Page
1
of
29
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
MEMORANDUM
DATE:
June
14,
2006
SUBJECT:
Human
Health
Risk
Assessment
for
Fenhexamid
 
IR­
4
Tolerance
Requests
on
Cilantro
(
Transplant
/
Greenhouse),
Non­
Bell
Pepper
(
Transplant)
and
Pomegranate
(
Post­
Harvest).

DP
Barcode:
D329137
Decision
#:
351276
PC
Code:
090209
Class:
Fungicide
Trade
Name:
Elevate
®
50
WDG
Fungicide
EPA
Reg.
No.:
66330­
35
TO:
Dan
Rosenblatt,
Branch
Chief
Risk
Integration
Minor
Use
Emergency
Response
Branch
(
RIMUERB)
Registration
Division
(
7505P)

FROM:
John
Redden,
Team
Leader
Risk
Integration
Minor
Use
Emergency
Response
Branch
(
RIMUERB)
Registration
Division
(
7505P)

THRU:
William
Cutchin,
Senior
Scientist,
ARIA
Team
Technical
Review
Branch
Registration
Division
(
7505P)
And
Christina
Swartz,
Chief
Registration
Action
Branch
III
(
RABIII)
Health
Effects
Division
(
7505P)

Under
Section
3
of
the
Federal
Insecticide,
Fungicide
and
Rodenticide
Act,
as
amended,
the
InterRegional
Research
Project
Number
4
(
IR
4)
and
the
Arvesta
Corporation
are
requesting
registration
of
the
fungicide
compound
fenhexamid
(
N­(
2,3­
dichloro­
4­
hydroxyphenyl)­
1­
methylcyclohexane
carboxamide)
for
use
on
cilantro
(
transplant
/
greenhouse),
non­
bell
pepper
(
transplant)
and
pomegranate
(
post­
harvest).
The
product
proposed
for
use
is
ELEVATE
®
50
WDG
Fungicide
(
EPA
Reg.
No.
66330­
35).
This
risk
assessment
incorporates
the
above
mentioned
tolerances
for
fenhexamid
as
of
June
2,
2006.
Page
2
of
29
TABLE
OF
CONTENTS
1.0
EXECUTIVE
SUMMARY.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.....
4
2.0.
PHYSICAL/
CHEMICAL
PROPERTIES
CHARACTERIZATION
....................................
8
2.1.
Identification
of
Active
Ingredient
............................................................................
8
2.2.
Structural
Formula
of
Fenhexamid
...........................................................................
9
2.3.
Physical
and
Chemical
Properties
.............................................................................
9
3.0.
HAZARD
CHARACTERIZATION....................................................................................
9
3.1.
Hazard
Profile..........................................................................................................
9
3.2.
FQPA
Considerations
...........................................................................................
10
3.2.1.
Cumulative
Risk
.....................................................................................
10
3.2.2.
Endocrine
Disruption..............................................................................
11
3.3.
Dose
Response
Assessment...................................................................................
12
4.0.
EXPOSURE
ASSESSMENT...........................................................................................
13
4.1.
Summary
of
Proposed
Uses
..................................................................................
13
4.2.
Dietary
Exposure
..................................................................................................
14
4.2.1.
Food
Exposure.......................................................................................
14
4.2.1.
a.
Nature
of
the
Residue
­
Plants
and
Livestock............................
14
4.2.1.
b.
Residue
Analytical
Method
­
Plants
and
Livestock....................
15
4.2.1.
c.
Multiresidue
Methods
..............................................................
16
4.2.1.
d.
Storage
Stability
Data
..............................................................
16
4.2.1.
e.
Crop
Field
Trials
......................................................................
17
4.2.1.
f.
Processed
Food/
Feed................................................................
18
4.2.1.
g.
Meat,
Milk,
Poultry
and
Eggs
..................................................
18
4.2.1.
h.
Confined
and
Field
Accumulation
in
Rotational
Crops..............
18
4.2.1.
i.
International
Harmonization
of
Tolerances
................................
19
4.2.2.
Drinking
Water......................................................................................
19
4.2.2.
a
Surface
and
Ground
Water
Assessment
.....................................
19
4.2.2.
b
Drinking
Water
Risk
.................................................................
20
4.2.3.
Dietary
Exposure
and
Risk
Analyses.......................................................
18
4.2.3.
a.
Acute
Dietary
Exposure
Analysis
.............................................
21
4.2.3.
b.
Chronic
Dietary
Exposure
Analysis
..........................................
21
4.2.3.
c.
Cancer
Dietary
Exposure
Analysis............................................
22
4.3.
Occupational/
Residential
Exposure
................................................................
22
4.3.1.
Summary
of
Use
Patterns
and
Formulations............................................
22
4.3.2.
Occupational
Exposure
Assessment
........................................................
20
4.3.2.
a.
Worker
Post­
Application
Exposure
Assumptions/
Assessment...
26
4.3.2.
b.
REI..........................................................................................
26
4.3.2.
c.
Incident
Reports.......................................................................
26
Page
3
of
29
4.3.3.
Residential
Exposure
...............................................................................
26
4.4.
Non­
Occupational
Off­
Target
Exposure.............................................................
26
5.0.
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATION..................
27
5.1.
Chronic
Aggregate
Risk
(
food
+
water)
.................................................................
27
6.0.
DATA
GAPS/
LABEL
CHANGES...................................................................................
27
7.0.
ATTACHMENTS.............................................................................................................
27
8.0.
REFERENCES
.................................................................................................................
27
Page
4
of
29
1.0
EXECUTIVE
SUMMARY
General
Background
Fenhexamid
is
of
the
hydroxyanilide
class
of
fungicides.
Fenhexamid
prevents
fungi
from
infecting
plants
by
inhibiting
germ
tube
elongation,
mycelial
growth
and
spore
germination.
Fenhexamid
is
absorbed
into
the
waxy
layer
of
the
cuticle
and
is
protected
from
being
washed
off.
Fenhexamid
is
effective
in
controlling
Botrytis
cinerea,
Monolinia
(
brown
rot
/
blossom
blight
/
twig
blight)
and
has
been
shown
to
suppress
Uncinula
necator
(
powdery
mildew).
It
also
provides
post­
infection
activity
when
applied
early
in
the
disease
life
cycle.

There
are
existing
permanent
tolerances
(
40
CFR
§
180.553(
a))
for
fenhexamid
in/
on
almond,
hull
(
2.0
ppm),
almond
(
0.02
ppm),
bushberry
subgroup
13B
(
5.0
ppm),
caneberry
subgroup
13A
(
20.0
ppm),
cucumber
(
2.0
ppm),
fruit,
stone,
group
12,
except
plum,
prune,
fresh,
postharvest
(
10.0
ppm),
grape
(
4.0
ppm),
grape,
raisin
(
6.0
ppm),
juneberry
(
5.0
ppm),
kiwifruit,
postharvest
(
15.0
ppm),
leafy
greens,
subgroups
4A,
except
spinach
(
30.0),
lingonberry
(
5.0
ppm),
pistachio
(
0.02
ppm),
plum,
prune,
dried
(
2.5
ppm),
plum,
prune,
fresh
(
1.5
ppm),
salal
(
5.0
ppm),
strawberry
(
3.0
ppm),
vegetable,
fruiting,
group
8,
except
nonbell
pepper
(
2.0
ppm)
and
ginseng
(
0.3
ppm).

Tolerances
are
proposed
for
the
combined
residues
of
fenhexamid
in
or
on
the
following
raw
agricultural
commodity
(
RAC):

pepper,
non­
bell
(
transplant)                 ...
0.02
ppm
pomegranate
(
post­
harvest)                  ..
3.0
ppm
cilantro                          .
30.0
ppm
The
most
recent
human
health
risk
assessment
for
fenhexamid
was
conducted
in
conjunction
with
an
IR­
4
request
for
uses
on
ginseng
(
PP#
4E6859,
DP
Barcode:
D316518,
B.
Hanson,
12/
19/
2005).

Hazard
Assessment
In
general,
the
toxicology
studies
conducted
on
fenhexamid
demonstrated
that
it
has
few
or
no
biologically
significant
toxic
effects
at
relatively
low
dose
levels
in
many
animal
studies
and
only
mild
or
no
toxic
effects
at
high
dose
levels
which
often
approach
or
exceed
the
limit
dose.
In
subchronic
and
chronic
oral
studies,
the
most
toxicologically
significant
effects
were
anemia
in
dogs,
and
decreased
body
weights,
increased
food
consumption
and
mild
liver
and/
or
kidney
effects
in
rats
and
mice.
Fenhexamid
is
not
acutely
toxic,
neurotoxic,
carcinogenic
or
mutagenic
and
is
not
a
developmental
or
reproductive
toxicant.
HED
concluded
that
there
is
low
concern
Page
5
of
29
for
pre­
and/
or
postnatal
toxicity
resulting
from
exposure
to
fenhexamid.
HED
determined
that
no
special
FQPA
safety
factor
is
needed
(
i.
e.
1X)
since
there
are
no
residual
uncertainties
for
pre
and/
or
post
natal
toxicity.
In
addition
the
HIARC
concluded
that
there
is
not
a
concern
for
developmental
neurotoxicity
resulting
from
exposure
to
fenhexamid.

On
13
February
2003,
the
Hazard
Identification
Assessment
Review
Committee
(
HIARC)
met
to
discuss
the
adequacy
of
the
toxicological
database
relative
to
fenhexamid
(
Memo,
B.
Tarplee,
TXR
NO.
0051704,
26
March
2003,
"
FENHEXAMID
­
2nd
Report
of
the
Hazard
Identification
Assessment
Review
Committee").
Relative
to
the
assessment
herein,
the
HIARC
identified
a
short­
term
dermal
toxicological
endpoint
(
1,000
mg
a.
i./
kg
bw/
day)
from
a
21­
day
dermal
developmental
study
in
the
rabbit.
The
effects
seen
were
decreased
body
weight
gain
and
food
consumption.
The
HIARC
determined
a
20%
absorption
factor
to
extrapolate
from
an
oral
study.
Incidentally
the
intermediate­
term
dermal
endpoint
is
the
same
and
identified
from
the
same
study.
Since
the
dermal
study
is
a
developmental
study,
a
60
kg
body
weight
is
used
in
calculating
the
margin
of
exposure
(
MOE).
The
HIARC
determined
that
a
separate
inhalation
risk
assessment
was
not
required
for
short­
and
intermediate­
term
inhalation
risk
assessments.

