Document ID: EPA-HQ-OPP-2006-0637-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-08-02T04:00Z

EPA
Registration
Division
contact:
Mary
Waller,
(
703)
308­
9354
Barbara
Madden
(
703)
305­
6463
Interregional
Project
Number
4
and
Bayer
CropScience
Pesticide
Petition
Nos.
1E6247,
0F6126
and
4F4281
EPA
has
received
pesticide
petition
(
PP#
1E6247)
from
Interregional
Project
No.
4,
New
Jersey
Agricultural
Experiment
Station,
Rutgers
University,
New
Brunswick,
New
Jersey
08903
and
petition
(
PP#
0F6126
and
4F4281)
from
Bayer
CropScience,
Research
Triangle
Park,
North
Carolina
27709
proposing,
pursuant
to
section
408(
d)
of
the
Federal
Food,
Drug,
and
Cosmetic
Act
(
FFDCA),
21
U.
S.
C.
346a(
d),
to
amend
40
CFR
part
180.399
by
establishing
a
tolerance
for
combined
residues
of
iprodione
[
3­(
3,5­
dichlorophenyl)­
N­(
1­
methylethyl)­
2,4­
dioxo­
1­
imidazolidinecarboxamide,
its
isomer
3­(
1­
methylethyl)­
N­(
3,5­
dichlorophenyl)­
2,4­
dioxo­
1­
imidazolidinecarboxamide,
and
its
metabolite
3­(
3,5­
dichlorophenyl)­
2,4­
dioxo­
1­
imidazolidinecarboxamide
in
or
on
the
raw
agricultural
commodities
pistachio
at
0.20
parts
per
million
(
ppm)
(
1E6247),
and
rapeseed
(
canola)
at
1.0
ppm
(
4F4281).
Additionally,
the
EPA
received
a
pesticide
petition
(
0F6126)
from
Bayer
CropScience
to
increase
the
tolerance
level
for
almond,
hulls
from
2.0
ppm
to
5.0
ppm.
EPA
has
determined
that
the
petition
contains
data
or
information
regarding
the
elements
set
forth
in
section
408(
d)(
2)
of
the
FFDCA;
however,
EPA
has
not
fully
evaluated
the
sufficiency
of
the
submitted
data
at
this
time
or
whether
the
data
supports
granting
of
the
petition.
Additional
data
may
be
needed
before
EPA
rules
on
the
petition.

EPA
published
a
previous
Notice
of
Filing
proposing
the
establishment
of
tolerance
for
residues
of
iprodione
in
or
on
rapeseed
(
canola)
and
increasing
the
tolerance
levels
for
almond
hulls
in
a
Federal
Register
Notice
of
July
13,
2001
(
66
FR
36769)
(
FRL­
6785­
8)
(
http://
www.
epa.
gov/
fedrgstr/
EPA­
PEST/
2001/
July/
Day­
13/
p17634.
htm).

A.
Residue
Chemistry
1.
Plant
metabolism.
The
metabolism
of
iprodione
in
plants
is
well
understood.
EPA
concluded
that
the
residues
of
concern
in
plants
are
the
parent,
its
isomer
3­(
1­
methylethyl)­
N­
(
3,5­
dichlorophenyl)­
2,4­
dioxo­
1­
imidazolidinecarboxamide,
and
its
metabolite
3­(
3,5­
dichlorophenyl)­
2,4­
dioxo­
1­
imidazolidinecarboxamide.

