Document ID: EPA-HQ-OPP-2004-0328-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-03-29T05:00Z

UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
March
30,
2005
MEMORANDUM
Subject:
Petition
Number:
4E6859
Dietary
Exposure
and
Risk
Analysis
for
the
Proposed
Interregional
Research
Project
No.
4
(
IR­
4)
Use
of
Fenhexamid
on
Ginseng
PC
Code:
090209
DP
Barcode:
D312267
Decision
Number:
351273
From:
Breann
Hanson,
Biologist
John
Redden,
Senior
Scientist
ARIA
Team
Registration
Division
(
7505C)

Through:
W.
Cutchin,
Chemist
Technical
Review
Branch
Registration
Division
(
7505C)

To:
Sidney
Jackson,
RM
05
MUIER
Branch
Registration
Division
(
7505C)

ACTION
REQUESTED
The
purpose
of
this
memorandum
is
to
provide
a
Tier
1
chronic
dietary
exposure
analysis
for
the
proposed
IR­
4
use
of
fenhexamid
on
commercially
grown
ginseng.
The
proposed
tolerance
level
of
0.3
ppm
was
recommended
by
TRB
(
Cutchin,
D312266,
Decision
Number:
351273,
03/
07/
2005).
In
this
analysis,
the
chronic
dietary
exposures
and
risk
estimates
resulting
from
food
intake
were
determined
for
the
general
U.
S.
population
and
various
population
subgroups.

EXECUTIVE
SUMMARY
A
chronic
Tier
1
dietary
exposure
to
fenhexamid
analysis
(
assuming
tolerance
level
residues,
default
processing
factors,
and
100
percent
crop
treated
(%
CT)
information)
was
conducted
for
fenhexamid.
Based
on
the
toxicological
data,
an
acute
dietary
analysis
for
fenhexamid
is
not
required.
This
analysis
incorporates
all
current,
pending,
and
proposed
tolerances
for
fenhexamid
as
of
February
17,
2005.
The
chronic
dietary
risk
assessment
indicates
that
for
all
registered
and
proposed
commodities,
the
chronic
dietary
risk
estimates
are
below
HED's
level
of
concern
(<
100%
chronic
population
adjusted
dose
(
cPAD))
for
the
general
U.
S.
population
(
10%
of
the
cPAD)
and
all
population
subgroups.
The
chronic
dietary
exposure
estimate
for
the
highest
exposed
population
subgroup
(
children
1­
2
years
old)
is
68%
of
the
cPAD.

The
toxicology
and
residue
chemistry
databases
are
adequate
to
support
the
following
tolerance
for
the
combined
residues
of
the
fungicide
fenhexamid
and
registration
for
the
use
of
fenhexamid
on
Ginseng
Group
1AB
in
terms
of
human­
health
risk:

Ginseng
Group
1AB
­
0.3
ppm
Refinement
using
anticipated
residues
(
ARs),
processing
factors,
and
percent
crop
treated
(%
CT)
data
would
result
in
even
lower
chronic
exposure
estimates.

Fenhexamid
has
been
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.

I.
Introduction
Dietary
risk
assessment
incorporates
both
exposure
and
toxicity
of
a
given
pesticide.
For
acute
and
chronic
assessments,
the
risk
is
expressed
as
a
percentage
of
a
maximum
acceptable
dose.
This
is
the
population
adjusted
dose
(
PAD),
which
HED
has
concluded
will
result
in
no
unreasonable
adverse
health
effects.
The
PAD
is
the
Reference
Dose
(
RfD)
divided
by
the
special
FQPA
Safety
Factor.
Dietary
risk
is
expressed
as
a
percentage
of
the
PAD.
For
acute
and
noncancer
chronic
exposures,
HED
is
concerned
when
estimated
dietary
risk
exceeds
100%
of
the
PAD.
HED
is
generally
concerned
when
estimated
cancer
risk
exceeds
one
in
one
million
(
i.
e.,
the
risk
exceeds
1
x
10­
6).
References
which
discuss
the
acute
and
chronic
risk
assessments
in
more
detail
are
available
on
the
EPA/
pesticides
web
site:
"
Available
Information
on
Assessing
Exposure
from
Pesticides,
A
User's
Guide",
6/
21/
2000,
web
link:
http://
www.
epa.
gov/
fedrgstr/
EPA­
PEST/
2000/
July/
Day­
12/
6061.
pdf
;
or
see
SOP
99.6
(
8/
20/
99).