The
HIARC
also
reassessed
FQPA
requirements
in
response
to
questions
posed
by
the
Natural
Resources
Defense
Council
(
NRDC).
No
new
data
have
been
reviewed
and
no
changes
were
made
to
the
toxicology
endpoints
previously
selected
for
fenhexamid
(
with
the
exception
of
the
FQPA
safety
factor
applied).
This
document
revises
the
previous
HIARC
report
dated
March
4,
1999
(
HED
DOC.
NO.
013258).

Dose
Response
Assessment
No
acute
dietary
endpoint
was
selected
since
no
appropriate
toxicological
endpoint
attributable
to
a
single
exposure
was
identified
in
the
available
toxicology
studies.
The
short­
and
intermediateterm
dermal
endpoints
are
based
on
decreased
body
weight
gain
and
food
consumption.
No
other
short­
and
intermediate­
term
endpoints
were
selected.
Chronic
dietary
and
long­
term
endpoints
are
based
on
decreased
RBC
count,
hemoglobin
and
hematocrit
and
increased
Heinz
bodies
in
males
and
females;
increased
adrenal
weights
and
intracytoplasmic
vacuoles
in
adrenal
cortex
in
females.

This
chemical
has
been
classified
by
HED
as
a
"
not
likely"
human
carcinogen
according
to
the
EPA
Proposed
Guidelines
for
Carcinogen
Risk
Assessment
(
April
10,
1996).
This
classification
is
based
on
the
lack
of
evidence
of
carcinogenicity
in
male
and
female
rats
as
well
as
in
male
and
female
mice
and
on
the
lack
of
genotoxicity
in
an
acceptable
battery
of
mutagenicity
studies.

Occupational
Handler
Exposure
Assessment
Existing
Uses
Page
6
of
29
Tolerances
for
residues
of
fenhexamid
per
se
are
currently
established
on
various
raw
agricultural
commodities
(
RAC)
from
almond
nut
meats
at
0.02
ppm
to
radicchio
at
30.0
ppm.

Proposed
Uses
IR­
4
has
submitted
field
trial
data
for
fenhexamid
on
cilantro
(
transplant
/
greenhouse),
non­
bell
pepper
(
transplant)
and
pomegranate
(
post­
harvest).
The
formulation
is
intended
for
ground
foliar
applications
in
fields
and
in
green
house
production
and
transplant
operations.

The
proposed
new
use
patterns
are
for
amendments
of
the
registered
product
ELEVATE
®
50
WDG
Fungicide
(
EPA
Reg.
No.
66330
­
35)
which
contains
50.0
%
by
weight
of
the
active
ingredient
fenhexamid.
The
use
pattern
summary
is
taken
from
the
IR
4
submissions.

POMEGRANATE
 
The
proposed
use
on
pomegranate
is
for
a
post­
harvest
fruit
dip
to
prevent
Botrytis
fruit
rot.
The
"
directions"
indicate
0.75
lb
active
ingredient
(
ai)
per
100
gallons
of
water.
Only
1
application
is
permitted.
No
other
directions
were
provided.

Cilantro
 
The
use
on
cilantro
is
for
transplant
production
and
for
greenhouse.
The
target
pest
is
Botrytis
cinerea
and
other
Botrytis
spp.
For
the
production
of
transplants,
the
rate
of
application
is
0.5
 
0.75
lb
ai/
A.
Applications
should
begin
when
conditions
favor
disease
occurrence.
There
is
a
7
day
application
interval.
On
transplants,
fenhexamid
should
be
applied
as
a
full
coverage
spray.
There
is
a
maximum
of
1.5
lb
ai/
A/
season
which
equates
to
2
applications
at
the
high
rate.
For
greenhouse
production
(
it
may
NOT
be
applied
in
the
field)
there
is
a
maximum
of
2
successive
applications
and
a
maximum
of
3
total
applications/
crop
at
the
low
rate
(
i.
e.,
0.5
lb
ai/
A).
There
is
a
3
day
preharvest
interval
(
PHI).

Non­
bell
pepper
 
As
indicated
earlier,
fenhexamid
is
currently
registered
for
use
on
Bell
peppers
and
other
varieties
of
pepper.
For
non­
Bell
pepper,
the
use
is
for
the
production
of
transplants.
The
target
pest
is
Botrytis
spp.
Fenhexamid
should
be
applied
to
the
point
of
run­
off
at
a
rate
of
0.75
lb
ai/
A.
There
is
a
maximum
of
4
applications
per
crop
and
a
maximum
of
3.0
lb
ai/
A/
yr.
No
other
directions
or
restrictions
were
given.

The
Elevate
®
label
indicates
applicators
and
other
handlers
must
wear
long­
sleeved
shirt,
long
pants,
socks,
shoes
and
waterproof
gloves
as
personal
protective
equipment
(
PPE)
when
mixing,
loading
or
applying
the
material.
See
Table
1.0
for
a
summary
of
the
proposed
use
pattern.

Margin
of
Exposure
(
MOE)

An
MOE
of
100
is
adequate
to
protect
agricultural
workers
from
post­
application
exposures
to
cilantro
(
transplant
/
greenhouse),
non­
bell
pepper
(
transplant)
and
pomegranate
(
post­
harvest).

Occupational
Post­
Application
Page
7
of
29
There
typically
is
the
possibility
for
agricultural
workers
to
experience
post­
application
exposure
to
dislodgeable
pesticide
residues.
For
the
proposed
new
uses,
there
is
the
possibility
of
postapplication
exposure
to
workers
who
sort,
cull
and
pack
treated
fruit.
There
is
also
the
possibility
that
workers
will
contact
foliar
dislodgeable
residues
on
plant
"
sets"
or
transplant.

The
post­
harvest
use
of
fenhexamid
(
as
an
in­
line
spray,
drench
or
fruit
dip)
will
result
in
exposure
to
workers
who
sort,
cull
or
pack
treated
fruit.
Typically,
HED
expects
fruit
"
packers"
would
be
exposed
to
short­
term
duration
exposures
(
1
­
30
days).
However,
exposures
of
intermediateterm
(
1
­
6
months)
might
be
possible.
In
this
case,
the
dermal
toxicological
endpoints
are
the
same
therefore,
estimates
of
risk
for
short­
term
duration
exposures
are
adequate
to
protect
workers
from
the
possibility
of
intermediate­
term
duration
exposures.

A
MOE
of
100
is
adequate
to
protect
workers
from
post­
harvest
treatment
of
fruit
during
the
course
of
culling,
sorting
or
packing
fruit
treated
with
fenhexamid.
Since
the
estimated
MOE
is
333,000
based
upon
conservative
assumptions,
the
proposed
use
does
not
exceed
HED's
level
of
concern.

Residue
Chemistry
Three
residue
trials
were
conducted
in
Georgia,
Florida
and
Texas.
Fenhexamid
was
applied
four
times
to
non­
bell
pepper
transplants
in
each
trial
as
a
foliar
broadcast
spray
at
the
rate
of
approximately
4
lb
a.
i./
A
(
maximum
season
rate
of
16
lb
a.
i./
A).
The
analytical
method
has
been
found
suitable
for
data
collection
and
enforcement
purposes.
The
results
from
these
trials
show
that
fenhexamid
applied
to
non­
bell
pepper
transplants
at
exaggerated
rates
resulted
in
residues
of
below
the
LOQ
level
(
0.02
ppm).
Storage
stability
data
indicate
that
the
residues
were
stable
under
the
conditions
in
which
the
samples
were
held
between
harvest
and
analysis.

The
5/
5/
04
ChemSAC
determined;
"
IR­
4
has
proposed
to
use
fenhexamid
on
nonbell
peppers
only
during
transplant
production.
Existing
tolerance
is
for
the
fruiting
vegetables
(
except
cucurbits)
group
(
except
nonbell
peppers)
at
2.0
ppm
but
this
tolerance
reflects
both
transplant
production
and
green
house
fruit
production
(
zero­
day
PHI)
treatments.
ChemSAC
decided
that
an
LOQ­
level
tolerance
may
be
established
for
residues
of
fenhexamid
in
nonbell
peppers."

One
trial
was
conducted
in
California
on
two
separate
lots
of
pomegranates
to
collect
data
on
the
residues
of
fenhexamid
following
a
post­
harvest
application
of
Elevate
50
WDG
as
a
30­
second
dip
at
a
rate
of
approximately
0.75
lb
a.
i./
100
gal.
The
analytical
method
has
been
found
suitable
for
data
collection
and
enforcement
purposes.
The
maximum
residue
on
pomegranates
was
1.845
ppm.
Storage
stability
data
indicate
that
the
residues
were
stable
under
the
conditions
in
which
the
samples
were
held
between
post­
harvest
treatments
and
analysis.
Page
8
of
29
The
proposed
tolerance
for
Pomegranate
was
3.0
ppm.
The
Tolerance
Calculator
(
see
NAFTA
Tolerance/
MRL
Harmonization
Workgroup;
May
9,
2005)
recommended
2.0
ppm.
The
registrant
must
submit
a
revised
Section
F.

Residential
Exposure
Assessments
There
are
currently
no
known
residential
uses
for
fenhexamid.

Chronic
Dietary
 
Food
+
Water
Based
on
the
toxicological
data,
an
acute
dietary
analysis
for
fenhexamid
is
not
required.

Chronic
dietary
exposure
analyses
for
fenhexamid
were
performed
using
the
Dietary
Exposure
Evaluation
Model
with
the
Food
Commodity
Intake
Database
(
DEEM
 
version
2.03),
which
uses
food
consumption
data
from
the
USDA's
Continuing
Surveys
if
Food
Intakes
by
Individuals
(
CSFII)
from
1994­
1996
and
1998.
The
analysis
was
performed
to
support
the
Interregional
Research
Project
No.
4
(
IR4)
action.