2.
Analytical
method.
An
adequate
analytical
method,
gas
liquid
chromatography
using
an
electron­
capture
detector,
is
available
in
the
Pesticide
Analytical
Manual,
Vol.
II,
for
enforcement
purposes.
2
3.
Magnitude
of
residues.
Canola.
a.
Foliar
application.
Residue
data
were
reported
for
11
field
trials
conducted
in
the
major
canola
production
areas
of
Canada.
Most
of
the
trial
locations
also
represent
major
canola
production
areas
of
the
United
States.
Residues
ranged
from
0.05
ppm
to
0.62
ppm.
b.
Seed
treatment.
Residue
data
were
reported
for
8
field
trials
conducted
in
EPA
Regions
II,
V,
VII,
and
XI.
The
seed
were
treated
with
iprodione
and
planted
with
equipment
customarily
used
for
canola
seed.
Mature
canola
seed
generated
from
the
treated
seed
was
collected
at
normal
commercial
harvest
and
analyzed.
Iprodione
residues
were
non­
detectable
in
all
samples.
The
LOD
was
estimated
to
be
0.005
ppm.
c.
Processing.
A
canola
processing
study
was
found
to
be
adequate
by
the
Agency
to
support
a
tolerance
on
canola.
Combined
residues
do
not
concentrate
in
canola
meal,
crude
oil,
or
refined
oil.
Food
or
feed
additive
tolerances
are
not
necessary.
ii.
Almonds.
A
residue
study
was
conducted
at
five
field
trial
locations
in
California,
the
only
state
with
commercial
almond
production.
The
product
was
applied
four
times
as
airblast
applications
using
equipment
customarily
used
to
apply
pesticides
to
almonds
at
a
nominal
rate
of
1.0
lb
ai/
A
per
application.
This
represents
a
rate
increase
compared
to
thecurrent
label
rate
of
0.5
lb
ai/
A
per
application.
All
resulting
iprodione
residues
in/
on
almond
nutmeat
samples
were
below
the
current
tolerance
of
0.3
ppm.
Residues
in
almond
hull
samples
ranged
from
1.6
ppm
to
3.9
ppm.
iii.
Pistachio.
Magnitude
of
residue
data
on
pistachios
were
collected
from
three
field
trials
conducted
in
EPA
region
10,
two
in
California
and
one
in
Arizona.
Two
foliar
directed
applications
of
product
were
made
at
a
rate
of
approximately
1.0
lb.
ai/
A
each,
for
a
total
of
2.0
lbs.
ai/
A.
The
first
application
was
made
at
early
bloom
in
the
California
trials
and
to
fruiting
trees
(
approximately
80
days
post
bloom)
in
the
Arizona
trial.
In
all
trials,
the
second
application
was
made
14
to
15
days
before
harvest.
Iprodione­
equivalent
residues
in
nutmeat
samples
ranged
from
0.050
to
0.11
ppm.

B.
Toxicological
Profile
1.
Acute
toxicity.
Iprodione
is
of
low
acute
toxicity
placing
the
active
ingredient
in
Toxicity
Category
III
and
IV.
Iprodione
is
non­
irritating
to
the
eyes
and
skin
and
is
not
a
skin
sensitizer.

2.
Genotoxicty.
Iprodione
has
been
evaluated
through
a
full
battery
of
mutagenicity
assays.
Iprodione
was
not
mutagenic
or
genotoxic
in
any
assay
in
either
the
presence
or
absence
of
metabolic
activation.

3.
Reproductive
and
developmental
toxicity.
a.
Teratology
­
Rat.
In
a
developmental
toxicity
study,
pregnant
rats
were
administered
iprodione
at
dose
levels
of
0,
40,
90,
and
200
mg/
kg/
day
via
gavage
from
day
6
through
15
of
gestation.
The
dams
were
sacrificed
on
day
20
of
gestation.
There
were
no
deaths.
Body
weights
were
comparable
among
the
groups.
There
3
were
no
significant
differences
observed
in
the
mean
number
of
viable
fetuses,
implantations,
corpora
lutea,
resorptions,
and
pre­
and
postimplantation
losses
were
comparable
among
the
groups.
The
developmental
NOAEL
was
90
mg/
kg/
day.
A
special
prenatal
developmental
toxicity
study,
pregnant
rats
received
iprodione
via
gavage
at
dose
levels
of
0,
20,
120,
or
250
mg/
kg/
day
during
gestation
days
6
through
19.
For
maternal
toxicity,
the
NOAEL
was
20
mg/
kg/
day
and
for
developmental
toxicity,
the
NOAEL
was
20
mg/
kg/
day.

