Document ID: EPA-HQ-OPP-2006-0282-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-04-12T04:00Z

EPA
Registration
Division
contact:
Barbara
Madden
703­
305­
6463
Interregional
Research
Project
No.
4
(
IR­
4)

PP#
1E6265
EPA
has
received
a
pesticide
petition
(
1E6265)
from
Interregional
Research
Project
No.
4
(
IR­
4),
Rutgers,
The
State
University
of
NJ,
681
US
Highway
1
South,
North
Brunswick,
NJ
08902
on
behave
of
the
registrant
Dow
AgroSciences,
9330
Zionsville
Road,
Indianapolis,
IN
46268
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
180.443
by
establishing
a
tolerance
for
residues
of
myclobutanil
in
or
on
the
raw
agricultural
commodity
hops,
dried
cone
at
10.0
parts
per
million
(
ppm).
The
residue
data
in
support
of
the
proposed
tolerance
were
generated
from
magnitude
of
residue
studies
of
myclobutanil
in
hops.
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.

A.
Residue
Chemistry
1.
Plant
metabolism.
i.
Plants.
Based
on
the
four
metabolism
studies
in
wheat,
apples,
sugar
beets
and
grapes,
which
indicate
a
similar
metabolic
route
for
crops
in
four
different
crop
groups,
Dow
AgroSciences
(
the
registrant)
concludes
that
the
nature
of
the
residue
is
adequately
understood
for
the
purpose
of
these
tolerances.

2.
Analytical
method.
For
Hops.
The
method
is
applicable
for
the
quantitative
determination
of
residues
of
myclobutanil
and
its
alcohol
metabolite
(
RH­
9090)
in
hops.
The
validated
method
limit
of
quantitation
(
LOQ)
was
0.5
ppm
for
analytes.

The
validation
of
myclobutanil
and
RH­
9090
demonstrated
estimated
limits
of
detection
defined
as
the
lowest
concentration
of
analyte
which
produces
a
peak
just
discernible
from
the
background.
The
limit
of
detection
thus
determined
in
dried
hops
was
0.15
ppm
for
each
test
compound.

3.
Magnitude
of
residues.
The
residue
data
in
support
of
the
proposed
tolerances
was
generated
from
the
magnitude
of
residue
studies
on
hops.

Magnitude
of
residue
studies
were
conducted
at
field
sites
located
within
the
major
hop
growing
regions
(
Washington,
Oregon
and
Idaho)
in
the
U.
S.
recommended
by
the
EPA.
The
residues
of
myclobutanil
and
RH­
9090
on
dried
hop
cones
follow
nine
foliar
directed
applications
of
RH­
3866
40W.
In
Oregon
and
Idaho,
the
first
two
applications
were
made
at
a
rate
of
approximately
0.125
lb
ai/
A
each;
the
remaining
seven
were
made
at
approximately
0.250
lb
ai/
A
each.
The
total
amount
of
test
substance
applied
at
these
trials
was
2.0
lb
ai/
A"
5%.
In
the
Washington
trial,
the
first
two
applications
were
made
based
on
the
rate
of
0.250
lb
ai/
A
and
overapplied
by
97%
and
237%,
respectively.
The
remaining
seven
applications
were
made
at
0.250
lb
ai/
A"
5%.
The
test
substance
was
overapplied
in
this
trial
by
approximately
20%
(
2.4
lb
ai/
A).
All
applications
were
made
7
to
12
days
apart,
and
samples
were
collected
12
to
14
days
following
the
final
application.
In
the
Idaho
trial,
samples
were
also
collected
at
0
And
6
days.
In
treated
14­
day
samples,
myclobutanil
residues
ranged
from
1.34
to
5.62
ppm.
The
highest
residues
observed
(
3.35
ppm
and
5.62
ppm)
were
in
samples
from
the
Idaho
trial.
In
the
Washington
trial,
where
the
test
substance
was
overapplied,
myclobutanil
residues
were
lowest
(
l.
34
ppm
in
both
treated
samples).
Samples
from
Idaho
collected
after
the
last
application
contained
8.37
ppm
and
8.64
ppm
myclobutanil;
residues
in
6­
day
samples
were
comparable.
No
quantifiable
residues
(>
0.50
ppm)
of
RH­
9090
were
observed
in
any
samples.
The
following
tolerance
is
proposed
hops,
dried
cone
at
10.0
ppm.

B.
Toxicological
Profile
1.
Acute
toxicity.
According
to
Dow
AgroSciences,
myclobutanil
wettable
powder
formulations
are
essentially
non­
toxic
after
administration
by
the
oral,
dermal
and
respiratory
routes
moderately
irritating
to
the
eyes,
and
no­
skin
sensitizers.