The
chronic
dietary
exposure/
risk
analysis
was
conducted
using
tolerance
values,
default
processing
factors,
100%
crop
treated
for
all
commodities,
and
average
(
chronic)
concentration
for
drinking
water.
Drinking
water
exposure
estimates
for
fenhexamid
were
calculated
using
the
screening
model
FIRST
(
FQPA
Index
Reservoir
Screening
Tool)
and
regression
model
SCIGROW
respectively.
.
Estimated
Environmental
Concentrations
(
EEC's)
for
fenhexamid
in
drinking
water
sources
are
29
ppb
(
acute)
and
1.1
ppb
(
chronic)
for
surface
water
and
0.0007
ppb
for
groundwater.

The
values
used
in
the
dietary
risk
assessment
for
drinking
water
were
provided
by
the
Environmental
Fate
and
Effects
Division
(
EFED)
in
the
following
memo:
DP
Barcode:
297963;
PC
Code:
090209
May
1,
2004;
Risk
Assessment
for
Proposed
Use
of
Fenhexamid
on
Pome
Fruit
Todd
Phillips,
Ph.
D.;
Environmental
Risk
Branch
IV
Environmental
Fate
and
Effects
Division
(
EFED).

Water
residues
were
incorporated
in
the
DEEM­
FCID
 
into
the
food
categories
"
water,
direct,
all
sources"
and
"
water,
indirect,
all
sources".

The
most
highly
exposed
population
subgroups
is
children
1­
2
years
of
age
at
28%
of
the
cPAD.
Chronic
dietary
risk,
for
food
and
water,
did
not
exceed
HED's
level
of
concern
(
DP
Barcodes:
None
;
CAL/
EPA
5/
22/
2006).

Aggregate
Exposure
and
Risk
Assessment
An
aggregate
exposure
risk
assessment
was
performed
for
chronic
aggregate
exposure
(
food
+
Page
9
of
29
water).
No
acute
or
short/
long­
term
aggregate
exposure
assessment
was
required
for
this
action.
A
cancer
aggregate
risk
assessment
was
not
performed
because
fenhexamid
is
classified
as
a
"
not
likely"
human
carcinogen
according
to
the
EPA
Proposed
Guidelines
for
Carcinogen
Risk
Assessment
(
April
10,
1996).
This
classification
is
based
on
the
lack
of
evidence
of
carcinogenicity
in
male
and
female
rats
as
well
as
in
male
and
female
mice
and
on
the
lack
of
genotoxicity
in
an
acceptable
battery
of
mutagenicity
studies.

Chronic
aggregate
risk
estimates
are
below
HED's
level
of
concern.
Since
there
are
no
residential
exposure
scenarios,
only
food
and
water
exposure
are
used
to
calculate
chronic
aggregate
risk.
For
chronic
dietary
risk
estimates,
HED's
level
of
concern
is
>
100%
of
the
chronic
population
adjusted
dose
(
cPAD).
For
the
chronic
Tier
1
analysis
(
assuming
tolerance
level
residues,
DEEM
 
default
processing
factors,
and
100%
CT
information)
the
chronic
dietary
risk
estimates
are
below
HED's
level
of
concern
(<
100%
chronic
population
adjusted
dose
(
cPAD))
for
the
general
U.
S.
population
(
11%
of
the
cPAD)
and
all
population
subgroups.
The
chronic
dietary
exposure
estimate
for
the
highest
exposed
population
subgroup
(
children
1­
2
years
old)
is
28%
of
the
cPAD.
Refinement
using
anticipated
residues
(
ARs),
processing
factors,
and
percent
crop
treated
(%
CT)
data
would
result
in
even
lower
chronic
exposure
estimates.

Recommendation
for
Tolerances
and
Registration
The
toxicology
and
residue
chemistry
databases
are
adequate
to
support
the
following
tolerance
for
residues
of
fenhexamid,
[
N­(
2,3­
dichloro­
4­
hydroxyphenyl)­
1­
methyl­
cyclohexane
carboxamide]
for
the
following
raw
agricultural
commodities
(
RAC):

pepper,
non­
bell
(
transplant)                 ...
0.02
ppm
pomegranate
(
post­
harvest)                  ..
2.0
ppm
cilantro                          .
30.0
ppm
Provided
a
revised
Section
F
is
received,
ARIA
concludes
that
the
proposed
tolerance
for
fenhexamid
in/
on
pepper,
non­
bell
(
transplant),
pomegranate
(
post­
harvest)
and
cilantro
is
adequate
and
appropriate
and
will
not
expose
humans,
animals
or
the
environment
to
unreasonable
adverse
effects.

2.0.
PHYSICAL/
CHEMICAL
PROPERTIES
CHARACTERIZATION
2.1.
Identification
of
Active
Ingredient
Table
1.
Test
Compound
Nomenclature
Common
name
Fenhexamid
Company
experimental
name
KBR
2738
Page
10
of
29
IUPAC
name
2,3­
dichloro­
4­(
1­
methylcyclohexyl­
carbonylamine)­
phenol
CAS
name
N­(
2,3­
dichloro­
4­
hydroxyphenyl)­
1­
methyl­
cyclohexanecarboxamide
CAS
#
126833­
17­
8
End­
use
product/
EP
ELEVATE
50
WDG
Fungicide
2.2.
Structural
Formula
of
Fenhexamid
2.3.
Physical
and
Chemical
Properties
Table
2.
Physicochemical
Properties
of
the
Technical
Grade
Test
Compound
Parameter
Value
Reference
Melting
point/
range
153
oC
pH
8.3
in
1%
solution
of
water
Density
1.34
g/
mL
@
20
oC
Water
solubility
(
20
°
C)
20
mg/
L
Solvent
solubility
(
mg/
L
at
20
°
C)
dichloromethane:
31000,
2­
propanol:
91000,
n­
hexane:
<
100,
Toluene:
5700
Vapor
pressure
at
25
°
C
7x10­
9
Torr
Dissociation
constant
(
pKa)
7.3
Octanol/
water
partition
coefficient
Log(
KOW)
3.51
(
pH
7,
20
oC
)

UV/
visible
absorption
spectrum
245
and
290
nm
(
wavelengths
of
maximum
absorption)
Fenhexamid:
Pesticide
Fact
Sheet
(
May
20,
1999)

Fenhexamid
(
KBR
2738)­
a
Botryticide
from
a
New
Chemical
Class,
Pflanzenschutz­
Nachrichten
Bayer
52/
1999,
2
Page
11
of
29
3.0
HAZARD
CHARACTERIZATION
3.1.
Hazard
Profile
The
acute
toxicity
of
fenhexamid
technical
is
shown
in
Table
3.

Table
3.
Acute
Toxicology
of
Fenhexamid
Technical
Material
Guideline
No./
Study
Type
MRIDs
#
Results
Toxicity
Category
870.1100
Acute
oral
toxicity
­
rat
44346769
M:
LD50>
5000
mg/
kg
F:
LD50>
5000
mg/
kg
IV
870.1200
Acute
dermal
toxicity
­
rat
44346770
M:
LD50>
5000
mg/
kg
F:
LD50>
5000
mg/
kg
IV
870.1300
Acute
inhalation
toxicity
­
rat
44366513
DUST
M:
LD50>
5000
mg/
kg
F:
LD50>
5000
mg/
kg
DUST
IV
870.2400
Acute
eye
irritation
­
rabbit
44346771
Not
an
eye
irritant.
IV
870.2500
Acute
skin
irritation
­
rabbit
44346771
Not
a
dermal
irritant.
IV
3.2.
FQPA
Considerations
The
FQPA
Safety
Factor
assumes
that
the
exposure
databases
(
dietary
food,
drinking
water,
and
residential)
are
complete
and
that
the
risk
assessment
for
each
potential
exposure
scenario
includes
all
metabolites
and/
or
degradates
of
concern
and
does
not
underestimate
the
potential
risk
for
infants
and
children.
No
special
FQPA
safety
factor
is
needed
(
i.
e.
1X)
since
there
are
no
residual
uncertainties
for
pre
and/
or
post
natal
toxicity.

3.2.1.
Cumulative
Risk
Section
408
(
b)(
2)(
D)(
v)
of
the
FFDCA
requires
that,
when
considering
whether
to
establish,
Page
12
of
29
modify,
or
revoke
a
tolerance,
the
Agency
consider
"
available
information"
concerning
the
cumulative
effects
of
a
particular
pesticides
residues
and
"
other
substances
that
have
a
common
mechanism
of
toxicity."

EPA
does
not
have,
at
this
time,
available
data
to
determine
whether
fenhexamid
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
fenhexamid
and
any
other
substances
and
fenhexamid
does
not
appear
to
produce
a
toxic
metabolite
produce
by
other
substances.
For
the
purposes
of
this
tolerance
action,
therefore,
EPA
has
not
assumed
that
fenhexamid
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/.

3.2.2.
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
Disrupter
Screening
and
Testing
Advisory
Committee
(
EDSTAC),
EPA
determined
that
there
was
scientific
basis
for
including,
as
part
of
the
program,
the
androgen
and
thyroid
hormone
systems,
in
addition
to
the
estrogen
hormone
system.
EPA
also
adopted
EDSTAC's
recommendation
that
the
Program
include
evaluations
of
potential
effects
in
wildlife.
For
pesticide
chemicals,
EPA
will
use
FIFRA
and,
to
the
extent
that
effects
in
wildlife
may
help
determine
whether
a
substance
may
have
an
effect
in
humans,
FFDCA
authority
to
require
the
wildlife
evaluations.
As
the
science
develops
and
resources
allow,
screening
of
additional
hormone
systems
may
be
added
to
the
Endocrine
Disrupter
Screening
Program
(
EDSP).

Fenhexamid
is
not
considered
to
be
an
"
endocrine
disruptor"
chemical.
Although
apparently
treatment­
related
effects
were
observed
in
the
adrenal
gland
in
the
1­
year
feeding
study
in
dogs
(
slightly
increased
adrenal
weights
and
slightly
increased
incidence
and
severity
of
intracytoplasmic
vacuoles
in
the
adrenal
cortex
of
female
dogs
only),
these
effects
were
mild
and
were
not
accompanied
by
any
other
toxicologically
significant
signs
of
adrenal
dysfunction
in
this
study
or
in
any
other
study
on
fenhexamid.
In
the
2­
year
chronic
feeding/
carcinogenicity
study
in
rats,
apparently
treatment­
related
effects
in
the
thyroid
gland
in
both
male
and
female
rats
(
decreased
follicle
volume
and
blue­
gray
clumps
of
colloid)
were
observed,
but
only
at
the
very
high
dose
of
1280/
2067
mg/
kg/
day
(
M/
F).
These
effects
were
not
accompanied
by
any
other
toxicologically
significant
signs
of
thyroid
dysfunction
in
this
study
or
in
any
other
study
on
fenhexamid.
Thyroid
hormone
levels,
however,
were
not
measured
in
the
2­
year
rat
study.
Page
13
of
29
When
the
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency's
EDSP
have
been
developed,
fenhexamid
may
be
subjected
to
additional
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.