b.
Teratology
­
Rabbit.
In
a
developmental
toxicity
study,
artificially
inseminated
female
rabbits
were
administered
iprodione
at
dose
levels
of
0,
20,
60,
and
200
mg/
kg/
day
via
gavage
from
day
6
through
18
of
gestation.
On
day
29
of
gestation,
the
does
were
sacrificed.
Seven
high­
dose
does
aborted
between
days
17
and
23
of
gestation,
and
prior
to
aborting
all
had
displayed
decreased
urination
and
defecation.
One
mid­
dose
doe
[
day
28]
and
one
control
doe
[
day
20]
also
aborted.
All
other
does
survived
until
study
termination,
and
nine
of
the
high­
dose
does
that
did
not
abort
displayed
decreased
urination
and
defecation.
During
the
dosing
period,
the
mid­
dose
does
gained
less
weight
than
the
control,
and
the
high­
dose
does
lost
weight.
The
maternal
NOAEL
is
20
mg/
kg/
day
and
the
developmental
toxicity
NOAEL
was
60
mg/
kg/
day.

c.
Two­
Generation
Reproduction
­
Rat.
In
a
2­
generation
reproduction
study,
28
rats/
sex/
group
were
administered
iprodione
via
the
diet
at
dose
levels
of
0,
300
ppm,
1000
ppm,
and
3000/
2000
ppm
for
two
generations.
The
systemic
maternal/
parental
NOAEL
was
300
ppm,
and
the
LOAEL
was
1000
ppm,
based
on
decreased
body
weight,
body­
weight
gain,
and
food
consumption
in
both
sexes
and
both
generations.
The
reproductive
[
offspring]
NOAEL
was
1000
ppm,
and
the
reproductive
LOAEL
was
2000
ppm,
based
on
decreased
pup
viability.

4.
Subchronic
toxicity.
a.
90
Day
Dietary
­
Rat.
In
a
subchronic
feeding
study,
10
rats/
sex/
group
were
administered
iprodione
via
the
diet
at
dose
levels
of
0,
1000
ppm,
2000
ppm,
3000
ppm,
and
5000
ppm
for
90
days.
The
5000
ppm
dose
group
was
terminated
early
[
week
8].
Dose­
related
microscopic
lesions
were
observed
in
the
sex
organs
and
adrenals
of
both
sexes
at
the
2000,
3000,
and
5000
ppm
dose
levels.
The
NOAEL
is
1000
ppm.

b.
90
Day
oral
­
Dog.
In
a
subchronic
feeding
study,
2
Beagle
dogs/
sex/
group
were
administered
iprodione
via
the
diet
at
dose
levels
of
0,
800
ppm,
2400
ppm,
and
7200
ppm
for
90
days.
Body
weights
were
comparable
among
the
groups
in
both
sexes.
High­
dose
dogs
displayed
increased
alkaline
phosphatase
and
transaminase
values
compared
to
the
controls.
There
were
no
effects
reported
in
clinical
chemistry
and
urinalysis.
No
treatment­
related
microscopic
lesions
were
observed.
The
NOAEL
is
2400
ppm.

5.
Chronic
toxicity.
a.
Chronic
Toxicity
­
Dog.
In
a
chronic
feeding
study,
6
Beagle
dogs/
sex/
group
were
administered
iprodione
via
the
diet
at
dose
levels
of
0,
100
ppm,
600
ppm,
and
3600
ppm
for
12
months.
There
were
no
treatment­
related
deaths,
and
no
adverse
effects
were
observed
on
body
weight,
food
consumption,
or
clinical
signs
in
either
sex.
At
the
highdose
level,
there
were
increases
in
absolute
and
relative
liver
weight,
alkaline
phosphatase,
SGOT,
SGPT
and
LDH
enzyme
levels,
and
increased
absolute
and
relative
adrenal
weights.
At
4
the
mid­
and
high­
dose
levels,
males
displayed
an
increased
number
of
erythrocytes
with
Heinz
bodies
and
decreased
prostate
weights.
The
NOAEL
is
100
ppm.
In
a
second
chronic
feeding
study
designed
to
complement
the
study
cited
above,
6
dogs/
sex/
group
were
administered
iprodione
via
the
diet
at
dose
levels
of
0,
200
ppm,
300
ppm,
400
ppm,
and
600
ppm
for
12
months.
There
were
no
treatment­
related
deaths,
and
no
adverse
effects
were
observed
on
clinical
signs,
body
weight/
gain,
and
food
consumption
in
either
sex.
At
the
high­
dose
level,
decreases
were
observed
in
the
red
blood
cell
parameters.
The
NOAEL
for
is
400
ppm.