Of
these
test
results,
ocular
irritation
at
Toxicity
Category
III
(
Caution)
was
shown
to
be
the
worst
case
acute
toxicity.

2.
Genotoxicty.
Myclobutanil
was
negative
(
non­
mutagenic)
in
an
Ames
assay
with
and
without
hepatic
enzyme
activation.
Myclobutanil
was
negative
in
a
hypoxanthine
guanine
phosphoribosyl
transferase
(
HGPRT)
gene
mutation
assay
using
Chinese
hamster
ovary
(
CHO)
cells
in
culture
when
tested
with
and
without
hepatic
enzyme
activation.
In
isolated
rat
hepatocytes,
myclobutanil
did
not
induce
unscheduled
DNA
synthesis
(
UDS)
or
repair.
Myclobutanil
did
not
produce
chromosome
effects
in
vivo
using
mouse
bone
marrow
cells
or
in
vitro
using
CHO
cells.
On
the
basis
of
the
results
from
this
battery
of
tests,
it
is
concluded
that
myclobutanil
is
not
mutagenic
or
genotoxic.

3.
Reproductive
and
developmental
toxicity.
i.
Developmental
toxicity
in
the
rat.
Myclobutanil
has
been
evaluated
in
a
standard
two­
generation
reproduction
study
at
dietary
concentrations
of
0,
4,
16,
and
80
mg/
kg
bw/
day.
At
a
dietary
concentration
of
80
mg/
kg
bw/
day,
myclobutanil
was
associated
with
reproductive
effects
as
noted
by
reduced
numbers
of
females
delivering
litters
and
increased
incidences
of
still­
born
pups.
In
addition,
testicular
atrophy
in
P2
males
and
decreased
weight
gain
for
offspring
during
lactation
were
observed.
General
systemic
effects
were
observed
at
16
mg/
kg
bw/
day
as
noticed
by
increased
liver
weight
(
P1,
P2
males)
and
hepatocellular
hypertrophy
(
P2
males),
although
these
changes
were
not
considered
adverse.
The
NOEL
for
reproductive
effects
in
this
study
was
16
mg/
kg
bw/
day,
while
the
NOAEL
for
both
systemic
toxicity
and
developmental
toxicity
was
16
mg/
kg
bw/
day.
ii.
Developmental
toxicity
in
the
rabbit.
A
developmental
study
was
conducted
in
rabbits
with
myclobutanil
at
orally
administered
dosages
of
0,
20,60,
and
200
mg/
kg
bw/
day.
At
dosages
of
60
and
200
mg/
kg
bw/
day,
myclobutanil
was
maternally
toxic
to
rabbits
when
administered
on
Day
6
through
19
of
gestation
as
evidenced
by
transient
body
weight
loss.
At
a
dose
level
of
200
mg/
kg
bw/
day,
myclobutanil
was
embryotoxic,
although
fetuses
that
survived
to
Day
29
were
grossly
normal
in
appearance
and
weight.
Embryotoxicity
was
manifested
as
decreases
in
litter
size,
viability
index,
and
fetal
weight
and
an
increase
in
the
number
of
resorptions
per
litter.
The
material
(
dam)
NOAEL
in
this
study
was
20
mg/
kg
bw/
day,
while
the
litter
NOAEL
was
60
mg/
kg
bw/
day.

4.
Subchronic
toxicity.
i.
Rat
90­
day
oral
study.
A
13­
week
subchronic
feeding
study
was
conducted
in
rats
using
dietary
concentrations
of
0,
10,
30,
100,
300,
1000,
3000,
10,000,
and
30,000
ppm.
Equivalent
mg/
kg
bw/
day
compound
intake
was
0.52,
1.60,
5.22,
15.3,
51.5,
158,
585
and
1730
for
males
and
0.67,
2.03,
6.85,
19.7,
65.8,
195.2,
665,
and
1811
for
females.
Toxicologically
adverse
findings
were
observed
at
3000
ppm
(
158
and
195
mg/
kg
bw/
day
for
males
and
females,
respectively)
and
greater
following
90
days
of
dietary
exposure
to
myclobutanil.
Findings
included
decreased
body
weights,
increased
organ
weights,
and
gross
and
histopathological
changes
primarily
in
the
liver
and
kidneys.
A
NOAEL
for
this
study
was
1000
ppm
(
52
and
66
mg/
kg
bw/
day
for
males
and
females,
respectively).
ii.
Dog
90­
day
oral
study.
A
13­
week
subchronic
feeding
study
was
conducted
in
dogs
using
dietary
concentrations
of
0,
10,
200,
800,
1600
ppm
which
corresponded
to
mg/
kg
bw/
day
intakes
of
0.34,
7.26,
29.13,
and
56.8
for
males
and
0.42,
7.88,
32.43,
and
57.97
for
females.