The
most
recent
dietary
risk
assessment
for
fenhexamid
was
conducted
by
Eugenia
McAndrew;
DP
Barcode:
D305979;
August
4,
2004.

II.
Residue
Information
ACTIVE
INGREDIENT:
Fenhexamid
RESIDUE
OF
CONCERN:
On
3/
2/
99
the
HED
Metabolism
Assessment
Review
Committee
concluded
that
the
tolerance
expression
for
fungicide
fenhexamid
[
N­(
2,3­
dichlor­
4­
hydroxyphenyl)­
1­
methyl­
cyclohexanecarboxamide]
need
only
consider
the
parent
compound
(
Herndon;
D253792;
3/
2/
99).
Tolerances
for
residues
of
fenhexamid,
ranging
from
0.02
to
6.0
ppm,
have
been
established
(
40
CFR
180.553)
for
a
number
of
agricultural
commodities.
For
this
chronic
dietary
exposure
analysis,
tolerance­
level
residues
were
used
for
all
commodities
with
registered
or
proposed
uses
(
Attachment
1).
Default
processing
factors
in
the
DEEM
 
software
were
used
for
all
commodities
except
processed
tomato
commodities.
This
application
is
for
Ginseng
Group
1AB.

The
following
conservative
assumptions
were
made
for
the
chronic
dietary
analysis:
HEDrecommended
tolerance
level
residues
(
associated
with
the
current
petition
and
previously
registered
uses),
default
processing
factors
for
all
RACs,
and
all
RACs
were
100%
treated
with
fenhexamid.
Additional
refinement
using
ARs,
processing
factors,
and
%
CT
data
would
result
in
even
lower
chronic
exposure
estimates.

III.
DEEM­
FCID
 
Program
and
Consumption
Information
The
Fenhexamid
chronic
dietary
exposure
assessment
was
conducted
using
the
Dietary
Exposure
Evaluation
Model
software
with
the
Food
Commodity
Intake
Database
(
DEEM­
FCID
 
,
Version
1.3),
which
incorporates
consumption
data
from
USDA's
Continuing
Surveys
of
Food
Intakes
by
Individuals
(
CSFII),
1994­
1996
and
1998.
The
1994­
96,
98
data
are
based
on
the
reported
consumption
of
more
than
20,000
individuals
over
two
non­
consecutive
survey
days.
Foods
"
as
consumed"
(
e.
g.,
apple
pie)
are
linked
to
EPA­
defined
food
commodities
(
e.
g.
apples,
peeled
fruit
­
cooked;
fresh
or
N/
S;
baked;
or
wheat
flour
­
cooked;
fresh
or
N/
S,
baked)
using
publicly
available
recipe
translation
files
developed
jointly
by
USDA/
ARS
and
EPA.
Consumption
data
are
averaged
for
the
entire
U.
S.
population
and
within
population
subgroups
for
chronic
exposure
assessment,
but
are
retained
as
individual
consumption
events
for
acute
exposure
assessment.

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

IV.
Toxicological
Information
On
March
26,
2003
the
Health
Effects
Division
(
HED)
Hazard
Identification
Assessment
Review
Committee
(
HIARC)
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).

The
HIARC
concluded
that
there
is
low
concern
for
pre­
and/
or
postnatal
toxicity
resulting
from
exposure
to
Fenhexamid.
The
HIARC
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.
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.

Table
1.
Summary
of
Toxicological
Dose
and
Endpoints
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.

*
NOTE:
The
Special
FQPA
Safety
Factor
recommended
by
the
HIARC
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.