b.
Combined
Chronic
Toxicity/
Oncogenicity
­
Rat.
In
the
combined
chronic
toxicity/
carcinogenicity
study
in
rats,
iprodione
was
administered
to
60
rats/
sex/
dose
via
the
diet
at
dose
levels
of
0,
150,
300,
and
1600
ppm
for
24
months.
Body­
weight
gains
were
decreased
in
both
sexes
at
the
high­
dose
level
compared
to
the
controls.
There
were
no
treatment­
related
clinical
pathology
findings
in
either
sex.
At
the
terminal
sacrifice,
increased
liver
weight
was
observed
in
males
at
the
mid­
and
high­
dose
levels.
At
the
high­
dose
level
in
males,
testes
with
epididymides
and
thyroid
weights
were
increased
at
the
terminal
sacrifice.
At
the
terminal
sacrifice,
interstitial
cell
hyperplasia
in
the
testes,
reduced
spermatozoa
in
the
epididymides,
and
absent/
empty
secretory
colloid
cells
or
reduced
secretion
in
the
seminal
vesicles
were
observed
in
the
mid­
and
high­
dose
males.
Atrophy
of
the
seminiferous
tubules
in
the
testes,
with
atrophy
of
the
prostate
and
absence
of
spermatozoa
in
the
epididymides
were
observed
at
the
high­
dose
level.
Adrenal
lesions
were
observed
in
both
sexes
at
the
mid­
and
high­
dose
levels,
although
the
males
displayed
more
lesions
than
the
females.
There
was
an
increase
in
the
incidence
of
both
unilateral
and
bilateral
benign
interstitial
cell
tumors
in
the
testes
of
males
at
the
1600
ppm
dose
level,
however
this
effect
should
be
considered
a
threshold
phenomenon
and
not
relevant
at
lower
doses.
The
NOAEL
is
150
ppm.

c.
Oncogenicity
­
Mouse.
Iprodione
was
administered
in
the
diet
to
50
mice/
sex/
dose
for
99
weeks
at
dose
levels
of
0,
160
ppm,
800
ppm,
and
4000
ppm.
Decreased
body­
weight
gains
were
observed
in
both
sexes
at
the
highest
dose
level.
There
was
an
increase
in
the
incidence
of
liver
tumors
in
both
sexes
at
the
high­
dose
level,
which
was
accompanied
by
increases
in
several
liver
lesions.
SGOT
and
SGPT
levels
were
elevated
at
the
high­
dose
level
in
both
sexes
compared
to
the
controls
at
the
interim
sacrifice.
Liver
weight
was
increased
at
the
high­
dose
level
in
both
sexes
at
both
the
interim
and
terminal
sacrifices.
The
NOAEL
is
160
ppm.

6.
Animal
metabolism.
A
general
metabolic
pathway
for
Iprodione
in
the
rat
indicates
that
biotransformation
results
in
hydroxylation
of
the
aromatic
ring,
degradation
of
the
isopropylcarbamoyl
chain
and
rearrangement
followed
by
cleavage
of
the
hydantoin
moiety.
Additionally,
structural
isomers
of
Iprodione
resulting
from
molecular
rearrangement,
as
well
as
intermediates
in
the
pathway,
were
detected.

7.
Metabolite
toxicology.
The
residues
of
concern
in
plants
for
tolerance
setting
purposes
are
the
parent,
its
isomer
3­(
1­
methylethyl)­
N­(
3,5­
dichlorophenyl)­
2,4­
dioxo­
1­
imidazolidinecarbox
amide,
and
its
metabolite
3­(
3,5­
dichlorophenyl)­
2,4­
dioxo­
1­
imidazolidinecarboxamide.
In
animal
commodities,
tolerances
are
established
on
the
parent,
its
5
isomer
3­(
1­
methylethyl)­
N­(
3,5­
dichlorophenyl)­
2,4­
dioxo­
1­
imidazolidinecarboxamide,
its
metabolite
3­(
3,5­
dichlorophenyl)­
2,4­
dioxo­
1­
imidazolidinecarboxamide,
and
an
additional
metabolite
N­(
3,5­
dichloro­
4­
hydroxyphenyl)­
ureidocarboxamide.

