UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
June
7,
2002
MEMORANDUM
SUBJECT:
Fenarimol.
Revised
HED
Human
Health
Assessment
for
the
Tolerance
Reassessment
Eligibility
Decision
(
TRED)
Document.
Chemical
No.
206600.
No
MRID
#.
DP
Barcode
No.
D283429.

FROM:
Barry
O'Keefe,
Residential
Exposure
Assessor/
Risk
Assessor
John
Doherty,
Toxicologist
Danette
Drew,
Chemist
Reregistration
Branch
3
Health
Effects
Division
(
7509C)

THRU:
Catherine
Eiden,
Branch
Senior
Scientist
Reregistration
Branch
3
Health
Effects
Division
(
7509C)

TO:
Tom
Myers,
Chemical
Review
Manager
Special
Review
and
Reregistration
Division
(
7508C)

This
memorandum
and
attachments
are
the
Revised
Health
Effects
Division's
Tolerance
Reassessment
Eligibility
Decision
(
TRED)
Document
for
fenarimol,
taking
into
consideration
comments
from
the
registrant,
Gowan
Company,
and
requirements
of
the
1996
Food
Quality
Protection
Act
(
FQPA).
This
assessment
only
discusses
the
human
health
risk
assessment
required
for
reassessment
of
tolerances
and
does
not
include
an
occupational
risk
assessment
required
for
reregistration
of
products.
Fenarimol
was
registered
after
1984,
so
it
is
not
subject
to
reregistration
under
FIFRA
88.
However,
fenarimol
is
subject
to
tolerance
reassessment
under
the
FQPA.
When
fenarimol
undergoes
product
reregistration,
SRRD
should
insure
that
all
product
labels
are
in
compliance
with
the
worker
protection
standard
(
WPS).
Cumulative
risk
assessment
considering
risks
from
other
pesticides
which
may
have
a
common
mechanism
of
toxicity
is
also
not
addressed
in
this
document.

Attachments:
Hazard
Identification
Assessment
Review
Committee
Revisit
(
HIARC)
report
(
J.
Doherty,
6/
02)
Hazard
Identification
Assessment
Review
Committee
(
HIARC)
report
(
J.
Doherty,
9/
5/
01)
FQPA
Committee
Report
(
B.
Tarplee,
9/
28/
01)
Mechanism
of
Toxicity
Committee
(
METARC)
report
(
J.
Doherty,
9/
17/
01),
Toxicology
Chapter
(
J.
Doherty,
D275392,
10/
12/
01)
Chemistry
Chapter
(
D.
Drew,
D277505,
10/
18/
01)
2
Dietary
Exposure
Analysis
(
D.
Drew,
D278898,
11/
19/
01)
Metabolism
Assessment
Review
Committee
report
(
D.
Drew,
D277692,
9/
17/
01)
Residential
Exposure
Analysis
(
B.
O'Keefe,
D280935,
2/
12/
02)
Drinking
Water
Assessment
to
Support
the
TRED
for
Fenarimol
(
L.
Libelo,
8/
6/
01).

1.0
EXECUTIVE
SUMMARY
Fenarimol
is
a
member
of
the
pyrimidine
class
of
fungicides,
which
also
includes
dimethirimol,
bupirimate,
and
ethirimol.
It
is
the
only
member
of
this
class
registered
for
use
in
the
U.
S.
Fenarimol
is
a
localized
systemic
foliar
fungicide
used
for
control
of
such
pests
as
scab,
powdery
mildew,
rusts,
and
leaf
spot.
Fenarimol
inhibits
fungal
growth
by
adversely
affecting
the
formation
of
the
fungal
sterol
ergosterol.
The
chemical
name
of
fenarimol
is
alpha­(
2
chlorophenyl)­
alpha­(
4­
chlorophenyl)­
5­
pyrimidinemethanol.

Use
Profile
Fenarimol
is
currently
registered
for
use
on
the
following
fruit
and
nut
crops:
apples,
cherries,
filberts,
grapes,
pears,
bananas
and
pecans.
It
is
also
registered
for
use
on
ornamental
plants,
trees,
grasses,
and
turf.
The
registration
of
fenarimol
is
being
supported
by
Gowan
Company.
Fenarimol
total
domestic
usage
for
years
1990­
1999
averaged
approximately
61,000
pounds
active
ingredient.
Its
largest
markets,
in
terms
of
total
pounds
active
ingredient
(
ai),
are
allocated
to
apples
(
33%),
outdoor
nurseries
(
20%),
turf
for
lawns
(
16%),
and
turf
for
golf
courses
(
12%).
The
remaining
usage
is
primarily
on
raisin
and
wine
grapes,
cherries,
filberts,
and
pears.
Crops
with
a
high
percentage
of
the
total
U.
S.
planted
acres
treated
include
apples
(
25%),
raisin
grapes
(
21%),
sweet
cherries
(
13%),
tart
cherries,
wine
grapes,
and
filberts
(
9%
each),
and
table
grapes
(
8%).

Fenarimol
formulations
include
granular
(
0.78%
ai,
turf
use
only),
soluble
concentrate/
liquid
(
11.6%
ai),
flowable
concentrate
(
2.4%
ai)
and
emulsifiable
concentrates
(
11.6%
ai
and
12%
ai).
Only
applications
to
lawns
and
turf
are
expected
to
result
in
residential
exposures.
Although
some
end
use
products
have
label
restrictions
and
wording
indicative
of
non­
homeowner
use,
fenarimol
is
not
a
restricted­
use
pesticide
and
can
be
purchased
and
applied
by
anyone.
However,
only
the
granular
formulation
is
assumed
to
be
applied
by
residents.
However,
due
to
communications
with
the
Agency,
Riverdale
Chemical
Company,
the
registrant
of
this
granular
product,
has
agreed
to
change
the
label
to
prohibit
the
sale
to
and
use
by
homeowners
of
the
granular
product.

Hazard
Identification
and
Dose
Response
Assessment
The
toxicity
database
for
fenarimol
is
substantially
complete,
with
the
following
data
gaps
identified:
Primary
Dermal
Irritation
Study
(
870.2400);
28­
Day
Subchronic
Inhalation
Study
(
870.3465);
and
Special
Developmental
Study
(
870.6300).

Fenarimol
has
moderate
acute
toxicity
via
the
oral,
dermal
or
inhalation
routes
(
all
Category
III).
Fenarimol
causes
corneal
opacity
in
rabbit
eyes
(
Category
II).
There
are
no
data
on
dermal
irritation.
Fenarimol
was
not
shown
to
be
a
contact
dermal
sensitizer
in
the
guinea
pig.

The
rat
metabolism
study
indicates
that
following
oral
administration,
fenarimol
is
rapidly
absorbed
3
and
excreted,
with
the
biliary
route
being
the
major
route
of
excretion.
Subchronic
oral
dosing
in
rats
demonstrates
very
little
toxicity
except
for
some
slight
body
weight
changes
and
liver
pathology
of
low
degree
and
consistency
(
liver
weight
increase
and
fatty
liver).
In
dogs,
there
was
little
overt
toxicity.
Dermal
absorption
was
estimated
by
HIARC
(
9/
6/
01)
to
be
20%
based
on
a
weight
of
the
evidence
assessment
using
rabbit
and
monkey
dermal
absorption
studies
along
with
a
comparison
of
the
rabbit
oral
developmental
toxicity
and
rabbit
21­
day
dermal
toxicity
studies.
However,
based
on
additional
data
supplied
by
the
registrant
(
Gowan
Company),
the
HIARC
(
5/
23/
02)
determined
that
a
dermal
absorption
rate
estimate
of
5%
was
more
appropriate
for
risk
assessment
purposes.

The
liver
is
the
most
evident
target
organ
for
chronic
toxicity,
aside
from
the
effects
of
fenarimol
on
aromatase.
Liver
toxicity
was
manifested
by
liver
weight
increases
and
the
presence
of
"
fatty
liver"
in
rats.
In
dogs,
liver
weight
was
increased
and
there
were
also
increases
in
serum
enzymes
indicative
of
liver
toxicity.
The
data
base
for
carcinogenicity
is
considered
complete.
Fenarimol
has
been
classified
as
a
"
not
likely"
human
carcinogen
(
Group
E).
The
mutagenicity/
genetic
toxicity
data
base
is
considered
complete
and
indicates
no
mutagenicity
concern.

The
data
base
for
prenatal
developmental
and
reproductive
toxicity
is
considered
complete.
The
developmental
and
reproductive
toxicity
studies
showed
no
evidence
of
increased
sensitivity
or
susceptibility
of
young
rats
or
rabbits
following
pre­
or
postnatal
exposure
to
fenarimol.
The
studies
demonstrated
that
fenarimol
is
associated
with
hydronephrosis
that
is
reversible.

The
most
prominent
aspect
of
fenarimol
toxicity
was
evident
in
the
rat
multi­
generation
reproduction
studies
and
relates
to
inhibition
of
aromatase.
Aromatase,
also
known
as
estrogen
synthetase,
is
the
key
enzyme
for
the
conversion
of
androgens
to
estrogens
and
is
therefore
a
potentially
critical
enzyme
in
maintaining
hormone
balance
in
human
physiology.
Without
aromatase,
there
could
potentially
be
deficits
in
estrogens
which
are
important
for
a
variety
of
physiological
functions.
Estrogens
are
largely
responsible
for
the
changes
that
take
place
during
puberty
in
human
females
and
affect
secondary
sexual
characteristics.
It
is
also
recognized
that
aromatase
deficient
males
do
not
develop
normal
skeletal
characteristics.
The
Mechanism
of
Toxicity
Assessment
Review
Committee
(
METARC)
met
to
evaluate
the
data
concerning
fenarimol's
effects
on
aromatase
and
their
decision
memorandum
contains
a
more
detailed
discussion
of
aromatase
(
J.
Doherty,
9/
16/
01).

The
multi­
generation
reproduction
studies
indicate
that
fenarimol
causes
reduced
fertility
and
dystocia
(
difficult
labor).
Separate
cross
dosing
studies
(
dosing
males
and
mating
with
untreated
females
and
dosing
females
and
mating
with
untreated
males)
indicated
that
the
reduced
fertility
is
due
to
an
effect
in
males
and
the
dystocia
is
an
effect
in
females.
These
effects
of
fenarimol
were
demonstrated
to
be
attributed
to
inhibition
of
aromatase
in
adult
animals.
The
decrease
in
fertility
in
males
results
from
the
decreased
conversion
of
testosterone
(
an
androgen)
to
estradiol
which
is
essential
for
male
sexual
development.
The
increase
in
dystocia
in
rats
was
also
attributed
to
inhibition
of
aromatase
because
in
the
rat,
progesterone
is
converted
to
estrogen
by
aromatase
to
facilitate
parturition
(
birth).

The
FQPA
required
the
Agency
to
consider
potential
special
sensitivity
to
infants
and
children
from
exposure
to
fenarimol.
Submitted
toxicity
studies
showed
that
there
is
no
increased
sensitivity
or
susceptibility
to
infants
and
children
based
mainly
on
the
results
of
the
developmental/
reproductive
toxicity
studies.
However,
a
special
developmental
study
is
required
to
determine
if
the
potential
hormonal
effects
as
elicited
by
inhibition
of
aromatase
will
result
in
effects
in
offspring.
Additionally,
4
the
environmental
fate
database
is
incomplete
for
the
aquatic
photolytic
degradate
of
fenarimol,
4­
chloro­
2­(
5­
pyrimidyl)­
2'­
chlorobenzophenone.
A
screening
level
drinking
water
assessment,
which
includes
this
degradate
of
potential
toxicological
concern,
is
not
possible
at
this
time.
Therefore,
the
FQPA
committee
determined
that
the
10x
FQPA
factor
should
be
retained
for
all
fenarimol
risk
assessments.

The
METARC
recommended,
and
the
HIARC
confirmed,
that
the
reduced
male
fertility
and
dystocia
effects
of
fenarimol
should
be
endpoints
for
human
health
risk
assessment.
It
is
noted
that
the
endpoint
from
the
multi­
generation
reproduction
study
is
based
on
decreased
litter
size.
This
decrease
in
litter
size
may
be
a
reflection
of
the
maternal
toxicity
(
dystocia)
or
the
potential
for
fenarimol
to
inhibit
aromatase
in
males
(
reduced
fertility).
Because
both
males
and
females
are
affected,
the
toxicological
endpoint
from
the
multi­
generation
reproduction
study
is
applicable
to
all
populations.

After
examining
all
of
the
available
toxicity
data,
the
HIARC
concluded
that
an
acute
toxicity
endpoint
and
dose
for
risk
assessment
could
not
be
identified.
That
is,
no
appropriate
endpoint
was
available
to
quantitate
risk
to
the
general
population
or
females
13­
50
years
old
from
a
single­
dose
administration
of
fenarimol.
Although
hydronephrosis
seen
in
the
rat
developmental
and
multigeneration
reproductive
toxicity
studies
had
been
identified
as
an
acute
adverse
toxic
effect
(
endpoint)
in
earlier
fenarimol
risk
assessments,
the
HIARC
concluded
that
it
is
not
appropriate
because:
1)
the
hydronephrosis
is
not
severe
(
its
is
considered
an
effect
of
low
degree
or
magnitude);
2)
the
hydronephrosis
was
shown
to
be
reversible;
3)
the
hydronephrosis
developed
after
multiple
exposures
and
there
is
no
indication
that
it
would
develop
following
a
single
exposure;
and,
4)
the
hydronephrosis
may
be
related
to
a
developmental
delay
and
not
a
target
specific
effect
of
fenarimol.

For
risks
associated
with
chronic
dietary
exposures,
the
HIARC
identified
a
reference
dose
for
chronic
exposure
(
cRfD)
of
0.006
mg/
kg/
day
from
the
multi­
generation
reproduction
study
based
on
a
no
observed
adverse
effect
level
(
NOAEL)
of
0.6
mg/
kg/
day,
and
a
10X
uncertainty
factor
for
interspecies
extrapolation
and
a
10X
uncertainty
factor
for
intraspecies
variation.
The
NOAEL
of
0.6
mg/
kg/
day
is
based
on
decreased
live
born
litter
size
in
the
F
1
and
F
2
generations
at
a
lowest
observed
adverse
effect
level
(
LOAEL)
of
1.2
mg/
kg/
day.
HED
calculated
a
chronic
Population
Adjusted
Dose
(
cPAD)
of
0.0006
mg/
kg/
day.
The
cPAD
is
the
RfD
divided
by
the
FQPA
safety
factor
(
10X).
Chronic
dietary
exposure
estimates
greater
than
100%
of
the
cPAD
would
exceed
HED's
level
of
concern.

For
risks
associated
with
intermediate­
term
residential
exposures
(
1­
6
months),
the
same
endpoint
(
NOAEL
of
0.6
mg/
kg/
day)
was
used
for
incidental
oral,
dermal,
and
inhalation
risk
assessments.
A
Margin
of
Exposure
or
MOE,
which
is
the
ratio
of
the
NOAEL
to
the
exposure
estimate,
of
greater
than
or
equal
to1000
does
not
exceed
HED's
level
of
concern
for
intermediate­
term
risk
assessments.
A
MOE
of
greater
than
or
equal
to1000
is
required
for
these
intermediate­
term
exposure
scenarios
because
of
the
10x
interspecies
factor,
the
10x
intraspecies
factor
and
the
10x
FQPA
factor.
Because
the
same
endpoint
was
used
for
all
intermediate­
term
exposure
assessments,
the
risk
estimates
for
the
various
routes
of
exposure
may
be
aggregated.

For
the
short­
term
(
1­
30
day)
incidental
oral,
dermal,
and
inhalation
risk
assessments,
a
LOAEL
of
35
mg/
kg/
day
was
selected.
This
endpoint
is
based
on
decreased
fertility
and
dystocia,
an
indicator
of
5
hormonal
effects,
observed
in
a
special
non­
guideline
cross
breeding
reproduction/
developmental
toxicity
study
in
rats.
Because
a
NOAEL
could
not
be
identified
in
the
study,
and
effects
were
seen
at
the
lowest
dose
tested,
a
LOAEL
was
used,
and
is
used
an
additional
3x
uncertainty
factor
was
applied.
Therefore,
a
MOE
greater
than
3000
does
not
exceed
HED's
level
of
concern
for
short­
term
risk
assessments.
Because
the
same
endpoint
was
used
for
all
short­
term
exposure
assessments,
the
risk
estimates
for
the
various
routes
of
exposure
may
be
aggregated.