3.3.
Dose
Response
Assessment
The
doses
and
toxicological
endpoints
selected
for
various
exposure
scenarios
are
summarized
in
Table
4.

Table
4.
Summary
of
Toxicological
Dose
and
Endpoints
for
Fenhexamid
for
Use
in
Human
Risk
Assessment
.

Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
(
General
Population
including
infants
and
children)
None
UF
=
NA
Acute
RfD
=
None
FQPA
SF
=
1X
aPAD
=
acute
RfD
FQPA
SF
=
None
Not
selected.
No
appropriate
toxicological
endpoint
attributable
to
a
single
exposure
was
identified
in
the
available
toxicology
studies.

Chronic
Dietary
(
All
populations)
NOAEL
=
17
mg
ai/
kg/
day
UF
=
100
Chronic
RfD
=
0.17
mg/
kg/
day
1X
cPAD
=
chronic
RfD
FQPA
SF
=
0.17
mg/
kg/
day
1­
Year
Feeding­
Dog.
Decreased
RBC
count,
hemoglobin
and
hematocrit
and
increased
Heinz
bodies
in
males
and
females;
increased
adrenal
weights
and
intracytoplasmic
vacuoles
in
adrenal
cortex
in
females.
at
the
LOAEL
of
124
mg/
kg/
day.

Short­
Term
(
1
­
30
days)
and
Intermediate­
Term
(
1
­
6
months)
Dermal
NOAEL
=
1000
mg
ai/
kg/
day
Residential
MOE
=
NA
Occupational
MOE
=
100
21­
Day
Dermal­
Rabbit.
[
In
the
developmental
toxicity
study
in
rabbits,
decreased
body
weight
gain
and
food
consumption
at
LOAEL
of
1500
mg/
kg/
day
(
dermal
equivalent
dose
using
20%
dermal
absorption
factor);
NOAEL
was
500
mg/
kg/
day
(
dermal
equivalent
dose)]

Long­
Term
Dermal
(>
6
months)
None
Residential
MOE
=
NA
Occupational
MOE
=
NA
Not
selected.
It
was
determined
that
no
long
term
exposure
would
occur
with
current
proposed
registrations
(
see
TXR
No.
013258).

Short­
Term
(
1
­
30
days)
and
Intermediate­
Term
(
1
­
6
months)
Inhalation
None
Residential
MOE
=
NA
Occupational
MOE
=
NA
Not
selected.
It
was
determined
that
a
separate
inhalation
risk
assessment
is
not
required
for
short­
and
intermediate­
term
inhalation
risk
assessments
(
see
TXR
NO.
013258).
Page
14
of
29
Table
4.
Summary
of
Toxicological
Dose
and
Endpoints
for
Fenhexamid
for
Use
in
Human
Risk
Assessment
.

Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Long­
Term
Inhalation
(>
6
months)
None
Residential
MOE
=
NA
Occupational
MOE
=
NA
Not
selected.
It
was
determined
that
no
long
term
exposure
would
occur
with
current
proposed
registrations
(
see
TXR
NO.
013258).

UF
=
uncertainty
factor,
FQPA
SF
=
Special
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,
NA
=
Not
Applicable
4.0.
EXPOSURE
ASSESSMENT
4.1.
Summary
of
Proposed
Uses
POMEGRANATE
 
The
proposed
use
on
pomegranate
is
for
a
post­
harvest
fruit
dip
to
prevent
Botrytis
fruit
rot.
The
"
directions"
indicate
0.75
lb
active
ingredient
(
ai)
per
100
gallons
of
water.
Only
1
application
is
permitted.
No
other
directions
were
provided.

CILANTRO
 
The
use
on
cilantro
is
for
transplant
production
and
for
greenhouse.
The
target
pest
is
Botrytis
cinerea
and
other
Botrytis
species.
For
the
production
of
transplants,
the
rate
of
application
is
0.5
 
0.75
lb
a.
i./
A.
Applications
should
begin
when
conditions
favor
disease
occurrence.
There
is
a
7
day
application
interval.
On
transplants,
fenhexamid
should
be
applied
as
a
full
coverage
spray.
There
is
a
maximum
of
1.5
lb
a.
i./
A/
season
which
equates
to
2
applications
at
the
high
rate.
For
greenhouse
production
(
it
may
NOT
be
applied
in
the
field)
there
is
a
maximum
of
2
successive
applications
and
a
maximum
of
3
total
applications/
crop
at
the
low
rate
(
i.
e.,
0.5
lb
a.
i./
A).
There
is
a
3
day
preharvest
interval
(
PHI).

NON­
BELL
PEPPER
 
As
indicated
earlier,
fenhexamid
is
currently
registered
for
use
on
bell
peppers
and
other
varieties
of
pepper.
For
non­
bell
pepper,
the
use
is
for
the
production
of
transplants.
The
target
pest
is
Botrytis
spp.
Fenhexamid
should
be
applied
to
the
point
of
run­
off
at
a
rate
of
0.75
lb
a.
i./
A.
There
is
a
maximum
of
4
applications
per
crop
and
a
maximum
of
3.0
lb
a.
i./
A/
yr.
No
other
directions
or
restrictions
were
given.

4.2.
Dietary
Exposure
4.2.1.
Food
Exposure
4.2.1.
a.
Nature
of
the
Residue
­
Plants
and
Livestock
Plants
Page
15
of
29
Acceptable
fenhexamid
metabolism
studies
on
grapes,
tomatoes,
and
apples
have
previously
been
submitted
and
reviewed
by
HED.
The
results
of
those
metabolism
studies
indicate
that
most
of
the
terminal
residue
is
unmetabolized
parent.
Fenhexamid
residues
are
non­
systemic
and
primarily
surface
residues.
HED's
Metabolism
Assessment
Review
Committee
(
MARC)
has
concluded
that
only
residues
of
parent
fenhexamid
per
se
need
to
be
included
in
the
tolerance
expression.
Metabolism
studies
labeled
in
a
different
position
are
not
required;
however,
additional
14Cfenhexamid
metabolism
studies
(
on
dissimilar
crops)
may
be
required
to
support
future
requests
for
tolerances
and
registrations.
For
the
purposes
of
this
action,
the
nature
of
fenhexamid
residues
in
plants
is
adequately
understood.
Livestock
Since
there
are
no
cilantro,
pomegranate
or
non­
bell
pepper
feed
items
of
regulatory
interest,
a
discussion
of
the
metabolism
of
fenhexamid
in
animal
commodities
is
not
germane
to
this
action.

4.2.1.
b.
Residue
Analytical
Method
­
Plants
and
Livestock
Method
validation
was
accomplished
by
fortification
of
untreated
control
samples
of
pomegranate
with
fenhexamid
at
levels
of
0.02,
0.5
and
5
ppm
and
recoveries
ranged
from
64
to
94%.
Untreated
pomegranate
samples
were
fortified
at
levels
of
0.02,
0.5,
2.0
and
5.0
ppm
and
analyzed
concurrently
with
the
treated
field
samples.
The
method
concurrent
recoveries
ranged
from
87
to
99%.
The
limit
of
quantification
(
LOQ)
of
0.03
ppm
and
a
limit
of
detection
(
LOD)
of
0.01
ppm
were
reported.
The
method
is
adequate
for
data
collection.
However,
since
these
are
non­
field
trials,
the
number
and
location
are
adequate.

Bayer
AG
Method
00362
(
HPLC
 
ECD),
is
the
tolerance
enforcement
method
for
fenhexamid
residues.
It
has
previously
undergone
a
successful
independent
laboratory
validation
(
ILV)
using
grapes
as
the
test
matrix.
The
method
has
also
undergone
successful
validation
by
the
Analytical
Chemistry
Branch
(
ACB)/
BEAD>
A
copy
of
Bayer
AG
Method
00362
has
been
sent
to
FDA
for
publication
in
the
PAM,
Volume
II,
as
a
Roman
numeral
method.

4.2.1.
c.
Multiresidue
Methods
Fenhexamid
has
previously
been
subjected
to
testing
via
the
FDA
multiresidue
methods
protocols.
Fenhexamid
was
adequately
recovered
(>
80%)
from
non­
oily
matrices
using
Protocol
B,
but
recovery
from
an
oily
matrix
was
only
ca
15%.
The
FDA
multiresidue
method,
Protocol
B
would
be
adequate
as
an
enforcement
method
for
non­
oily
crops.

4.2.1.
d.
Storage
Stability
Data
Freezer
storage
stability
data
were
previously
submitted.
The
data
demonstrated
the
stability
of
fenhexamid
residues
on
kiwifruit
(
145
days),
peach
(
223
days),
cherry
(
216
days)
and
tomato
(
365
days).
Storage
stability
data
presented
indicates
that
the
residues
of
fenhexamid
are
stable
Page
16
of
29
for
the
duration
of
the
residue
field
trial
study,
up
to
182
days.

4.2.1.
e.
Crop
Field
Trials
Pomengranate:
MRID
No.
46362601:
IR­
4
has
submitted
field
trial
data
for
post­
harvest
treatment
of
pomegranate
with
fenhexamid.
The
pomegranate
fruit
was
collected
from
two
separate
field
sites
(
Mendota
and
Kettleman,
California)
and
dipped
for
approximately
30
seconds
in
an
Elevate
50
WDG
solution
at
a
rate
of
approximately
0.75
lb
a.
i./
100
gal
water.
The
fruit
from
each
site
was
treated
with
a
separate
independently
mixed
solution.
The
number
and
locations
of
field
trials
are
not
in
accordance
with
OPPTS
Guideline
860.1500
and
Directive
98­
02;
Section
9.
A
minimum
of
three
trials
is
required
on
pomegranate.