Treatment­
related
changes
were
observed
in
the
livers
of
dogs
treated
at
200
ppm
or
greater,
and
included
increased
relative
liver
weights
and
centrilobular
hepatocellular
hypertrophy,
accompanied
by
minimal
changes
in
serum
clinical
chemistry.
However,
these
were
considered
to
be
adaptive
changes,
and
not
adverse
to
the
general
clinical
condition
of
the
animals.
Based
on
these
findings,
the
NOAEL
in
dogs
is
considered
to
be
1600
ppm
(
57
mg/
kg
bw/
day)
for
males
and
females.
iii.
Rat
28­
day
dermal
study.
The
toxicological
endpoint
selected
for
dermal
exposure
was
based
on
studies
using
two
formulations
of
myclobutanil,
at
doges
of
1,
10,
and
100
mg/
kg
bw/
day
and
100
mg/
kg
bw/
day,
respectively.
When
applied
dermally
to
rats
for
4
weeks
under
non­
occluded
conditions,
no
changes
indicative
of
systemic
toxicity
were
observed.
Skin
irritation
and/
or
minimal
gross
and
microscopic
changes
in
the
treated
skin
were
observed
after
application
of
both
formulations.
The
NOAEL
in
this
study
for
systemic
toxicity
for
both
formulations
was
100
mg/
kg
bw/
day.
The
in
vivo
dermal
absorption
of
14C­
myclobutanil
was
determined
in
male
Crl:
CD
BR
rats
following
a
10
hr
and
24
hr
dermal
exposure
period.
Groups
of
rats
were
dermally
exposed
to
a
representative
undiluted
commercial
formulation
of
myclobutanil,
as
well
as
to
a
1:
400
dilution
of
the
same
formulation,
which
is
representative
of
a
use
dilution
of
the
product.
Following
dermal
administration
to
male
rats,
7.7
­
9.4%
(
10
hour
exposure)
and
9.8
­
10.9%
(
24
hours
exposure)
of
the
low
dose
(
0.19
mg
a.
i./
kg)
were
absorbed.
Similarly,
14%
(
10
hour
exposure)
and
22.1%
(
24
hour
exposure)
of
the
high
dose
(
75
mg
a.
i./
kg)
were
absorbed.
iv.
Mouse
90­
Day
Oral
Study.
A
13­
week
subchronic
feeding
study
was
conducted
in
mice
using
dietary
concentrations
of
0,
3,
10,
30,
100,
300,
1000,
3000,
and
10,000
ppm.
Equivalent
mg/
kg
bw/
day
compound
intake
was
0.40,
1.54,
4.79,
14.1,
42.7,
132,
542,
and
2035
for
males
and
0.62,
2.11,
6.94,
22.9,
65.5,
232,
710,
and
2027
for
females.
The
liver
was
the
primary
target
organ
in
the
mouse
following
3
months
dietary
exposure
to
myclobutanil.
The
primary
changes
were
related
to
hypertrophy
or
necrosis
and
inflammation,
as
evidenced
by
changes
in
clinical
pathology,
hepatic
MFO
activity,
organ
weights,
and
histopathology.
The
NOAEL
for
these
effects
in
mice
is
300
ppm
(
43
mg/
kg
bw/
day)
in
males
and
1000
ppm
(
232
mg/
kg
bw/
day)
in
females.
5.
Chronic
toxicity.
i.
Dog.
A
1­
year
dog
feeding
was
conducted
using
dietary
concentrations
of
0,
10,
100,
400
and
1600
ppm
with
corresponding
mg/
kg
bw/
day
equivalents
of
0.34,
3.09,
14.28,
and
54.22
in
males
and
0.40,
3.83,
15.68
and
58.20
in
females.
Treatment­
related
changes
were
observed
in
the
livers
of
dogs
treated
at
400
ppm,
and
included
increased
relative
liver
weights
(
females
only),
and
minimal
centrilobular
hepatocellular
hypertrophy
(
both
sexes),
accompanied
by
increases
in
serum
ALP
(
females
only).
However,
these
were
considered
to
be
adaptive
changes,
and
not
adverse
to
the
general
clinical
condition
of
the
animals.
In
addition
to
these
effects,
dogs
at
1600
ppm
also
showed
effects
on
ALT
(
males),
GGT
(
females),
albumin,
inorganic
phosphorous,
RBC
(
males)
and
platelets
(
males),
and
an
accentuated
lobular
architecture
of
the
liver
and
ballooning
of
hepatocytes
(
females).
Based
on
the
limited
effects,
the
NOAEL
in
beagle
dogs
is
considered
to
be
400
ppm
(
14.3­
15.7
mg/
kg
bw/
day)
for
males
and
females.
ii.
Mouse.