V.
Results/
Discussion
As
stated
above,
for
acute
and
chronic
assessments,
HED
is
concerned
when
dietary
risk
exceeds
100%
of
the
cPAD.
The
DEEM­
FCID
 
analyses
estimate
the
dietary
exposure
of
the
U.
S.
population
and
26
population
subgroups.
The
results
reported
in
Table
2
are
for
the
general
U.
S.
Population,
all
infants
(<
1
year
old),
children
1­
2,
children
3­
5,
children
6­
12,
youth
13­
19,
females
13­
49,
adults
20­
49
and
adults
50+
years.
The
results
for
the
other
population
subgroups
are
included
in
Attachment
2.

Table
2.
Summary
of
Tier
1
Estimates
of
Exposure
and
Risk
from
Chronic
Dietary
Exposure
to
Fenhexamid
Population
Subgroup
Exposure,
mg/
kg
bwt/
day
%
cPAD
U.
S.
Pop
­
48
states
­
all
seasons
0.017489
10
All
infants
(<
1
year)
0.086111
51
Children
(
1­
2
years)
0.115348
68
Children
(
3­
5
years)
0.070176
41
Females
(
13­
49
years)
0.008387
5
Youths
(
13­
19
years)
0.009446
6
Adults
(
20­
49
years)
0.007415
4
Seniors
(
50+
years)
0.009274
6
VI.
Conclusions
The
chronic
dietary
exposure
and
risk
assessment
indicates
that
for
all
registered
uses
and
including
the
proposed
section
3
uses
of
fenhexamid
on
Ginseng
Group
1AB,
the
chronic
dietary
risk
estimates
are
below
HED's
level
of
concern
(<
100%
cPAD)
for
the
general
U.
S.
population
(
10%
of
the
cPAD)
and
all
population
subgroups.
The
chronic
dietary
exposure
estimate
for
the
highest
exposed
population
subgroup
(
children
1­
2
years
old)
is
68%
of
the
cPAD.
Refinement
using
ARs,
processing
factors,
and
%
CT
data
would
result
in
even
lower
chronic
exposure
estimates.

