­(
4­
methoxy­[
1,1'­
biphenyl]­
3­
yl),
1­
methylethyl
ester
CAS
registry
number
149877­
41­
8
End­
use
products
(
EPs)
AcramiteTM
50WS
(
50%
WP;
EPA
Reg.
No.
400­
503)

Table
3.
Physicochemical
Properties
of
the
Technical
Grade
of
Bifenazate.

Melting
range
124­
125
º
C
pH
6.78
Density
1.19
g/
cm3
Water
solubility
2.1
mg/
L
(
20
°
C)

Solvent
solubility
102
mg/
mL
ethyl
acetate
(
20
°
C)

Vapor
pressure
<
1
x
10­
8
atm
M3/
mole
(
25
°
C)

Dissociation
constant,
pKa
12.94
at
23
°
C
Octanol/
water
partition
coefficient,
Log(
KOW)
3.4
UV/
visible
absorption
spectrum
Max
264
nm
in
water
MRID
46064101
Bifenazate
(
000586)
Human­
Health
Risk
Assessment
D323893
Page
8
of
24
3.0
HAZARD
CHARACTERIZATION
A
detailed
hazard
characterization
for
bifenazate
is
presented
in
a
previous
HED
risk
assessment
(
D286170,
T.
Bloem
et
al.,
30­
May­
2003)
and
a
summary
of
the
bifenazate
toxicological
profile
is
provided
in
the
executive
summary.
The
HIARC
met
on
four
occasions
to
examine
the
toxicology
database
for
bifenazate
and
to
determine
the
appropriate
toxicological
endpoints
for
dietary
and
occupational/
residential
exposure
assessment
(
meeting
dates
­
21­
Aug­
2001
(
TXR
No.
0014658),
24­
Apr­
2001
(
TXR
No.
0014576),
13­
Apr­
1999
(
TXR
No.
0013335),
and
4­
Feb­
1999
(
TXR
No.
0013277)).
The
HIARC
found
the
toxicological
database
to
be
complete
with
the
exception
of
a
28­
day
inhalation
study.
The
FQPA
SFC
met
on
27­
August­
2001
to
evaluate
the
bifenazate
toxicological
database
in
reference
to
the
potential
for
enhanced
sensitivity
to
infants
and
children
and
concluded
that
the
FQPA
SF
may
be
reduced
to
1x
(
TXR
No.
0014661);
therefore,
based
on
toxicological
considerations
and
the
residue
assumptions
used
in
the
dietary
(
D330587,
T.
Bloem,
19­
July­
2006)
and
residential
(
D284802,
M.
Dow
and
D.
Vogel,
15­
Aug­
2002)
exposure
analyses,
HED
concluded
that
the
FQPA
SF
may
be
reduced
to
1x.
Table
4
is
a
summary
of
the
endpoints
used
in
the
current
assessment.

Table
4.
Summary
of
Toxicological
Dose
and
Endpoints
for
Bifenazate1
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
FQPA
SF
and
LOC
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary;
all
populations
An
acute
dietary
endpoint
was
not
selected
based
on
the
absence
of
an
appropriate
endpoint
attributed
to
a
single
dose.

Chronic
Dietary;
all
populations
NOAEL=
1.0
mg/
kg/
day
UF
=
100
cRfD
=
0.01
mg/
kg/
day
FQPA
SF
=
1x
cPAD
=
0.01
mg/
kg/
day
LOAEL
=
8.9/
10.4
mg/
kg/
day
[
M/
F]
based
on
changes
in
hematological
and
clinical
chemistry
parameters,
and
histopathology
in
bone
marrow,
liver,
and
kidney
in
the
One­
Year
Dog
Feeding
Study
Incidental
Oral,
Short
Term
(
1
­
30
days)
oral
NOAEL
=
10
mg/
kg/
day
LOC
for
MOE
 
100
(
residential
and
occupational)
maternal
LOAEL
=
100
mg/
kg/
day
based
on
clinical
signs,
decreased
body
weight
and
food
consumption
during
the
dosing
period
in
the
Rat
Developmental
Study
Incidental
Oral,
Intermediate
Term
(
30
days
­
six
months)
oral
NOAEL
=
0.9
mg/
kg/
day
LOC
for
MOE
 
100
(
residential
and
occupational)
LOAEL
=
10.4/
10.7
mg/
kg/
day
[
M/
F]
based
on
changes
in
hematologic
parameters
in
the
90­
Day
Subchronic
Dog
Study
Short­,
Intermediate­
and
Long­
Term
Dermal
(
1­
30
days,
30
days
­
six
months,
and
six
months
to
lifetime)
dermal
NOAEL
=
80
mg/
kg/
day
LOC
for
MOE
 
100
(
residential
and
occupational)
LOAEL
=
400
mg/
kg/
day
based
on
decreased
body
weight
and
food
consumption,
hematologic
effects,
increased
spleen
weight
and
extramedullary
hemapoiesis
in
the
spleen
in
the
21­
Day
Dermal
Toxicity
Study
in
Rats
Short­
Term
Inhalation
(
1­
30
days)
oral
NOAEL=
10
mg/
kg/
day
inhalation
absorption
rate
=
100%
LOC
for
MOE
 
100
(
residential
and
occupational)
maternal
LOAEL
=
100
mg/
kg/
day
based
on
clinical
signs,
decreased
body
weight
and
food
consumption
during
the
dosing
period
in
the
Rat
Developmental
Study
Intermediate­
Term
Inhalation
(
30
days­
six
months)
oral
NOAEL=
0.9
mg/
kg/
day
inhalation
absorption
rate
=
100%
LOC
for
MOE
 
100
(
residential
and
occupational)
LOAEL
=
10.4/
10.7
mg/
kg/
day
based
on
changes
in
hematologic
parameters
in
the
90­
Day
Dog
Feeding
Study
Long­
Term
Inhalation
(
six
months­
lifetime)
Oral
study
NOAEL=
1.0
mg/
kg/
day
(
inhalation
absorption
rate
=
100%)
LOC
for
MOE
 
100
(
residential
and
occupational)
LOAEL
=
8.9/
10.4
mg/
kg/
day
[
M/
F]
based
on
changes
in
hematological
and
clinical
chemistry
parameters,
and
histopathology
in
bone
marrow,
liver,
and
kidney
in
the
One­
Year
Dog
Feeding
Study
Cancer
(
oral,
dermal,
inhal.)
bifenazate
is
classified
as
"
not
likely"
to
be
a
human
carcinogen
1
UF
=
uncertainty
factor;
NOAEL
=
no­
observed
adverse­
effect­
level;
LOAEL
=
lowest­
observed
adverse­
effect
level;
RfD
=
reference
dose
(
NOAEL
÷
100);
PAD
=
population­
adjusted
dose
(
NOAEL
÷
FQPA
SF);
LOC
=
level
of
concern;
MOE
=
margin
of
exposure
Bifenazate
(
000586)
Human­
Health
Risk
Assessment
D323893
Page
9
of
24
3.1
Endocrine
Disruption
EPA
is
required
under
the
Federal
Food
Drug
and
Cosmetic
Act
(
FFDCA),
as
amended
by
FQPA,
to
develop
a
screening
program
to
determine
whether
certain
substances
(
including
all
pesticide
active
and
other
ingredients)
"
may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen,
or
other
such
endocrine
effects
as
the
Administrator
may
designate."
Following
the
recommendations
of
its
Endocrine
Disruptor
Screening
and
Testing
Advisory
Committee
(
EDSTAC),
EPA
determined
that
there
was
scientific
bases
for
including,
as
part
of
the
program,
the
androgen
and
thyroid
hormone
systems,
in
addition
to
the
estrogen
hormone
system.
EPA
also
adopted
EDSTAC's
recommendation
that
the
Program
include
evaluations
of
potential
effects
in
wildlife.
For
pesticide
chemicals,
EPA
will
use
FIFRA
and,
to
the
extent
that
effects
in
wildlife
may
help
determine
whether
a
substance
may
have
an
effect
in
humans,
FFDCA
has
authority
to
require
the
wildlife
evaluations.
As
the
science
develops
and
resources
allow,
screening
of
additional
hormone
systems
may
be
added
to
the
Endocrine
Disruptor
Screening
Program
(
EDSP).

In
a
90­
day
oral
toxicity
study
(
MRID
44464941),
bifenazate
caused
vacuolation
of
the
zona
fasicula
in
the
adrenal
cortex
of
male
rats.
When
the
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency's
EDSP
have
been
developed,
bifenazate
may
be
subjected
to
additional
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.