8.
Endocrine
disruption.
In
the
carcinogenicity
studies
conducted
for
iprodione,
the
primary
lesion
at
the
level
of
the
target
organs
(
testes,
ovaries
&
adrenals)
is
likely
to
be
related
to
an
inhibition
of
steroid/
androgen
biosynthesis.
This
inhibition
of
steroid/
androgen
biosynthesis
occurs
only
at
high
dose
levels
and
is
reversible
within
24
hours.
Iprodione
is
not
expected
to
induce
any
adverse
effects
related
to
endocrine
disruption
in
members
of
the
general
population
via
the
consumption
of
food
containing
residues
of
this
compound.

C.
Aggregate
Exposure
1.
Dietary
exposure.
Bayer
CropScience
expects
that
potential
residues
resulting
from
the
proposed
use
of
iprodione
on
pistachios
and
canola
will
not
significantly
affect
EPA's
exposure
and
risk
assessments
for
currently
registered
uses
of
iprodione.

i.
Food.
Dietary
exposures
for
iprodione
were
reevaluated
by
EPA
as
part
of
the
reregistration
process
(
1998).
The
lifetime
cancer
risk
from
potential
iprodione
residues
in
foods
with
existing
tolerances
and
drinking
water
was
estimated
to
be
1.8
x
10­
6.
This
cancer
risk
corresponds
to
a
dietary
exposure
of
0.000041
mg/
kg/
day
or
0.2%
of
the
chronic
reference
dose
(
RfD).
A
chronic
dietary
exposure
analysis
was
conducted
to
determine
the
incremental
risk
resulting
from
the
proposed
uses
on
pistachios
and
canola.
Chronic
exposure
estimates
for
these
new
uses
were
less
than
0.01%
of
the
RfD
for
all
population
subgroups
examined.
The
corresponding
lifetime
cancer
risk
was
estimated
to
be
1.0
x
10­
8
for
the
U.
S.
population.
Thus,
the
incremental
chronic
dietary
risk
resulting
from
the
proposed
uses
on
pistachios
and
canola
does
not
increase
the
cancer
risk
to
an
unacceptable
level.
Acute
dietary
exposure
was
estimated
for
the
population
subgroup
of
concern,
women
13
years
of
age
and
older.
Utilizing
the
Tier
3
methodology
(
Monte
Carlo)
for
acute
exposure,
Margins
of
Exposure
(
MOEs)
up
to
the
99.9th
percentile
of
exposure
for
this
population
subgroup
were
at
least
351
for
currently
registered
crops.
Adding
residues
in
pistachios
and
canola
to
the
assessment
also
resulted
in
a
MOE
of
351
at
the
99.9th
percentile
.
The
EPA
has
determined
that
a
MOE
of
at
least
300
is
acceptable
for
iprodione.