Exposure
and
Risk
Assessment
Dietary
Exposure
and
Risk
Estimates
The
residue
chemistry
database
for
fenarimol
is
substantially
complete
and
is
adequate
for
tolerance
reassessment.
The
Metabolism
Assessment
Review
Committee
(
MARC)
has
determined
that
for
enforcement
purposes,
the
tolerance
for
plant
commodities
should
be
expressed
as
parent
only.
However
the
dietary
assessment
for
grapes
and
bananas
should
include
the
metabolites
[
alpha­(
2­
chlorophenyl)­
alpha­(
4­
chlorophenyl)­
1,4­
dihydro­
5­
pyrimidinemethanol]
and
(
5­[
2­
chlorophenyl)­
(
4­
chlorophenyl)
methyl]­
3,4­
dihydro­
4­
pyrimidinol]),
because
of
their
structural
similarity
to
fenarimol.
The
residue
of
concern
in
livestock
commodities
is
fenarimol
per
se.
Tolerances
for
fenarimol
are
generally
low,
ranging
from
0.01
to
1.0
ppm
Because
an
acute
toxicity
endpoint
was
not
identified,
an
acute
dietary
exposure
assessment
was
neither
required
nor
conducted.
The
chronic
dietary
exposure
assessment
for
fenarimol
is
highly
refined
using
anticipated
residues
based
on
Food
and
Drug
Administration
(
FDA)
monitoring
data
for
apples,
bananas,
cherries,
grapes
and
pears.
There
were
no
USDA
Pesticide
Data
Program
(
PDP)
monitoring
data
available
for
fenarimol.
The
FDA
monitoring
data
indicated
no
detectable
residues
for
apples,
bananas,
grapes
and
pears.
Field
trial
residue
data
were
used
for
pecans
and
filberts.
Percent
crop
treated
(%
CT)
information
and
processing
factors,
where
available,
were
used
in
the
assessment.
Anticipated
residues
were
calculated
for
cattle
meat,
fat,
and
meat
by­
products.
Wet
apple
pomace
is
the
only
animal
feed
item
associated
with
the
registered
uses
of
fenarimol.
There
are
no
poultry
or
hog
feedstuffs.
Milk
was
classified
as
Category
3
of
40
CFR
180.6(
a)
­
that
is,
there
is
no
reasonable
expectation
of
finite
residues.

Chronic
dietary
risk
estimates
are
provided
for
the
general
U.
S.
population
and
various
population
subgroups.
This
assessment
concludes
that
for
all
supported
registered
commodities,
the
chronic
risk
estimates
are
below
the
HED's
level
of
concern
(<
100%
of
the
chronic
population
adjusted
dose,
cPAD)
for
the
general
U.
S.
population
and
all
population
subgroups.
Dietary
(
food)
exposure
estimates
were
all
very
low
(
all
<
1%
of
the
cPAD).
This
is
not
surprising
based
on:
the
lack
of
detectable
residues
for
many
commodities
in
the
FDA
monitoring
data;
no
residues
expected
in
milk,
poultry
and
hogs;
and,
low
anticipated
residues
for
cattle
meat,
fat,
and
meat
by­
products.

Environmental
fate
data
show
that
fenarimol
is
persistent
and
mobile
in
the
environment.
In
field
studies,
fenarimol
dissipated
with
half­
lives
of
3
months
to
several
years
from
soil
and
turf
surfaces.
Fenarimol
is
stable
to
hydrolysis,
anaerobic
microbial
degradation
and
photolysis
on
soil.
It
is
degraded
very
slowly,
if
at
all,
by
aerobic
microbial
processes
with
reported
mean
aerobic
soil
metabolism
half­
life
of
about
4
years.
It
is
degraded
by
photolysis
in
aqueous
solution.
The
primary
photolysis
product
was
4­
chloro­
2­(
5­
pyrimidyl)­
2'­
clorobenzophenone.
The
MARC
elected
not
to
exclude
this
degradate
in
the
drinking
water
exposure
assessment
because:
1)
its
potential
to
occur
in
surface
water;
and
2)
the
lack
of
data
to
determine
whether
it
is
of
toxicological
concern.
6
The
environmental
fate
studies
were
conducted
in
the
1970s
and
early
1980s.
The
quality
of
the
data
provided
by
these
studies
is
significantly
lower
then
currently
required.
By
current
standards
most
of
these
studies
would
not
be
considered
acceptable
and
the
results
would
not
be
considered
of
sufficient
quality
to
allow
a
reasonably
accurate
assessment
of
the
environmental
fate
of
this
compound.
Therefore,
the
estimated
environmental
concentrations
(
EECs)
presented
here
are
somewhat
uncertain,
and
may
change
substantially
when
better
data
become
available.
It
is
not
possible,
using
the
existing
data,
to
provide
a
more
refined
assessment.

To
estimate
risks
from
exposure
to
fenarimol
residues
potentially
present
in
drinking
water,
HED
has
compared
EECs
for
fenarimol
in
surface
water
and
groundwater
to
calculated
drinking
water
levels
of
comparison
(
DWLOCs).
The
DWLOC
chronic
is
the
concentration
in
drinking
water
as
a
part
of
the
aggregate
chronic
exposure
that
occupies
no
more
than
100%
of
the
cPAD
when
considered
together
with
other
sources
of
exposure.
If
the
EECs
are
greater
than
the
DWLOCs,
there
is
a
potential
drinking
water
concern.
Screening­
level
assessments,
using
conservative
modeling
to
estimate
highend
average
concentrations
(
EECs)
of
fenarimol
in
surface
water
and
groundwater,
were
conducted
by
the
Environmental
Fate
and
Effects
Division
(
EFED).
Tier
I
modeling
was
performed
for
both
surface
water
(
FIRST
model)
and
groundwater
(
SCI­
GROW
model).
EFED
modeled
the
turf
application
use
scenario
in
both
cases.
A
Tier
II
model
is
not
available
for
turf.
Upon
comparison
of
the
chronic
DWLOCs
with
the
chronic
EECs,
average
concentrations
of
fenarimol
in
surface
and
groundwater
are
greater
than
the
DWLOCs
for
several
populations.
For
surface
water,
EECs
were
approximately
three
(
children
1­
6
yrs
and
all
infants)
to
ten
(
females
13­
50
yrs
and
the
general
U.
S.
population)
times
higher
than
the
DWLOC
chronic.
For
those
populations
with
ground
water
EECs
greater
than
the
DWLOC
chronic,
the
EECs
were
approximately
two
times
higher
than
the
DWLOCs.
Consequently,
there
is
a
potential
concern
for
chronic
exposure
through
drinking
water
from
surface
water
sources
for
all
populations,
and
for
infants
and
children
from
groundwater
sources.

Residential
Exposure
and
Risk
Estimates
Potential
residential
exposures
may
occur
as
a
result
of
applications
of
fenarimol
to
residential
lawns
or
turf
by
residents
and
by
professional
lawn
care
operators
(
LCOs).
Residential
exposures
have
been
estimated
based
on
label
application
rates
and
frequency,
and
the
persistence
of
fenarimol.
The
following
use
patterns
have
been
assessed
for
non­
occupational
(
residential)
handler
exposures:
1)
granular
application
to
turf
with
a
belly
grinder
spreader;
2)
granular
application
to
turf
with
a
pushtype
spreader;
and
3)
granular
spot
treatment
to
turf
by
hand.
The
short­
term
risks
to
residential
handlers
were
assessed
using
the
updated
draft
Standard
Operating
Procedures
(
SOPs)
for
Residential
Exposure
Assessment,
and
includes
surrogate
data
from
the
Pesticide
Handlers
Exposure
Database
(
PHED)
for
loading/
applying
with
a
belly
grinder
type
granular
spreader
and
applying
by
hand,
and
the
Outdoor
Residential
Exposure
Task
Force
(
ORETF)
for
loading/
applying
with
a
push­
type
granular
spreader.
The
ORETF
data
are
recent
high­
quality
studies.
The
data
used
for
the
hand
dispersal
and
belly
grinder­
type
granular
spreader
are
not
as
high
quality.
Central
tendency
exposure
data
were
used
together
with
the
label
maximum
rate
for
short­
term
exposures,
so
the
assessment
is
considered
protective
for
most
uses,
but
not
conservative.

For
residential
adult
handlers
applying
granular
product
to
turf,
risk
estimates
for
short­
term
dermal
exposures
exceed
HED's
level
of
concern
(
MOEs
are
less
than
3000)
for
the
application
by
a
belly
grinder
type
spreader
(
MOE
=
280)
or
by
hand
dispersal
for
spot
treatments
(
MOE
=
1600).
However,
for
the
other
short­
term
handler
exposures
to
fenarimol
(
using
a
push
type
spreader),
HED's
level
of
concern
is
not
exceeded,
i.
e.
all
risk
estimates
(
MOEs)
are
3000
or
greater.
Note:
If
7
label
restrictions
prohibiting
sale
to
or
use
by
homeowners
of
the
granular
product,
as
agreed
to
by
the
registrant,
are
implemented,
then
these
homeowner
handler
scenarios
should
not
occur.

Several
post­
application
exposure
scenarios
following
application
to
turf
are
anticipated;
these
are
as
follows:
1)
short­
term
(
1­
30
days)
and
intermediate­
term
(
30
days
to
6
months)
dermal
exposure
to
adults
and
children
(
toddlers);
2)
incidental
episodic
oral
exposure
to
children
from
ingestion
of
fenarimol
granules;
and
3)
short­
and
intermediate­
term
oral
exposure
to
children
from
incidental
ingestion
of
soil,
turf
grass
mouthing,
and
hand­
to­
mouth
activity.
These
exposures
could
occur
whether
a
professional
or
resident
applied
fenarimol.

The
updated
Residential
SOPs
were
used
to
address
the
exposures
of
children
contacting
treated
turf.
The
SOPs
for
turf
use
a
high
contact
activity
based
on
the
use
of
Jazzercise
®
to
represent
the
exposures
of
an
actively
playing
child
or
active
adult.
Lower­
contact
activities,
such
as
walking,
mowing,
or
golfing,
for
example,
use
transfer
coefficients
based
on
mowing
studies.
Chemical
specific
data
from
a
turf
transferable
residue
(
TTR)
study
were
available
and
were
used
to
estimate
the
dissipation
of
fenarimol.
Dislodgeable
foliar
residue
(
DFR)
data
were
also
available
for
apple
trees.
These
apple
DFR
data
support
the
EFED
conclusions
concerning
the
persistence
of
fenarimol
in
the
environment.
In
the
DFR
study,
detectable
residues
were
still
present
on
leaf
surfaces
65
days
after
treatment.

Risk
estimates
for
short­
term
dermal
contact
with
treated
turf
during
high
contact
lawn
activities
on
day
zero
following
application
exceed
HED's
estimated
level
of
concern
for
adults
and
toddlers
(
MOEs
of
950
and
660,
respectively).
For
low
contact
activities
(
such
as
grass
mowing
or
golfing
),
MOEs
were
3000
or
greater
and
did
not
exceed
the
level
of
concern.
Risk
estimates
for
intermediateterm
dermal
contact
with
treated
turf
MOEs
were
1000
or
greater
and
did
not
exceed
the
level
of
concern
for
high
contact
lawn
activities
(
MOE
of
1400
for
adults,
1000
for
toddlers).
Risk
estimates
for
adults
were
well
below
the
level
of
concern
for
the
low
contact
activities
of
golfing
and
mowing,
with
all
MOEs

10,000.

HED
assessed
short­
term
exposures
of
small
children
following
application
of
fenarimol
to
residential
lawns,
including
exposures
from
incidental
episodic
ingestion
of
fenarimol
granules,
and
exposures
from
incidental
ingestion
of
fenarimol
residues
from
turf
grass
mouthing,
hand­
to­
mouth
activity,
and
soil
ingestion.
The
risk
estimates
for
small
children's
ingestion
of
fenarimol
from
treated
turf
indicate
that
risks
exceed
the
level
of
concern
(
MOEs
less
than
3000)
for
ingestion
of
granules
(
MOE
=
220)
and
hand­
to­
mouth
(
MOE
=
860)
activity.
However,
HED
considers
the
incidental
episodic
risk
of
ingestion
of
fenarimol
granules
to
be
unlikely
given
the
smaller
particle
size
of
fenarimol
granules
and
the
fact
that
watering­
in
should
occur
immediately
or
soon
after
application
in
order
for
the
pesticide
to
be
efficacious.
Incidental
ingestion
of
soil
and
incidental
turf
grass
mouthing
did
not
exceed
the
level
of
concern.
The
small
children's
combined
oral
hand­
to­
mouth
scenarios
(
except
granular
ingestion)
also
exceeds
the
level
of
concern
(
MOE
=
690).
When
risk
estimates
for
small
children
from
short­
term
dermal
exposures
are
combined
with
risk
estimates
from
short­
term
incidental
oral
exposures
(
except
granular
ingestion),
the
combined
short­
term
MOE
exceeds
the
level
of
concern
(
MOE
=
340).

Based
upon
the
slow
dissipation
rate
of
fenarimol
and
the
possibility
of
multiple
applications
to
turf,
HED
estimated
risks
for
intermediate­
term
exposures
of
small
children
from
incidental
ingestion
of
soil,
hand­
to­
mouth
transfer,
and
incidental
turf
grass
mouthing.
Intermediate­
term
risk
estimates
were
below
the
level
of
concern
for
ingestion
of
soil
(
MOE
=
24,000).
However,
the
intermediate­
8
N
N
OH
Cl
Cl
term
risk
estimates
for
the
turf
grass
mouthing
(
MOE
=
320)
and
hand­
to­
mouth
activities
(
MOE
=
78)
exceed
the
level
of
concern.
The
small
children's
combined
oral
hand­
to­
mouth
scenarios
(
except
granular
ingestion)
also
exceed
the
level
of
concern
(
MOE
=
62).
When
risks
from
dermal
exposures
from
fenarimol
to
small
children
are
combined
with
risks
from
incidental
oral
exposures,
the
combined
intermediate­
term
risk
estimates
exceed
the
level
of
concern
(
MOE
=
58).
These
intermediate­
term
incidental
risk
estimates
do
not
account
for
the
fact
that
turf
periodically
receives
irrigation
and/
or
precipitation
and
is
routinely
mowed
resulting
in
the
removal
of
grass
and
residues,
and
therefore,
may
overestimate
exposure.
Additionally,
the
assumption
that
toddlers
will
play
on
turf
for
two
hours
per
day,
for
more
than
30
consecutive
days,
may
be
a
conservative
assumption.
Therefore,
intermediate­
term
risks
to
toddlers
playing
on
turf
may
not
be
as
great
of
a
concern
as
the
risk
estimates
indicate.

Mitigating
circumstances
for
residential
exposure
to
fenarimol
residues
may
include
watering­
in
after
application
to
turf.
This
instruction,
however,
does
not
prevent
contact
with
treated
turf
prior
to
watering­
in.
The
current
granular
label
(
EPA
Reg.
No.
228­
298)
recommends,
but
does
not
require
watering­
in.
The
soluble
concentrate
label
(
EPA
Reg.
No.
62719­
142)
does
not
mention
watering­
in.
Therefore,
label
language
should
be
strengthened
to
ensure
that
watering­
in
occurs
immediately
after
application.
Additionally,
the
current
labeling
does
not
clearly
specify
whether
the
granular
product
(
EPA
Reg.
No.
228­
298)
is
for
professional
use
only.
Specific
labeling
would
help
eliminate
unintentional
use
by
residents.
Labeling
should
also
specifically
advise
against
the
hand
dispersal
and
belly
grinder­
type
application
methods.
Note:
If
label
restrictions
prohibiting
sale
to
or
use
by
homeowners,
as
agreed
to
by
the
registrant
of
the
granular
product,
are
implemented,
then
these
homeowner
handler
scenarios
should
not
occur.

Aggregate
Exposure
and
Risk
Estimates
Because
no
acute
toxicity
endpoint
was
identified
for
risk
assessment,
an
aggregate
acute
risk
assessment
was
not
conducted.
Short
and
intermediate­
term
aggregate
risk
estimates
exceed
HED's
level
of
concern.
These
risk
assessments
consider
residential
as
well
as
dietary
(
food
and
water)
exposures.
Because
risk
estimates
for
the
residential
uses
alone
exceed
HED's
level
of
concern,
additional
exposure
from
food
or
drinking
water
would
only
cause
risk
estimates
to
further
exceed
the
level
of
concern.
Chronic
aggregate
risk
estimates
also
exceed
HED's
level
of
concern.
Although
chronic
dietary
(
food)
estimates
are
low
(<
1%
of
the
cPAD),
EECs
for
ground
water
and
surface
water
exceed
DWLOCs
for
several
population
subgroups.