The
samples
were
analyzed
using
the
reference
method:
Bayer
AG
method
"
Method
for
Determination
of
KBR
2738
(
TM­
402)
Residues
in
Plant
Material
by
HPLC"
(
J.
Bachmann
and
F.
Nublein,
dated
6­
16­
95).
Residues
of
fenhexamid
were
extracted
with
acetone
and
filtered.
After
evaporation
of
acetone,
the
aqueous
residue
was
cleaned
up
on
a
ChemElute
column
and
eluted
with
cyclohexane
/
ethyl
acetate
(
85/
15).
The
sample
was
then
evaporated
to
dryness
and
taken
up
in
0.1
%
acetic
acid
/
methanol
(
40/
60).
LC/
MS/
MS
was
utilized
for
simultaneous
quantization
and
confirmation
of
fenhexamid.

Method
validation
was
accomplished
by
fortification
of
untreated
control
samples
of
pomegranate
with
fenhexamid
at
levels
of
0.02,
0.5
and
5
ppm
and
recoveries
ranged
from
64
to
94%.
Untreated
pomegranate
samples
were
fortified
at
levels
of
0.02,
0.5,
2.0
and
5.0
ppm
and
analyzed
concurrently
with
the
treated
field
samples.
The
method
concurrent
recoveries
ranged
from
87
to
99%.
The
limit
of
quantification
(
LOQ)
of
0.03
ppm
and
a
limit
of
detection
(
LOD)
of
0.01
ppm
were
reported.
The
method
is
adequate
for
data
collection.
However,
since
these
are
non­
field
trials,
the
number
and
location
are
adequate.

The
results
from
these
trials
show
that
fenhexamid
applied
to
pomegranate
fruit
as
a
post­
harvest
dipping
resulted
in
residues
of
1.6
to
1.8
ppm.
The
submitted
storage
stability
data
are
adequate
to
indicate
that
the
residues
were
stable
under
the
conditions
in
which
the
samples
were
held
between
treatment
and
analysis.

The
proposed
tolerance
for
pomegranate
was
3.0
ppm.
The
Tolerance
Calculator
(
see
NAFTA
Tolerance/
MRL
Harmonization
Workgroup;
May
9,
2005)
recommended
2.0
ppm
Non­
bell
pepper:
IR­
4
has
submitted
a
summary
report
(
No
MRID)
of
field
trial
data
for
fenhexamid
on
non­
bell
pepper
(
transplant
use).
Three
trials
were
conducted
in
Georgia
(
EPA
Region
2),
Florida
(
EPA
Region
3),
and
Texas
(
EPA
Region
6).
The
number
and
locations
of
field
trials
are
in
accordance
with
OPPTS
Guideline
860.1500
and
Directive
98­
02;
Section
9.

At
each
test
location,
four
applications
of
Elevate
50
WDG
were
applied
to
the
non­
bell
pepper
transplants
(
prior
to
transplanting)
as
a
foliar
broadcast
till
run­
off
at
the
rate
of
approximately
4
Page
17
of
29
lb
a.
i./
A
(
season
maximum
16
lb
a.
i./
A).
An
adjuvant
was
not
used
for
any
application.

The
samples
were
analyzed
using
the
reference
method:
Bayer
AG
method
"
Method
for
Determination
of
KBR
2738
(
TM­
402)
Residues
in
Plant
Material
by
HPLC"
(
J.
Bachmann
and
F.
Nublein,
dated
6­
16­
95).
Method
validation
was
accomplished
by
fortification
of
untreated
control
samples
of
non­
bell
pepper
with
fenhexamid
at
levels
of
0.02
ppm
and
recoveries
ranged
from
70
to
100%.
The
LOQ
of
0.021
ppm
and
a
LOD
of
0.007
ppm
were
reported.
The
method
is
adequate
for
data
collection.

The
results
from
these
trials
show
that
fenhexamid
applied
to
non­
bell
pepper
transplants
at
the
exaggerated
rates
resulted
in
residues
of
below
the
LOQ
level
(
0.02
ppm).
The
submitted
storage
stability
data
are
adequate
to
indicate
that
the
residues
were
stable
under
the
conditions
in
which
the
samples
were
held
between
harvest
and
analysis.

The
5/
5/
04
ChemSAC
determined;
"
IR­
4
has
proposed
to
use
Fenhexamid
on
nonbell
peppers
only
during
transplant
production.
Existing
tolerance
is
for
the
Fruiting
vegetables
(
except
cucurbits)
group
(
except
nonbell
peppers)
at
2.0
ppm
but
this
tolerance
reflects
both
transplant
production
and
green
house
fruit
production
(
zero­
day
PHI)
treatments.
ChemSAC
decided
that
an
LOQ­
level
tolerance
may
be
established
for
residues
of
fenhexamid
in
nonbell
peppers."

4.2.1.
f.
Processed
Food/
Feed
There
are
no
pomegranate,
cilantro
or
non­
bell
pepper
use
processed
food
items
of
regulatory
interest,
therefore
a
discussion
of
processed
food
commodities
is
not
germane
to
this
action.

4.2.1.
g.
Meat,
Milk,
Poultry
and
Eggs
There
are
no
pomegranate,
cilantro
or
non­
bell
pepper
uses
of
fenhexamid
residues
in
animal
commodities
of
regulatory
interest,
therefore
a
discussion
of
processed
pomegranate
or
non­
bell
pepper
(
transplant)
food
commodities
is
not
germane
to
this
action.

4.2.1.
h.
Confined
and
Field
Accumulation
in
Rotational
Crops
A
fenhexamid
confined
rotational
crop
study
has
previously
been
submitted
and
reviewed.
In
that
study,
a
single
application
of
the
proposed
fenhexamid
formulation
was
made
to
bare
soil
prior
to
planting
representative
rotational
crops
at
3.09
lbs
ai/
A.
Fenhexamid
was
only
detected
at
levels
>
0.01
ppm
in/
on
Swiss
chard
(
max.
0.03
ppm)
at
the
30­
day
plantback
interval.
Residues
were
<
0.01
ppm
in/
on
other
rotational
crop
commodities:
turnips
(
tops,
roots)
and
wheat
(
forage,
hay,
straw,
and
grain).
HED
concluded
that
a
30­
day
plantback
interval
should
appear
on
the
label
and
apply
to
all
crops
without
a
registered
use.
The
Elevate
50
WDG
registered
label
does
specify
a
30­
day
plantback
restriction
for
non­
label
crops.
The
label
plantback
interval
is
adequate.
Page
18
of
29
4.2.1.
i.
International
Harmonization
of
Tolerances
Fenhexamid
per
se
is
the
residue
to
be
regulated
in
pomegranate,
cilantro
or
non­
bell
pepper.
There
are
no
Canadian,
Mexican,
or
Codex
MRLs
for
fenhexamid,
therefore
there
are
no
issues
for
international
harmonization.

4.2.2.
Drinking
Water
The
proposed
use
of
fenhexamid
on
pomegranate,
cilantro
or
non­
bell
pepper
(
is
not
expected
to
raise
the
value
of
any
previous
Estimated
Environmental
Concentrations
(
EEC's)
due
to
the
very
small
acreage
of
pomegranate
or
non­
bell
pepper
(
transplant)
grown.
Thus,
the
values
cited
in
the
previous
risk
assessment
(
PP#
4E6859,
DP:
316518,
B.
Hanson,
12/
19/
05),
and
presented
again
here,
are
still
current
and
are
recommended
for
use
in
this
risk
assessment
.

4.2.2.
a.
Surface
and
Ground
Water
Based
on
the
environmental
fate
and
ecological
effects,
EFED
does
not
expect
the
proposed
uses
of
fenhexamid
to
present
a
risk
to
nontarget
organisms,
including
endangered
species.
Fenhexamid
is
nonpersistent
to
slightly
persistent
in
the
environment
under
aerobic
and
anaerobic
conditions,
which
greatly
limits
its
transport
to
surface
water
or
groundwater.
Also,
the
rapid
rate
of
aqueous
photolysis
of
fenhexamid,
combined
with
its
tendency
to
bind
to
sediments,
greatly
reduces
its
bioavailability
in
an
aquatic
environment.

Drinking
water
exposure
estimates
for
fenhexamid
in
surface
water
and
groundwater
were
calculated
using
the
screening
model
FIRST
(
FQPA
Index
Reservoir
Screening
Tool)
and
regression
model
SCI­
GROW,
respectively.
Estimated
Environmental
Concentrations
(
EEC's)
for
fenhexamid
in
drinking
water
sources
are
29
ppb
(
acute)
and
1.1
ppb
(
chronic)
for
surface
water
and
0.0007
ppb
for
groundwater.

Table
7.
EFED
Estimated
Environmental
Concentrations
(
EECS)

Ground
water
(
µ
g/
L)
Surface
water
(
µ
g/
L)

0.0007
(
acute
&
chronic)
29
(
acute)
1.14
(
chronic)

4.2.3.
Dietary
Exposure
(
Food
+
Water)
and
Risk
Analyses
HED
conducts
dietary
(
food
only)
risk
assessments
using
DEEM
 
,
which
incorporates
consumption
data
generated
in
USDA's
Continuing
Surveys
of
Food
Intakes
by
Individuals
(
CSFII),
1989­
1992.
For
acute
dietary
risk
assessments,
one­
day
consumption
data
are
summed
and
a
food
consumption
distribution
is
calculated
for
each
population
subgroup
of
interest.
The
consumption
distribution
can
be
multiplied
by
a
residue
point
estimate
for
a
deterministic
Page
19
of
29
exposure/
risk
assessment,
or
be
used
with
a
residue
distribution
in
a
probabilistic
type
risk
assessment.
Acute
exposure
estimates
are
expressed
in
mg/
kg
bw/
day
and
as
a
percent
of
the
aPAD.
For
chronic
risk
assessments,
residue
estimates
for
foods
or
food­
forms
of
interest
are
multiplied
by
the
average
consumption
estimate
of
each
food/
food­
form
of
each
population
subgroup.
Chronic
exposure
estimates
are
expressed
in
mg/
kg
bw/
day
and
as
a
percent
of
the
cPAD.

4.2.3.
a.
Acute
Dietary
Exposure
Analysis
Based
on
the
toxicological
data,
an
acute
dietary
analysis
for
fenhexamid
is
not
required.