Table
3.
Summary
of
Dietary
Exposure
and
Risk
for
Fenhexamid
Population
Subgroup**
Chronic
Dietary
Cancer
Dietary
Exposure
(
mg/
kg/
day)
%
cPAD
Risk
General
U.
S.
Population
0.017489
10
N/
A
All
Infants
(<
1
year
old)
0.086111
51
N/
A
Children
1­
2
years
old
0.115348
68
Table
3.
Summary
of
Dietary
Exposure
and
Risk
for
Fenhexamid
Population
Subgroup**
Chronic
Dietary
Cancer
Dietary
Exposure
(
mg/
kg/
day)
%
cPAD
Risk
Children
3­
5
years
old
0.070176
41
Children
6­
12
years
old
0.025800
15
Youth
13­
19
years
old
0.009446
6
Adults
20­
49
years
old
0.007415
4
Females
13­
49
years
old
0.008387
5
Adults
50+
years
old
0.009274
6
Attachment
1
­
Residue
Inputs
for
Tier
1
Dietary
Assessment
of
Fenhexamid
U.
S.
Environmental
Protection
Agency
Ver.
2.00
DEEM­
FCID
Chronic
analysis
for
FENHEXAMID
1994­
98
data
Residue
file:
C:\
My
Documents\
Breann's
Work\
ARIA\
Fenhexamid\
Fenhexamid
R98.
R98
Adjust.
#
2
NOT
used
Analysis
Date
02­
16­
2005
Residue
file
dated:
02­
16­
2005/
09:
17:
42/
8
Reference
dose
(
RfD)
=
0.17
mg/
kg
bw/
day
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
Food
Crop
Residue
Adj.
Factors
Comment
EPA
Code
Grp
Food
Name
(
ppm)
#
1
#
2
­­­­­­­­
­­­­
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
­­­­­­­­­­
­­­­­­
­­­­­­
­­­­­­­
14000030
14
Almond
0.020000
1.000
1.000
14000031
14
Almond­
babyfood
0.020000
1.000
1.000
11000070
11
Apple,
fruit
with
peel
10.000000
1.000
1.000
11000080
11
Apple,
peeled
fruit
10.000000
1.000
1.000
11000081
11
Apple,
peeled
fruit­
babyfood
10.000000
1.000
1.000
11000090
11
Apple,
dried
10.000000
1.000
1.000
11000091
11
Apple,
dried­
babyfood
10.000000
1.000
1.000
11000100
11
Apple,
juice
10.000000
1.000
1.000
11000101
11
Apple,
juice­
babyfood
10.000000
1.000
1.000
11000110
11
Apple,
sauce
10.000000
1.000
1.000
11000111
11
Apple,
sauce­
babyfood
10.000000
1.000
1.000
12000120
12
Apricot
6.000000
1.000
1.000
12000121
12
Apricot­
babyfood
6.000000
1.000
1.000
12000130
12
Apricot,
dried
6.000000
6.000
1.000
12000140
12
Apricot,
juice
6.000000
1.000
1.000
12000141
12
Apricot,
juice­
babyfood
6.000000
1.000
1.000
13010550
13A
Blackberry
20.000000
1.000
1.000
13010560
13A
Blackberry,
juice
20.000000
1.000
1.000
13010561
13A
Blackberry,
juice­
babyfood
20.000000
1.000
1.000
13020570
13B
Blueberry
5.000000
1.000
1.000
13020571
13B
Blueberry­
babyfood
5.000000
1.000
1.000
13010580
13A
Boysenberry
20.000000
1.000
1.000
12000900
12
Cherry
6.000000
1.000
1.000
12000901
12
Cherry­
babyfood
6.000000
1.000
1.000
12000910
12
Cherry,
juice
6.000000
1.500
1.000
12000911
12
Cherry,
juice­
babyfood
6.000000
1.500
1.000
11001290
11
Crabapple
10.000000
1.000
1.000
13021360
13B
Currant
5.000000
1.000
1.000
13011420
13A
Dewberry
20.000000
1.000
1.000
13021490
13B
Elderberry
5.000000
1.000
1.000
01011680
1AB
Ginseng,
dried
0.300000
1.000
1.000
13021740
13B
Gooseberry
5.000000
1.000
1.000
95001750
O
Grape
4.000000
1.000
1.000
95001760
O
Grape,
juice
4.000000
1.200
1.000
95001761
O
Grape,
juice­
babyfood
4.000000
1.200
1.000
95001770
O
Grape,
leaves
4.000000
1.000
1.000
95001780
O
Grape,
raisin
6.000000
4.500
1.000
95001790
O
Grape,
wine
and
sherry
4.000000
0.500
1.000
13021910
13B
Huckleberry
5.000000
1.000
1.000
13012080
13A
Loganberry
20.000000
1.000
1.000
11002100
11
Loquat
10.000000
1.000
1.000
12002300
12
Nectarine
6.000000
1.000
1.000
12002600
12
Peach
6.000000
1.000
1.000
12002601
12
Peach­
babyfood
6.000000
1.000
1.000
12002610
12
Peach,
dried
6.000000
7.000
1.000
12002611
12
Peach,
dried­
babyfood
6.000000
7.000
1.000
12002620
12
Peach,
juice
6.000000
1.000
1.000
12002621
12
Peach,
juice­
babyfood
6.000000
1.000
1.000
11002660
11
Pear
10.000000
1.000
1.000
11002661
11
Pear­
babyfood
10.000000
1.000
1.000
11002670
11
Pear,
dried
10.000000
6.250
1.000
11002680
11
Pear,
juice
10.000000
1.000
1.000
11002681
11
Pear,
juice­
babyfood
10.000000
1.000
1.000
14002820
14
Pistachio
0.020000
1.000
1.000
12002850
12
Plum
0.500000
1.000
1.000
12002851
12
Plum­
babyfood
0.500000
1.000
1.000
12002870
12
Plum,
prune,
dried
1.000000
5.000
1.000
12002871
12
Plum,
prune,
dried­
babyfood
1.000000
5.000
1.000
12002880
12
Plum,
prune,
juice
0.500000
1.400
1.000
12002881
12
Plum,
prune,
juice­
babyfood
0.500000
1.400
1.000
11003100
11
Quince
10.000000
1.000
1.000
13013200
13A
Raspberry
20.000000
1.000
1.000
13013201
13A
Raspberry­
babyfood
20.000000
1.000
1.000
95003590
O
Strawberry
3.000000
1.000
1.000
95003591
O
Strawberry­
babyfood
3.000000
1.000
1.000
95003600
O
Strawberry,
juice
3.000000
1.000
1.000
95003601
O
Strawberry,
juice­
babyfood
3.000000
1.000
1.000
08003750
8
Tomato
2.000000
1.000
1.000
08003751
8
Tomato­
babyfood
2.000000
1.000
1.000
Attachment
2
­
Results
of
Tier
1
Chronic
Dietary
Analysis
for
Fenhexamid
U.
S.
Environmental
Protection
Agency
Ver.
2.00
DEEM­
FCID
Chronic
analysis
for
FENHEXAMID
(
1994­
98
data)
Residue
file
name:
C:\
My
Documents\
Breann's
Work\
ARIA\
Fenhexamid\
Fenhexamid
R98.
R98
Adjustment
factor
#
2
NOT
used.
Analysis
Date
02­
16­
2005/
09:
19:
05
Residue
file
dated:
02­
16­
2005/
09:
17:
42/
8
Reference
dose
(
RfD,
Chronic)
=
.17
mg/
kg
bw/
day
===============================================================================
Total
exposure
by
population
subgroup
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
Total
Exposure
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
Population
mg/
kg
Percent
of
Subgroup
body
wt/
day
Rfd
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
­­­­­­­­­­­­­
­­­­­­­­­­­­­­­
U.
S.
Population
(
total)
0.017489
10.3%