2.0
PHYSICAL
CHEMICAL
PROPERTIES
CHARACTERIZATION
The
chemical
name
for
fenarimol
is
alpha­(
2­
chlorophenyl)­
alpha­(
4­
chlorophenyl)­
5­
pyridinemethanol.
The
structure
is
as
follows:
9
Empirical
Formula:
C
17
H
12
Cl
2
N
2
O
Molecular
Weight:
331.2
CAS
Registry
No.:
60168­
88­
9
PC
Code:
206600
Fenarimol
is
a
white
to
buff
crystalline
solid
with
a
melting
point
of
117­
119

C,
bulk
density
of
0.66­
0.81
g/
cc
(
packed),
octanol/
water
partition
coefficient
(
log
K
ow)
of
3.69,
and
vapor
pressure
of
2.2
x
10­
7
Torr
at
25

C.
Fenarimol
is
practically
insoluble
in
water
(
13.7
ppm
at
pH
7
and
25

C)
and
is
soluble
in
most
organic
solvents:
hexane
(
1.1
mg/
mL);
acetonitrile,
heavy
aromatic
naphtha,
and
xylene
(

50
mg/
mL);
benzene
and
methanol
(
100­
125
mg/
mL);
acetone
(>
250
mg/
mL);
and
chloroform
and
cyclohexanone
(>
500
mg/
mL).

3.0
HAZARD
CHARACTERIZATION
3.1
Hazard
Profile
Toxicology
data
are
used
by
HED
to
assess
the
potential
hazards
to
humans.
The
data
are
derived
from
a
variety
of
acute,
subchronic,
and
chronic
toxicity
tests;
developmental/
reproductive
tests;
and
tests
to
assess
mutagenicity
and
pesticide
metabolism.
The
database
for
fenarimol
is
adequate
to
support
this
TRED.

Acute
toxicity
values
and
toxicity
categories
for
fenarimol
are
summarized
in
Table
1.
The
data
indicate
that
fenarimol
has
low
acute
oral,
dermal,
and
inhalation
toxicity
(
category
III).
Fenarimol
is
category
II
with
respect
to
ocular
irritation.
It
is
not
a
dermal
sensitizer.
A
primary
dermal
irritation
study
is
not
available.

Table
1.
Acute
Toxicity
of
Fenarimol.

Study
Type
MRID
No.:
Result
870.1100
Acute
Oral
Toxicity
­
rat.
Elanco,
Study
No.:
R­
O­
289­
82,
December
30,
1982
00125392
LD50
>
599
mg/
kg.
Toxicity
Category
III
Classification:
Guideline
Study
Type
MRID
No.:
Result
10
870.1200
Acute
Dermal
Toxicity
­
rabbit.
Elanco
Study
No.:
B­
D­
27­
82,
February
17,
1983
00125392
LD50
>
1998
mg/
kg.
Toxicity
Category
III
Classification:
Minimum
870.1300.
Acute
Inhalation
Toxicity
­
rat.
Elanco,
Study
No.:
R­
H­
102­
82,
November
16,
1982.
00125292
LC50
>
5.20
mg/
L
for
males.
LC50
between
2.87
and
5.2
mg/
L
for
females.
Toxicity
Category
III
Classification:
Guideline
870.2400
Primary
Ocular
Irritation
­
Rabbit.
Elanco,
Study
No.:
B­
E­
32­
82,
February
1,
1982
00125392
Day
1:
6/
6
corneal
opacity
(
score
of
5);
5/
6
iris
irritation
(
score
5);
6/
6
conjunctival
irritation
(
score
of
1­
2).
Day
7:
3/
6
corneal
opacity
and
conjunctival
irritation.
Day
14
all
irritation
cleared.
Toxicity
Category
II
Classification:
Minimum
870.2500
Primary
Dermal
Irritation
­
rabbit.
­­
No
study
available.

870.2600
Dermal
Sensitization
­
guinea
pig.
Elanco,
Study
No.;
GP­
9538,
January
1,
1980.
00084966
No
evidence
of
sensitization
in
the
Guinea
Pig
Maximization
test
of
Magnusson
and
Kligman.
Classification:
Minimum.

Table
2
presents
a
summary
of
subchronic
and
chronic
toxicity
studies
for
fenarimol.
Subchronic
oral
dosing
in
rats
demonstrates
very
little
toxicity
except
for
some
slight
body
weight
changes
and
liver
pathology
of
low
degree
and
inconsistency.
In
dogs
there
was
also
little
overt
toxicity
with
there
being
some
effects
in
the
liver.
A
28­
day
subchronic
inhalation
study
is
required.
The
Gowan
Company
requested
that
the
Agency
rescind
the
data
requirement
for
the
28­
day
inhalation
study.
They
disagree
on
its
need
and
cite
that
this
issue
was
addressed
recently
by
CropLife
America,
an
industrial
organization.
They
also
stated
that
the
sprays
that
will
typically
result
from
fenarimol
use
will
have
droplets
that
will
be
tens
or
thousands
of
micrometers
in
diameter
or
much
larger
than
the
respirable
droplets
of
a
few
micrometers
in
diameter.
These
larger
droplets
will
not
reach
the
alveoli
and
will
become
trapped
in
the
upper
respiratory
tract
and
eventually
swallowed.
Thus,
they
contended
that
the
endpoint
from
an
oral
toxicity
study
is
a
more
appropriate
endpoint.
In
a
written
response
to
comments
(
5/
8/
02),
the
HED
stated
there
have
been
some
recent
changes
in
HED
policy
regarding
the
need
for
subchronic
inhalation
toxicity
studies.
The
comments
of
the
CropLife
America
organization
have
been
taken
into
consideration
at
a
recent
presentation
to
the
Agency.
As
a
result
of
these
recent
changes,
the
Gowan
Company
may
submit
a
waiver
for
the
28­
day
inhalation
study.
This
waiver
must
contain
sufficient
data
on
the
particle
size
of
the
sprays
and
other
preparations
that
may
result
in
inhalation
exposure.
It
also
must
contain
sufficient
other
information
regarding
the
potential
inhalation
exposure
such
as
duration
of
exposure
in
terms
of
hours
per
day,
per
week,
etc.
The
completed
waiver
request
will
be
presented
to
a
peer
review
committee
that
will
determine
the
need
for
the
subchronic
inhalation
toxicity
study.
This
peer
review
group
will
consist
of
toxicologists
with
expertise
in
inhalation
toxicology
as
well
as
occupational
and
residential
exposure
representatives.
The
decision
on
the
need
for
the
subchronic
inhalation
toxicity
study
will
be
based
on
all
relevant
factors.
The
more
complete
the
information
in
the
waiver
request
is,
the
better
the
chance
for
the
waiver
to
be
granted.
The
limited
information
provided
in
the
April
10,
2002
letter
is
not
sufficient
11
to
bring
to
a
peer
review
committee
to
consider
a
waiver
for
an
inhalation
toxicity
study.
Lastly,
the
HED
is
already
using
an
oral
toxicity
endpoint
for
the
inhalation
exposure
scenarios.
However,
the
subchronic
inhalation
toxicity
study
is
considered
more
appropriate
for
risk
assessment
based
on
inhalation
exposures.

Adequate
data
are
available
to
assess
the
chronic
toxicity
and
carcinogenic
potential
of
fenarimol.
The
liver
appears
to
be
the
most
evident
target
organ
for
chronic
toxicity
aside
from
the
effects
of
fenarimol
on
aromatase.
Liver
toxicity
was
manifested
by
liver
weight
increases
and
the
presence
of
"
fatty
liver"
in
rats.
In
dogs,
liver
weight
was
increased
and
there
was
also
associated
increases
in
serum
enzymes
to
indicate
liver
toxicity.
p­
Nitroanisole
o­
demethylase
was
also
increased
indicating
stimulation
of
liver
enzymes.
Fenarimol
has
been
classified
as
a
Group
E
"
not
likely"
carcinogen
(
no
evidence
of
carcinogenicity
for
humans).
Similarly,
the
genetic
toxicity
data
indicate
there
is
no
mutagenicity
concern.

Developmental
studies
in
rats
and
rabbits,
designed
to
identify
possible
adverse
effects
on
the
developing
organism
which
may
result
from
the
in­
utero
exposure
to
the
pesticide
were
also
conducted.
The
data
base
for
prenatal
developmental
toxicity
is
considered
complete.
The
initial
guideline
study
was
classified
as
unacceptable,
but
this
study
together
with
a
special
study
to
assess
for
the
reversibility
of
hydronephrosis
are
combined
with
another
special
study
to
assess
for
reproductive
performance.
All
of
these
studies
combine
to
make
an
acceptable
study
and
to
satisfy
the
guideline
requirement.
The
rat
studies
revealed
that
fenarimol
is
associated
with
hydronephrosis
that
is
reversible.

The
developmental
toxicity
studies
showed
no
evidence
of
increased
sensitivity
or
susceptibility
of
young
rats
or
rabbits
following
pre­
or
postnatal
exposure
to
fenarimol.
The
data
base
for
reproductive
toxicity
is
considered
complete.
The
multi­
generation
reproduction
studies
indicate
that
fenarimol
causes
reduced
fertility
and
dystocia.
Separate
cross
dosing
studies
(
dosing
males
and
mating
with
untreated
females
and
dosing
females
and
mating
with
untreated
males)
indicated
that
the
reduced
fertility
is
due
to
an
effect
in
males
and
the
dystocia
is
an
effect
in
females.
These
effects
of
fenarimol
were
attributed
to
inhibition
of
aromatase
or
the
enzyme
that
converts
androgens
to
estrogens.
In
addition
to
the
guideline
multi­
generation
reproduction
study
in
rats,
there
are
nonguideline
studies
that
assess
for
the
reproductive
performance
in
mice
(
MRID
No.:
45502307),
guinea
pigs
(
MRID
No.:
00126525,
00133474
and
00137159)
and
rabbits
(
MRID
No.:
00084967).
The
mouse
study
indicated
that
mice
are
similar
to
rats
in
that
there
is
a
decrease
in
the
reproductive
performance
in
the
males.
However,
neither
the
guinea
pig
or
rabbit
studies
demonstrated
a
decrease
in
reproductive
performance
indicating
that
the
effect
of
fenarimol
on
male
reproductive
performance
is
not
seen
in
all
species
tested.

There
is
no
Guideline
870.7600
dermal
absorption
study
available
with
rats.
The
upper
bound
limit
for
dermal
absorption
was
estimated
by
HIARC
(
J.
Doherty,
9/
6/
01)
to
be
20%
based
on
an
assessment
of
the
rabbit
and
monkey
dermal
absorption
studies
along
with
a
comparison
of
the
rabbit
developmental
toxicity
and
rabbit
21­
day
dermal
toxicity
studies.
Subsequently,
Gowan
Company
responded
by
submitting
additional
information
regarding
the
dermal
absorption
study
in
monkeys,
as
well
as
other
background
information.
This
information
was
evaluated
during
a
special
HIARC
12
revisit,
on
5/
23/
02.
The
HIARC
decided
that
a
5%
dermal
absorption
factor
is
appropriate
to
use
for
risk
assessment
purposes.
The
5%
dermal
absorption
factor
was
derived
primarily
from
the
monkey
dermal
absorption
study
(
MRID
No.:
00162538,
1985)
using
the
Feldman­
Maibach
model.
Dermal
absorption
rates
of
1.36%,
2.32%,
3.12%
and
4.12%
(
mean
2.73%
±
1.17%)
were
observed
for
the
four
individual
monkeys
in
the
study.
However,
from
8
to
29%
of
the
dermally
applied
radioactivity
was
not
accounted
for.
Since
there
was
variation
in
the
dermal
absorption
in
the
four
monkeys
and
there
was
unaccounted
for
radioactivity,
a
dermal
absorption
value
of
5%
from
this
study
was
considered
appropriate
for
risk
assessment.
In
addition,
the
result
of
a
dermal
absorption
study
with
rabbits
(
MRID
No.:
00046639,
1980),
using
three
formulations,
indicated
up
to
approximately
15%
dermal
absorption.
By
comparison
the
rabbit
developmental
toxicity
study
(
MRID
No.:
47716001)
and
the
rabbit
21­
day
dermal
toxicity
study
(
MRID
No.:
00153312)
also
indicated
approximately
15%
dermal
absorption.
However,
the
rabbit
is
recognized
as
being
a
poor
model
for
estimating
dermal
absorption
in
humans,
since
rabbit
skin
is
more
permeable;
therefore,
the
5%
value
based
primarily
on
the
monkey
study
is
considered
appropriate.
Refer
to
the
HIARC
Revisit
report
(
J.
Doherty,
6/
02)
for
a
more
detailed
discussion
of
dermal
absorption.

The
database
for
metabolism
is
considered
to
be
complete.
The
biliary
route
is
the
predominant
route
of
elimination
in
the
rat
but
the
urinary
route
is
the
most
prominent
route
of
elimination
in
the
rabbit.
In
rats,
fenarimol
is
rapidly
absorbed
from
the
gastro­
intestinal
tract
and
the
half
life
of
the
plasma
level
was
determined
to
be
11.8
to
16.8
hours.
Most
of
the
radiolabeled
material
was
recovered
in
the
urine
(
5
to
15%)
or
feces
(~
80%
of
the
recovered
isotope)
by
day
7.
Biliary
excretion
was
the
major
route
of
elimination.
Fenarimol
is
extensively
metabolized
in
the
rat;
less
than
one
percent
of
the
parent
is
recovered,
while
more
than
30
metabolites
are
recovered.
Metabolism
of
fenarimol
occurs
by
the
oxidation
of
the
carbinol
phenyl­
ring
and
pyrimidine
ring
and
some
qualitative
and
quantitative
differences
in
sexes
and
dose
level
were
noted.

There
are
no
acute,
subchronic
or
developmental
neurotoxicity
studies
available.
The
HIARC
(
July
10,
2001)
determined
that
a
special
developmental
study
with
special
inclusions
to
assess
for
hormonal
effects
in
adults
and
post­
weaning
pups,
and
in
vivo
inhibition
of
aromatase
should
be
required.
Acute
and
subchronic
neurotoxicity
studies
are
not
required.
The
toxicology
profile
of
fenarimol
is
shown
in
Table
2
of
this
document.

Table
2.
Toxicology
Profile
for
Fenarimol.
13
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
870.3100
(
12
and
18
month
oral
toxicity
rodents
fulfill
this
guideline)
00235175,
45502302
and
45502304
(
1978)/
Acceptable/
Non­
Guideline
0,
2.5,
6.5
or
17.5
both
sexes.
NOAEL
=
6.5
mg/
kg/
day
LOAEL
=
17.5
mg/
kg/
day
based
on
increased
relative
liver
weight
and
increased
severity
of
fatty
liver.

870.3150
90­
Day
oral
toxicity
in
nonrodents
00056090
(
1975)/
Acceptable/
Guideline
0,
1.25,
5
or
20
mg/
kg/
day.
NOAEL
and
LOAEL
>
20
mg/
kg/
day
(
HDT).
A
one­
year
study
(
MRID
00146959
satisfies
this
guideline).

870.3200
21/
28­
Day
dermal
toxicity
(
rat)
00153312
(
1985)
Acceptable/
Guideline
0,
500
or
1000
mg/
kg/
day
for
RUBIGAN
(
emulsifiable)
formulation
and
1000
mg/
kg/
day
for
technical
fenarimol.
NOAEL
<
1000
mg/
kg/
day
LOAEL
=
1000
mg/
kg/
day
based
on
slight
liver
weight
effects.
Although
this
study
is
acceptable,
it
is
of
limited
usefulness
for
risk
assessment
because
it
did
no
assess
for
reproductive
effects
or
possible
effects
on
aromatase.

870.3250
90­
Day
dermal
toxicity
No
study.
No
study.

870.3465
90­
Day
inhalation
toxicity
No
study.
No
study
870.3700a
Prenatal
developmental
in
rodents
00042543/(
1979)
Unacceptable/
Guideline
but
acceptable
with
other
studies
(
see
below).
0,
5,
13,
35
mg/
kg/
day
Maternal
NOAEL
>
35
mg/
kg/
day
(
HDT)
LOAEL
not
established
Developmental
NOEL
=
13
mg/
kg/
day
LOAEL
=
35
mg/
kg/
day
based
on
hydronephrosis
(
this
effect
was
shown
to
be
reversible
and
is
not
considered
adverse).