4.2.3.
b.
Chronic
Dietary
(
Food
+
Water)
Exposure
Analysis
A
Tier
1
chronic
dietary
exposure
was
performed
assuming
tolerance
level
residues,
100%
CT
and
incorporating
EECs.
Default
processing
factors
were
used
for
all
commodities.
For
chronic
dietary
risk,
HED's
level
of
concern
is
>
100%
cPAD.
Dietary
exposure
estimates
for
the
U.
S.
population
and
other
representative
subgroups
are
presented
in
Table
8.

Table
8.
Summary
of
Results
from
Chronic
DEEMTM
Analysis
Chronic
Dietary
Cancer
Population
Subgroup*
Dietary
Exposure
(
mg/
kg/
day)
%
cPAD
Risk
General
U.
S.
Population
0.018220
11
All
Infants
(<
1
year
old)
0.0035239
21
Children
1­
2
years
old
0.048219
28
Children
3­
5
years
old
0.035835
21
Children
6­
12
years
old
0.022574
13
Youth
13­
19
years
old
0.014283
8
Adults
20­
49
years
old
0.015498
9
Females
13­
49
years
old
0.015590
9
Adults
50+
years
old
0.015590
9
N/
A
*
HED
notes
that
there
is
a
degree
of
uncertainty
in
extrapolating
exposures
for
certain
population
subgroups
which
may
not
be
sufficiently
represented
in
the
consumption
surveys,
(
e.
g.,
non­
nursing
infants,
etc.).
Therefore,
risks
estimated
for
these
subpopulations
were
included
in
representative
populations
having
sufficient
numbers
of
survey
respondents
(
e.
g.,
all
infants,
females,
13­
50
years,
etc.).
Page
20
of
29
The
most
highly
exposed
population
subgroups
is
children
1­
2
years
of
age
at
28%
of
the
cPAD.
The
addition
of
the
proposed
tolerance
petitions
(
non­
bell
pepper,
pomegranate
and
cilantro)
to
current
existing
fenhexamid
tolerances
(
40
CFR
180.553)
is
supported
and
do
not
result
in
an
unacceptable
level
of
chronic
dietary
exposure
and
risk.
Except
for
cilantro,
the
pomegranate
and
non­
bell
pepper
proposed
tolerances
were
established
based
on
results
from
magnitude
of
the
residue
(
MOR)
field
trial
studies.
The
proposed
cilantro
tolerance
uses
the
leafy
greens
(
except
spinach)
Crop
Subgroup
4A
as
a
surrogate.
Other
commodities
with
existing
section
3
or
18
fenhexamid
tolerances
are
not
described
herein,
but
are
instead
found
in
the
DEEM­
FCID
 
chronic
dietary
residue
file
attachment.
The
proposed
cilantro,
pomegranate
and
non­
bell
pepper
commodity
tolerance
residue
data
from
IR­
4
project
were
reviewed
for
U.
S.
EPA
by
the
California
Department
of
Pesticide
Regulation
(
DPR
memo
to
U.
S.
EPA
dated
11/
16/
2005;
C.
Peoples
and
M.
Papathakis).
The
results
of
the
chronic
analysis
indicate
that
the
estimated
chronic
dietary
risk
associated
with
the
existing
and
HED
recommended
uses
of
fenhexamid
is
below
HED's
level
of
concern
(<
100%
cPAD).

4.2.3.
c.
Cancer
Dietary
Exposure
Analysis
The
HIARC
classified
fenhexamid
as
a
"
not
likely"
human
carcinogen
according
to
the
EPA
Proposed
Guidelines
for
Carcinogen
Risk
Assessment
(
April
10,
1996).
This
classification
is
based
on
the
lack
of
evidence
of
carcinogenicity
in
male
and
female
rats
as
well
as
in
male
and
female
mice
and
on
the
lack
of
genotoxicity
in
an
acceptable
battery
of
mutagenicity
studies.

4.3.
Occupational/
Residential
Exposure
4.3.1.
Summary
of
Use
Patterns
and
Formulation
Tolerances
are
established
for
fenhexamid
on
many
raw
agricultural
commodities.
There
are
no
residential
uses.

The
proposed
new
use
patterns
are
for
amendments
of
the
registered
product
ELEVATE
®
50
WDG
Fungicide
(
EPA
Reg.
No.
66330
­
35)
which
contains
50.0
%
by
weight
of
the
active
ingredient
fenhexamid.
The
use
pattern
summary
is
taken
from
the
IR
4
submissions.

POMEGRANATE
 
The
proposed
use
on
pomegranate
is
for
a
post­
harvest
fruit
dip
to
prevent
Botrytis
fruit
rot.
The
"
directions"
indicate
0.75
lb
active
ingredient
(
ai)
per
100
gallons
of
water.
Only
1
application
is
permitted.
No
other
directions
were
provided.

CILANTRO
 
The
use
on
cilantro
is
for
transplant
production
and
for
greenhouse.
The
target
pest
is
Botrytis
cinerea
and
other
Botrytis
spp.
For
the
production
of
transplants,
the
rate
of
application
is
0.5
 
0.75
lb
ai/
A.
Applications
should
begin
when
conditions
favor
disease
occurrence.
There
is
a
7
day
application
interval.
On
transplants,
fenhexamid
should
be
applied
as
a
full
coverage
spray.
There
is
a
maximum
of
1.5
lb
ai/
A/
season
which
equates
to
2
applications
at
the
high
rate.
For
greenhouse
production
(
it
may
NOT
be
applied
in
the
field)
Page
21
of
29
there
is
a
maximum
of
2
successive
applications
and
a
maximum
of
3
total
applications/
crop
at
the
low
rate
(
i.
e.,
0.5
lb
ai/
A).
There
is
a
3
day
preharvest
interval
(
PHI).

NON­
BELL
PEPPER
 
As
indicated
earlier,
fenhexamid
is
currently
registered
for
use
on
bell
peppers
and
other
varieties
of
pepper.
For
non­
bell
pepper,
the
use
is
for
the
production
of
transplants.
The
target
pest
is
Botrytis
spp.
Fenhexamid
should
be
applied
to
the
point
of
run­
off
at
a
rate
of
0.75
lb
ai/
A.
There
is
a
maximum
of
4
applications
per
crop
and
a
maximum
of
3.0
lb
ai/
A/
yr.
No
other
directions
or
restrictions
were
given.

The
Elevate
®
label
indicates
applicators
and
other
handlers
must
wear
long­
sleeved
shirt,
long
pants,
socks,
shoes
and
waterproof
gloves
as
personal
protective
equipment
(
PPE)
when
mixing,
loading
or
applying
the
material.
See
Table
9
for
a
summary
of
the
proposed
use
pattern.

Proposed
Uses
Table
9.
Summary
of
Proposed
Use
Pattern
for
Fenhexamid
Use
Site
Pomegranate
post­
harvest
fruit
dip;

Cilantro
 
transplant
and
greenhouse
production;

Non­
Bell
pepper
 
transplant
production.

Pest
Botrytis
cinerea
and
other
Botrytis
spp.

Formulation
Product:
ELEVATE
®
50
WDG;
50
%
active
ingredient
water
dispersible
granule;
EPA
Reg.
No.
66330
­
35
Application
Rate
0.75
lb
ai/
100
gallons
water
as
a
post­
harvest
fruit
dip;

0.5
 
0.75
lb
ai/
A
for
cilantro
transplant
or
greenhouse
production;

0.75
lb
ai/
A
for
non­
Bell
pepper
transplant
production
Application
Method
high­
pressure
hand­
wand,
ground­
boom
sprayer
fruit
dip,
drench
or
in­
line
spray
(
post­
harvest)

Frequency
1
application
for
fruit
dip
3
applications
possible
for
cilantro
4
applications
possible
for
non­
Bell
pepper
PreHarvest
Interval
3
day
PHI
for
greenhouse
production
of
cilantro
Restricted
Entry
Interval
12
hours
Manufacturer
Arvesta
Corporation.
Page
22
of
29
4.3.2.
Occupational
Exposure
Assessment
Based
upon
the
proposed
new
use
patterns,
HED
believes
that
the
most
highly
exposed
occupational
pesticide
handlers
will
be
1)
mixer/
loader
using
open­
pour
loading
of
granules;
2)
an
applicator
using
high­
pressure
hand­
wand
sprayers
in
enclosed
situations
such
as
a
greenhouse
and
3)
an
applicator
using
open­
cab,
ground­
boom
sprayer.
The
latter
is
likely
not
to
be
of
the
size
and
capability
of
"
field
scale"
machines
as
beds
for
transplant
production
are
not
expected
to
be
of
the
same
size
as
actual
"
production"
fields.
However,
lacking
specific
information
as
to
the
sizes
of
transplant
"
fields"
or
beds,
HED
assumes
a
default
200
acre
per
day
spray
capability
for
a
ground­
boom
sprayer.
Therefore,
the
resulting
exposure
and
risk
estimates
may
be
conservative
i.
e.,
overestimates.

The
post­
harvest
fruit
treatment
is
an
automated
process
in
which
the
fruit
passes
along
a
"
line"
and
is
either
dipped
or
sprayed
in
an
automatic,
hooded
situation.
There
is
no
applicator
per
se.
The
only
occupational
pesticide
handler
in
this
case
is
the
"
loader"
who
pours
granules
into
the
mini­
bulk
spray
tank
in
preparation
for
fruit
to
pass
by
on
the
processing
line
for
sorting,
culling
and
finally
packing.
Post­
treatment
exposure
will
be
discussed
later.

HED
believes
that
in
these
cases,
most
occupational
pesticide
handlers
are
likely
to
be
private,
grower
handlers.
Short­
term
duration
(
1
 
30
days)
exposures
are
expected.
There
might
be
occasions
where
some
handlers
might
experience
a
small
number
of
short­
term
exposures.
But
due
to
the
timing
and
proposed
uses,
it
is
unlikely
that
intermediate­
term
duration
(
1
 
6
months)
exposures
will
occur.

It
is
not
uncommon
for
grower
(
private),
pesticide
handlers
to
perform
all
three
handling
activities
that
is,
to
mix,
load
and
apply
the
material.
However,
the
available
exposure
data
for
combined
mixer/
loader/
applicator
scenarios
are
limited
in
comparison
to
the
monitoring
of
these
two
activities
separately.
These
exposure
scenarios
are
outlined
in
the
PHED
(
Pesticide
Handler's
Exposure
Database)
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
personal
protective
equipment
(
PPE)
for
each
aspect
of
a
job
without
requiring
an
applicator
to
wear
unnecessary
PPE
that
may
be
required
for
a
mixer/
loader
(
e.
g.,
chemical
resistant
gloves
may
only
be
necessary
during
the
pouring
of
a
liquid
formulation).