3.2
Residues
of
Concern
for
Dietary
Risk
Assessment
Table
5
is
a
summary
of
the
MARC
decisions
concerning
the
residues
of
concern
in
plants,
livestock,
rotational
crops,
and
drinking
water
(
D276801,
T.
Bloem,
16­
Aug­
2001;
D290053,
T.
Bloem,
29­
May­
2003).
Subsequent
to
these
decisions,
the
petitioner
submitted
radiovalidation
data
for
the
livestock
enforcement
method
(
46691301.
der.
wpd;
D313261,
T.
Bloem,
19­
July­
2006).
These
data
indicated
that,
contrary
to
what
was
presented
in
the
ruminant
metabolism
study,
the
major
residue
in
milk
is
D9569
not
A1530­
sulfate.
HED
requested
that
the
petitioner
submit
data
confirming
the
identity
of
the
major
residues
in
milk.
Based
on
structure
activity
relationships
and/
or
the
identification
of
the
residues
of
concern
in
the
rat
metabolism
study,
HED
concludes
that
the
metabolites/
degradates
are
not
likely
to
be
more
toxic
than
parent
and
that
use
of
bifenazate
toxicological
endpoints
for
risk
assessment
is
acceptable.

Table
5.
Residues
for
Tolerance
Expression
and
Risk
Assessment
Matrix
Residues
included
in
Risk
Assessment
Residues
included
in
Tolerance
Expression
Plants
bifenazate,
D3598
(
expressed
as
parent)
bifenazate,
D3598
(
expressed
as
parent)

Livestock
(
excluding
fat)
1
bifenazate,
D3598
(
expressed
as
parent),
A1530,
A1530­
sulfate
(
expressed
as
A1530)
bifenazate,
D3598
(
expressed
as
parent),
A1530,
A1530­
sulfate
(
expressed
as
A1530)

Livestock
­
fat
bifenazate,
D3598
(
expressed
as
parent)
bifenazate,
D3598
(
expressed
as
parent)

Rotational
Crops
could
not
be
determined2
could
not
be
determined2
Drinking
Water
D1989
D1989
1
HED
has
requested
additional
information
concerning
the
residues
of
concern
in
milk
(
46691301.
der.
wpd;
D313261,
T.
Bloem,
19­
July­
2006)
2
based
on
the
results
of
the
confined
rotational
crop
study
conducted
0.5
lb
ai/
acre
and
the
application
rate
for
the
registered
crops
which
are
likely
to
be
rotated,
HED
concluded
that
residues
in
rotated
crops
were
unlikely
and
that
tolerances
were
unnecessary
Bifenazate
(
000586)
Human­
Health
Risk
Assessment
D323893
Page
10
of
24
4.0
EXPOSURE
ASSESSMENT
AND
CHARACTERIZATION
D324430,
T.
Bloem,
19­
July­
2006
(
residue
chemistry
­
tuberous
and
corm
vegetables
and
succulent
pea)
D277089,
T.
Bloem,
16­
Aug­
2001;
D288660,
T.
Bloem,
20­
Mar­
2003;
D313261,
T.
Bloem,
19­
July,
2006
(
residue
chemistry
summary
­
stone
fruit)
D330587,
T.
Bloem,
19­
July­
2006
(
dietary
exposure)
D286171,
T.
Nguyen,
9­
Oct­
2003
(
drinking
water).
D285897,
M.
Dow,
13­
March­
2003
(
residential
exposure
assessment)

4.1
Summary
of
Registered
Uses
Bifenazate
is
currently
registered
for
application
to
nectarine,
peach,
plum,
grape,
strawberry,
cotton,
hops,
peppermint,
spearmint,
tree
nuts,
pome
fruit,
fruiting
vegetables,
and
cucurbit
vegetables
(
0.25­
0.75
lb
ai/
acre;
0­
60­
day
preharvest
interval
(
PHI))
with
tolerances
for
the
combined
residues
of
bifenazate
and
D3598
ranging
from
0.20
­
35
ppm
(
40
CFR
180.572).
Section
18
registrations
have
also
been
established
for
application
of
bifenazate
to
cherry,
potato,
soybean,
and
timothy
with
tolerances
for
the
combined
residues
of
bifenazate
and
D3598
of
0.05­
150
ppm.
Milk,
fat
(
cattle,
goat,
hog,
horse,
and
sheep),
meat
(
cattle,
goat,
hog,
horse,
and
sheep),
and
meat
byproduct
cattle,
goat,
hog,
horse,
and
sheep)
tolerances
are
also
established
as
a
result
of
secondary
residues
(
0.02­
0.10
ppm).

4.2
Summary
of
Proposed
Uses
The
proposed
Acramite
®
­
50WS
(
50%
wettable
powder
(
WP)
in
water­
soluble
bags,
EPA
Reg.
No.
­
400­
503)
and
Acramite
®
­
4SC
(
4
lb
ai/
gal
soluble
concentrate;
EPA
Reg.
No.
­
400­
514)
labels
include
a
restricted
entry
interval
(
REI)
of
12
hours
Stone
Fruit:
The
50%
WP
bifenazate
formulation
(
WP
in
water­
soluble
bags)
is
currently
registered
for
application
to
nectarine,
peach,
and
plum
(
1
x
0.375­
0.500
lb
ai/
acre;
PHI
=
3
days).
The
petitioner
proposed
expanding
this
use
to
cover
all
stone
fruits
(
proposed
application
scenario
is
identical
to
that
registered
for
nectarine,
peach,
and
plum).
The
proposed
label
indicates
that
application
through
irrigation
equipment
is
prohibited.
The
submitted
label
adequately
describes
the
proposed
application
scenario.
Table
6
is
a
summary
of
the
proposed
application
scenario.

Tuberous
and
Corm
Vegetables
and
Succulent
Pea:
The
petitioner
proposed
single
foliar
applications
of
Acramite
®
­
4SC
(
4
lb
ai/
gal;
EPA
Reg.
No.
­
400­
514)
to
succulent
pea
and
tuberous
and
corm
vegetables
(
crop
subgroup
1c).
The
proposed
label
indicates
that
application
through
irrigation
equipment
is
prohibited
and
does
not
include
rotational
crop
restrictions.
Based
on
the
current
rotational
crop
data,
HED
concludes
that
a
30­
day
rotational
crop
restriction
is
appropriate
for
all
nonlabeled
crops
(
labeled
crops
may
be
planted
at
anytime;
see
section
OPPTS
860.1850).
A
revised
Section
B
is
requested.
Table
6
is
a
summary
of
the
proposed
application
scenario.
Bifenazate
(
000586)
Human­
Health
Risk
Assessment
D323893
Page
11
of
24
Table
6:
Proposed
Application
Scenarios
Formulation
Crop
App.
Rate
(
lb
ai/
acre)
PHI1
(
days)
Comments
tuberous
and
corm
veg.
(
crop
subgroup
1c)
2
1x
0.50­
0.75
14
­
apply
with
ground
(
min
20
gallons
per
acre
(
GPA))
or
aerial
(
min
5
GPA)
equipment
­
do
not
apply
more
than
one
application
per
year
­
12
hour
restricted
entry
interval
4
lb
ai/
gal
SC
succulent
pea
1x
0.38­
0.50
14
­
apply
with
ground
(
min
20
GPA)
or
aerial
(
min
5
GPA)
equipment
­
do
not
apply
more
than
one
application
per
year
­
12
hour
restricted
entry
interval
50%
WS
(
in
water­
soluble
bags)
stone
fruit3
1
x
0.375­
0.500
3
­
apply
in
a
minimum
of
50
GPA
­
do
not
apply
more
than
one
application
per
season
­
12
hour
restricted
entry
interval
1
PHI
=
preharvest
interval
2
arracacha,
arrowroot,
Chinese
artichoke,
Jerusalem
artichoke,
edible
canna,
cassava,
bitter
and
sweet
chayote
(
root),
chufa,
dasheen
(
taro),
ginger,
leren,
potato,
sweet
potato,
tanier,
yam
bean,
true
yam
3
apricot,
cherry
(
sweet
and
tart),
nectarines,
peach,
plum/
prune,
chickasaw
plum,
damson
plum,
Japanese
plum,
and
plumcot
4.3
Dietary
Exposure/
Risk
Pathway
Nature
of
the
Residue
­
Plants:
Based
on
apple,
orange,
and
cotton
metabolism
studies,
the
MARC
determined
that
for
tolerance
expression
and
risk
assessment
purposes,
the
residues
of
concern
in
these
crops
are
bifenazate
and
D3598
(
D276801,
T.
Bloem,
16­
Aug­
2001).
The
metabolic
route
in
apple,
orange,
and
cotton
were
similar
and
proceeded
via
oxidation
of
the
hydrazine
moiety
of
bifenazate
to
form
D3598
which
is
further
degraded
to
D1989,
D9963,
D4642,
and/
or
A1530
and
to
bound
residues
by
reaction
with
natural
products.