U.
S.
Population
(
spring
season)
0.017162
10.1%
U.
S.
Population
(
summer
season)
0.016851
9.9%
U.
S.
Population
(
autumn
season)
0.018252
10.7%
U.
S.
Population
(
winter
season)
0.017658
10.4%

Northeast
region
0.019929
11.7%
Midwest
region
0.017521
10.3%
Southern
region
0.014953
8.8%
Western
region
0.019293
11.3%

Hispanics
0.019275
11.3%
Non­
hispanic
whites
0.017276
10.2%
Non­
hispanic
blacks
0.016507
9.7%
Non­
hisp/
non­
white/
non­
black
0.019482
11.5%

All
infants
(<
1
year)
0.086111
50.7%
Nursing
infants
0.048827
28.7%
Non­
nursing
infants
0.100265
59.0%
Children
1­
6
yrs
0.080530
47.4%
Children
7­
12
yrs
0.022879
13.5%

Females
13­
19
(
not
preg
or
nursing)
0.010451
6.1%
Females
20+
(
not
preg
or
nursing)
0.008358
4.9%
Females
13­
50
yrs
0.010106
5.9%
Females
13+
(
preg/
not
nursing)
0.015080
8.9%
Females
13+
(
nursing)
0.013403
7.9%

Males
13­
19
yrs
0.008439
5.0%
Males
20+
yrs
0.007603
4.5%
Seniors
55+
0.009624
5.7%

Children
1­
2
yrs
0.115348
67.9%
Children
3­
5
yrs
0.070176
41.3%
Children
6­
12
yrs
0.025800
15.2%
Youth
13­
19
yrs
0.009446
5.6%
Adults
20­
49
yrs
0.007415
4.4%
Adults
50+
yrs
0.009274
5.5%
Females
13­
49
yrs
0.008387
4.9%

­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­