Special
study
to
assess
for
reversibility
of
hydronephrosis.
00132988/(
1983)
Acceptable/
Non­
Guideline.
0
and
35
mg/
kg/
day.
Maternal
NOAEL
=
not
established.
LOAEL
=
35
mg/
kg/
day
based
on
sporadic
dystocia.
Developmental
NOEL
<
35
mg/
kg/
day.
LOAEL
=
35
mg/
kg/
day
based
on
kidney
effects
(
hydronephrosis,
this
effect
was
shown
to
be
reversible
and
is
not
considered
adverse)

Above
two
studies
combine
to
satisfy
the
guideline
requirement
for
a
developmental
toxicity
study
in
rats.

870.3700b
Prenatal
developmental
in
rabbits
44716001/
1990/
Acceptable/
Guideline
0,
15,
50
or
150
mg/
kg/
day.
Maternal
NOAEL
=
50
mg/
kg/
day
LOAEL
=
150
mg/
kg/
day
based
on
increased
abortions
and
decreased
body
weights
and
gain
and
food
consumption.
Developmental
NOAEL
=
>
150
mg/
kg/
day
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
14
870.3800
Reproduction
and
fertility
effects
00235175,
45502301
(
1977)
Unacceptable/
Not
upgradeable
0,
2.9,
7.9
or
20
mg/
kg/
day
in
males;
0,
3.4,
9
or
23.5
mg/
kg/
day
in
females.
Parental/
Systemic
NOAEL
>
23.5
mg/
kg/
day
(
HDT)
LOAEL
not
established
Reproductive
LOAEL
<
2.9
mg/
kg/
day
based
on
decreased
fertility
in
the
F1
generation
second
mating.
Offspring
NOAEL
and
LOAEL
could
not
be
established
due
to
anti­
fertility
effects
in
the
parental
generations,
which
prevented
valid
assessment
of
the
pup
generations.

Second
study
00235175,
45502302
(
1978)
Acceptable/
Guideline
0,
0.6,
1.2,
2.5
mg/
kg/
day
in
males
and
0,
0.8,
1.7
or
3.2
mg/
kg/
day
in
females.
Parental/
Systemic
NOAEL
>
2.5
mg/
kg/
day
in
males
and
3.2
mg/
kg/
day
in
females
(
HDT)
LOAEL
not
established
Parental
Reproductive
NOAEL
=
0.6
mg/
kg/
day.
LOAEL
=
1.2
mg/
kg/
day
based
on
decreased
liveborn
litter
size
in
the
F1
and
F2
generations.
Offspring.
NOAEL
=
1.2
mg/
kg/
day.
LOAEL
=
2.5
mg/
kg/
day
based
on
decreased
survival
indices
and
possible
presence
of
hydronephrosis
Above
two
studies
combine
to
satisfy
the
guideline
requirement
for
a
multi
generation
reproduction
study
in
rats.

870.3800
Reproduction
and
fertility
effects
(
Special
Study)
00084968
Acceptable/
Non­
Guideline
0,
35
mg/
kg/
day
LOAEL
for
males
and
females
>
35
mg/
kg/
d
(
males
decreased
mating
and
epididymal
weight,
females
dystocia
and
related
parameters)
NOAEL
not
established
870.4100a
Chronic
toxicity
rodents
See
combined
chronic
feeding
and
carcinogenicity
study.

870.4100b
Chronic
toxicity
dogs
00146959/
1985/
Acceptable/
Guideline
0,
1.25,
12.5
or
125
mg/
kg/
day.
NOAEL
=
12.5
mg/
kg/
day
LOAEL
=
125
mg/
kg/
day
based
on
reversible
increase
in
liver
weight
and
increase
in
alkaline
phosphatase.

870.4200
Combined
Chronic
Feeding
and
Carcinogenicity
rats
00235175/
1978/
Acceptable/
Guideline
0,2,
5.3,
or
14.6
mg/
kg/
day
for
male
and
0,
2.8,
7.6
or
21.55
mg/
kg/
day
for
females.
NOAEL
=
5.3
mg/
kg/
day.
LOAEL
=
14.6
mg/
kg/
day
based
on
hormonal
changes
(
prolactin
and
luteinizing
hormone)
and
possibly
fatty
liver
change
and
decreased
WBC
count
in
females.

870.4200
Combined
Chronic
Feeding
and
Carcinogenicity
rats
00153313/
1985/
Acceptable/
Guideline
0.5,
1,
2
mg/
kg/
day
for
males
and
0,
0.6,
1.2
or
2.3
mg/
kg/
day
for
females.
NOAEL
=
1
mg/
kg/
day
in
males
and
>
2.3
mg/
kg/
day
in
females.
LOAEL
=
2
mg/
kg/
day
in
males
based
on
minimal
gross
and
microscopic
changes
in
liver
and
possibly
testis.
There
was
no
evidence
of
carcinogenicity
or
increase
in
liver
tumors.
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
15
The
above
two
studies
combine
to
satisfy
the
guideline
requirement
for
carcinogenicity
testing
in
rats.
It
should
be
noted
that
the
potential
for
fenarimol
to
cause
decreased
fertility
and
dystocia
at
the
dose
levels
tested
in
the
rat
studies
contributed
to
the
weight
of
evidence
that
the
rat
was
assessed
at
adequate
dose
levels.

870.4300
Carcinogenicity
mice
0071920/
1978/
Acceptable/
Guideline
0,
7,
24
and
86
mg/
kg/
day
for
both
sexes.
NOAEL
=
>
86
mg/
kg/
day
(
HDT).
The
HIARC
and
CARC
concluded
that
there
was
no
evidence
of
carcinogenicity
although
liver
tumors
were
highest
in
the
high
dose
group
but
incidence
was
considered
too
low
to
be
meaningful.

Mutagenticity
870.
See
Table2.
a.
below.

870.6200a
Acute
neurotoxicity
screening
battery
No
study.
No
study.
Not
required.

870.6200b
Subchronic
neurotoxicity
screening
battery
No
study.
No
study.
Not
required.

870.6300
Developmental
neurotoxicity
Study
is
being
required
and
special
inclusions
to
assess
for
possible
effects
due
to
hormonal
disruption
required.

870.7485
Metabolism
and
pharmacokinetics
00261349
and
00261350
(
1985)
A
series
of
studies
with
radioactive
label
in
different
positions
established
that
fenarimol
is
readily
absorbed
and
excreted
with
the
biliary
route
being
most
important
in
rats
but
the
urinary
route
being
important
in
rabbits.
Metabolism
was
extensive
with
30
or
more
metabolites
noted.
Little
radioactivity
remained
in
the
tissue.
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
16
870.7600
Dermal
absorption
­
monkeys
00162538
(
1985)
A
5%
dermal
absorption
factor
is
appropriate
to
use
for
risk
assessment
purposes.
It
was
derived
primarily
from
the
monkey
study
(
00162538)
using
the
Feldman­
Maibach
model.
Dermal
absorption
rates
of
1.36%,
2.32%,
3.12%
and
4.12%
(
mean
2.73%
±
1.17%)
were
observed
for
the
four
individual
monkeys.
However,
from
8
to
29%
of
the
dermally
applied
radioactivity
was
not
accounted
for.
Since
there
was
variation
in
the
dermal
absorption
in
the
four
monkeys
and
there
was
unaccounted
for
radioactivity,
a
value
of
5%
was
considered
appropriate.
In
addition,
the
result
of
a
dermal
absorption
study
with
rabbits
(
00046639),
using
three
formulations,
indicated
up
to
approximately
15%
dermal
absorption.
By
comparison
the
rabbit
developmental
toxicity
study
(
47716001)
and
the
rabbit
21­
day
dermal
toxicity
study
(
00153312)
also
indicated
approximately
15%
dermal
absorption.
However,
the
rabbit
is
recognized
as
being
a
poor
model
for
estimating
dermal
absorption
in
humans,
since
rabbit
skin
is
more
permeable;
therefore,
the
5%
value
based
primarily
on
the
monkey
study
is
considered
appropriate.

Special
studies
Several
special
studies
were
presented
to
investigate
the
mechanism
of
the
decreased
fertility
and
dystocia.
These
are
listed
above
in
this
table
under
the
heading
for
the
study
type
which
they
most
closely
resemble
(
i.
e.
reproduction
or
developmental)

Table
2.
a.
Mutagenticity/
Genotoxicity
Studies
Study
Results
Bacterial
mutagenicity
(
Ames
test)
­
Salmonella
typhimurium
and
Escherichia
coli.
Elanco,
1976.
MRID
No.:
243372
(
Acc.
No.:).
Not
mutagenic
with
and
without
metabolic
activation
at
doses
up
to
100

g/
plate.
Classification:
"
Minimum"
(
Acceptable)

Forward
mutation
assay
in
TK
±
mouse
lymphoma
assay.
Elanco,
August
1,
1979.
MRID
No.:
00042538
No
evidence
of
mutagenicity
when
tested
at
0,
3,
6,
12,
50
or
100

g/
mL.
The
100

g/
mL
dose
level
was
toxic.
Classification:
"
minimum"
(
acceptable).

DNA
repair
synthesis.
Elanco,
Study
No.:
790503­
1,
June
1979.
MRID
No.:
00042541
No
evidence
of
induction
of
DNA
repair
at
dose
levels
of
0,
0.05,
0.1,
0.5,
10,
50
or
100
nanomoles/
mL
for
five
hours
incubation.
Cytotoxicity
resulted
at
50
and
100
nano
moles/
mL.
Classification:
"
minimum"
(
acceptable).

In
vivo
cytogenetics
in
hamsters.
Cabinet
d'Etudes
et
de
Recherches
en
Tox.
Study
No.:
658,
May
10,
1982.
MRID
No.:
00144051
Negative
for
mutagenic
effects
at
does
of
250
mg/
kg
(
times
2
doses)
in
bone
marrow
cells.
Classification:
Acceptable.
Study
Results
17
micronucleus
assay
­
mouse
Cabinet
d'Etudes
et
de
Recherches
en
Tox.
Study
No.:
650,
May
1,
1982.
MRID
No.:
00144050
Positive
for
clastogenic
effects
in
male
mice
at
1
gm/
kg
at
24
hours.
Assessments
at
48
and
72
hours
were
considered
confounded
since
there
were
no
positive
controls.
Classification:
UNACCEPTABLE
for
48
and
72
hours.
ACCEPTABLE
for
24
hours.

Evaluation
of
carcinogenicity
in
the
mouse
C3H/
10T
½
embryonic
mouse
fibroblast
culture
system.
Elanco,
August
1,
1980.
MRID
No.:
00046637.
No
malignant
transformations
were
observed
in
fenarimol­
treated
cultures
between
4
and
256
nanomoles/
mL.

Classification:
"
minimum"
(
acceptable).

Dominant
lethal
­
rat.
Lilly,
Study
No.:
R­
346
January,
1977
MRID
No.:
00042542
A
single
dose
of
350
mg/
kg
fenarimol
(
in
acacia
solution)
did
not
result
in
symptoms
of
toxicity
to
the
males
and
did
not
indicate
a
dominant
lethal
effect
when
the
rats
were
mated
4
days
after
treatment.
Classification:
"
minimum"
(
acceptable).

Armoatase
inhibition
assay
in
stimulated
rat
ovarian
microsomal
system.
Elanco,
January
1,
1982.
MRID
No.:
00093876
Fenarimol
is
a
moderately
weak
inhibitor
of
aromatase
activity
in
the
stimulated
rat
ovarian
microsomal
system
Classification:
Supplementary.

3.2
FQPA
Considerations
The
FQPA
Safety
Factor
committee
addressed
the
potential
enhanced
sensitivity
of
infants
and
children
from
exposure
to
fenarimol
as
required
by
the
FQPA
of
1996.
HIARC
examined
the
prenatal
developmental
toxicity
studies
in
rats
and
rabbits
and
the
two­
generation
reproduction
study
in
rats,
and
concluded
that
the
database
does
not
show
evidence
of
increased
susceptibility
to
fetuses
and
young
(
HIARC,
9/
5/
01).
The
HIARC
determined
that
a
special
developmental
toxicity
study
should
be
required
based
on
the
need
to
determine
if
the
potential
hormonal
effects
as
elicited
by
inhibition
of
aromatase
will
result
in
effects
in
the
rat
pups.

The
FQPA
Safety
Factor
Committee
(
B.
Tarplee,
9/
28/
01)
recommended
that
the
10x
Safety
Factor
should
be
retained
at
10x
for
fenarimol
due
to
the
following
data
gaps:


a
special
developmental
toxicity
study
with
fenarimol
is
required
to
determine
if
the
potential
hormonal
effects
elicited
by
inhibition
of
aromatase
will
result
in
effects
in
the
rat
pups;
and

the
environmental
fate
database
is
incomplete
for
the
aquatic
photolytic
degradate
of
fenarimol,
4­
chloro­
2­(
5­
pyrimidyl)­
2'­
chlorobenzophenone.
A
screening
level
drinking
water
assessment
which
includes
this
degradate
of
concern
is
not
possible
at
this
time
because
of
a
lack
of
data.

The
FQPA
committee
determined
that
the
10x
FQPA
safety
factor
should
be
retained
for
all
populations
and
all
fenarimol
risk
assessments.
18
In
comments
received
on
4/
11/
02,
Gowan
Company
requested
that
the
HED
re­
evaluate
this
determination
to
retain
the
10x
FQPA
safety
factor,
and
they
rebuted
the
need
for
a
developmental
neurotoxicity
(
DNT)
study.

In
a
special
revisit
on
May
23,
2002,
the
HIARC
reviewed
and
evaluated
the
potential
for
increased
susceptibility
of
infants
and
children
from
exposure
to
fenarimol
as
required
by
the
Food
Quality
Protection
Act
(
FQPA)
of
1996
and
in
accordance
with
changes
in
HED's
policy
in
determining
the
FQPA
Safety
Factor.
The
HIARC
noted
that
fenarimol
was
not
indicated
as
being
neurotoxic,
but
rather
was
demonstrated
to
cause
hormonal
effects
in
rats,
especially
related
to
inhibition
of
aromatase.
Thus,
the
need
for
a
special
developmental
toxicity
study
that
assesses
the
effects
of
fenarimol
on
hormones.
Evidence
that
suggests
requiring
a
special
developmental
toxicity
study
to
assess
hormonal
effects
is
as
follows:


The
NOAEL
and
LOAEL
for
risk
assessments
are
based
on
reduced
fertility
in
males
and
dystocia
in
females
associated
with
fenarimol's
potential
to
affect
hormones
in
adult
rats.
The
potential
for
fenarimol
to
affect
the
hormonal
system
in
developing
rats
needs
to
be
assessed
to
determine
if
the
developing
fetus
and
neonate
may
also
be
affected
as
can
be
judged
by
the
special
developmental
toxicity
study
that
will
have
special
emphasis
on
potential
disruption
of
the
hormonal
system
by
biochemical
methods
and
include
special
provisions
to
assess
for
physiological
manifestations
of
hormonal
disruption.
The
LOAEL
on
which
risk
assessments
are
based
is
related
to
potential
hormonal
effects.

Based
on
the
weight
of
evidence
presented,
the
HIARC
concluded
that
a
special
developmental
toxicity
study
to
assess
for
hormonal
effects
is
required
for
fenarimol.
This
study
should
follow
the
same
dosing
regimen
as
a
developmental
neurotoxicity
study,
but
does
not
need
to
include
all
of
the
functional
observational
battery
(
FOB)
assessments.
The
protocol
for
this
study
should
be
submitted
to
HED
for
review
prior
to
initiating
the
study.

In
accordance
with
the
2002,
OPP
Guidance
Document
on
Determination
of
the
Appropriate
FQPA
Safety
Factor(
s)
in
Tolerance
Assessment,
this
data
requirement
is
considered
to
be
"
for
cause"
and
therefore
the
HIARC
concluded
that
a
Database
Uncertainty
Factor
of
3X
is
required
until
the
data
are
received
and
evaluated.

3.3
Dose
Response
Assessment
and
Hazard
Endpoint
Selection
The
strengths
and
weaknesses
of
the
fenarimol
toxicology
database
were
considered
during
the
process
of
toxicity
endpoint
and
dose
selection.
In
general,
most
of
the
required
guideline
studies
on
fenarimol
were
available
and
provided
reasonable
confidence
when
the
toxicity
endpoints
and
doses
for
risk
assessment
were
selected.
Based
on
the
evaluation
of
the
above
summarized
studies,
the
Hazard
Identification
Assessment
Review
Committee
(
HIARC)
identified
the
toxicity
endpoints
and
the
dose
levels
for
use
in
risk
assessment
(
HIARC
document
of
9/
5/
01).
The
selected
toxicity
endpoints
are
summarized
in
Table
3.