Subsequent
to
this
decision,
the
petitioner
submitted
a
radish
metabolism
study.
The
metabolic
route
in
radish
was
similar
to
that
of
apple,
orange,
and
cotton
with
the
major
identified
residues
being
bifenazate
and
D3598.
HED
concludes
that
the
nature
of
the
residue
in
plants
is
adequately
understood
and
the
residues
of
concern
for
tolerance
expression
and
risk
assessment
purposes
are
bifenazate
and
D3598.

Nature
of
the
Residue
­
Livestock:
The
MARC
reviewed
goat
and
hen
metabolism
studies
and
determined
that
for
tolerance
expression
and
risk
assessment
purposes,
the
residues
of
concern
in
livestock
tissue
(
excluding
fat),
eggs,
and
milk
are
bifenazate,
D3598
(
expressed
as
bifenazate),
A1530,
and
A1530­
sulfate
(
expressed
as
A1530).
The
residues
of
concern
for
tolerance
expression
and
risk
assessment
purposes
in
fat
are
bifenazate
and
D3598
(
expressed
as
bifenazate).
The
metabolic
route
in
goats
and
hens
were
similar
and
proceeded
via
oxidation
of
the
hydrazine
moiety
of
bifenazate
to
form
D3598
which
is
further
degraded
to
D1989,
D9569,
A1530,
and/
or
A1530
­
sulfate
and
to
bound
residues
by
reaction
with
natural
products
(
D276801,
T.
Bloem,
16­
Aug­
2001).

Subsequent
to
this
decision,
the
petitioner
submitted
a
radiovalidation
study
which,
for
purposes
of
sample
generation,
dosed
goats
with
14C­
bifenazate
uniformly
labeled
in
the
o­
methyl
phenyl
ring
for
four
consecutive
days
(
20­
ppm
daily
dietary
burden;
46691301.
der.
wpd).
Milk,
liver,
and
fat
samples
were
collected,
extracted
with
a
variety
of
solvents,
and
analyzed
using
the
same
methods
employed
in
the
goat
metabolism
study
(
lactating
goat;
10
ppm
dietary
burden;
D277089,
T.
Bloem,
16­
Aug­
2001).
Residue
identification
was
performed
via
retention
time
comparison
with
a
mixed
standard
containing
bifenazate,
D3598,
A1530,
A1530­
sulfate,
D9569,
D9472,
and
D1989.
For
liver
and
fat,
Bifenazate
(
000586)
Human­
Health
Risk
Assessment
D323893
Page
12
of
24
these
analyses
yielded
some
difference
from
those
attained
in
the
original
goat
metabolism
study
but
none
of
which
are
of
concern
to
HED.
For
milk,
the
major
identified
residue
in
the
goat
metabolism
study
was
A1530­
sulfate
(
41%
total
radioactive
residue
(
TRR))
while
in
the
radiovalidation
study
the
major
identified
residue
was
D9569
(
24%
TRR;
A1530­
sulfate
was
included
as
a
reference
standard
but
was
not
identified).
HED
notes
that
the
mixed
reference
standard
resulted
in
D9569
and
A1530­
sulfate
eluting
very
close
to
one
another.
HED
requested
that
the
petitioner
submit
data
confirming
the
identification
of
D9569
in
milk
(
D313261,
T.
Bloem,
19­
Jul­
2006).

Magnitude
of
the
Residue
­
Plants:
The
following
are
summaries
of
the
stone
fruit,
potato
tuber,
and
succulent­
shelled/
podded
pea
magnitude
of
the
residue
studies.

Tuberous
and
Corm
Vegetables
(
crop
subgroup
1c)
­
Combined
residues
of
bifenazate/
D3598
were
<
0.01­
0.015
ppm
in/
on
potato
tuber
samples
harvested
13­
15
days
following
two
broadcast
spray
applications
at
0.75
lb
ai/
acre
(
2x;
RTI
=
13­
14
days;
n=
28)
and
were
<
0.01
ppm
in/
on
potato
tuber
samples
harvested
14
days
following
two
broadcast
spray
applications
at
3.73
lb
ai/
acre
(
10x;
RTI
=
13
days;
n=
2).

Based
on
Tables
3
and
5
of
OPPTS
860.1500,
an
additional
potato
field
trial
in
Region
11
is
needed
to
fulfill
the
requested
geographical
distribution
to
support
a
crop
subgroup
1c
registration.
In
addition,
the
potato
storage
stability
data
indicate
that
residues
may
have
declined
83­
89%
during
the
interval
from
harvest
to
analysis.
However,
HED
concludes
the
currently­
available
data
indicate
that
a
0.10
ppm
tolerance,
for
the
combined
residues
of
bifenazate
and
D3598
in/
on
tuberous
and
corm
vegetables
crop
subgroup
1c,
is
acceptable
for
the
following
reasons
(
a
revised
Section
F
is
requested;
no
additional
field
trial
data
are
required):
(
1)
all
of
the
field
trials
were
conducted
at
2x
the
proposed
seasonal
rate
and
resulted
in
residues
 
0.015
ppm;
(
2)
the
exaggerated­
rate
field
trial
(
10x
the
proposed
seasonal
rate)
resulted
in
residues
<
LOQ;
and
(
3)
the
radish
metabolism
study
result
in
TRRs
in
the
root
of
 
0.0043
ppm
(
1
x
0.75
lb
ai/
acre;
7­
day
PHI).

Succulent
Shelled/
Podded
Pea
­
Combined
residues
of
bifenazate/
D3598
were
0.028­
0.173
ppm
in/
on
succulent­
shelled
pea
(
n=
12)
and
were
0.91­
3.74
ppm
in/
on
edible­
podded
pea
samples
(
n=
10)
harvested
2­
4
days
following
two
broadcast
spray
applications
at
0.75
lb
ai/
acre
(
3x;
RTI
=
12­
14
days;
n=
28).

The
succulent­
shelled
pea
and
edible­
podded
pea
residue
data
were
conducted
with
application
rates
1.5x
the
single
application
rate
and
3.0x
the
seasonal
application
rate.
As
a
result,
these
data
are
not
indicative
of
the
magnitude
of
the
residue
following
application
at
the
proposed
rate.
Therefore,
HED
requests
that
the
petitioner
submit
succulent­
shelled
pea
(
Regions
1
or
2
(
n=
1),
5
(
n=
3),
11(
n=
1),
and
12
(
n=
1))
and
edible­
podded
pea
(
n=
3;
Regions
at
the
discretion
of
the
petitioner)
field
trial
data
conducted
at
the
proposed
rate
(
storage
stability
data
supporting
the
relevant
storage
intervals
should
also
be
submitted).
Provided
the
petitioner
agrees
to
submit
these
data,
HED
concludes
that
the
available
data
support
a
tolerance
for
the
combined
residues
of
bifenazate
and
D3598
in/
on
succulent
garden­
pea
and
edible­
podded
pea
of
0.20
ppm
and
4.0
ppm,
respectively.
A
revised
Section
F
is
requested.
Bifenazate
(
000586)
Human­
Health
Risk
Assessment
D323893
Page
13
of
24
Stone
Fruit
­
Following
a
single
application
at
0.50
lb
ai/
acre
(
1x;
PHI
=
3
days),
combined
residues
of
bifenazate/
D3598
were
as
follows:
cherry
­
0.107­
1.670
ppm;
peach
­
0.100­
1.450
ppm;
apricot
­
0.219­
0.899
ppm;
and
plum
­
0.010
­
0.150
ppm.