No
chemical
specific
data
are
available
with
which
to
assess
potential
exposure
to
pesticide
Page
23
of
29
handlers.
The
estimates
of
exposure
to
pesticide
handlers
are
based
upon
surrogate
study
data
available
in
the
PHED
(
v.
1.1,
1998).
For
pesticide
handlers,
it
is
HED
policy
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
and
for
"
baseline"
with
the
use
of
protective
gloves
or
other
PPE
as
might
be
necessary.
The
ELEVATE
®
label
directs
applicators
and
other
handlers
to
wear
long­
sleeved
shirt,
long
pants,
socks,
shoes
and
waterproof
gloves.

Fenhexamid
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.
The
HIARC
identified
a
dermal
toxicological
endpoint
with
a
No
Observable
Adverse
Effect
Level
(
NOAEL)
of
1000
mg
a.
i./
kg
bw/
day
from
a
21
day
dermal
developmental
toxicity
study
in
the
rabbit.
The
LOAEL
was
not
observed
in
this
study.
However,
results
in
this
study
were
consistent
with
those
in
the
oral
developmental
toxicity
study
in
rabbits
(
MRID
44346801)
in
which
maternal
effects
(
decreased
body
weight
gain
and
decreased
feed
consumption)
were
observed,
particularly
during
the
first
week
of
dosing,
at
the
LOAEL
of
300
mg/
kg/
day.
The
NOAEL
for
maternal
toxicity
in
oral
study
was
100
mg/
kg/
day.
Using
a
20%
dermal
absorption
factor,
the
oral
NOAEL
(
100
mg/
kg/
day)
is
equivalent
to
a
dermal
NOAEL
of
500
mg//
kg/
day
and
the
oral
LOAEL
(
300
mg/
kg/
day)
is
equivalent
to
a
dermal
LOAEL
of
1500
mg/
kg/
day.
The
dermal
NOAEL
was
for
short­
term
(
1
­
30
days)
and
intermediate­
term
(
1
­
6
months)
exposure
durations.
Although
a
dermal
absorption
factor
has
been
identified,
it
is
not
used
for
purposes
of
assessing
dermal
exposure
and
risk
since
the
NOAEL
was
identified
from
a
21­
day
dermal
(
developmental)
study
and
dermal
absorption
is
already
accounted
for
in
the
study.

Based
on
the
lack
of
evidence
of
carcinogenicity
in
male
and
female
rats
as
well
as
male
and
female
mice,
HED
classified
fenhexamid
as
not
likely
to
be
a
human
carcinogen.
Therefore
an
assessment
of
cancer
risk
is
not
necessary.
See
Table
10
for
a
summary
of
exposures
and
risks
to
occupational
pesticide
handlers.

Table
10.
Summary
of
Exposures
and
Risks
to
Occupational
Pesticide
Handlers
Unit
Exposures1
mg
ai/
kg
bw/
day
Application
Rate2
lb
ai/
unit
Units
Treated/
Day3
Average
Daily
Dose4
mg
ai/
kg
bw/
day
Margin
of
Exposure5
Mixer/
Loader
Using
Open
Pour
(
Dry
Flowable)

Dermal:
SL
No
Gloves
0.066
LC
SL
W
Gloves
0.066
HC
0.75
lb
ai/
A
200
A
SL
No
Gloves
0.14
SL
With
Gloves
0.14
No
Gloves
7,100
With
Gloves
7,100
Applicator
Using
High­
pressure
Hand­
wand
Sprayer
Dermal:
SL
No
Gloves
1.8
LC
SL
W
Gloves
0.64
LC
0.75
lb
ai/
A
2
A**
SL
No
Gloves
0.039
SL
With
Gloves
0.014
No
Gloves
26,000
With
Gloves
73,000
Applicator
Using
Open­
cab
Ground­
boom
Sprayer
Dermal:
SL
No
Gloves
0.014
HC
0.75
lb
ai/
A
200
A
SL
No
Gloves
0.03
SL
With
Gloves
0.03
No
Gloves
33,300
With
Gloves
33,300
Page
24
of
29
SL
W
Gloves
0.014
MC
1.
Unit
Exposures
are
taken
from
"
PHED
SURROGATE
EXPOSURE
GUIDE",
Estimates
of
Worker
Exposure
from
The
Pesticide
Handler
Exposure
Database
Version
1.1,
August
1998.
SL
No
Gloves
=
Dermal
Single
Layer
Work
Clothing
No
Gloves;
SL
W
Gloves
=
Dermal
Single
Layer
Work
Clothing
With
Gloves;
Units
=
mg
a.
i./
pound
of
active
ingredient
handled.
Data
Confidence:
LC
=
Low
Confidence,
MC
=
Medium
Confidence,
HC
=
High
Confidence.
2.
Applic.
Rate.
=
Taken
from
IR
4
submissions
3.
Units
Treated
are
taken
from
"
Standard
Values
for
Daily
Acres
Treated
in
Agriculture";
SOP
No.
9.1.
Science
Advisory
Council
for
Exposure;
Revised
5
July
2000;
**
Acres
of
greenhouse
treated
per
day
is
taken
from:
Stamper,
J.
H.,
1989,
Arch.
Environm.
Contam.
Toxicol.
18:
515
 
529.
4.
Average
Daily
Dose
=
Unit
Exposure
*
Applic.
Rate
*
Units
Treated
÷
Body
Weight
(
70
kg).
A
70
kg
bw
is
used
in
calculations.
5.
MOE
=
Margin
of
Exposure
=
No
Observeable
Adverse
Effect
Level
(
NOAEL)
(
1000
mg
a.
i./
kg
bw/
day)
÷
ADD.
(
ADD
=
dermal).
The
HIARC
did
not
identify
an
inhalation
exposure
NOAEL.
6.
HED
does
not
have
unit
exposure
data
for
water
dispersible
granules
therefore,
as
a
surrogate,
unit
exposures
for
a
dry
flowable
formulation
are
used.

A
Margin
of
Exposure
of
100
is
adequate
to
protect
occupational
pesticide
handlers.
Since
all
estimated
MOEs
are
>
100,
the
proposed
use
does
not
exceed
HED's
level
of
concern.

4.3.2.
a.
Worker
Post­
Application
Exposure
Assumptions/
Assessment
There
typically
is
the
possibility
for
agricultural
workers
to
experience
post­
application
exposure
to
dislodgeable
pesticide
residues.
For
the
proposed
new
uses,
there
is
the
possibility
of
postapplication
exposure
to
workers
who
sort,
cull
and
pack
treated
fruit.
There
is
also
the
possibility
that
workers
will
contact
foliar
dislodgeable
residues
on
plant
"
sets"
or
transplants.

The
Science
Advisory
Council
for
Exposure
(
ExpoSAC)
and
the
Agricultural
Reentry
Task
Force
(
ARTF)
have
identified
numerous
post­
application,
agricultural
activities
which
can
result
in
worker
exposure
to
dislodgeable
foliar
pesticide
residues
(
SOP
003.1,
Rev.
7
Aug.
2000,
Regarding
Agricultural
Transfer
Coefficients;
Amended
ExpoSAC
Meeting
notes
­
13
Sept
01).

In
addition
to
identifying
the
post­
application
agricultural
activities,
the
ExpoSAC
SOP
(
No.
003.1
Rev.
7
Aug
2000)
also
identifies
Transfer
Coefficients
(
TC)
expressed
as
cm
²
/
hr
for
each
of
the
post­
application,
agricultural
activities.
The
TCs
are
derived
from
data
in
surrogate
exposure
studies
conducted
during
the
various
activities
listed.

The
TCs
used
in
this
assessment
are
taken
from
an
interim
TC
SOP
developed
by
HED's
ExpoSAC
using
proprietary
data
from
the
ARTF
database
(
SOP
No.
3.1).
It
is
the
intention
of
the
HED's
Science
Advisory
Council
for
Exposure
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.

There
are
no
compound
specific
foliar
dislodgeable
residue
data
available
for
use
in
estimating
post­
application
exposure
to
fenhexamid
while
transplanting
treated
"
sets".
There
are
no
TC
data
regarding
transplanting.
The
highest
TC
for
any
agricultural
activity
in
Bell
peppers
is
1,000
Page
25
of
29
cm
²
/
hr
for
hand
harvesting.
To
be
conservative
for
the
sake
of
safety,
HED
uses
the
1,000
cm
²
/
hr
value.
Also
lacking
compound
specific
data,
HED
assumes
20%
of
the
application
rate
is
available
as
dislodgeable
foliar
residue
(
DFR)
on
day
zero
after
application.
This
is
adapted
from
the
ExpoSAC
SOP
No.
003
(
7
May
1998
­
Revised
7
August
2000).
The
following
convention
may
be
used
to
estimate
post­
application
exposure.

Surrogate
Dislodgeable
Foliar
Residue
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
and
the
Average
Daily
Dose
(
ADD)
=
DFR
µ
g/
cm2
*
TC
cm2/
hr
*
hr/
day
*
0.001
mg/
µ
g
*
1/
60
kg
bw
 

0.75
lb
a.
i./
A
*
.20
*
(
1­
0)
0
*
4.54
x
108
µ
g/
lb
*
2.47
x10­
8
A/
cm
²
=
1.68
µ
g/
cm2
 

1.68
µ
g/
cm2
*
1,000
cm2/
hr
*
8
hr/
day
*
0.001
mg/
µ
g
*
1/
70
kg
bw
=
0.192
mg/
kg
bw/
day
Since
MOE
=
NOAEL
÷
ADD
then
1000
mg/
kg
bw/
day
÷
0.192
mg/
kg
bw/
day
=
5,200.

A
MOE
of
100
is
adequate
to
protect
agricultural
workers
from
post­
application
exposures
to
fenhexamid.
The
estimated
MOE
is
based
upon
conservative
assumptions
and
is
>
100,
therefore
estimated
risks
from
post­
application
exposures
do
not
exceed
HED's
level
of
concern.