The
METARC
recommended
(
J.
Doherty,
9/
17/
01),
and
the
HIARC
confirmed,
that
the
reduced
male
fertility
and
dystocia
effects
of
fenarimol
should
be
endpoints
for
human
health
risk
assessment.
It
is
noted
that
the
endpoint
from
the
multi­
generation
reproduction
study
is
based
on
decreased
litter
size.
This
decrease
in
litter
size
may
be
a
reflection
of
the
maternal
toxicity
or
the
potential
for
19
fenarimol
to
inhibit
aromatase.
In
this
regard,
it
is
a
meaningful
endpoint
for
all
populations,
males
and
females.

Consequently,
HED
identified
a
reference
dose
for
chronic
exposure
(
cRfD)
of
0.006
mg/
kg/
day
from
the
multi­
generation
reproduction
study
based
on
a
no
observed
adverse
effect
level
(
NOAEL)
of
0.6
mg/
kg/
day,
and
a
10X
uncertainty
factor
for
interspecies
extrapolation
and
a
10X
uncertainty
factor
for
intraspecies
variation.
The
NOAEL
of
0.6
mg/
kg/
day
is
based
on
decreased
live
born
litter
size
in
the
F
1
and
F
2
generations
at
a
lowest
observed
adverse
effect
level
(
LOAEL)
of
1.2
mg/
kg/
day.
HED
calculated
a
chronic
Population
Adjusted
Dose
(
cPAD)
of
0.0006
mg/
kg/
day.
The
cPAD
is
the
RfD
divided
by
the
FQPA
safety
factor
(
10X).
Chronic
dietary
exposure
estimates
greater
than
100%
of
the
cPAD
would
exceed
HED's
level
of
concern.

For
risks
associated
with
intermediate­
term
(
IT)
exposures
(
1­
6
months),
the
same
endpoint
(
NOAEL
of
0.6
mg/
kg/
day)
was
used
for
incidental
oral,
dermal,
and
inhalation
risk
assessments.
A
Margin
of
Exposure
or
MOE,
which
is
the
ratio
of
the
NOAEL
to
the
exposure
estimate,
of
greater
than
1000
does
not
exceed
HED's
level
of
concern
for
IT
risk
assessments.
An
MOE
of
greater
than
1000
is
required
because
of
the
10x
interspecies
factor,
the
10x
intraspecies
factor
and
the
10x
FQPA
factor.

For
the
short­
term
(
1­
30
day)
incidental
oral,
dermal,
and
inhalation
risk
assessments,
a
LOAEL
of
35
mg/
kg/
day
was
selected.
This
endpoint
is
based
on
decreased
fertility
and
dystocia,
an
indicator
of
hormonal
effects,
observed
in
a
special
non­
guideline
cross
breeding
reproduction/
developmental
toxicity
study
in
rats.
Because
a
NOAEL
could
not
be
identified,
and
effects
seen
at
the
lowest
dose
tested,
a
LOAEL
was
used,
and
an
additional
3x
uncertainty
factor
was
applied.
Therefore,
a
MOE
greater
than
3000
does
not
exceed
HED's
level
of
concern
for
short­
term
risk
assessments.
Dermal
absorption
was
estimated
to
be
5%
based
on
data
from
a
monkey
dermal
absorption
study
(
see
section
3.1
for
details).
An
acute
dietary
toxicity
endpoint
was
not
identified
by
HIARC,
and
consequently,
no
acute
risk
assessment
was
required.
20
Table
3.
Summary
of
Toxicity
Endpoints
and
Doses
for
Risk
Assessment.

EXPOSURE
SCENARIO
DOSE
(
mg/
kg/
day)
ENDPOINT
STUDY
Acute
Dietary
No
appropriate
study
for
a
single
dose
risk
assessment.

Chronic
Dietary
NOAEL
=
0.6
UF
=
100X
FQPA
=
10X
Decreased
liveborn
litter
size
in
rat
reproduction
study.
LOAEL
=
1.2
mg/
kg/
day
Rat
reproduction
MRID
#
00235175
Chronic
RfD
=
0.006
mg/
kg/
day
Chronic
PAD
=
0.0006
mg/
kg/
day
Incidental
Oral,
Short­
Term
LOAEL=
35
UF
=
300X
FQPA
=
10X
Decreased
fertility
and
dystocia
an
indication
of
hormonal
effects.
Special
reproduction
study
MRID
#
0084968
Incidental
Oral,
Intermediate­
Term
NOAEL=
0.6
UF
=
100X
FQPA
=
10X
Decreased
liveborn
litter
size.
LOAEL
=
1.2
mg/
kg/
day
Rat
reproduction
MRID
#
00235175
Dermal,
Short­
Term
Oral
LOAEL=
35
UF
=
300X
FQPA
=
10X
Decreased
fertility
and
dystocia
an
indication
of
hormonal
effects.
Special
reproduction
study
MRID
#
0084968
Dermal,
Intermediate­
Term
Oral
NOAEL=
0.6
UF
=
100X
FQPA
=
10X
Decreased
liveborn
litter
size.
LOAEL
=
1.2
mg/
kg/
day
Rat
reproduction
MRID
#
00235175
Dermal,
Long­
Term
Oral
NOAEL=
0.6
UF
=
100X
FQPA
=
10X
Decreased
liveborn
litter
size.
LOAEL
=
1.2
mg/
kg/
day
Rat
reproduction
MRID
#
00235175
Inhalation,
Short­
Term
Oral
NOAEL
=
35
UF
=
100X
FQPA
=
10X
Decreased
fertility
and
dystocia
an
indication
of
hormonal
effects
Special
reproduction
study
MRID
#
0084968
Inhalation,
Intermediate­
Term
Oral
NOAEL=
0.6
UF
=
100X
FQPA
=
10X
Decreased
liveborn
litter
size.
LOAEL
=
1.2
mg/
kg/
day
Rat
reproduction
MRID
#
00235175
Inhalation,
Long­
Term
Oral
NOAEL=
0.6
UF
=
100X
FQPA
=
10X
Decreased
liveborn
litter
size.
LOAEL
=
1.2
mg/
kg/
day
Rat
reproduction
MRID
#
00235175
Because
a
toxicity
endpoint
from
an
oral
study
was
selected
for
dermal
and
inhalation
endpoints,
a
dermal
absorption
factor
of
5%
must
be
used
for
oral
to
dermal
route
to
route
exposures
and
a
100%
inhalation
absorption
factor
must
be
used
for
inhalation
exposures.

3.4
Endocrine
Disruption
The
Agency
is
required
under
the
FFDCA,
as
amended
by
FQPA,
to
develop
a
screening
program
to
determine
whether
certain
substances
(
including
all
pesticide
active
and
other
ingredients)
"
may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen,
or
other
such
endocrine
effects
as
the
Administrator
may
designate."
Following
the
recommendations
of
its
Endocrine
Disruptor
Screening
and
Testing
Advisory
Committee
(
EDSTAC),
EPA
determined
that
there
was
scientific
bases
for
including,
as
part
of
the
program,
the
androgen
and
thyroid
hormone
systems,
in
addition
to
the
estrogen
hormone
system.
EPA
also
adopted
EDSTAC's
recommendation
21
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
Disruptor
Screening
Program
(
EDSP).

Fenarimol
has
demonstrated
effects
on
hormonal
systems.
When
the
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency's
EDSP
have
been
developed,
fenarimol
may
be
subjected
to
additional
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.

4.0
EXPOSURE
ASSESSMENT
4.1
Summary
of
Registered
Uses
Fenarimol
is
currently
registered
for
use
on
fruit
and
nut
crops
such
as
apples,
cherries,
filberts,
grapes,
pears,
and
pecans
as
well
as
on
ornamental
plants,
trees,
grasses,
and
turf.
Fenarimol
is
also
used
on
imported
bananas.
The
registration
of
fenarimol
is
being
supported
by
Gowan
Company.
The
sole
fenarimol
formulation
class
which
is
registered
for
use
on
fruit
and
nut
crops
is
an
emulsifiable
concentrate
sold
under
the
trade
name
RubiganJ,
and
this
formulation
is
typically
applied
using
ground
equipment.

4.2
Dietary
Exposure
and
Risk
Assessment
4.2.1
Residue
Profile
The
established
permanent
and
time­
limited
tolerances
for
fenarimol
are
published
in
40
CFR
§
180.421
and
are
expressed
in
two
different
ways.
Tolerances
listed
under
40
CFR
§
180.421(
a)(
1)
and
§
180.421(
b)
are
expressed
in
terms
of
residues
of
fenarimol
per
se.
Tolerances
listed
under
40
CFR
§
180.421(
a)(
2)
are
expressed
in
terms
of
the
combined
residues
of
fenarimol
and
its
metabolites
[
alpha­(
2­
chlorophenyl)­
alpha­(
4­
chlorophenyl)­
1,4­
dihydro­
5­
pyrimidinemethanol(
Metabolite
B)
and
5­[
2­
chlorophenyl)­(
4­
chlorophenyl)
methyl]­
3,4­
dihydro­
4­
pyrimidinol]
(
Metabolite
C)
measured
as
the
total
of
fenarimol
and
5­[
2­
chlorophenyl)­(
4­
chlorophenyl)
methyl]
pyrimidine
(
calculated
as
fenarimol).

The
registration
requirements
for
plant
metabolism
are
fulfilled.
Acceptable
studies
depicting
the
metabolism
of
[
14C]
fenarimol
in
apples,
cherries,
and
grapes
are
available.
The
apple
and
cherry
metabolism
studies
indicate
that
the
parent
fenarimol
is
the
major
residue
component
whereas
the
grape
metabolism
study
identified
the
parent
plus
Metabolites
B
and
C
as
the
principal
residue
components.
The
Metabolism
Assessment
Review
Committee
(
MARC)
has
determined
that
for
enforcement
purposes,
the
tolerance
should
be
expressed
as
parent
only.
However,
the
dietary
assessment
for
grapes
and
bananas
should
include
the
Metabolites
B
and
C,
because
of
their
structural
similarity
to
parent
fenarimol
and
because
there
are
existing
residue
data
for
the
metabolites
on
those
commodities
(
D277692,
9/
17/
01,
D.
DREW).
Combined
residues
of
Metabolites
B
and
C
occur
on
banana
pulp
samples
at
a
range
of
0.24x
to
1.7x
that
of
parent
fenarimol,
and
on
grapes
at
a
range
of
0.59x
to
3.3x
that
of
parent
fenarimol.
Analytical
methods
exist
for
determining
residues
of
Metabolites
B
and
C
(
measured
as
deshydroxyfenarimol)
in
plants.
The
chemical
names
and
structures
of
fenarimol
and
Metabolites
B
and
C
are
depicted
below
in
Figure
1.
22
N
N
OH
Cl
Cl
NH
N
OH
Cl
Cl
N
NH
Cl
Cl
OH
Figure
1.
Chemical
Names
and
Structures
of
Fenarimol
and
Metabolites
B
and
C.

Common
Name
Chemical
Structure
Chemical
Name
Common
Name
Chemical
Structure
Chemical
Name
Common
Name
Chemical
Structure
Chemical
Name
Fenarimol
Metabolite
B
(
Compound
212746)
Metabolite
C
(
Compound
210302)

[
alpha­(
2
chlorophenyl)­
alpha­(
4­
chlorophenyl)­
5­
pyrimidinemethanol]
[
alpha­(
2­
chlorophenyl)­
alpha­(
4­
chlorophenyl)­
1,4­
dihydro­
5­
pyrimidinemethanol]
[
5­[
2­
chlorophenyl)­(
4­
chlorophenyl
methyl]­
3,4­
dihydro­
4­
pyrimidinol]

The
qualitative
nature
of
the
residue
in
milk
and
ruminant
tissues
is
adequately
understood.
For
the
purpose
of
registration,
the
terminal
residue
of
concern
in
milk
and
ruminant
and
hog
tissues
is
fenarimol
per
se.
Wet
apple
pomace
is
the
only
animal
feed
item
associated
with
the
registered
uses
of
fenarimol.
There
are
no
hog
or
poultry
feed
items.

The
registration
requirements
for
residue
analytical
methods
are
fulfilled.
Adequate
methods
are
available
for
data
collection
and
enforcement
of
tolerances
for
residues
of
fenarimol
per
se
in/
on
plants
and
livestock.
Adequate
methods
are
also
available
for
determination
of
residues
of
fenarimol
and
Metabolites
B
and
C
in
plants
[
Pesticide
Analytical
Manual
(
PAM)
Volume
II,
Methods
I
(
AMAA
CA­
R039­
AB­
755),
II
(
AM­
AA­
CA­
R072­
AA­
755),
and
III
(
AM­
AA­
CA­
R124­
AA­
755].

The
requirements
for
data
depicting
magnitude
of
the
residue
in/
on
plants
are
fulfilled
for
the
following
raw
agricultural
commodities
(
RACs):
apples,
cherries,
filberts,
grapes,
pears,
and
imported
bananas.
Overall,
a
sufficient
number
of
field
trials
were
conducted,
and
the
trials
were
conducted
using
representative
fenarimol
formulations
at
the
maximum
registered
application
rates.
In
some
cases,
residue
data
were
translated
from
closely
related
plant
groups
with
identical
use
patterns.
Adequate
processing
data
are
also
available.
Studies
indicate
that
fenarimol
per
se
concentrate
in
wet
apple
pomace
(
3.7x)
but
not
in
apple
juice
(
0.05x).
Grape
processing
studies
indicate
that
the
combined
residues
of
fenarimol
and
its
metabolites
concentrate
in
grape
juice
(
1.6x)
and
raisins
(
1.2x).
The
concentration
factors
for
grape
products
are
of
such
small
magnitude
that
tolerances
will
not
have
to
be
established
for
grape
juice
or
raisins.

4.2.2
Dietary
Exposure
Risk
from
Food
Sources
HED
conducts
dietary
risk
assessments
using
the
Dietary
Exposure
Evaluation
Model
(
DEEMJ
Version
7.075),
which
incorporates
consumption
data
generated
in
USDA's
Continuing
Surveys
of
Food
Intakes
by
Individuals
(
CSFII),
1989­
1992.
For
chronic
dietary
risk
assessments,
the
three­
day
average
of
consumption
for
each
sub­
population
is
combined
with
average
residues
in
commodities
to
23
determine
average
exposures
in
mg/
kg/
day.

The
chronic
dietary
exposure
assessment
for
fenarimol
is
highly
refined
using
anticipated
residues
based
on
1996­
1999
Food
and
Drug
Administration
(
FDA)
monitoring
data
for
apples,
bananas,
cherries,
grapes
and
pears.
Field
trial
residue
data
were
used
for
pecans
and
filberts.
Percent
crop
treated
(%
CT)
information
and
processing
factors,
where
available,
were
used
in
the
assessment.
There
were
no
PDP
monitoring
data
available
for
fenarimol.

Residues
of
fenarimol
per
se
were
nondetectable
(
below
the
method
limit
of
detection,
or
LOD)
in
all
1996­
1999
FDA
monitoring
samples
of
apples,
bananas,
grapes,
and
pears
(
a
total
of
more
than
3,000
samples).
Out
of
214
cherry
samples,
three
had
detectable
residues.
Residues
of
fenarimol
per
se
were
nondetectable
(<
LOD)
in/
on
all
but
one
pecan
nut
meat
sample
from
seven
trials.
There
were
no
detectable
residues
in
filbert
samples
from
four
field
trials.

FDA
results
for
bananas
and
grapes
were
adjusted
to
account
for
potential
residues
of
Metabolites
B
and
C.
Banana
and
grape
field
trial
data
indicate
that
total
metabolites
of
fenarimol
occur
in
banana
pulp
at
a
maximum
2X
of
fenarimol
per
se,
and
in
grape
at
a
maximum
of
3x.

The
anticipated
secondary
residues
of
fenarimol
in
ruminant
tissues
(
meat,
fat
and
meat
byproducts)
are
derived
from
a
cattle
feeding
study
(
MRID
40098605,
PP#
4F3108,
F.
Boyd,
9/
20/
84).
Wet
apple
pomace
is
the
only
feedstuff
associated
with
registered
uses
of
fenarimol.
Anticipated
residues
were
all
very
low
(
all
less
than
0.003
ppm).
Milk,
eggs,
poultry
tissue
and
hog
tissue
were
not
included
in
the
dietary
assessment
because
the
Agency
has
determined
that
there
is
no
reasonable
expectation
of
finite
residues
of
fenarimol
in
these
animal
commodities,
and
is
recommending
that
established
tolerances
for
milk,
hog
tissues,
poultry
tissues,
and
eggs
be
revoked
as
per
Category
3
of
40
CFR
§
180.6(
a).
There
are
no
poultry
or
hog
feed
items
associated
with
the
registered
uses
of
fenarimol.