Based
on
Tables
2
and
5
of
OPPTS
860.1500,
the
submitted
field
trial
data
fulfill
the
requested
geographical
distribution
to
support
a
stone
fruit
crop
group
registration.
Using
the
tolerance
spreadsheet,
cherry,
peach,
apricot,
and
plum
tolerances
for
the
combined
residues
of
bifenazate
and
D3598
of
2.5
ppm,
1.5
ppm,
1.1
ppm,
and
0.20
ppm,
respectively,
were
recommended.
Based
on
these
data,
HED
concludes
that
the
following
tolerances
for
the
combined
residues
of
bifenazate
and
D3598
are
appropriate:
fruit,
stone,
group
12
(
except
plum)
­
2.5
ppm;
plum
­
0.20
ppm.
A
revised
Section
F
is
requested.

Magnitude
of
the
Residue
­
Livestock:
Cattle,
goat,
hog,
horse,
and
sheep
meat
(
0.02
ppm),
meat
byproduct
(
0.02
ppm),
and
fat
(
0.1
ppm)
tolerances
are
currently
established;
a
milk
(
0.01
ppm)
tolerance
is
also
currently
established.
Poultry
tolerances
are
not
currently
established.
These
ruminant
tolerances
are
derived
from
secondary
residues
resulting
from
the
wet
apple
pomace
(
1.2
ppm)
and
cotton
gin
byproduct
(
20
ppm)
tolerances.

The
only
feed
items
associated
with
the
current
petition
are
potato
culls
and
processed
potato
waste
(
ruminant
feed
commodities;
no
poultry
feed
commodities).
Based
on
the
wet
apple
pomace
and
cotton
gin
byproduct
tolerances
and
the
recommended
tuberous
and
corm
vegetable
tolerance
of
0.02
ppm,
HED
concludes
that
the
contribution
to
the
dietary
burden
from
the
currently­
requested
crops
is
minimal
and
adjustment
in
the
livestock
tolerances
are
unnecessary.
However,
HED
notes
that
the
current
fat
tolerance
is
0.1
ppm.
The
risk
assessment
associated
with
the
establishment
of
the
fat
tolerance
recommended
for
a
0.10
ppm
fat
tolerance
(
D264893,
W.
Dykstra
et.
al.,
27­
Sep­
2001).
Therefore,
HED
requests
a
section
F
which
indicates
a
cattle,
goat,
hog,
horse,
and
sheep
fat
tolerance
of
for
the
combined
residues
of
bifenazate,
D3598,
A1530,
and
A1530­
sulfate
of
0.10
ppm.

As
indicated
in
the
nature
of
the
residue
in
livestock
section,
the
petitioner
submitted
data
which
indicates
that
the
major
residue
in
milk
is
D9569
and
not
A1530­
sulfate
as
previously
indicated.
HED
requested
that
the
petitioner
submit
data
confirming
the
identity
of
the
major
residues
in
milk
(
D313261,
T.
Bloem,
19­
July­
2006).
The
ruminant
metabolism
study
indicated
that
major
residue
in
milk,
originally
identified
as
A1530­
sulfate
but
now
thought
to
be
D9569,
occupied
41%
of
the
TRR
and
combined
residues
of
bifenazate
and
D3598
occupied
9%
of
the
TRR.
Therefore,
the
ratio
of
the
major
residue
in
milk
to
combined
residues
of
bifenazate/
D3598
is
4.6.
The
ruminant
feeding
study
resulted
in
combined
residues
of
bifenazate/
D3598
in/
on
milk
of
<
0.01
ppm
(<
LOQ)
at
a
10
ppm
dietary
burden.
Based
on
the
current
maximum
theoretical
dietary
burden
of
6.99
ppm
and
4.6
ratio
from
the
ruminant
metabolism
study
and
assuming
a
combined
bifenazate/
D3598
residue
of
0.01
ppm
(
A1530
was
included
as
a
residue
of
concern
only
because
the
method
did
not
distinguish
between
A1530­
sulfate
and
A1530),
a
milk
residue
of
0.0391
ppm
is
calculated
((
0.01
+
(
0.01
x
4.6))
x
(
6.99
÷
10)
=
0.0391).
Therefore,
for
purposes
of
risk
assessment,
HED
will
assume
a
residue
of
0.0391
in
milk
and
will
assume
the
maximum
theoretical
concentration
factor
for
milk
fat
of
25x.
Conclusions
concerning
the
need
for
a
new
ruminant
feeding
study
will
be
made
upon
submission
of
data
confirming
the
identity
of
the
major
residue
in
milk.
Bifenazate
(
000586)
Human­
Health
Risk
Assessment
D323893
Page
14
of
24
Residues
in
Rotational
Crops:
A
confined
rotational
crop
study
has
been
previously
submitted
and
reviewed
(
D277089,
T.
Bloem,
16­
Aug­
2001;
field
rotational
crop
study
has
not
been
submitted).
The
MARC
concluded
that
residues
of
concern
in/
on
rotational
crops
could
not
be
determined
from
the
available
data
(
D276801,
T.
Bloem,
16­
Aug­
2001).
On
the
basis
of
the
confined
rotational
crop
study
and
the
proposed
maximum
seasonal
application
rates,
HED
concludes
that
a
30­
day
plantback
interval
(
PBI)
for
the
currently
requested
crops
is
appropriate.

Analytical
Enforcement
Method
­
Plants:
A
method
is
available
for
enforcement
of
the
currentlyestablished
plant
tolerances
(
D281973,
T.
Bloem,
29­
Aug­
2002;
D281979,
T.
Bloem,
29­
Aug­
2002).
The
methods
used
in
the
field
trial
and
processing
studies
were
similar
to
the
current
enforcement
method
(
D281973,
T.
Bloem,
29­
Aug­
2002;
D281979,
T.
Bloem,
29­
Aug­
2002).
Since
the
procedures
are
similar
and
adequate
method
validation
and
concurrent
recoveries
were
attained
in
the
field
trial
and
processing
studies,
HED
concludes
that
the
current
enforcement
method
is
appropriate
for
enforcement
of
the
tolerances
associated
with
this
petition.

Multiresidue
Methods:
HED
reviewed
the
petitioner
submitted
Food
and
Drug
Administration
(
FDA)
Multiresidue
Method
studies
for
bifenazate,
D3598,
A1530,
and
A1530­
sulfate.
These
data
indicate
that
bifenazate,
D3598,
A1530,
and
A1530­
sulfate
are
not
quantitatively
recovered
through
the
FDA
Multiresidue
Methods.

International
Harmonization
of
Tolerances:
Canada,
Codex,
and
Mexico
do
not
have
maximum
residue
limits
(
MRLs)
for
residues
of
bifenazate
in/
on
tuberous
and
corm
vegetables
or
succulent
pea;
therefore,
harmonization
is
not
an
issue
for
these
crops.
However,
Codex
MRLs
are
established
in/
on
peach,
nectarines,
plum,
and
prunes
(
no
Canadian
or
Mexican
stone
fruit
MRLs)
Since
the
Codex
MRL
residue
definition
is
for
bifenazate
per
se,
harmonization
is
not
possible.

Tolerance
Summary:
Based
on
the
proposed
application
rates
and
the
magnitude
of
the
residue,
processing,
and
feeding
studies,
HED
concludes
that
the
tolerances
listed
in
Table
7
for
the
combined
residues
of
bifenazate
and
D3598
are
appropriate.

Table
7.
HED­
Recommended
Tolerances
Commodity
Definition
Tolerance
(
ppm)

pea,
garden,
succulent
0.20
pea,
edible
podded,
succulent
1.0
vegetable,
tuberous
and
corm,
subgroup
1C
0.10
fruit,
stone,
group
12
(
except
plum)
2.5
plum
0.30
Bifenazate
(
000586)
Human­
Health
Risk
Assessment
D323893
Page
15
of
24
4.4
Water
Exposure/
Risk
Pathway
Environmental
Fate
Assessment:
Parent
bifenazate
degrades
rapidly
in
aerobic
soil
conditions
with
a
half­
life
of
approximately
30
minutes.
The
first
degradate
formed
(
D3598;
half­
life
of
7
hours)
was
reported
in
a
concentration
of
95%
of
the
applied
radioactivity.
D3598
degrades
to
D1989
(
reported
at
a
maximum
of
26%
of
the
applied
radioactivity),
which
is
moderately
persistent
with
an
EFEDcalculated
half­
life
of
approximately
96
days.
Photodegradation
and
other
routes
of
dissipation
of
parent
bifenazate
do
not
appear
to
be
significant.