ii.
Drinking
water.
Iprodione,
applied
according
to
labeled
use
and
good
agricultural
management
practices,
is
predicted
and
demonstrated
to
present
no
significant,
if
any,
concentrations
in
drinking
water
sources.
Iprodione's
physical­
chemical
properties
and
actual
measured
environmental
concentrations
in
field
dissipation/
monitoring
studies
provide
support
for
this
conclusion.
Five
conservative
aggregate
exposure
and
risk
assessments
were
conducted
by
EPA
for
the
Iprodione
RED.
These
risk
assessments
include
combined
exposures
to
iprodione
through
food
and
water
in
the
diet:
i)
acute
dietary;
ii)
chronic
dietary;
iii)
cancer;
iv)
short­
term;
and
v)
intermediate­
term
risk.
EPA
concludes
in
the
RED
document
that
residues
of
6
iprodione
are
not
expected
to
exceed
the
Agency's
drinking
water
level
of
concern
for
either
acute
or
chronic
exposure.
EPA
also
concluded
with
reasonable
certainty
that
residues
of
iprodione
in
drinking
water
(
when
considered
along
with
exposure
from
food)
would
not
result
in
unacceptable
short­
term
and
intermediate
term
aggregate
human
health
risk
estimates.
Since
the
completion
of
the
RED,
EPA
issued
a
Data
Call­
In
requiring
the
submission
of
3,5­
dichloroaniline
(
3,5­
DCA)­
targeted
surface
and
ground
water
monitoring
studies
relating
to
golf
course
use
of
iprodione
products.
Bayer
has
since
submitted
to
the
Agency
an
aerobic
soil
metabolism
study
and
a
soil
adsorption/
desorption
study
conducted
with
3,5­
DCA.
Risk
analyses
using
these
recent
data
and
EPA's
standard
operating
procedures
confirm
that
there
is
no
concern
for
contamination
of
drinking
water
resulting
from
the
use
of
iprodione
products
on
golf
courses.
Bayer
CropScience
expects
that
potential
residues
resulting
from
the
proposed
use
of
iprodione
on
pistachios
and
canola
will
not
significantly
affect
EPA's
exposure
and
risk
assessments
for
drinking
water.

2.
Non­
dietary
exposure.
This
assessment
is
not
applicable
since
all
residential
uses
of
iprodione
products
have
been
cancelled.

D.
Cumulative
Effects
The
Agency
has
previously
noted
both
structural
and
toxicological
similarities
between
iprodione,
procymidone
and
vinclozolin.
There
are
clear
differences
in
both
the
type
and
magnitude
of
effects
observed
after
exposure
to
iprodione
in
contrast
to
vinclozolin
and
procymidone.
Vinclozolin
and
procymidone
are
known
to
exert
their
identical
endocrine
effects
via
a
blockage
of
the
androgen
receptor.
By
contrast,
iprodione
has
poor
binding
affinity
to
the
androgen
receptor
and
the
primary
lesion
appears
to
be
a
blockage
of
testosterone
biosynthesis
and
secretion.
Subsequently,
Iprodione
only
appears
to
induce
transient
changes
in
plasma
hormone
levels
until
compensatory
mechanisms
take
effect.
Consequently,
Bayer
CropScience
concludes
that
consideration
of
a
common
mechanism
of
toxicity
is
not
appropriate
at
this
time
since
there
is
no
reliable
data
to
indicate
that
the
toxic
effects
caused
by
Iprodione
would
be
cumulative
with
those
of
any
other
compound.

E.
Safety
Determination
1.
U.
S.
population.
Dietary
exposures
for
iprodione
were
reevaluated
by
EPA
as
part
of
the
reregistration
process
(
1998).
The
lifetime
cancer
risk
from
potential
iprodione
residues
in
foods
with
existing
tolerances
and
drinking
water
is
estimated
to
be
1.8
x
10­
6.
This
cancer
risk
corresponds
to
a
dietary
exposure
of
0.000041
mg/
kg/
day
or
0.2%
of
the
chronic
reference
dose
(
RfD).
Chronic
dietary
exposure
to
iprodione
residues
in/
on
pistachios
and
canola
only
was
estimated
to
be
less
than
0.01%
of
the
RfD
for
the
U.
S.
population.
The
lifetime
cancer
risk
from
potential
iprodione
residues
in
pistachios
and
canola
only
was
estimated
to
be
1.0
x
10­
8
for
the
U.
S.
population
and
does
not
increase
the
overall
risk
significantly.
The
cancer
risk
estimates
for
currently
registered
crops,
drinking
water,
and
the
proposed
uses
on
pistachios
and
7
canola
are
within
the
range
the
Agency
considers
acceptable
for
excess
life­
time
cancer
risk.
For
crops
with
existing
tolerances,
acute
dietary
exposure
at
the
99.9th
percentile
was
estimated
to
be
0.056839
mg/
kg/
day
for
women
13
years
of
age
and
older.
This
corresponds
to
a
MOE
of
351.
Adding
residues
in
pistachios
and
canola
to
the
assessment
also
resulted
in
a
MOE
of
351.
EPA
determined
that
MOEs
above
300
are
not
considered
to
be
of
concern.
Iprodione
uses
are
not
expected
to
impact
ground
water.
Upper
bound
estimates
of
iprodione
in
surface
waters
from
conservative
screening
models
indicate
concentrations
of
a
few
parts
per
billion.
Both
the
chronic
and
acute
dietary
exposure
assessments
clearly
demonstrate
a
reasonable
certainty
that
no
harm
will
result
from
the
use
of
iprodione
on
currently
registered
crops
plus
proposed
uses
on
pistachios
and
canola.