A
two­
year
carcinogenicity
study
was
conducted
in
mice
using
dietary
concentrations
of
0,
20,
100,
and
500
ppm
(
equivalent
to
0,
2.7,
13.7,
and
70.2
mg/
kg
bw/
day
for
males
and
0,
3.2,
16.5,
and
85.2
mg/
kg
bw/
day
for
females).
The
NOEL
for
chronic
effects
other
than
carcinogenicity
was
20
ppm
while
the
LOEL
was
100
ppm,
based
on
a
slight
increase
in
liver
mixed­
function
oxidase
(
MFO).
Microscopic
changes
in
the
liver
were
evident
in
both
sexes
at
the
top
dose
of
500
ppm.
There
were
no
carcinogenic
effects
in
either
sex
at
any
dose
level
tested.
The
highest
dose
level
selected
was
satisfactory
for
evaluating
carcinogenic
potential
in
male
mice,
but
was
considered
lower
than
MTD
for
females.
Accordingly,
a
second
carcinogenicity
study
was
conducted
with
female
mice
using
a
top
dose
of
2000
ppm
(
393.5
mg/
kg
bw/
day),
which
approaches
the
MTD,
to
evaluate
carcinogenic
potential.
At
this
dose
level,
no
carcinogenic
effects
were
observed.
iii.
Rat.
A
two­
year
oncogenicity
study
in
rats
at
dose
levels
of
0,
2.5,
9.8,
39.2
(
males)
and
0,
3.2,
12.8,
52.3
(
females)
revealed
a
marginal
effect
on
body
weight
of
high
dose
males
and
possibly
females.
Absolute
liver
weights
were
slightly
decreased
for
high
dose
males
and
females,
although
statistical
significance
for
this
finding
was
only
evident
at
6
months.
Hepatic
MFO
activity
was
slightly
increased
in
high­
dose
males
and
females
up
to
12
months.
Testicular
weights
were
significantly
decreased
in
mid­
dose
males
at
termination,
and
in
high­
dose
males
at
12
months
and
at
termination.
Testicular
atrophy
was
slightly
and
moderately
increased
in
mid
and
high­
dose
males,
respectively
at
24
months.
No
other
significant
effects
were
observed
in
either
sex
at
the
dose
levels
employed
over
the
24­
month
period.
There
was
no
increased
incidence
of
neoplastic
lesions
in
any
organ
for
either
sex.
The
NOAEL
in
male
rats
is
2.5
mg/
kg
bw/
day,
based
on
the
testicular
findings,
while
the
female
NOAEL
is
52.3
mg/
kg
bw/
day.
iv.
Carcinogenicity.
The
Agency
has
classified
myclobutanil
as
a
"
Group
E
­
not
likely
a
human
carcinogen"
and,
therefore,
quantification
of
human
cancer
risk
is
not
required.
6.
Animal
metabolism.
[
The
adsorption,
distribution,
excretion,
and
metabolism
of
myclobutanil
was
completely
and
rapidly
absorbed,
extensively
metabolized
to
at
least
seven
major
metabolites,
and
rapidly
excreted
evenly
distributed
between
urine
and
feces.
Myclobutanil
did
not
accumulate
in
tissues.
7.
Metabolite
toxicology.
Common
metabolic
pathways
for
myclobutanil
have
been
identified
in
both
plants
(
grapes,
apples,
wheat,
sugar
beets)
and
animals
(
rat,
goat,
hen).
The
metabolic
pathway
common
to
both
plants
and
animals
involves
oxidation
of
the
nûbutyl
alkyl
side­
chain
in
the
3­
and
4­
positions,
oxidation
of
the
cyano­
group,
and
subsequent
conjugation.
Extensive
degradation
and
elimination
of
polar
metabolites
occurs
in
animals
such
that
residues
are
unlikely
to
accumulate
in
humans
or
animals
exposed
to
these
residues
through
the
diet.
8.
Endocrine
disruption.
The
mammalian
endocrine
system
includes
estrogen
and
androgens
as
well
as
other
hormonal
systems.
Myclobutanil
is
not
known
to
interfere
with
reproductive
hormones;
thus,
the
registrant
believes
that
myclobutanil
should
not
be
considered
to
be
estrogenic
or
androgenic.
Dow
AgroSciences
is
not
aware
of
any
instances
of
proven
or
alleged
adverse
reproductive
or
developmental
effects
to
people,
domestic
animals,
or
wildlife
as
a
result
of
exposure
to
myclobutanil
or
its
residues.
C.
Aggregate
Exposure
1.
Dietary
exposure.
i.
Food.
The
exposure
and
risk
resulting
from
agricultural
uses
of
myclobutanil
was
considered
for
the
U.
S.
population
and
special
sub­
populations.
There
are
three
direct
sources
of
exposure
to
humans
considering
myclobutanil's
uses
across
all
labels:
from
food
intake,
from
consuming
drinking
water,
and
from
residential
applications
around
homes.