This
assessment
concludes
that
for
all
supported
registered
commodities,
the
chronic
risk
estimates
are
below
the
Agency's
level
of
concern
(<
100%
of
the
chronic
population
adjusted
dose,
cPAD)
for
the
general
U.
S.
population
and
all
population
subgroups
(<
1%
of
the
cPAD).

Table
4.
Results
of
Chronic
Dietary
Exposure
Analysis
Population
Subgroup
Exposure
(
mg/
kg/
day)
%
cPAD1
U.
S.
Population
(
total)
0.000000
<
1
All
Infants
(<
1
year)
0.000001
<
1
Children
1­
6
years
0.000002
<
1
Children
7­
12
years
0.000001
<
1
Females
13­
50
0.000000
<
1
Males
13­
19
0.000000
<
1
Males
20+
years
0.000000
<
1
Seniors
55+
0.000000
<
1
1
cPAD
=
0.0006
mg/
kg/
day
4.3
Water
Exposure
Pathway
24
This
assessment
is
based
on
environmental
fate
studies
conducted
in
the
1970s
and
early
1980s.
The
quality
of
the
data
provided
by
these
studies
is
significantly
lower
than
currently
required.
By
current
standards
most
of
these
studies
would
not
be
considered
acceptable
and
the
results
would
not
be
considered
of
sufficient
quality
to
allow
a
reasonably
accurate
assessment
of
the
environmental
fate
of
this
compound.

Fenarimol
is
persistent
and
moderately
mobile
in
the
environment.
In
field
studies,
fenarimol
reportedly
dissipated
with
half­
lives
of
3
months
to
several
years
from
soil
and
turf
surfaces
and
much
slower
when
incorporated
into
soil.
Based
on
fenarimol's
chemical
properties
it
is
likely
that
this
chemical
will
move
to
surface
water
and
groundwater,
and
it
may
accumulate
in
the
environment.
It
is
believed
to
be
stable
to
hydrolysis,
anaerobic
microbial
degradation
and
photolysis
on
soil.
It
is
degraded
very
slowly,
if
at
all,
by
aerobic
microbial
processes
with
reported
mean
aerobic
soil
metabolism
half­
life
of
about
4
years.
It
is
degraded
by
photolysis
in
aqueous
solution.
The
primary
photolysis
product
is
4­
chloro­
2­(
5­
pyrimidyl)­
2'­
clorobenzophenone.
The
MARC
elected
not
to
exclude
this
aquatic
photolysis
degradate
in
the
drinking
water
exposure
assessment
because:
1)
its
potential
to
occur
in
surface
water;
and,
2)
the
lack
of
data
to
determine
whether
or
not
it
is
of
toxicological
concern.

Tier
I
surface
water
and
groundwater
Estimated
Environmental
Concentrations
(
EECs)
for
fenarimol
were
calculated
using
FIRST
(
surface
water)
and
SCI­
GROW
(
groundwater)
modeling
of
application
to
turf.
FIRST
is
a
first
tier
screening
model
designed
as
a
coarse
screen
to
estimate
the
pesticide
concentrations
found
in
an
`
Index
Reservoir'
located
in
Shipman,
Illinois
for
use
in
environmental
risk
assessments
for
drinking
water.
As
such,
it
provides
high­
end
estimates
of
the
concentrations
of
a
pesticide
in
drinking
water
that
might
be
derived
from
surface
water.
This
first
level
tier
is
designed
as
a
coarse
screen
and
estimates
concentrations
from
only
a
few
basic
chemical
parameters
and
pesticide
label
application
information.
The
FIRST
program
is
designed
to
mimic
a
more
complex
simulation
such
as
using
the
linked
PRZM
and
EXAMS
models,
but
requires
less
time
and
effort
to
complete.
If
a
risk
assessment
performed
using
FIRST
output
does
not
exceed
the
level
of
concern,
then
one
can
be
reasonably
confident
that
the
acute
risk
will
not
be
exceeded.
However,
for
stable
chemicals
with
long
environmental
half­
lives
FIRST
may
significantly
underestimate
long
term
EECs.

SCI­
GROW
provides
a
groundwater
screening
exposure
value
to
be
used
in
determining
the
potential
risk
to
human
health
from
drinking
water
contaminated
with
the
pesticide.
SCI­
GROW
estimates
EEC
values
in
shallow
groundwater
for
only
a
single
season
and
so
is
much
less
useful
in
estimating
EEC
values
for
stable
compounds
that
may
persist
in
the
environment.
The
EEC
value
calculated
using
SCI­
GROW
should
therefore
be
used
with
caution
since
it
probably
underestimates
possible
groundwater
concentrations.

EECs
for
surface
and
ground
water
are
summarized
in
Table
5.
The
surface
water
acute
EEC
is
242
ppb.
The
surface
water
chronic
EEC
is
59
ppb.
These
values
represent
the
maximum
surface
water
concentration,
and
the
mean
yearly
concentration,
respectively,
resulting
from
fenarimol
use
on
turf.
The
groundwater
screening
concentration
calculated
using
SCI­
GROW
is
14
ppb
and
represents
a
90­
day
average
concentration
value.
This
value
should
be
used
for
both
chronic
and
acute
groundwater
estimates.
It
is
not
possible
to
identify
possible
degradates
of
concern
at
this
time.

Table
5.
Modeling
Results
(
Estimated
Environmental
Concentrations
(
EECs))
for
Application
of
Fenarimol
to
Turf.
25
Model
Concentrationa
FIRST
Peak
Day
(
Acute)
Surface
Water
242
ppb
FIRST
Annual
Average
(
Chronic)
Surface
Water
59
ppb
SCIGROW
Ground
Water
Value
14
ppb
a
EECs
are
for
parent
fenarimol
only
and
do
not
include
aqueous
photolytic
degradate.

4.4
Residential
Exposure
Potential
residential
exposures
may
occur
as
a
result
of
applications
of
fenarimol
to
residential
lawns
or
turf
by
residents
and
by
professional
lawn
care
operators
(
LCOs).
Residential
exposures
have
been
estimated
based
on
label
application
frequency,
and
the
persistence
of
fenarimol.
Most
assumptions
for
risk
estimation
were
based
on
the
Residential
SOPs.
Chemical
specific
data
from
a
turf
transferable
residue
(
TTR)
study
were
available
and
were
used
to
estimate
the
dissipation
of
fenarimol.
As
a
result
of
home
lawn
uses,
the
HED
has
concerns
for
potential
exposures
to
both
adults
and
children.

Application
and
subsequent
exposure
in
residential
settings
for
the
use
sites
other
than
turf
(
i.
e.
ornamentals,
roses,
grapes,
apples,
pears,
cherries,
and
pecans)
is
considered
unlikely.
Dow
AgroSciences,
the
previous
registrant,
has
asserted
to
HED
that
product
for
these
use
sites
is
intended
for
and
used
only
in
commercial
operations.
Product
packaging
and
label
language
suggest
that
applications
in
residential
settings
would
not
occur.
Label
language
restrictions
include
equipment
requirements
such
as
personal
protective
equipment
(
PPE)
requirements,
worker
protection
standard
(
WPS)
requirements,
restrictions
for
use
by
PCOs,
and
application
methods
that
would
never
occur
in
residential
settings.

4.4.1
Home
Uses
4.4.1.1
Handler
Exposure
The
following
use
patterns
have
been
assessed
for
non­
occupational
(
residential)
handler
exposures:
1)
granular
application
to
turf
with
a
belly
grinder
spreader;
2)
granular
application
to
turf
with
a
push­
type
spreader;
and
3)
granular
spot
treatment
application
by
hand.
Short­
term
dermal
and
inhalation
exposures
to
adults
are
likely
from
residents
handling
(
i.
e.
mixing,
loading
and
applying)
granular
product
to
lawns.
As
stated
above,
fenarimol
can
be
applied
to
residential
turf
by
residents
or
LCOs,
either
once
at
the
maximum
application
rate
(
2.73
lb
ai/
acre)
or
twice
as
a
split
application
of
half
the
maximum
rate
per
application.
Additionally,
fenarimol
could
be
applied
to
residential
turf
by
LCOs
as
many
as
12
times
per
season
at
significantly
lower
rates;
i.
e.

0.51
lb
ai/
acre
per
application.
However,
the
registrants
have
stated
that
only
one
to
two
applications
per
season
to
turf
are
anticipated,
since
users
rotate
between
different
systemic
and
contact
fungicides.
To
estimate
aggregate
risks,
the
short­
term
dermal
risk
estimates
from
handler
exposures
and
dermal
risk
estimates
from
post
application
exposures
(
post
application
inhalation
exposures
are
not
anticipated)
can
be
combined.
Additionally,
short­
term
dermal
and
inhalation
risk
estimates
from
handler
exposures
were
combined.

Table
10
details
the
exposure
and
risk
estimates
for
residents
handling
fenarimol.
Note:
If
label
restrictions
prohibiting
sale
to
or
use
by
homeowners
of
the
granular
product,
as
agreed
to
by
the
registrant,
are
implemented,
then
these
homeowner
handler
scenarios
should
not
occur.
Data
26
confidence
levels
are
described
in
Table
13.
For
short­
term
(
1­
30
days)
non­
occupational
risk
assessments,
HED
has
established
a
level
of
concern
for
MOEs
less
than
3000.
Estimated
risks
to
residential
handlers
from
short­
term
dermal
exposures
exceed
HED's
level
of
concern
for
the
scenarios
involving
broadcast
application
to
lawns
by
loading/
applying
the
granular
formulation
with
a
belly
grinder
(
MOE
=
280)
and
by
hand
dispersal
for
spot
treatments
(
MOE
=
1600).
The
risk
estimate
from
dermal
exposures
did
not
exceed
the
level
of
concern
for
residents
applying
fenarimol
granular
formulations
via
a
push­
type
spreader
(
MOE
=
45,000).
Additionally,
handler
risk
estimates
from
short­
term
inhalation
exposures
did
not
exceed
the
level
of
concern
for
residents
applying
fenarimol
granular
formulations
with
a
belly
grinder
(
MOE
=
25,000),
a
push­
type
spreader
(
MOE
=
1,700,000),
or
by
hand
dispersal
spot
treatments
(
MOE
=
71,000).
The
combined
short­
term
dermal
and
inhalation
risk
estimates
were
as
follows:
i.
e.
for
belly
grinder
(
MOE
=
280),
hand
dispersal
(
MOE
=
1500),
and
push­
type
spreader
(
MOE
=
44,000).
These
estimates
are
not
significantly
different
from
the
dermal
estimates,
because
estimated
inhalation
exposures
are
much
less
than
the
estimated
dermal
exposures
for
homeowner
pesticide
handlers.

4.4.1.2
Postapplication
Exposure
Several
post­
application
exposure
scenarios
following
application
to
turf
are
anticipated;
these
are
as
follows:
1)
short­
and
intermediate­
term
dermal
exposure
to
adults
and
children
(
toddlers,
1­
6
years
old);
2)
short­
term
incidental
episodic
oral
exposure
to
children
from
ingestion
of
fenarimol
granules;
and
3)
short­
and
intermediate­
term
oral
exposure
to
children
from
incidental
ingestion
of
soil,
turf
grass
mouthing,
and
hand­
to­
mouth
activity.

Postapplication
dermal
and
inhalation
exposure
and
risk
estimates
are
presented
in
detail
in
Tables
11
and
12.
For
post
application
residential
exposures,
the
scenarios
with
risks
estimates
that
exceed
HED's
level
of
concern
(
short­
term
(
ST)
MOEs
<
3000;
intermediate­
term
(
IT)
MOEs
<
1000)
are
as
follows:
1)
the
high
contact
ST
dermal
exposure
activities
(
adults
&
toddlers)
of
working
or
playing
on
lawns;
2)
the
ST
&
IT
incidental
oral
exposure
by
toddlers
through
hand­
to­
mouth
activities,
and
mouthing
treated
turf
while
playing
on
treated
lawns;
and
3)
the
ST
incidental
episodic
oral
exposure
activity
by
toddlers
of
ingesting
fenarimol
granules
while
playing
on
treated
lawns
[
Note:
HED
considers
this
risk
unlikely
given
the
smaller
particle
size
of
fenarimol
granules
and
the
fact
that
watering
in
likely
occurs
immediately
or
soon
after
application,
in
order
for
the
pesticide
to
be
efficacious.].
However,
for
post
application
residential
exposures,
the
scenarios
with
risks
estimates
that
do
not
exceed
HED's
level
of
concern
(
ST
MOEs

3000;
IT
MOEs

1000)
are
as
follows:
1)
the
high
contact
IT
dermal
exposure
activities
of
working
or
playing
on
lawns
by
adults
or
toddlers;
2)
the
low
contact
ST
&
IT
dermal
exposure
activities
of
mowing
lawns
and
golfing
on
treated
turf;
and
3)
the
ST
&
IT
incidental
oral
exposure
activity
by
toddlers
of
ingesting
soil
while
playing
on
treated
lawns.

Combining
risk
estimates
for
exposure
scenarios
that
are
likely
to
occur
together
resulted
in
risk
estimates
of
greater
concern.
For
example,
it
is
possible
that
the
same
individual
could
apply
granular
fenarimol
product
to
a
residential
lawn
and
immediately
afterwards
perform
high
contact
activities
on
that
lawn.
Combining
the
risk
estimates
for
the
residential
handler
using
a
belly
grinder
spreader
and
the
high
contact
post
application
activities
on
a
lawn
resulted
in
a
MOE
that
exceeds
HED's
level
of
concern
(
MOE
=
214).
Combining
the
post
application
turf
short­
term
risk
estimates
for
the
incidental
oral
non­
dietary
exposures
to
small
children
(
except
episodic
ingestion
of
fenarimol
granules)
resulted
in
a
risk
estimate
(
MOE
=
690)
that
exceeds
HED's
level
of
concern
(
MOE
<
3000).
Also,
combining
the
post
application
turf
intermediate­
term
risk
estimates
for
incidental
oral
non­
dietary
exposures
to
small
children
(
except
episodic
ingestion
of
fenarimol
granules)
resulted
in
a
27
risk
estimate
(
MOE
=
62)
that
exceeds
HED's
level
of
concern
(
MOE
<
1000).
Additionally,
combining
the
post
application
turf
dermal
and
incidental
oral
risk
estimates
for
small
children
(
except
episodic
ingestion
of
fenarimol
granules)
resulted
in
MOEs
(
short­
term
MOE
=
340;
intermediateterm
MOE
=
58)
that
exceed
HED's
levels
of
concern
(
MOEs
<
3000
&
1000,
respectively).

Summary
of
Risk
Estimates
HED
calculates
risk
estimates
and
expresses
them
as
Margins
of
Exposure
(
MOEs).
For
fenarimol,
MOEs
that
are
less
than
3000
exceed
HED's
level
of
concern
for
short­
term
(
ST)
exposures,
and
MOEs
less
than
1000
exceed
HED's
level
of
concern
for
intermediate­
term
(
IT)
exposures.
Therefore,
the
target
MOEs
for
non­
occupational
ST
and
IT
exposures
to
fenarimol
are

3000
and

1000,
respectively.
Exposure
scenarios
and
their
associated
risk
estimates
are
summarized
in
Table
6.
Risk
estimates
exceeding
HED's
level
of
concern
have
been
bolded
in
the
table.
Tables
10­
13
in
Appendix
1
present
a
more
detailed
description
of
the
results
summarized
in
Table
6.