2.
Infants
and
children.
In
assessing
the
potential
for
additional
sensitivity
of
infants
and
children
to
residues
of
Iprodione
the
available
teratology
and
reproductive
toxicity
studies
and
the
potential
for
endocrine
modulation
by
Iprodione
were
considered.
Developmental
studies
in
two
species
indicate
that
Iprodione
has
no
teratogenic
potential,
even
at
maternally
toxic
dose
levels.
Maternal
and
developmental
NOELs
and
LOELs
were
generally
comparable
indicating
no
increased
susceptibility
of
developing
organisms.
In
addition
the
results
of
a
recently
completed
study
have
confirmed
that
Iprodione
has
no
effects
on
sex
differentiation.
Multigeneration
rodent
reproduction
studies
indicated
that
Iprodione
has
no
adverse
effects
on
reproductive
performance,
fertility,
fecundity
or
sex
ratio.
Effects
on
pup
weight
and
viability
were
only
noted
in
the
presence
of
severe
parental
toxicity.
The
mechanism
of
endocrine
modulation
associated
with
Iprodione
(
inhibition
of
testosterone
biosynthesis)
appears
to
be
distinct
from
that
of
anti­
androgens
acting
at
the
level
of
the
androgen
receptor
and
may
help
to
explain
the
lack
of
adverse
effects
on
reproductive
function
observed
with
Iprodione.
Therefore,
based
upon
the
completeness
and
reliability
of
the
toxicity
data
and
the
conservative
exposure
assessment,
there
is
a
reasonable
certainty
that
no
harm
will
result
to
infants
and
children
from
exposure
to
residues
of
Iprodione
and
no
additional
uncertainty
factor
is
warranted.
The
EPA
Health
Effects
Division
(
HED)
determined
that
the
developmental
NOAEL
for
iprodione
was
relevant
only
to
women
of
childbearing
age
and
concluded
that
the
developmental
NOAEL
is
not
relevant
to
acute
dietary
exposures
to
infants
and
children.
Because
no
non­
developmental
acute
effects
have
been
identified,
there
is
no
acute
toxicological
endpoint
to
assess
acute
dietary
risk
to
infants
and
children.
Based
on
the
chronic
exposure
assessment
conducted
by
EPA
for
uses
currently
registered,
aggregate
exposure
to
iprodione
from
food
utilizes
1.6%
of
the
RfD
for
non­
nursing
infants
less
than
1
year
old
and
less
than
1%
for
all
other
population
subgroups.
Chronic
dietary
exposure
to
iprodione
residues
in/
on
pistachios
and
canola
only
was
estimated
to
be
less
than
0.01%
of
the
RfD.
EPA
generally
has
no
concern
for
exposures
below
100%
of
the
RfD.
Since
the
potential
for
exposure
to
iprodione
in
drinking
water
is
low
and
there
is
no
risk
from
non­
dietary,
non­
occupational
exposure,
the
aggregate
exposure
is
expected
to
be
well
below
100%
of
the
RfD
when
accounting
for
the
proposed
uses
on
pistachios
and
canola.
Thus,
there
is
a
reasonable
certainty
that
no
harm
will
result
to
infants
and
children
from
aggregate
exposure
to
iprodione
residues.

F.
International
Tolerances
8
An
MRL
of
1.0
ppm
is
established
in
Canada
for
iprodione
in
rapeseed
oil
[
canola].
A
Codex
MRL
of
0.5
ppm
is
established
for
iprodione
in
rapeseed
oil.
A
Codex
MRL
is
not
established
for
iprodione
on
pistachios.
A
Codex
MRL
for
iprodione
on
almonds
is
established
at
0.2
ppm.