The
exposure
and
risk
are
estimated
in
this
report
for
different
durations
of
all
three
routes
of
exposure
and
their
aggregated
contribution.
An
acute
Tier­
III
probabilistic
assessment
was
done
using
highly
refined
estimates
of
food
residues
using
a
combination
of
PDP
residues
and
tolerances
for
inadvertent
residues
and
proposed
uses.
In
addition,
tolerances
for
emergency
exemptions
(
i.
e.
Section
18
uses),
were
included
to
provide
as
complete
an
assessment
as
possible.
In
an
aggregate
assessment,
exposures
from
food
residues
were
combined
with
conservative
estimates
of
potential
water
residues.
The
current
approach
of
the
EPA
Office
of
Pesticide
Programs
(
OPP)
is
to
use
a
tiered
approach
for
acute
dietary
risk
assessment
that
proceeds
from
very
conservative
assumptions
about
food
residues,
to
inclusion
of
more
realistic
residue
values
measured
closer
to
the
point
of
consumption.
The
process
of
dietary
risk
assessment
of
pesticides
considers
chronic
and
acute
exposures
to
the
U.
S.
population
and
sensitive
population
sub­
groups.
Critical
to
any
dietary
assessment
is
residue
and
consumption
data.
Because
of
the
number
of
years
myclobutanil
has
been
used
on
crops,
a
substantial
public
dataset
exists
of
food
residues
as
measured
by
the
USDA's
Pesticide
Data
Program
(
PDP).
The
PDP
monitoring
data
realistically
estimate
the
magnitude
of
pesticide
residue
on
food
as
it
is
purchased
by
the
consumer,
since
samples
are
taken
closer
to
the
point
of
consumption,
and
more
accurately
represent
actual
patterns
of
use
and
food
distribution
than
measurements
from
a
typical
field
trial.
Additional
exposures
from
potential
residues
in
drinking
water
were
also
estimated.
The
Dietary
Exposure
Evaluation
Model
(
DEEM­
FCID,
version
2.02),
a
commercially
available
software
package,
was
used
to
estimate
exposure
to
myclobutanil
via
food
consumption
by
the
general
U.
S.
population
and
certain
subgroups.
The
model
combined
the
consumption
data
and
residue
data
for
a
given
pesticide
to
analyze
dietary
risk.
For
the
tier
III
acute
assessment,
DEEM
developed
a
conditional,
joint
probability
function
from
the
individual
pesticide
residues
and
the
food
intake
information.
Food
consumption
data
from
the
USDA
Continuing
Survey
of
Food
Intakes
by
Individuals
(
CSFII)
conducted
from
1994
through
1998
including
the
children's
supplemental
survey
were
used
in
this
assessment.
The
food
consumption
data,
i.
e.,
foods
as
consumed,
were
translated
into
raw
agricultural
commodities
and
their
food
forms
using
recipe
translation
files
contained
within
the
DEEM
software.
For
example,
if
a
person
reported
consumption
of
apple
pie,
the
model
evaluated
exposure
to
a
pesticide
via
the
ingredients
of
the
pie
such
as
apples,
sugar,
wheat
flour,
leavening
agents,
animal
fat,
spices,
water,
etc.
For
acute
assessments,
individual,
daily,
food
consumption
amounts
by
each
survey
respondent
were
use
to
establish
a
probability
distribution
of
exposures;
for
chronic
assessments,
food
consumption
values
averaged
across
the
populations
of
interest
were
used.
The
exposure
estimates
in
this
report
incorporate
residue
estimates
from
existing
uses
(
Section
3),
temporary
uses
(
Section
18),
inadvertent
exposures,
and
proposed
uses.
Each
exposure
category
is
considered
in
the
following
sections.
Because
of
the
number
of
years
that
myclobutanil
has
been
used
in
agriculture,
the
PDP
data
provides
the
best
available
information
on
residues
that
may
result
from
established
uses
on
food
crops.
Since
PDP
data
would
not
give
an
adequate
representation
of
these
uses,
for
purposes
of
this
assessment,
the
temporary
tolerances
were
used
in
place
of
residue
data.
In
addition,
it
is
recognized
that
residues
may
occur
on
crops
from
inadvertent
exposures
to
myclobutanil
from
windblown
drift,
or
rotational
crops
grown
in
fields
previously
treated
with
the
fungicide.
The
inadvertent
tolerances
were
used
in
place
of
specific
residue
data.
A
final
consideration
is
for
proposed
new
uses,
primarily
on
tropical
fruits.
For
these
crops,
the
proposed
tolerance
is
used
as
a
surrogate
for
actual
residue
data.
It
should
be
noted
that
a
number
of
the
myclobutanil
uses
are
supported
by
residue
data
supplied
by
the
IR­
4
program.