Ground
and
Surface
Water
EECs:
The
MARC
concluded
that
the
residue
of
concern
in
drinking
water
is
D1989
(
D276801,
T.
Bloem,
16­
Aug­
2001).
Parent
and
D3598
were
not
included
as
a
residue
of
concern
in
drinking
water
due
to
the
short
half­
lives
of
these
compounds
and
the
lack
of
an
acute
dietary
endpoint
(
toxicity
of
D3598
is
assumed
to
be
equivalent
to
bifenazate).
Since
ground
or
surface
water
monitoring
data
are
not
available,
EFED
provided
Tier
I
ground
(
SCI­
GROW)
and
surface
water
(
FIRST)
EECs
for
D1989.
Both
models
were
conducted
using
the
strawberry
application
scenario
(
2
x
0.50
lbs
ai/
acre;
21­
day
RTI;
highest
registered/
proposed
application
rate).
The
resulting
ground
and
chronic
surface
water
EECs
are
<
0.001
ppb
and
6.38
ppb,
respectively.

4.5
Dietary
Exposure
Analysis
Chronic
dietary
risk
assessments
were
conducted
using
DEEM­
FCID
 
(
ver.
2.03).
DEEM­
FCID
 
incorporates
the
food
consumption
data
from
the
USDA's
CSFII
(
1994­
1996
and
1998).
The
chronic
analyses
incorporated
tolerance­
level
residues
for
all
commodities
excluding
squash,
peach,
tomato,
and
soybean
(
average
field­
trial
residues
were
assumed)
and
milk
(
anticipated
residue
was
assumed).
The
chronic
analyses
incorporated
average
percent
crop
treated
information
provided
by
the
BEAD
(
J.
Carter,
13­
Jul­
2006).
DEEM
 
(
ver.
7.81)
default
processing
factors
were
assumed
for
all
commodities
excluding
apple
juice,
grape
juice,
wine/
sherry,
tomato
paste,
and
tomato
puree.
The
processing
factors
for
these
commodities
were
reduced
to
0.23,
0.17,
0.17,
5.0,
and
5.0,
respectively,
based
on
data
from
processing
studies.
The
analyses
also
included
the
chronic
surface
water
point
estimate
generated
using
the
Tier
1
model
FIRST
and
the
strawberry
application
scenario
(
2
x
0.50
lb
ai/
acre;
21­
day
RTI;
highest
registered/
proposed
rate).
The
chronic
exposure
estimates
are
 
94%
cPAD
and
are,
therefore,
less
than
HED's
level
of
concern
(
children
1­
2
years
old
were
the
most
highly­
exposed
population).
Based
on
a
critical­
commodity
analysis
conducted
in
DEEM­
FCID
 
,
the
major
contributor
to
the
risk
was
soybean
oil
(
16­
55%
of
the
cPAD).
Table
8
is
a
summary
of
the
chronic
dietary
exposure
estimates.

Table
8.
Summary
of
Chronic
Dietary
Exposure
and
Risk
(
drinking
water
included)

Population
cPAD
(
mg/
kg/
day)
Exposure
(
mg/
kg/
day)
%
cPAD
General
U.
S.
Population
0.003835
38
All
Infants
(<
1
year
old)
0.007938
79
Children
1­
2
years
old
0.009386
94
Children
3­
5
years
old
0.008595
86
Children
6­
12
years
old
0.005942
59
Youth
13­
19
years
old
0.003712
37
Adults
20­
49
years
old
0.003084
31
Adults
50+
years
old
0.002554
26
Females
13­
49
years
old
0.01
0.002864
29
Bifenazate
(
000586)
Human­
Health
Risk
Assessment
D323893
Page
16
of
24
4.6
Residential
Exposure
and
Risk
Assessment
HED
previously
reviewed
a
petition
for
homeowner
application
of
bifenazate
to
"
all
ornamental
plants,
including
bedding
plants,
flowering
plants,
foliage
plants,
bulb
crops,
perennials,
trees,
and
shrubs."
In
conjunction
with
this
petition,
labeling
for
FloramiteTM
SC
(
2lb
ai/
gal)
was
submitted
and
the
assessment
was
conducted
using
the
instructions
on
this
label.
HED
noted
that
the
petition
indicated
that
Florimite,
Floramite
LS,
Floramite
GN,
and
Floramite
SC/
LS
may
also
be
applied
to
ornamentals.
Copies
of
those
product
labels
were
not
forwarded
for
review;
therefore,
HED
is
not
aware
of
any
differences
in
labels
that
might
exist.

HED
anticipated
only
short­
term
dermal
and
inhalation
exposure
for
residential
handlers.
The
proposed
formulation
was
appropriate
for
application
via
pump
up
sprayers,
garden
hose­
end
sprayers,
or
similar
"
homeowner"
pesticide
devices.
HED
policy
indicates
a
larger
area
per
day
may
be
treated
with
a
hose­
end
sprayer
than
with
a
"
pump­
up"
compressed­
air
sprayer,
which
in
turn
results
in
possibly
greater
contact
with
the
active
ingredient
per
day.
Therefore,
exposure
from
a
hose­
end
sprayer
was
assessed
rather
than
that
of
a
compressed­
air
sprayer.
The
resulting
dermal
and
inhalation
MOEs
were
4200
and
430000,
respectively,
and
yielded
a
combined
MOE
of
4200;
therefore,
residential
exposure
to
bifenazate
is
less
than
HED's
level
of
concern.
With
respect
to
post­
application
residential
exposures,
current
HED
policy
(
see
minutes
to
ExpoSAC
meeting,
26­
Jul­
2001)
specifies
that
no
significant
post­
application
exposure
is
anticipated
from
landscape
ornamentals,
either
by
residents
or
professional
applicators;
therefore,
no
residential
post­
application
assessment
was
conducted.

4.7
Non­
occupational
Off­
Target
Exposure
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
ground
application.
The
Agency
has
been
working
with
the
Spray
Drift
Task
Force,
EPA
Regional
Offices,
State
Lead
Agencies
for
pesticide
regulation,
and
other
parties
to
develop
the
best
spray
drift
management
practices.
On
a
chemical
by
chemical
basis,
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
data
base
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
with
specific
products
with
significant
risks
associated
with
drift.
Bifenazate
(
000586)
Human­
Health
Risk
Assessment
D323893
Page
17
of
24
5.0
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATION
In
general,
HED
conducts
aggregate
risk
assessments
by
summing
dietary
(
food
and
water)
and
residential
exposures
(
residential
or
other
non­
occupational
exposures).
Based
on
the
registered/
proposed
agricultural
and
residential
uses
and
since
a
common
toxicological
endpoint
has
been
identified
for
assessment
of
oral,
dermal,
and
inhalation
exposures
(
all
durations;
changes
in
body
weights
and
body
weight
gains,
and
hematological
effects),
HED
conducted
short­
term
(
food,
water,
residential
dermal,
and
residential
inhalation)
and
chronic
(
food
and
water)
aggregate
risk
assessments.
The
HIARC
did
not
select
an
acute
dietary
endpoint
for
the
general
US
population,
infants,
children,
and
females
13­
50
years
old
and
bifenazate
has
been
classifieds
as
"
not
likely"
to
be
a
human
carcinogen
according
to
EPA
Proposed
Guidelines
for
Carcinogen
Risk
Assessment
(
10­
Apr­
1996).
Therefore,
acute
and
cancer
aggregate
exposure
analyses
were
not
conducted.

Short­
Term
Aggregate
Risk
Assessment:
Since
a
common
endpoint
has
been
identified
for
assessment
of
short­
term
oral,
dermal,
and
inhalation
exposures
(
changes
in
body
weights
and
bodyweight
gains,
and
hematological
effects)
the
short­
term
aggregate
risk
assessment
considered
exposure
from
food,
water,
and
residential
sources.
Since
the
doses
corresponding
to
the
identified
oral,
dermal,
and
inhalation
endpoints
were
different
but
the
level
of
concern
for
all
three
routes
of
exposure
are
identical,
the
short­
term
aggregate
exposures
were
calculated
using
the
1
÷
MOE
approach.
HED
combines
chronic
dietary
(
food
and
water)
exposure
estimates
with
residential
exposure
estimates
when
conducting
short­
term
aggregate
risk
assessments.
Short­
term
exposure
has
been
defined
as
from
1­
30
days
and
HED
has
concluded
that
chronic
dietary
exposure
estimates
will
more
accurately
reflect
actual
dietary
exposure
over
these
time
periods
than
will
highend
acute­
dietary
exposures.
The
proposed
residential
scenarios
result
in
exposure
to
only
adults.
Therefore,
short­
term
aggregate
assessments
were
not
conducted
for
infants
and
children.
Table
9
is
a
summary
of
the
short­
term
aggregate
exposures
and
risk
estimates.
Since
the
aggregate
MOEs
are
 
1600,
short­
term
aggregate
exposure
to
bifenazate
is
less
than
HED's
level
of
concern.