Table
6.
Summary
of
Exposure
Scenarios
and
Risk
Estimates
Exposure
Scenario
Route
of
Exposure
Population
ST
MOEa
IT
MOEb
Residential
Handlers
(
Mixers/
Loaders/
Applicators)
Exposures
Applying
Granular
Product
by
Hand
Application
Dermal
Adult
1600
N/
A
Loading/
Applying
Granular
for
Belly
Grinder
Application
Dermal
Adult
280
N/
A
Loading/
Applying
Granular
for
Push­
type
Spreader
Application
Dermal
Adult
45,000
N/
A
Applying
Granular
Product
by
Hand
Application
Inhalation
Adult
71,000
N/
A
Loading/
Applying
Granular
for
Belly
Grinder
Application
Inhalation
Adult
25,000
N/
A
Loading/
Applying
Granular
for
Push­
type
Spreader
Application
Inhalation
Adult
1.7E+
6
N/
A
Combined
Residential
Handlers
Exposures
Applying
Granular
Product
by
Hand
Application
Dermal
&
Inhalation
Adult
1500
N/
A
Loading/
Applying
Granular
for
Belly
Grinder
Application
Dermal
&
Inhalation
Adult
280
N/
A
Loading/
Applying
Granular
for
Push­
type
Spreader
Application
Dermal
&
Inhalation
Adult
44,000
N/
A
Postapplication
Exposures
High
Contact
Activities
­
e.
g.
Working
Dermal
Adult
950
1400
High
Contact
Activities
­
e.
g.
Playing
Dermal
Toddler
660
1000
Low
Contact
Activity
­
Mowing
Dermal
Adult
27,000
21,000
Low
Contact
Activity
­
Golfing
Dermal
Adult
14,000
10,000
Exposure
Scenario
Route
of
Exposure
Population
ST
MOEa
IT
MOEb
28
Hand
to
Mouth
Activity
Oral
Toddler
860
78
Incidental
Turf
grass
Mouthing
Oral
Toddler
3400
320
Incidental
Ingestion
of
Soil
Oral
Toddler
2.6E+
5
2.4E+
4
Ingestion
of
Fenarimol
Product
Granules
Oral
Toddler
220
N/
A
Combined
Post
application
Exposures
All
Incidental
Oral
Non­
Dietary
(
except
granular
ingestion)
Oral
Toddler
690
62
Dermal
&
All
Incidental
Oral
Non­
Dietary
(
except
granular
ingestion)
Oral
&
Dermal
Toddler
340
58
Residential
Handler
(
Belly
Grinder
Spreader)
&
High
Contact
Post­
Application
Activities
Dermal
Adult
214
N/
A
a
ST
MOE
=
Short­
term
Margin
of
Exposure.
MOEs
that
are
<
3000
are
of
concern
for
short­
term
exposures
and
are
shown
in
bold.
N/
A
=
Not
Applicable.

b
IT
MOE
=
Intermediate­
term
Margin
of
Exposure.
MOEs
that
are
<
1000
are
of
concern
for
intermediate­
term
exposures
and
are
shown
in
bold.
N/
A
=
Not
Applicable.

Uncertainties
Chemical
specific
data
from
a
turf
transferable
residue
(
TTR)
study
(
MRID
44690801)
were
available.
However,
these
TTR
data
were
found
to
be
generally
unacceptable
for
use
in
postapplication
exposure
assessment.
These
data
had
limitations,
as
follows:
1)
the
sampling
period
was
not
sufficiently
long
enough
to
adequately
characterize
dissipation;
2)
only
duplicate
samples
were
collected
at
each
sampling
interval,
not
the
Agency
recommended
triplicate
sampling;
and
3)
the
day
0
(
DAT
0)
data
from
the
California
site
were
inconsistent
with
data
from
the
other
two
sites.
Therefore,
based
on
the
weight
of
evidence
these
data
were
discounted.
However,
a
dissipation
rate
(
8%
daily)
derived
from
these
data
was
used
and
translated
to
residential
application
and
the
Residential
SOPs
were
utilized
to
estimate
initial
residues
(
i.
e.
DAT
0
residues)
based
on
application
rate
and
to
estimate
contact
rates
with
turf.
This
is
a
slow
dissipation
rate.
Also,
the
data
show
that
6.1%,
0.85%,
and
0.59%
(
for
CA,
IN
&
MS,
respectively)
of
the
applied
fenarimol
was
detected
on
DAT
0.
By
comparison,
the
Agency's
SOP
uses
a
transfer
efficiency
(
percent
of
application
rate)
of
5%.
Therefore,
due
to
the
variability
of
the
study
transfer
efficiency
data,
the
poor
quality
of
the
study
itself,
and
because
no
transfer
coefficient
exists
for
the
California
roller
method
that
was
used
in
this
study,
the
HED
will
use
the
5%
transfer
efficiency
rate
for
risk
assessment
purposes.
However,
the
HED
notes
that
the
6.1%
transfer
efficiency
rate
measured
from
the
CA
site
may
be
an
outlier,
since
the
DAT
1
data
(
residues
detected
one
day
after
application)
from
the
CA
site
were
an
order
of
magnitude
lower,
and
the
DAT
0
and
DAT
1
data
from
the
IN
and
MS
sites
were
considerably
lower.
Therefore,
use
of
the
5%
transfer
efficiency
rate
may
be
a
conservative
assumption.
Better
data
may
indicate
a
value
closer
to
1%,
which
would
increase
the
MOEs
by
five
fold.

Dislodgeable
foliar
residue
(
DFR)
data
were
available
for
apple
trees.
These
apple
DFR
data
support
the
EFED
conclusions
concerning
the
persistence
of
fenarimol
in
the
environment.
In
the
DFR
study,
detectable
residues
were
still
present
on
leaf
surfaces
65
days
after
treatment.

The
exposure
estimates
generated
for
the
residential
turf
uses
using
the
Draft
SOPs
are
based
on
29
some
upper­
percentile
assumptions
(
i.
e.,
duration
of
exposure
and
maximum
application
rate
for
short­
term
assessments,
and
duration
of
exposure
for
intermediate­
term
assessments)
and
are
considered
to
be
representative
of
high
end
exposures.
The
uncertainties
associated
with
this
assessment
stem
from
the
use
of
an
assumed
amount
of
pesticide
retained
on
turf,
and
assumptions
regarding
the
transfer
of
fenarimol
residues.
The
turf
risk
estimates
are
believed
to
be
reasonable
and
protective
estimates,
that
are
based
on
Agency
residential
SOPs
that
incorporated
dissipation
data
from
a
fenarimol
turf
transferrable
residue
study
which
met
most
of
the
OPPTS
guidelines.
Therefore,
the
level
of
confidence
is
fairly
high.

By
using
surrogate
study
data
from
PHED,
it
is
assumed
that
pesticides
of
similar
formulation
result
in
similar
exposures
when
handled
in
the
same
manner.
Several
handler
assessments
were
completed
using
"
low
quality"
PHED
data
due
to
the
lack
of
a
more
acceptable
data.

HED
assumes
that
the
general
public's
exposure
may
not
be
mitigated
by
use
of
personal
protective
gear.
Therefore,
only
administrative
controls
(
e.
g.,
formulation
changes
or
use
rate
reductions)
are
feasible
methods
of
risk
reduction.
Mitigating
circumstances
for
residential
exposure
to
fenarimol
residues
may
include
the
watering­
in
of
the
granular
formulation
to
turf.
This
instruction,
however,
does
not
prevent
contact
with
treated
turf
prior
to
watering­
in.
The
current
granular
label
(
EPA
Reg.
No.
228­
298)
recommends,
but
does
not
require
watering­
in.
The
soluble
concentrate
label
(
EPA
Reg.
No.
62719­
142)
does
not
mention
watering­
in.
Therefore,
label
language
should
be
strengthened
to
ensure
that
watering­
in
occurs
immediately
after
application.
Additionally,
the
current
labeling
does
not
clearly
specify
whether
the
granular
product
(
EPA
Reg.
No.
228­
298)
is
for
professional
use
only.
Specific
labeling
would
help
eliminate
unintentional
use
by
residents.
Labeling
should
also
specifically
advise
against
the
hand
dispersal
and
belly
grinder­
type
application
methods.
Note:
If
label
restrictions
prohibiting
sale
to
or
use
by
homeowners
of
the
granular
product,
as
agreed
to
by
the
registrant,
are
implemented,
then
these
homeowner
handler
scenarios
should
not
occur.

4.4.2
Spray
Drift
Spray
drift
is
always
a
potential
source
of
exposure
to
the
public
near
spraying
operations.
This
is
particularly
the
case
with
aerial
application,
but,
to
a
lesser
extent,
could
also
be
a
potential
source
of
exposure
from
groundboom
application
methods.
The
Agency
has
been
working
with
the
Spray
Drift
Task
Force,
EPA
Regional
Offices
and
State
Lead
Agencies
for
pesticide
regulation
and
other
parties
to
develop
the
best
spray
drift
management
practices.
The
Agency
is
now
requiring
interim
mitigation
measures
for
aerial
applications
that
must
be
placed
on
product
labels/
labeling.
The
Agency
has
completed
its
evaluation
of
the
new
data
base
submitted
by
the
Spray
Drift
Task
Force,
a
membership
of
U.
S.
pesticide
registrants,
and
is
developing
a
policy
on
how
to
appropriately
apply
the
data
and
the
AgDRIFT
computer
model
to
its
risk
assessments
for
pesticides
applied
by
air,
orchard
airblast
and
ground
hydraulic
methods.
After
the
policy
is
in
place,
the
Agency
may
impose
further
refinements
in
spray
drift
management
practices
to
reduce
off­
target
drift
and
risks
associated
with
aerial
as
well
as
other
application
types
where
appropriate.

5.0
AGGREGATE
RISK
ASSESSMENT
AND
RISK
CHARACTERIZATION
5.1
Acute
Aggregate
Risk
Assessment
Because
an
acute
toxicity
endpoint
was
not
identified
by
HIARC,
an
acute
aggregate
risk
assessment
is
not
required.
30
5.2
Short­
and
Intermediate­
Term
Aggregate
Risk
Assessment
Because
short
and
intermediate­
term
risk
estimates
from
the
turf
use
of
fenarimol
exceed
HED's
level
of
concern,
a
short
and
intermediate­
term
aggregate
risk
assessment
cannot
be
performed.
Additional
exposure
to
fenarimol
residues
in
food
or
drinking
water
would
only
cause
short
and
intermediateterm
risk
estimates
to
further
exceed
HED's
level
of
concern.

5.3
Chronic
Aggregate
Risk
Assessment
5.3.1
Aggregate
Chronic
Risk
Assessment
The
aggregate
chronic
risk
assessment
for
fenarimol
considers
both
chronic
food
and
drinking
water
exposure
to
fenarimol.
Chronic
exposure
to
residues
of
fenarimol
in/
on
food
does
not
exceed
HED's
level
of
concern.
However,
the
EECs
for
both
surface
and
ground
water
exceed
the
chronic
DWLOCs
for
some
or
all
population
subgroups
(
see
below),
indicating
a
potential
concern
for
exposure
through
drinking
water.
Tier
I
EECs
were
calculated
for
the
turf
use
of
fenarimol.
A
Tier
II
model
is
not
available
for
turf.

5.3.2
Chronic
DWLOC
Calculations
HED
has
calculated
drinking
water
levels
of
comparison
(
DWLOCs)
for
chronic
exposure
to
fenarimol
in
surface
and
groundwater
which
are
presented
in
Table
7.
The
DWLOC
chronic
is
the
concentration
in
drinking
water
as
a
part
of
the
aggregate
chronic
exposure
that
occupies
no
more
than
100%
of
the
chronic
PAD.
To
calculate
the
DWLOC
for
chronic
exposure
relative
to
a
chronic
toxicity
endpoint,
the
chronic
dietary
food
exposure
(
from
DEEMJ)
was
subtracted
from
the
chronic
PAD
to
obtain
the
acceptable
chronic
exposure
to
fenarimol
in
drinking
water.
DWLOCs
were
then
calculated
using
default
body
weights
and
drinking
water
consumption
figures.
Assumptions
used
in
calculating
the
DWLOCs
include
70
kg
body
weight
for
the
U.
S.
population,
60
kg
body
weight
for
adult
females,
10
kg
body
weight
for
children,
two
liters
of
water
consumption
per
day
for
adults,
and
one
liter
consumption
for
children.

To
estimate
the
potential
risks
associated
with
chronic
exposure
to
fenarimol
in
drinking
water,
HED
compared
estimated
environmental
concentrations
(
EECs)
of
fenarimol
in
surface
and
ground
water
to
chronic
DWLOCs.
If
EECs
are
greater
than
DWLOCs,
then
risk
estimates
exceed
HED's
levels
of
concern.
The
surface
water
EECs
represent
annual
average
concentrations
of
fenarimol,
and
the
ground
water
EECs
represent
90­
day
average
concentrations
of
fenarimol.

Table
7.
Fenarimol
­
Summary
of
Chronic
DWLOC
Calculations
31
Population
Subgroup
cPAD
(
mg/
kg/
day
)
Food
Exposure
(
mg/
kg/
day)
Available
Water
Exposure
(
mg/
kg/
day)
Chronic
DWLOC
(

g/
L)
EFED
Generated
EECs
Surface
Water
(
Chronic)
(

g/
L)
Ground
Water
(
SCI­
GROW)
(

g/
L)

U.
S.
Populationa
0.0006
0.000000
0.0006
21
59
14
Females
13­
50
yrs
0.000000
0.0006
18
Children
1­
6
yrs
b
0.000002
0.000598
6
All
Infants
0.000001
0.000599
6
EEC
=
Estimated
Environmental
Concentrations
for
fenarimol
(
does
not
include
aqueous
photolytic
degradate)
Fenarimol
surface
water
EECs
are
from
FIRST
modeling
.

DWLOC
chronic
=
water
exposure
X
body
weight
(
where
water
exposure
=
cPAD
­
average
food
exposure)
Liters
of
water/
day
X10­
3
Body
weight
=
70
kg
for
U.
S.
Population,
60
kg
for
females,
10
kg
for
infants
and
children
Consumption
=
2L/
day
for
Adults
and
1L/
day
for
infants
and
children
a
Also
represents
Males
13­
19
years,
Males
20+
years,
and
Seniors
55+

b
Also
represents
Children
7­
12
years
old.

Upon
comparison
of
the
chronic
DWLOCs
with
the
EECs
for
fenarimol,
estimated
using
conservative
modeling
(
Table
7)
there
is
a
potential
concern
for
exposure
from
drinking
water
from
surface
water
sources
for
all
populations,
and
for
infants
and
children
from
ground
water
sources.
That
is,
the
EEC
for
surface
water
is
greater
than
all
DWLOCs,
and
the
EEC
for
ground
water
is
greater
than
the
DWLOCs
for
infants
and
children.

6.0
Cumulative
Exposure
To
Substances
with
Common
Mechanism
of
Toxicity.

The
Food
Quality
Protection
Act
(
1996)
stipulates
that
when
determining
the
safety
of
a
pesticide
chemical,
EPA
shall
base
its
assessment
of
the
risk
posed
by
the
chemical
on,
among
other
things,
available
information
concerning
the
cumulative
effects
to
human
health
that
may
result
from
dietary,
residential,
or
other
non­
occupational
exposure
to
other
substances
that
have
a
common
mechanism
of
toxicity.
The
reason
for
consideration
of
other
substances
is
due
to
the
possibility
that
low­
level
exposures
to
multiple
chemical
substances
that
cause
a
common
toxic
effect
by
a
common
mechanism
could
lead
to
the
same
adverse
health
effect
as
would
a
higher
level
of
exposure
to
any
of
the
other
substances
individually.
A
person
exposed
to
a
pesticide
at
a
level
that
is
considered
safe
may
in
fact
experience
harm
if
that
person
is
also
exposed
to
other
substances
that
cause
a
common
toxic
effect
by
a
mechanism
common
with
that
of
the
subject
pesticide,
even
if
the
individual
exposure
levels
to
the
other
substances
are
also
considered
safe.

HED
did
not
perform
a
cumulative
risk
assessment
as
part
of
this
risk
assessment
for
fenarimol
because
HED
has
not
yet
initiated
a
review
to
determine
if
there
are
any
other
chemical
substances
that
have
a
mechanism
of
toxicity
common
with
that
of
fenarimol.
For
purposes
of
this
tolerance
reassessment
review,
EPA
has
assumed
that
fenarimol
does
not
have
a
common
mechanism
of
toxicity
with
other
substances.

7.0
TOLERANCE
REASSESSMENT
RECOMMENDATIONS
32
7.1
Tolerance
Reassessment
Recommendation
Table
8
summarizes
the
tolerance
reassessment
for
fenarimol.

Table
8.
Reassessed
fenarimol
tolerances.

Commodity
Established
Tolerance
(
ppm)
Reassessed
Tolerance
(
ppm)
Comment
[
Correct
Commodity
Definition]

Tolerance
Listed
Under
40
CFR
§
180.421(
a)(
1)

Apple
pomace
(
wet
and
dry)
2.0
0.3
The
available
data
indicate
that
the
tolerance
for
wet
apple
pomace
should
be
reduced.
Dry
apple
pomace
is
no
longer
considered
a
significant
livestock
feed
item.
[
Apple,
wet
pomace]

Apples
0.1
0.1
[
Apple]

Cattle,
fat
0.1
0.01
Cattle,
meat
0.01
0.01
Cattle,
mbyp
0.01
0.05
[
Cattle,
meat
byproducts,
except
kidney]

Cattle,
kidney
0.1
0.01
Cattle,
liver
0.1
Revoke
[
included
in
meat
byproducts]

Eggs
0.01
Revoke
There
are
no
poultry
feed
items
associated
with
presently
registered
uses.