The
section
3
tolerance
value
was
used
for
those
foods
that
were
not
sampled
by
the
PDP
residue
program,
and
for
which
there
is
no
established
policy
for
surrogation
from
another
crop.
These
crops
include
such
uses
as
almonds,
cane
berries,
and
peppermint.
a.
Acute
dietary
exposure.
A
summary
of
the
results
of
the
acute
exposures
from
food
consumption
is
given
in
the
following
table.
All
estimates
are
given
for
the
upper
99.9%
tile
of
females
of
child
bearing
age,
i.
e.,
the
subpopulation
considered
susceptible
to
acute
exposures
from
myclobutanil.
Cumulative
Exposures
from
Existing
and
Proposed
Uses
Section
3
Section
18
Inadvertent
Proposed
Females
13­
50
Exposure
(
mg/
kg­
bwt/
day
0.003987
0.004205
0.004362
0.007371
%
aPAD
0.66
0.70
0.73
1.23
Exposures
from
all
existing,
proposed,
and
inadvertent
residues
result
in
very
low
acute
exposures.
Consumption
of
food
by
females
of
child
bearing
age
is
expected
to
result
in
approximately
0.007
mg/
kg­
bw/
day
exposure
to
myclobutanil
or
approximately
one
percent
of
the
acute
reference
dose.
The
acute
drinking
water
estimates
were
estimated
using
FIRST,
GENEEC
and
SCIGRO
and
are
known
to
overestimate
potential
water
residues.
Such
water
estimates
are
very
sensitive
to
the
input
parameters;
however,
they
can
still
serve
as
a
screening
estimate
for
exposure
considerations.
Water
residues
were
incorporated
as
a
single
point
estimate
for
both
direct
and
indirect
water
sources
assuming
a
constant
value
of
115
ppb
(
0.115
ppm).
The
potential,
acute,
aggregate
exposures
from
food
and
drinking
water
for
females
of
child
bearing
age
is
approximately
0.0181
mg/
kg­
bwt/
day
or
3%
of
the
acute
reference
dose
for
the
upper
99.9%
tile
of
the
population.
b.
Chronic
dietary
exposure.
A
summary
of
the
chronic,
long
term
exposures
to
the
highest
exposed
subpopulations
is
given
in
the
following
table.
After
considering
all
existing
and
proposed
uses,
the
exposure
to
myclobutanil
residues
is
less
than
11%
of
the
chronic
population
adjusted
dose
(
cPAD)
for
children
aged
one
to
two
years
old.
c.
Cancer
dietary
exposure.
The
Agency
has
classified
myclobutanil
as
a
"
Group
E
­
not
likely
a
human
carcinogen"
and,
therefore,
quantification
of
human
cancer
risk
is
not
required.]
ii.
Drinking
water.
Direct
measurements
of
myclobutanil
in
drinking
water
were
not
available.
Estimates
of
potential
water
concentrations
resulting
from
agricultural
use
of
myclobutanil
were
estimated
using
three
environmental
models,
assuming
certain
environmental
degradation
properties
for
myclobutanil
and
modeled
dynamics
of
ground
water
and
surface
water
bodies.
These
three
models
provide
conservative,
screening
level
estimates
of
water
concentrations.
SciGrow2.1
is
used
for
ground
water
while
GENEEC2
and
FIRST
is
used
to
give
estimates
of
ground
water
concentrations.
Assuming
a
myclobutanil
application
rate
of
0.25
lbs/
acre
and
a
measured
field
half
life
of
66
days,
SciGrow2.1
gave
a
ground
water
estimate
of
0.27
parts
per
billion
(
ppb).
Assuming
a
half
life
of
354
days,
derived
from
laboratory
studies,
the
estimate
was
1.1
ppb.
Both
GENEEC2
and
FIRST
gave
comparable
peak
and
average
surface
water
concentration
estimates.
Using
an
environmental
half
life
of
66
days
gave
a
peak
concentration
of
48
ppb
with
GENEEC2
and
60
ppb
for
FIRST.
The
average,
long
term
concentrations
were
60
ppb
and
41
ppb
respectively.
These
values
differ
somewhat
from
the
values
used
by
the
USEPA
in
their
2001
assessment.
In
their
document,
based
on
the
GENEEC2
and
FIRST
models
the
estimated
environmental
concentrations
(
EECs)
of
myclobutanil
for
acute
exposures
are
estimated
to
be
115
parts
per
billion
(
ppb)
for
surface
water
and
2
ppb
for
ground
water.
The
EECs
for
chronic
exposures
are
estimated
to
be
92
ppb
for
surface
water
and
2
ppb
for
ground
water.
Acute
exposures
to
myclobutanil
from
residues
in
food
and
water
were
calculated
using
DEEM­
FCID.