Table
9.
Short­
Term
Aggregate
Exposure
Population
Target
Aggregate
MOE1
dietary
MOE2
dermal
MOE3
inhalation
MOE4
agg.
MOE
(
dietary
and
residential)
5
General
U.
S.
pop.
2600
4200
430000
1600
Youth
13­
19
years
old
2700
4200
430000
1600
Adults
20­
49
years
old
3200
4200
430000
1800
Adults
50+
years
old
3900
4200
430000
2000
Females
13­
49
years
old
100
3500
4200
430000
1900
1
total
uncertainty
factor
for
all
routes
of
exposure
is
100x;
therefore,
the
target
MOE
is
100
2
dietary
MOE
=
short­
term
incidental
oral
NOAEL
÷
chronic
dietary
exposure
3
dermal
MOE
=
short­
term
dermal
NOAEL
÷
dermal
residential
exposure
(
see
Section
4.5)
4
inhalation
MOE
=
short­
term
inhalation
NOAEL
÷
inhalation
residential
exposure
(
see
Section
4.5)
5
aggregate
MOE
(
dietary
and
residential)
=
1
÷
(
(
1
÷
MOEdietary)+
(
1
÷
MOEdermal)
+
(
1
÷
MOEinhalation))

Chronic
Aggregate
Risk
Assessment:
Since
there
are
no
registered/
proposed
uses
which
result
in
chronic
residential
exposures,
the
chronic
aggregate
exposure
assessment
is
concerned
only
with
exposure
from
food
and
water.
Since
the
dietary
exposure
analysis
included
drinking
water,
the
discussion
and
exposure
estimates
presented
in
Section
4.5
represent
aggregate
chronic
exposure.
Bifenazate
(
000586)
Human­
Health
Risk
Assessment
D323893
Page
18
of
24
6.0
CUMULATIVE
RISK
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
for
bifenazate
and
any
other
substances,
and
bifenazate
does
not
appear
to
produce
a
toxic
metabolite
produced
by
other
substances.
For
the
purposes
of
this
tolerance
action,
therefore,
EPA
assumed
that
bifenazate
does
not
have
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
OPP
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
AND
RISK
ASSESSMENT
D324431,
M.
Dow,
7­
Feb­
2006
(
tuberous
and
corm
vegetables)
D277204,
J.
Swackhammer,
21­
Aug­
2001
(
stone
fruit)

HED
previously
conducted
occupational
exposure
assessment
for
application
of
bifenazate
to
apricot,
nectarine,
peach,
plum,
and
prune
orchards
as
well
as
apples,
cotton,
grape,
hops,
pears,
and
strawberries.
The
assessment
was
not
conducted
for
all
stone
fruit.
HED
concludes
that
the
previous
assessment
is
adequate
for
all
stone
fruits
for
the
following
reasons:
(
1)
application
methods
and
post­
application
activities
for
all
stone
fruit
are
similar
and
(
2)
the
proposed
stone
fruit
application
scenario
is
the
same
as
that
previously
evaluated.

7.1
Handler
Exposure
and
Risk
Assessment
HED
notes
that
the
Acramite
®
­
4SC
(
4
lb
ai/
gal;
EPA
Reg.
No.
­
400­
514)
and
Acramite
®
­
50WS
(
50%
ai;
EPA
Reg.
No.
­
400­
503)
labels
indicate
that
applicators
and
other
handlers
should
wear
a
long­
sleeved
shirt,
long
pants,
shoes,
and
socks.
The
Acramite
®
­
4SC
label
also
indicates
that
when
not
using
a
closed
system,
an
apron
and
chemical
resistant
gloves
should
be
worn
for
mixing
loading
activities
(
this
statement
is
not
included
on
the
Acramite
®
­
50WS
label).
HED
notes
that
the
Acramite
®
­
50WS
is
a
wettable
powder
in
water
soluble
bags
and
is
therefore
considered
a
closed
system
by
HED.

No
chemical­
specific
data
were
available
with
which
to
assess
potential
exposure
to
pesticide
handlers.
The
estimates
of
exposure
to
pesticide
handlers
are
based
upon
surrogate
study
data
available
in
the
PHED.
For
pesticide
handlers,
it
is
HED
standard
practice
to
present
estimates
of
dermal
exposure
for
"
baseline,"
that
is,
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
personal
protective
equipment
(
PPE)
as
might
be
necessary.
The
proposed
product
label
involved
in
this
assessment
directs
applicators
and
other
handlers
to
wear
long­
sleeved
shirt,
long
pants,
shoes
plus
socks.
When
not
using
a
closed
system,
handlers
must
wear
an
apron
and
chemical­
resistant
gloves
made
of
any
waterproof
material
for
mixing/
loading
activities.
HED
notes
that,
for
stone
fruit,
the
formulation
is
packed
in
water­
soluble
bags
and
that
this
is
considered
a
closed
loading
system.
Bifenazate
(
000586)
Human­
Health
Risk
Assessment
D323893
Page
19
of
24
It
is
expected
that
some
private
(
i.
e.,
grower)
applicators
may
perform
all
tasks,
that
is
mix,
load
and
apply
the
material.
However,
ExpoSAC
draft
SOP
(
29
March
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
(
August
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
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
(
e.
g.,
chemicalresistant
gloves
may
only
be
necessary
during
the
pouring
of
a
liquid
formulation).

Stone
Fruit:
As
stated
above,
the
stone
fruit
occupational
exposure
assessment
evaluated
occupational
exposure
to
stone
fruit
as
well
as
apples,
cotton,
grape,
hops,
pears,
and
strawberries.
To
evaluate
occupation
handler
exposure
to
these
crops,
the
assessment
picked
the
application
scenario
which
was
likely
to
result
in
the
highest
exposure.
Therefore,
the
specific
assessment
evaluated
may
not
have
been
for
stone
fruit
but
it
can
be
stated
that
the
calculated
occupational
exposures
will
be
equal
to
or
greater
than
that
expected
for
stone
fruit.
The
following
is
a
summary
of
the
previous
occupational
assessment
for
stone
fruit,
apples,
cotton,
grape,
hops,
pears,
and
strawberries
(
D277204,
J.
Swackhammer,
21­
Aug­
2001):

Based
on
the
proposed
use
patterns
of
bifenazate,
commercial
applicators
and
grower/
applicators
are
anticipated
to
have
short­
term
exposures
(
1­
30
days)....
dermal
and
inhalation
exposure
assessments
for
the
following
scenarios
are
presented
based
on
the
rationale
discussed
below:

(
1)
commercial
mixer/
loaders
supporting
aerial
applications
(
cotton);
rationale:
cotton
crops
are
considered
to
be
higher
acreage
crops
as
compared
to
the
other
crops
in
the
proposed
use,
and
aerial
application
methods
can
treat
more
acres
per
day
than
ground­
based
applications.

(
2)
commercial
applicators
for
groundboom
applications,
open
cab
(
cotton);
rationale:
groundboom
applicators
are
anticipated
to
have
a
higher
exposure
potential
as
compared
to
aerial
applicators.

(
3)
commercial
airblast
applicator,
open
cab
(
hops);
rationale:
airblast
application
methods
have
a
relatively
high
exposure
potential
as
compared
to
groundboom
applications,
and
the
proposed
maximum
application
rate
to
hops
is
higher
than
for
tree
fruit
crops.