POST­
HARVEST
EXPOSURE
TO
FRUIT
"
PACKERS"

The
post­
harvest
use
of
fenhexamid
(
as
an
in­
line
spray,
drench
or
fruit
dip)
will
result
in
exposure
to
workers
who
sort,
cull
or
pack
treated
fruit.
Typically,
HED
expects
fruit
"
packers"
would
be
exposed
to
short­
term
duration
exposures
(
1
­
30
days).
However,
exposures
of
intermediateterm
(
1
­
6
months)
might
be
possible.
In
this
case,
the
dermal
toxicological
endpoints
are
the
same
therefore,
estimates
of
risk
for
short­
term
duration
exposures
are
adequate
to
protect
workers
from
the
possibility
of
intermediate­
term
duration
exposures.

To
estimate
possible
fruit
packer
exposure,
HED
assumes
all
residues
occur
on
the
surface
of
the
fruit.
HED
also
assumes
that
residues
occur
at
the
proposed
tolerance
level
of
2.0
ppm.
Therefore
there
would
be
2.0
µ
g
fenhexamid
residue
per
gram
of
fruit.
All
surface
residues
are
assumed
to
be
"
bioavailable"
for
transfer.
The
assumed
residue
value
was
derived
by
the
Alternative
Risk
Integration
Assessment
Team
of
the
Registration
Division
(
pers.
comm.
e­
mail
,
J.
Redden,
17
MAY
2006).

Pomegranate
fruit
may
typically
be
2.5
 
5.0"
in
diameter
(
www.
crfg.
org).
An
average
fruit
is
approximately
9.0
oz
(
255
g)
(
www.
globalgourmet.
com).
A
large
pomegranate
may
weigh
460
g
(
www.
ressources.
ciheam.
org).
Page
26
of
29
A
fruit
packing
work
shift
is
assumed
to
last
8
hr.
A
Transfer
Coefficient
of
750
cm
²
/
hr
is
taken
from
D.
Jaquith
(
Memo,
14
SEP
2000,
DP
267084)
who
cites
Nigg,
H.
N.,
J.
H.
Stamper,
and
R.
M.
Queen
(
1984)
"
The
Development
and
Use
of
a
Universal
Model
to
Predict
Tree
Crop
Harvester
Pesticide
Exposure"
(
J.
Am.
Ind.
Hyg.
Assoc.;
45:
182­
186.)

The
Agency
has
no
data
addressing
sorting/
culling/
packing
of
post­
harvest
treated
fruit.
Therefore,
Jaquith
used
the
"
hands
only"
data
from
the
worker
reentry
study
of
citrus
harvesting
to
derive
a
Transfer
Coefficient.
HED
believes
that
exposure
from
packing,
sorting
or
culling
will
not
be
greater
than
what
is
measured
during
harvest.
The
Residue
Value
of
a
single
fruit
=
2.0
µ
g
a.
i./
g
fruit
*
460
g
fruit
=
920
µ
g
a.
i./
fruit.

The
surface
area
of
a
fruit
is
assumed
to
be
4 r2.
A
5.0
in
diameter
fruit
has
a
radius
of
2.5
in.
And
2.5
in
*
2.54
cm/
in
=
6.35
cm.

Therefore,
4 r2
=
4
*
3.14
*
6.35
cm2
=
506
cm
²
.

920
µ
g
a.
i./
fruit
÷
506
cm
²
/
fruit
=
1.8
µ
g
a.
i./
cm
²

 
1.8
µ
g
a.
i./
cm
²
*
750
cm
²
/
hr
*
8
hr/
day
*
0.001
mg/
µ
g
=
10.8
mg
a.
i./
day.
10.8
mg
a.
i./
day
÷
70
kg
bw
=
0.15
mg
a.
i./
kg
bw/
day.

In
a
study
by
Brouwer,
H.,
R.
Kroese
and
J.
Van
Hemmen,
1999
(
Transfer
of
Contaminants
from
Surface
to
Hands:
Experimental
Assessment
of
Linearity
of
the
Exposure
Process,
Adherence
to
the
Skin,
and
Area
Exposed
During
Fixed
Pressure
and
Repeated
Contact
with
Surfaces
Contaminated
with
a
Powder
in
Appl.
Occupat.
and
Environm.
Hyg.
14:
231­
239)
it
was
determined
that
repeated
hand
contacts
with
contaminated
surfaces
resulted
in
a
transfer
efficiency
of
about
2
%.

D.
Jaquith
(
Memo,
DP
280908,
"
Revision
to
Occupational
and
Residential
Exposure
Assessment
for
Thiabendazole
use
for
Post
Harvest
Treatment,
7
FEB
2002)
utilized
the
data
from
Brouwer
et
al.
In
a
similar
manner,
the
estimated
exposure
for
packing/
handling
fenhexamid
treated
pomegranate
fruit
is
adjusted
according
to
the
data
presented
by
Brouwer
et
al.

0.15
mg
a.
i./
kg
bw/
day
*
0.02
=
0.003
mg
a.
i./
kg
bw/
day
MOE
=
NOAEL
÷
ADD
 
1000
mg
a.
i./
kg
bw/
day
÷
0.003
mg
a.
i./
kg
bw/
day
=
333,000.

A
MOE
of
100
is
adequate
to
protect
workers
from
post­
harvest
treatment
of
fruit
during
the
course
of
culling,
sorting
or
packing
fruit
treated
with
fenhexamid.
Since
the
estimated
MOE
is
333,000
based
upon
conservative
assumptions,
the
proposed
use
does
not
exceed
HED's
level
of
concern.
Page
27
of
29
4.3.2.
b.
Restricted
Entry
Interval
Fenhexamid
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)
restricted
entry
interval
(
REI)
of
12
hours
is
adequate
to
protect
agricultural
workers
from
post­
application
exposures
(
i.
e.,
field
treatment)
to
fenhexamid
under
these
circumstances.

4.3.2.
c.
Incident
Reports
There
are
no
known
incidents
reported
for
fenhexamid.

4.3.3.
Residential
Exposure
There
are
currently
no
known
residential
uses
for
fenhexamid
and
so
no
residential
exposure
assessment
is
required.

4.4.
Non­
Occupational
Off­
Target
Exposure
Since
there
are
only
occupational
uses
for
fenhexamid
no
non­
occupational
off­
target
exposure
assessment
is
required.

5.0.
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATION
An
aggregate
exposure
risk
assessment
was
performed
for
chronic
aggregate
exposure
(
food
+
drinking
water).
No
acute
or
short/
long­
term
aggregate
exposure
assessment
were
required.
Ground
and
surface
water
estimates
are
cited
from
the
previous
risk
assessment.
A
cancer
aggregate
risk
assessment
was
not
performed
because
the
HIARC
classified
Fenhexamid
as
a
"
not
likely"
human
carcinogen
according
to
the
EPA
Proposed
Guidelines
for
Carcinogen
Risk
Assessment
(
April
10,
1996).

5.1.
Chronic
Aggregate
Risk
(
food
+
drinking
water)

Chronic
aggregate
risk
estimates
are
below
HED's
level
of
concern.
Since
there
are
no
residential
exposure
scenarios,
only
food
and
water
exposure
are
used
to
calculate
chronic
aggregate
risk.
For
chronic
dietary
risk
estimates,
HED's
level
of
concern
is
>
100%
of
the
chronic
population
adjusted
dose
(
cPAD).
For
the
chronic
Tier
1
analysis
(
assuming
tolerance
level
residues,
DEEM
 
default
processing
factors,
and
100%
CT
information)
the
chronic
dietary
risk
estimates
are
below
HED's
level
of
concern
(<
100%
chronic
population
adjusted
dose
(
cPAD))
for
the
general
U.
S.
population
(
11%
of
the
cPAD)
and
all
population
subgroups.
The
chronic
dietary
exposure
estimate
for
the
highest
exposed
population
subgroup
(
children
1­
2
years
old)
is
28%
of
the
cPAD.
Chronic
aggregate
exposure
from
fenhexamid
residues
in
food
and
drinking
water
will
not
exceed
the
Agency's
level
of
concern
(
100%
of
the
cPAD)
for
chronic
dietary
aggregate
Page
28
of
29
exposure
by
any
population
subgroup.
Refinement
using
anticipated
residues
(
ARs),
processing
factors,
and
percent
crop
treated
(%
CT)
data
would
result
in
even
lower
chronic
exposure
estimates.
HED
has
determined
that
there
are
no
residential
uses
or
exposure
for
fenhexamid.
Based
on
the
analysis
of
the
general
population,
Children
1­
2
years
(
highest
dietary
(
food
+
water),
Adults
50
+
years
and
Females
13­
19
years,
Chronic
dietary
(
food
+
water)
MOEs
ranged
from
352
to
1154.

6.0.
DATA
GAPS/
LABEL
CHANGES
Residue
Chemistry:
Revised
Section
F.

7.0.
ATTACHMENTS
None
for
this
action.

8.0
REFERENCES
CHEMISTRY
DP
Barcode:
D244844
&
D249061,
G.
Herndon,
3/
25/
1999
MARC
Decision,
DP
Barcode:
D253792,
G.
Herndon
3/
11/
1999
PP#
s:
2E6463,
2E6496,
3E6532,
3E6541,
DP
Barcodes:
D285209,
D285214,
D287732,

D287860,
M.
Nelson,
12/
2/
2003
MRID
46371501,
W.
Cutchin,
3/
7/
2005
PP#:
7F4890,
DP
Barcode:
D254172,
MRID
44346764,
G.
Herndon,
3/
15/
1999
PP#
s:
2E6463,
2E6496,
3E6532,
3E6541,
DP
Barcodes:
D285209,
D285214,
D287732,
D287860,
M.
Nelson,
12/
2/
2003
MRID
46371501,
W.
Cutchin,
3/
7/
2005
PP#
7F04890,
DP
Barcode:
D244844
&
D249061,
G.
Herndon,
3/
25/
1999
DEEM
DP
Barcodes:
D328660,
W.
Carr,
Cal/
EPA,
22
May
2006
ORE
DP
Code:
328715,
328716,
M.
Dow,
17
May
2006
HIARC
Memo,
B.
Tarplee,
TXR
NO.
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26
March
2003
Page
29
of
29
Residue
Chemistry
DP
Barcode:
None.