For
the
Section
3
uses,
individual
residue
data
from
the
PDP
monitoring
surveys
for
the
years
1999
through
2003
were
combined,
adjusted
by
the
applicable
EPA­
SOP's,
and
used
to
generate
residue
data
files
(.
rdf
files)
for
use
by
the
DEEM
software.
For
food
forms
considered
as
not
blended
and
partially
blended,
the
entire
distribution
of
residues
was
used
with
individual
data
points
sampled
in
the
probabilistic
assessment.
2.
Non­
dietary
exposure.
[
i.
Residential
uses.
Myclobutanil
is
a
fungicide
registered
for
use
on
turfgrass
(
including
established
lawns,
and
golf
courses),
landscape
ornamentals,
greenhouse
and
nursery
ornamentals,
home
orchards,
vineyards,
or
fruit
trees,
and
non­
commercial
tree
fruits
and
vines.
The
exposure
and
risk
from
the
home
use
application
of
myclobutanil
were
estimated
for
hose­
end
sprayer,
back
pack
sprayer
and
low
pressure
hand
wand
sprayer
when
used
for
garden,
trees
and
vines
and
turf
treatments.
The
resultant
MOEs
for
mixer/
loader­
applicator
(
M/
L/
A)
range
from
11,000
(
low
pressure
hand
wand)
to
210,000
(
backpack)
for
garden
and
fruit
tree
applications.
MOEs
for
turf
application
are
770
for
the
hose
end
sprayer,
2,000
for
low
pressure
hand
wand,
and
39,000
for
the
back
pack
sprayer.
MOEs
were
acceptable
for
all
post­
application
activities
in
all
crops.
MOEs
for
garden
activities
ranged
from
5,800
for
grape
girdling
and
vine
turning
to
370,000
for
limb
propping
of
fruit
trees.
Exposure
for
children
of
an
age
to
be
expected
to
be
working
in
the
garden
(
i.
e.
body
weight
39.1
kg)
resulted
in
a
similar
range
of
MOEs.
These
ranged
from
3,800
for
grape
girdling
and
vine
turning
to
200,000
for
limb
propping
of
fruit
trees.
Reentry
into
treated
lawns,
home
orchards,
vineyards,
and
gardens
also
resulted
in
acceptable
MOEs
for
all
crops
and
scenarios.
Aggregated
reentry
into
lawns
by
children
resulted
in
MOEs
>
570
and
MOEs
>
1,600
for
adults
(
based
on
CA
data).
Working
in
the
garden
resulted
in
MOEs
that
ranged
from
5,800
to
370,000
for
adults
and
from
3,800
to
200,000
for
children.
ii.
Recreational
uses.
Myclobutanil
is
used
on
golf
courses.
Use
on
golf
courses
is
very
low.
Therefore,
as
a
conservative
estimate,
the
MOE
for
residential
lawns
(
above)
is
used.
Since
myclobutanil
is
a
Group
E
(
not
likely
a
human
carcinogen),
no
human
cancer
risk
was
calculated.]
D.
Cumulative
Effects.
Myclobutanil
is
a
member
of
the
triazole
derivative
(
T­
D)
fungicides.
At
this
time,
there
is
no
data
available
to
determine
whether
myclobutanil
exhibits
a
common
mechanism
of
toxicity
with
other
T­
D
fungicides.
For
the
purpose
of
this
assessment
therefore,
it
is
assumed
that
myclobutanil
does
not
have
a
mechanism
of
toxicity
common
with
other
substances
and
no
cumulative
risk
assessment
is
required.
E.
Safety
Determination
1.
U.
S.
population.
Using
the
above
conservative
exposure
assumptions
(
Level
1/
Tier
1)
and
taking
into
account
the
completeness
and
reliability
of
the
toxicity
data,
chronic
dietary
exposure
to
myclobutanil
from
all
registered
and
proposed
uses
and
drinking
water
will
utilize
11.1%
of
the
cRfD
for
the
U.
S.
population
(
total).
The
major
identifiable
subgroup
with
the
highest
chronic
food
exposure
is
non­
nursing
infants
using
37.4%
of
the
cRfD.
Generally,
EPA
has
no
concern
for
exposures
below
100%
of
the
cRfD
because
the
chronic
RfD
represents
the
level
at
or
below
which
daily
dietary
exposures
over
a
lifetime
will
not
pose
appreciable
risks
to
human
health.
Likewise,
the
acute
dietary
food
exposure
at
99.9th
percentile
for
females
13+
yrs,
the
population
sub­
group
of
concern
is
3%
of
aRfD
which
is
well
below
100%
of
the
aRFD.
Therefore,
there
is
no
concern
for
exposure
because
the
acute
RfD
represents
the
level
at
or
below
which
a
single
daily
exposure
will
not
pose
appreciable
risks
to
human
health.