Provided
handlers
wear
a
single
layer
of
work
clothing,
the
estimated
MOEs
were
 
270
and
therefore
do
not
exceed
HED's
level
of
concern.
Table
10
is
a
summary
of
the
occupational
exposures.
Bifenazate
(
000586)
Human­
Health
Risk
Assessment
D323893
Page
20
of
24
Tuberous
and
Corm
Vegetables
and
Succulent
Pea:
Based
upon
the
proposed
use
pattern,
HED
believes
the
most
highly­
exposed
occupational
pesticide
handlers
are
likely
to
be
mixer/
loaders
using
open­
pour
of
liquids
and
applicators
using
open­
cab
groundboom
sprayers
or
aircraft.
HED
expects
most
exposures
will
be
short­
term
duration
(
1
­
30
days).
Typical
field
size
is
expected
to
be
small
as
compared
to
traditional
field
crops
such
as
corn,
cotton,
soybeans
or
wheat.
Most
ground
applications
are
likely
to
be
made
by
the
grower.
There
is
only
one
application
per
acre
per
year.
Therefore
there
may
be
several
short­
term
duration
exposures
but
it
is
not
likely
that
any
particular
applicator
would
be
exposed
from
1
­
6
months
(
intermediate­
term
duration
exposure)
applying
bifenazate
to
succulent
peas
or
tuberous/
corm
vegetables.
Provided
handlers
wear
protective
gloves
in
addition
to
a
single
layer
of
work
clothing,
the
estimated
MOEs
were
 
660
and
therefore
do
not
exceed
HED's
level
of
concern
(
label
indicates
when
not
using
a
closed
system
gloves
should
be
worn
for
mixing
loading
activities).
Table
10
is
a
summary
of
the
occupational
exposures.

Table
10.
Pesticide
Handlers
Worker
Exposure
Estimates
to
Bifenazate.

Unit
Exposure1
(
mg
ai/
lb
handled)
App.
Rate
(
lb
ai/
acre)
Units
Treated2
(
acres/
day)
Avg.
Daily
Dose3
(
mg
ai/
kg/
day)
NOAEL
(
mg
ai/
kg/
day)
MOE
Combined
MOE
Tuberous
and
Corm
Vegetable
(
subgroup
1c)
and
Succulent
Pea
Mixer/
Loader
­
Liquid
Open
Pour
­
Supporting
Aerial
Operations
Dermal
SLNG
2.9
HC
SLWG
0.023
HC
Inhal
0.0012
LC
0.75
350
Dermal
NG
10.87
WG
0.086
Inhal
0.0045
Derm
­
80
Inhal
­
10
Derm
NG
7
WG
930
Inhal
2,200
NG
7
WG
660
Applicator
­
Open­
Cab
Groundboom
Dermal
SLNG
0.014
HC
SLWG
0.014
MC
Inhal
0.00074
LC
0.75
350
Dermal
NG
0.053
WG
0.053
Inhal
0.0028
Derm
­
80
Inhal
­
10
Derm
NG
1,500
WG
1,500
Inhal
3,600
NG
1,100
WG
1,100
Applicator
­
Aerial
Fixed
Wing
Dermal
SLNG
0.0050
MC
Inhal
0.000068
MC
0.75
350
Dermal
NG
0.019
Inhal
0.00026
Derm
­
80
Inhal
­
10
Derm
NG
4,211
Inhal
38,462
NG
3,800
Stone
Fruit4
Mixer/
Loader
­
WP
in
Water­
Soluble
Bags
­
Supporting
Aerial
Applications
Dermal
SLNG
0.021
LC
SLWG
0.0098
LC
Inhal
0.00024
LC
0.75
1200
Dermal
NG
0.27
WG
0.126
Inhal
0.0031
Derm
­
80
Inhal
­
10
Derm
NG
300
WG
630
Inhal
3,200
NG
270
WG
530
Applicator
­
Open­
Cab
Groundboom
Dermal
SLNG
0.014
HC
SLNG
0.014
HC
Inhal
0.00074
LC
0.75
200
Dermal
NG
0.030
WG
0.030
Inhal
0.0016
Derm
­
80
Inhal
­
10
Derm
NG
2,700
WG
2,700
Inhal
6,300
NG
1,800
WG
1,800
Bifenazate
(
000586)
Human­
Health
Risk
Assessment
D323893
Page
21
of
24
Table
10.
Pesticide
Handlers
Worker
Exposure
Estimates
to
Bifenazate.

Unit
Exposure1
(
mg
ai/
lb
handled)
App.
Rate
(
lb
ai/
acre)
Units
Treated2
(
acres/
day)
Avg.
Daily
Dose3
(
mg
ai/
kg/
day)
NOAEL
(
mg
ai/
kg/
day)
MOE
Combined
MOE
Applicator
­
Open­
Cab
Airblast
Dermal
SLNG
0.36
HC
SLWG
0.24
HC
Inhal
0.0045
HC
0.75
40
Dermal
NG
0.154
WG
0.103
Inhal
0.0019
Derm
­
80
Inhal
­
10
Derm
NG
520
WG
780
Inhal
4,400
NG
470
WG
680
1
taken
from
the
PHED
Surrogate
Exposure
Guide
(
ver.
1.1;
August
1998);
SLNG
=
single
layer
of
work
clothing
(
long­
sleeved
shirt,
long
pants,
shoes;
socks]
and
no
gloves.
SLWG
=
single
layer
work
clothing
with
gloves;
HC
=
high­
confidence
data;
LC
=
lowconfidence
data
2
Acres
Treated
are
derived
from
ExpoSAC
SOP.
No.
9.1(
rev.
25
Sep
01)
3
Average
Daily
Dose
(
ADD)
=
Unit
Exposure
x
Application
Rate
x
Units
Treated
÷
70
kg.
4
The
stone
fruit
occupational
exposure
assessment
evaluated
occupational
exposure
to
stone
fruit
as
well
as
apples,
cotton,
grape,
hops,
pears,
and
strawberries.
To
evaluate
occupation
handler
exposure
to
these
crops,
the
assessment
picked
the
application
scenario
which
was
likely
to
result
in
the
highest
exposure.
Therefore,
the
specific
assessment
evaluated
may
not
have
been
for
stone
fruit
but
it
can
be
stated
that
the
calculated
MOE
will
be
equal
to
or
greater
than
that
expected
for
stone
fruit.

7.2
Post­
Application
Exposure
and
Risk
Assessment
It
is
possible
for
agricultural
workers
to
have
post­
application
exposure
to
pesticide
residues
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
and
which
may
result
in
post­
application
exposures
to
pesticide
residues.
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
identified.
The
transfer
coefficients
used
in
this
assessment
are
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
transfer
coefficients.
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.

Stone
Fruit:
As
stated
above,
the
stone
fruit
occupational
exposure
assessment
evaluated
occupational
exposure
to
stone
fruit
as
well
as
apples,
cotton,
grape,
hops,
pears,
and
strawberries.
To
evaluate
occupational
handler
exposure
to
these
crops,
the
assessment
picked
the
application
scenario
which
was
likely
to
result
in
the
highest
exposure.
Therefore,
the
specific
assessment
evaluated
may
not
have
been
for
stone
fruit
but
it
can
be
stated
that
the
calculated
occupational
exposures
will
be
equal
to
or
greater
than
that
expected
for
stone
fruit.
The
following
is
a
summary
of
the
previous
occupational
assessment
for
stone
fruit,
apples,
cotton,
grape,
hops,
pears,
and
strawberries
(
D277204,
J.
Swackhammer,
21­
Aug­
2001;
D264893.
W.
Dykstra
et
al.,
27­
Sep­
2001):

From
the
USDA
Crop
Profiles
and
ExpoSAC
Policy
No.
3.1
for
these
tree
crops,
typical
cultural
activities
range
from
scouting,
irrigation,
pruning,
weeding,
thinning
(
chemical
and
hand),
and
harvesting,
mostly
by
hand.
Of
these
activities,
thinning
and
hand
harvesting
are
considered
to
have
Bifenazate
(
000586)
Human­
Health
Risk
Assessment
D323893
Page
22
of
24
the
highest
exposure
potential
due
to
high
foliar
contact.
The
corresponding
transfer
coefficient
(
TC)
for
both
activities
is
3,000
cm2/
hr
for
hand
harvesting
(
ExpoSAC
Policy
No.
3,
revised
policy
on
apple
thinning
(
see
ExpoSAC
minutes,
13­
Sep­
2001),
MRID
424281­
01).
For
apples
specifically,
chemical
thinners
can
be
used
during
bloom
or
immediately
following
petal
fall.
Hand
thinning
is
often
used
to
"
clean­
up"
the
tree
after
chemical
thinning
(
Dr.
Curt
R.
Rom,
Professor
of
Horticulture,
University
of
Arkansas,
Gerber
Newsletter,
Spring
2001).
Also,
hand
thinning
the
fruit
about
six
to
eight
weeks
after
bloom
is
a
very
common
practice
(
USDA).
Fruit
thinning
serves
to
ensure
the
highest
fruit
quality
by
spacing
the
fruit
on
the
limb,
reducing
fruit
clusters
to
singles
and
removing
fruit
that
is
likely
to
rub
on
the
limbs.
Thinning
also
eliminates
fruit
that
appears
damaged
by
early
season
insects
or
diseases.
Heavy
mite
feeding
early
in
the
season
(
late
June
and
early
July)
not
only
can
reduce
tree
growth
and
yield,
but
also
can
drastically
affect
fruit
bud
formation,
and
thereby
reduce
yields
the
following
year.
Also,
based
on
personal
communications
with
Hollabaugh
Bros.,
Inc.
in
Biglerville,
PA
(
an
Eastern
U.
S.
grower
visited
on
the
IR­
4/
EPA/
USDA
Field
Tour,
June
2001),
fruit
thinning
and
mite
outbreaks
may
occur
simultaneously,
but
most
likely
mite
outbreaks
will
occur
in
late
July
or
early
August,
while
fruit
thinning
is
typically
conducted
in
early
summer
(
June).....
Thus,
even
though
the
conduct
of
hand
thinning
and
miticide
use
may
not
typically
coincide,
a
post­
application
exposure
assessment
for
thinning
is
included,
but
is
considered
to
represent
a
conservative
exposure
scenario.
In
addition
to
the
hand
thinning
assessment,
a
post­
application
assessment
for
hand
harvesting
is
also
included,
given
the
relatively
short
proposed
PHI
for
apricots,
nectarines,
peaches,
plums
and
prunes
(
three
days).......
As
mentioned
above,
there
are
no
chemicalspecific
post­
application
exposure
data
available
for
bifenazate
related
to
the
proposed
uses.
In
order
to
assess
the
highest
potential
post­
application
exposures......
an
estimate
of
dislodgeable
foliar
residues
(
DFR)
on
DAT
0
was
used
for
the
proposed
uses.
This
DFR
estimate
is
anticipated
to
represent
the
highest
post­
application
exposures
for
the
proposed
use
of
bifenazate.
In
order
to
determine
the
time
frame
at
which
workers
may
enter
treated
sites
to
perform
cultural
activities,
DFR
estimates
and
corresponding
MOEs
were
calculated
using
HED's
default
dissipation
rate
of
10%
of
foliar
residues
per
day.

The
estimated
MOEs
are
210
and
therefore
do
not
exceed
HED's
level
of
concern.
Table
11
is
a
summary
of
the
post­
application
occupational
exposures.

Tuberous
and
Corm
Vegetables
and
Succulent
Pea:
Post­
application
activities
in
tuberous
and
corm
vegetable
and
succulent
pea
fields
may
result
in
exposure
to
workers.
The
highest
TCs
listed
in
SOP
#
3.1
for
the
proposed
crop
sites
are
for
irrigation
activities
and
scouting
in
tuberous
and
corm
vegetables
(
1500
cm2/
hr)
and
hand­
harvesting
succulent
peas
(
2500
cm2/
hr).
The
estimated
MOEs
resulting
from
these
activities
are
170
and
therefore
do
not
exceed
HED's
level
of
concern.
Table
11
is
a
summary
of
the
post­
application
occupational
exposures.

Table
11.
Post­
Application
Worker
Exposure
Assessments
for
Bifenazate
Exposure
Scenario
AR
(
lb
ai/
acre)
DFR
on
Day
of
Treatment1
(
µ
g/
cm2)
Transfer
Coefficient
(
cm2/
hr)
Average
Daily
Dose2
(
mg/
kg/
day)
Short­
term
Dermal
MOE
on
Day
of
Treatment
tree
fruit
crops;
hand
thinning
3,000
0.384
210
tree
fruit
crops;
hand
harvesting
0.50
1.12
3,000
0.384
210
succulent
pea;
hand
harvesting
0.75
1.682
2500
0.48
170
1
Surrogate
DFR
=
application
rate
(
lb
ai/
acre)
x
20%
available
as
dislodgeable
residue
x
4.54E8
µ
g/
lb
x
2.47E­
8
acres/
cm2;
DAT
0
=
0
days
after
treatment
2
ADD
=
DFR
(
µ
g/
cm2)
x
TC
(
cm2/
hr)
x
8
hrs/
day
x
0.001
mg/
µ
g
x
1/
BW
x
%
dermal
absorption;
BW=
70kg
for
adults;
dermal
absorption
=
100%
as
NOAEL
based
on
21­
day
dermal
study.
Bifenazate
(
000586)
Human­
Health
Risk
Assessment
D323893
Page
23
of
24
7.3
REIs
Bifenazate
is
classified
in
Acute
Toxicity
Category
IV
for
acute
dermal,
acute
inhalation,
primary
eye
irritation
and
primary
skin
irritation.
It
is
not
a
dermal
sensitizer.
Therefore,
the
interim
Worker
Protection
Standard
(
WPS)
REI
of
12
hours
is
adequate
to
protect
agricultural
workers
from
post­
application
exposures
to
bifenazate.
The
proposed
labels
include
a
REI
of
12
hours.

8.0
DEFICIENCIES
8.1
Toxicology
Succulent
Pea
and
Tuberous
and
Corm
Vegetable
(
crop
subgroup
1c)
and
Stone
Fruit
Label
Amendment
 
The
HIARC
determined
that
a
28­
day
inhalation
toxicity
study
is
required
to
address
concerns
via
this
route
of
exposure
(
TXR
No.
0014658);
a
waiver
from
the
28­
day
inhalation
study
is
granted
for
the
following
reasons:
(
1)
bifenazate
technical
is
of
low
volatility;
(
2)
is
Toxicity
Category
IV
for
acute
inhalation;
and
(
3)
the
extrapolated
MOEs
for
anticipated
inhalation
exposures
resulting
from
the
proposed
bifenazate
uses
are
more
than
10x
the
target
MOE
of
100
(
HED
SOP
2002.01).

8.2
Residue
Chemistry
Succulent
Pea
and
Tuberous
and
Corm
Vegetable
(
crop
subgroup
1c)

 
Revised
Sections
B
and
F
 
succulent­
shelled
pea
(
Regions
1
or
2
(
n=
1),
5
(
n=
3),
11(
n=
1),
and
12
(
n=
1))
and
edible­
podded
pea
(
n=
3;
Regions
at
the
discretion
of
the
petitioner)
field
trial
data
(
storage
stability
data
validating
the
relevant
intervals
should
also
be
submitted)

Stone
Fruit
Label
Amendment
 
Section
F
 
storage
stability
data
for
hops
(
175
days;
7­
day
interval
from
homogenization
to
analysis
should
also
be
validated)

 
grape
field
trial
data
(
Region
1
(
n=
1))

 
confirmation
concerning
the
identification
of
D9569
as
the
major
residue
in
milk
(
see
page
13)

8.3
Occupational/
Residential
Succulent
Pea
and
Tuberous
and
Corm
Vegetable
(
crop
subgroup
1c)
and
Stone
Fruit
Label
Amendment
 
none
Attachment
1:
Structures
RDI:
Branch
(
26­
July­
2006)
T.
Bloem:
S10945:
PY1:(
703)
605­
0217:
7509P:
RAB1
Bifenazate
(
000586)
Human­
Health
Risk
Assessment
D323893
Page
24
of
24
Attachment
1:
chemical
structures
chemical
name
chemical
structure
bifenazate
(
D2341)

hydrazinecarboxylic
acid,
2­(
4­
methoxy­[
1,1'­
biphenyl]­
3­
yl),
1­
methylethyl
ester
O
NH
N
H
O
CH
3
O
CH
3
CH
3
D3598
diazinecarboxylic
acid,
2­(
4­
methoxy­[
1,1'­
biphenyl]­
3­
yl),
1­
methylethyl
ester
O
N
N
O
CH
3
O
CH
3
CH
3
D4642
diazinecarboxylic
acid,
2­(
4­
methoxy­[
1,1'­
biphenyl]­
3­
yl),
1­
methylethyl
ester
2­
oxide
OCH3
N
N
O
CH
3
O
CH
3
OH
D9963
4­
methoxy­[
1,1'­
biphenyl]­
3­
ol
OCH3
OH
D1989
1,1'­
biphenyl,
4­
methoxy
OCH3
D9569
[
1,1'­
biphenyl]­
4,4'­
diol
OH
HO
A1530
1,1'­
biphenyl,
4­
ol
OH
A1530­
sulfate
OSO3H
D9472
OH
OH
D23­
14;
biphenyl
hydrazine;
(
4­
methoxy­[
1,1'­
biphenyl]­
3­
yl)
hydrazine
OCH3
NH
NH2