Additionally,
the
potential
contribution
of
myclobutanil
from
residential
uses
in
home
gardens,
orchards,
vineyards
and
turf
showed
acceptable
margin
of
exposures
to
homeowners
(
MOE
>
770,
during
the
application
and
MOE
>
1,600
for
post­
application).
The
aggregate
exposure
from
diet,
drinking
water
and
residential
exposure
to
adults
has
also
resulted
in
a
safe
margin
of
exposure
to
homeowners
(
MOE
>
588).
The
calculated
DWLOCs
for
assessing
aggregate
acute
exposure
to
adults
from
food,
and
residential
exposure
is
0.59
mg/
kg­
bw/
day
(
20.5
ppm),
over
an
acute
RfD
established
for
women
age
13+,
at
0.60
mg/
kg­
bw/
day.
This
acute
DWLOC
is
much
higher
than
the
highest
estimated
environmental
concentrations
in
surface
water
(
EEC
=
0.115
ppm).
The
calculated
DWLOCs
for
assessing
aggregate
chronic
exposure
to
adults
from
food
is
0.024
mg/
kg­
bw/
day
(
846
ppm),
over
a
chronic
RfD
of
0.025
mg/
kg­
bw/
day.
This
acute
DWLOC
is
much
higher
than
the
average
estimated
environmental
concentrations
in
surface
water
(
EEC
=
0.092
ppm).
Short­
term
and
intermediate­
term
risks
are
considered
to
be
negligible
because
of
lack
of
significant
toxicological
effects
and
exposure.
Therefore,
based
on
these
risk
assessments,
Dow
AgroSciences
concludes
that
there
is
reasonable
certainty
that
no
harm
will
result
to
the
U.
S.
population
from
aggregate
exposure
to
myclobutanil
residues
from
all
supported
registered
uses.]
2.
Infants
and
children.
[
EPA
uses
a
weight
of
evidence
approach
in
determining
what
safety
factor
is
appropriate
for
assessing
risks
to
infants
and
children.
This
approach
takes
into
account
the
nature
and
severity
of
the
effects
observed
in
pre­
and
post­
natal
studies
and
other
information
such
as
epidemiological
data.
The
completeness
and
adequacy
of
the
toxicity
database
is
also
considered.
Toxicity
database
and
exposure
data
for
myclobutanil
are
complete.
No
indication
of
increased
susceptibility
of
rats
or
rabbits
to
in
utero
and/
or
postnatal
exposure
was
noted
in
the
acceptable
developmental
toxicity
studies
in
rats
and
rabbits
as
well
as
in
a
2­
generation
reproductive
toxicity
study
in
rats.
EPA
has
previously
determined
that
no
additional
safety
factor
to
protect
infants
and
children
is
necessary
for
myclobutanil
and
that
the
cRfD
at
0.025
mg/
kg/
day
is
appropriate
for
assessing
risk
to
infants
and
children.
Using
the
conservative
assumptions
(
Tier
1
or
Level
1)
described
above,
the
chronic
dietary
exposure
to
myclobutanil
including
all
existing
and
proposed
uses
will
utilize
4.8%
of
the
cRfD
for
all
infants
(<
1
yr
old),
5.9%
of
the
cRfD
for
non­
nursing
infants,
and
10.6%
of
the
cRfD
for
children
1­
2
yrs.
Even
when
considering
the
potential
exposure
to
drinking
water,
the
aggregate
exposure
is
not
expected
to
exceed
30.2%
of
the
cRfD
for
all
infants.
An
acute
DWLOC
is
not
assessed
since
an
aRfD
is
not
required
for
children,
or
any
other
subpopulation
group
than
women
of
age
13+.
The
calculated
chronic
DWLOC
for
children
1­
2
years
old
exposed
from
ingesting
food
is
0.022
mg/
kg­
bw/
day
(
0.22
ppm
in
drinking
water).
The
calculated
chronic
DWLOC
for
children
is
therefore
higher
than
the
estimated
environmental
concentration
in
surface
water
(
highest
EEC
yearly
average
=
0.092
ppm).
Therefore,
based
on
the
completeness
and
reliability
of
the
toxicity
data
and
the
conservative
exposure
assessment,
Dow
AgroSciences
concludes
with
reasonable
certainty
that
no
harm
will
result
to
infants
and
children
from
the
aggregate
exposure
to
myclobutanil
residues
from
registered
uses.
F.
International
Tolerances
International
CODEX
values
are
established
for
hops,
bananas,
prunes,
pears,
apples,
plums,
apricots,
cherries,
peaches,
nectarines,
quince,
tomatoes,
table
grapes,
wine
grapes,
strawberries,
currants,
cattle
fat,
meat,
milk
and
edible
offal,
poultry
meat,
fat,
and
edible
offal,
and
eggs.