Goat,
fat
0.1
0.01
Goat,
meat
0.01
0.01
Goat,
mbyp
0.01
0.05
[
Goat,
meat
byproducts,
except
kidney]

Goat,
kidney
0.1
0.01
Goat,
liver
0.1
Revoke
[
included
in
meat
byproducts]

Hog,
fat
0.1
Revoke
There
are
no
hog
feed
items
associated
with
presently
registered
uses.
Hog,
meat
0.01
Revoke
Hog,
mbyp
0.01
Revoke
Hog,
kidney
0.1
Revoke
Hog,
liver
0.1
Revoke
Horse,
fat
0.1
0.01
Horse,
meat
0.01
0.01
Horse,
mbyp
0.01
0.05
[
Horse,
meat
byproducts,
except
kidney]

Horse,
liver
0.1
Revoke
[
included
in
meat
byproducts]

Horse,
kidney
0.1
0.01
Milk
0.003
Revoke
Category
3
of
40
CFR
§
180.6(
a)

Pears
0.1
0.1
[
Pear]

Pecans
0.1
0.02
[
Pecan]
Commodity
Established
Tolerance
(
ppm)
Reassessed
Tolerance
(
ppm)
Comment
[
Correct
Commodity
Definition]

33
Poultry,
fat
0.01
Revoke
There
are
no
poultry
feed
items
associated
with
presently
registered
uses.
Poultry,
meat
0.01
Revoke
Poultry,
mbyp
0.01
Revoke
Sheep,
fat
0.1
0.01
Sheep,
meat
0.01
0.01
Sheep,
mbyp
0.01
0.05
[
Sheep,
meat
byproducts,
except
kidney]

Sheep,
kidney
0.1
0.01
Sheep,
liver
0.1
Revoke
[
included
in
meat
byproducts]

Tolerance
Listed
Under
40
CFR
§
180.421(
a)(
2)

Bananas
0.5
(
Not
more
than
0.25
ppm
shall
be
present
in
the
pulp
after
peel
is
removed)
0.25
[
Banana]

Cherries
1.0
1.0
[
Cherry]

Grape
juice
0.6
Revoke
Not
required
based
on
reexamination
of
available
grape
processing
data.

Grape
pomace
(
wet
and
dry)
2.0
Revoke
No
longer
considered
a
significant
livestock
feed
item.

Grapes
0.2
0.1
[
Grape]

Raisin
waste
3.0
Revoke
No
longer
considered
a
significant
livestock
feed
item.

Raisins
0.6
Revoke
Not
required
based
on
reexamination
of
available
grape
processing
data.

Tolerance
Listed
Under
40
CFR
§
180.421(
b)

Filberts
0.02
Revoke
(
expired)
Expiration/
revocation
date
of
12/
31/
98
*
Field
trial
data
support
a
0.02
ppm
tolerance
Hops
5
Revoke
(
expired)
Expiration/
revocation
date
of
12/
31/
98
7.2
Codex/
International
Harmonization
The
Codex
Alimentarius
Commission
has
established
several
maximum
residue
limits
(
MRLs)
for
residues
of
fenarimol
in/
on
various
raw
agricultural
and
processed
commodities.
The
Codex
MRLs
are
expressed
in
terms
of
fenarimol
per
se.
A
numerical
comparison
of
the
Codex
MRLs
and
the
corresponding
reassessed
U.
S.
tolerances
is
presented
in
Table
9.
Table
9
shows
that
except
for
cattle
liver,
cherries,
and
pecans,
the
U.
S.
tolerances
and
Codex
MRLs
are
not
in
harmony
with
respect
to
numerical
levels.
34
Table
9.
Codex
MRLs
and
applicable
U.
S.
tolerances
for
fenarimol.
Recommendations
are
based
on
conclusions
following
reassessment
of
U.
S.
tolerances.

Codex
Reassessed
U.
S.
Tolerance,
ppm
Recommendation
And
Comments
Commodity,
As
Defined
MRL
1
(
mg/
kg)

Apple
pomace,
dry
5
wet
apple
pomace
=
0.3
Dry
apple
pomace
is
no
longer
considered
a
significant
livestock
feed
item.

Artichoke
globe
0.1
­­

Banana
0.2
0.25
Cattle
kidney
0.02
(*)
0.01
(*)

Cattle
liver
0.05
Revoke
covered
by
tolerance
for
meat
byproducts
Cattle
meat
0.02
(*)
0.01
(*)

Cherries
1
1
Dried
grapes
(
currants,
raisins
and
sultanas)
0.2
Revoke
Grapes
0.3
0.1
Hops,
dry
5
­­

Melons,
except
watermelon
0.05
­­

Peach
0.5
­­

Pecan
0.02
(*)
0.02
(*)

Peppers,
sweet
0.5
­­

Pome
fruits
0.3
apple/
pear
=
0.1
Strawberry
1
­­

1
All
MRLs
are
at
CXL
step.
An
asterisk
(*)
signifies
that
the
MRL
or
US
tolerance
was
established
at
or
about
the
limit
of
detection.

8.0
DATA
NEEDS
Toxicology:

A
primary
dermal
irritation
study
(
870.2400);
a
28­
day
subchronic
inhalation
study
(
870.3465);
and
a
special
developmental
toxicity
study
(
870.6300).
The
special
developmental
toxicity
study
being
required
must
include
a
special
protocol
that
assesses
potential
hormonal
effects.

Product
and
Residue
Chemistry:

Additional
data
are
required
concerning
enforcement
analytical
methods,
stability,
storage
stability,
pH,
UV/
Visible
absorption,
density,
octanol/
water
partition
coefficient,
and
solubility
(
OPPTS
830.1800,
6313,
6317,
7000,
7050,
7300,
7550,
and
7840)
of
the
T/
TGAI.

Storage
stability
data
for
livestock
commodities
are
required
to
support
the
storage
intervals
used
in
the
livestock
feeding
studies.
35
Residential:

Mitigating
circumstances
for
residential
exposure
to
fenarimol
residues
may
include
watering­
in
after
application
to
turf.
This
instruction,
however,
does
not
prevent
contact
with
treated
turf
prior
to
watering­
in.
The
current
granular
label
(
EPA
Reg.
No.
228­
298)
recommends,
but
does
not
require
watering­
in.
The
soluble
concentrate
label
(
EPA
Reg.
No.
62719­
142)
does
not
mention
watering­
in.
Therefore,
label
language
should
be
strengthened
to
ensure
that
watering­
in
occurs
immediately
after
application.
Additionally,
the
current
labeling
does
not
clearly
specify
whether
the
granular
product
(
EPA
Reg.
No.
228­
298)
is
for
professional
use
only.
Specific
labeling
would
help
eliminate
unintentional
use
by
residents.
Labeling
should
also
specifically
advise
against
the
hand
dispersal
and
belly
grinder­
type
application
methods.
Note:
If
label
restrictions
prohibiting
sale
to
or
use
by
homeowners,
as
agreed
to
by
the
registrant
of
the
granular
product,
are
implemented,
then
these
homeowner
handler
scenarios
should
not
occur.
36
Appendix
1.
Detailed
tables
describing
residential
exposure
assessment.

Table
10:
Short­
Term
Baseline
Residential
Handler
Exposure
and
Risk
Estimates
Exposure
Scenario
(
Scenario
#)
Crop
Application
Ratea
Amount
Treatedb
Short­
Term
Baseline
Dermal
Unit
Exposure
(
mg/
lb
ai)
c
Dermal
Dose
(
mg/
kg/
day)
d
Dermal
MOE
e
Inhalation
Unit
Exposure
(
mg/
lb
ai)
f
Inhalation
Dose
(
mg/
kg/
day)
g
Inhalation
MOEh
Combined
Dermal
&
Inhalation
MOEi
Applicator
Applying
Granular
for
Hand
application
(
1)
Turf
2.73
lb
ai
per
acre
0.023
Acres
per
day
430
0.022
1600
0.470
0.00049
71,000
1500
Mixer/
Loader/
App
Loading/
Applying
Granular
for
Belly
Grinder
application
(
2)
Turf
2.73
lb
ai
per
acre
0.5
Acres
per
day
110
0.13
280
0.062
0.0014
25,000
280
Loading/
Applying
Granular
for
Push­
type
spreader
(
ORETF)
application
(
3)
Turf
2.73
lb
ai
per
acre
0.5
Acres
per
day
0.68
0.0008
45,000
0.00091
0.000021
1,700,000
44,000
*
Values
rounded
to
two
significant
figures
a
Maximum
application
rate
based
on
label.

b
Amounts
of
acreage
treated
per
day
are
from
the
Residential
SOP
for
area
treated
in
a
single
day
for
each
exposure
scenario
of
concern.

c
Dermal
Unit
Exposure
(
mg/
lb
ai)
for
hand
and
belly
grinder
application
from
PHED
represents
short­
sleeved
shirt
and
shorts,
no
gloves;
open
mixing/
loading
and
application
by
same
person.
Dermal
Unit
Exposure
for
push­
type
spreader
from
Outdoor
Residential
Exposure
Task
Force
(
ORETF)
study
OMA003
(
MRID
44972201).

d
Daily
Dermal
Dose
(
mg/
kg/
day)
=
Dermal
Unit
Exposure
(
mg/
lb
ai)
x
lb
ai/
acre
x
Acres
treated
/
day
x
Dermal
Absorption
Factor
(
5/
100)
/
Body
Weight
(
60
kg).

e
Dermal
MOE
=
LOAEL
(
35
mg/
kg/
day)
/
Daily
Dermal
Dose
mg/
kg/
day).

f
Inhalation
Unit
Exposure
from
PHED
for
hand
and
belly
grinder
application.
Inhalation
Unit
Exposure
for
push­
type
spreader
from
Outdoor
Residential
Exposure
Task
Force
(
ORETF)
study
OMA003
(
MRID
44972201).

g
Daily
Inhalation
Dose
(
mg/
kg/
day)
=
Inhalation
Unit
Exposure
(
mg/
lb
ai)
x
lb
ai/
acre
x
Acres
treated/
day
/
Body
Weight
(
60
kg).

h
Inhalation
MOE
=
LOAEL
(
35
mg/
kg/
day)
/
Daily
Inhalation
Dose
mg/
kg/
day).

i
Combined
MOE
=
1
/
(
1
/
Dermal
MOE
+
1
/
Inhalation
MOE)
37
Table
11:
Fenarimol:
Residential
Postapplication
Activities
on
Treated
Turf:
Dermal
Exposure
and
Non­
Cancer
Risk
Estimates
Short­
term
Risk
Estimates
at
DAT
0
Intermediate­
term
Risk
Estimates
Activity
TTR

g/
cm2
DAT
0
(
a)
Transfer
Coefficient
(
cm2/
hr)
(
b)
Dermal
Dose
(
mg/
kg/
day)
(
c)
MOE
(
d)
TTR

g/
cm2(
e)
Transfer
Coefficient
(
cm2/
hr)
(
b)
Dermal
Dose
(
mg/
kg/
day)
(
c)
MOE
(
f)

high
contact
lawn
activities:
adults
1.53
14,500
0.037
950
0.0346
7,300
0.00042
1400
high
contact
lawn
activities:
toddler
1.53
5,200
0.053
660
0.0346
2,600
0.0006
1000
mowing
turf:
adults
1.53
500
0.0013
27,000
0.0346
500
0.000029
21,000
golf
course
reentry:
adult
1.53
500
0.0026
14,000
0.0346
500
0.000058
10,000
a
TTR
source:
Standard
Operating
Procedures
(
SOPs)
for
Residential
Exposure
Assessments,
SOP
2.2:
Postapplication
dermal
potential
dose
from
pesticide
residues
on
turf.
DAT
0
residue
values
were
used
for
the
short­
term
assessments
at
day
0
after
application.
TTR
=
AR
x
F
x
(
1­
D)
t
x
CF1
x
Cf2,
where
AR
=
application
rate
(
lbs
a.
i./
acre),
F
=
fraction
of
a.
i.
retained
on
foliage
(
unitless),
D
=
fraction
of
residue
that
dissipates
daily
(
unitless),
t
=
postapplication
day
on
which
exposure
is
being
assessed,
CF1
=
weight
unit
conversion
factor
to
convert
the
lbs
a.
i.
in
the
application
rate
to

g
for
the
DFR
value
(
4.54E8

g/
lb),
and
CF2
=
area
unit
conversion
factor
to
convert
the
surface
area
units
(
ft2)
in
the
application
rate
to
cm2
for
the
DFR
value
(
24.7E­
9
acre/
cm2);
e.
g.
TTR
at
DAT
0
=
2.73
lbs
a.
i./
acre
x
0.05
x
4.54E8

g/
lb
x
24.7E­
9
acre/
cm2
=
1.53

g/
cm2.
The
fraction
of
residue
that
dissipates
daily
(
D
=
8%)
was
derived
from
the
turf
transferrable
residue
study
submitted
by
the
registrant,
i.
e.
MRID
44690801.
b
Transfer
coefficient
from
the
Residential
SOP's
(
02/
01).
c
Dermal
Dose
=
TTR
(

g/
cm2)
x
TC
(
cm2/
hr)
x
conversion
factor
(
1
mg/
1,000

g)
x
exposure
time
(
2
hrs/
day
playing
&
mowing;
4
hrs
golfing)
x
Dermal
Absorption
Factor
(
5/
100)/
body
weight
(
60
kg
adult
or
15
kg
child
1­
6
yrs).
Short­
term
MOEs
were
calculated
using
DAT
0
residue
values
and
intermediate­
term
MOEs
were
calculated
using
average
residue
values
(
see
below)
and
TC/
2
(
half
TC
values).
d
MOE
=
LOAEL
(
35
mg/
kg/
day;
based
on
a
oral
study)
/
dermal
dose;
Note:
Target
MOE
is
3000
or
greater,
since
a
NOAEL
was
not
established
and
a
LOAEL
is
used.
e
TTR
source:
MRID
44690801.
Although
this
study
was
unacceptable
for
regulatory
purposes,
average
residue
data
were
used
to
estimate
an
intermediate­
term
TTR
value.
An
average
residue
value
from
DAT
1
through
DAT
7
residue
values
from
all
three
sites
for
the
four
days
sampled
was
used;
i.
e.
0.185

g/
cm2/
day.
This
value
was
then
normalized
for
the
lower
application
rate
used
with
multiple
applications,
i.
e.

0.51
lbs
ai/
acre
versus
the
2.73
lbs
ai/
acre
maximum
application
rate
used
for
the
field
studies;
i.
e
0.51/
2.73
x
0.185
=
0.0346

g/
cm2/
day.
f
MOE
=
NOAEL
(
0.6
mg/
kg/
day;
based
on
a
oral
study)
/
dermal
dose;
Note:
Target
MOE
is
1000
or
greater.
Note:
TTR
=
turf
transferable
residue
DAT
=
days
after
treatment
38
Table
12.
Residential
Oral
Nondietary
Short­
term
Postapplication
Risks
to
Children
from
"
Hand­
to­
Mouth"
and
Ingestion
Exposure
When
Reentering
Lawns
Treated
with
Fenarimol
Type
of
Exposure
Short­
term
Oral
Dosea
(
mg/
kg/
day)
Short­
term
MOEb
Intermediate­
term
Oral
Dosea
(
mg/
kg/
day)
Intermediate­
term
MOEb
(
1)
Hand
to
Mouth
Activity
(
Finger
licking)
0.040768
860
0.007616
78
(
2)
Incidental
Turfgrass
Mouthing
0.010192
3400
0.002
320
(
3)
Incidental
Ingestion
of
Soil
1.367E­
4
260,000
0.0000255
2.4E+
4
(
4)
Ingestion
of
Granules
0.156
224
­­­
­­­

Combined
Oral
Nondietary
(
except
granular
ingestion)
c
0.0511
690
0.00964
62
Combined
Oral
(
except
granular
ingestion)
and
Dermald
­­­
340
­­­
58
Footnotes:

a
Application
rate
for
the
short­
term
estimates
represents
maximum
label
rate
from
current
EPA
registered
labels:
EPA
Reg.
No.
62719­
142
soluble
concentrate/
liquid
formulation
&
EPA
Reg.
No.
228­
298
granular
product
formulations,
max
rate
is
2.73
lb
ai/
acre
for
both.
For
intermediate­
term
estimates,

the
application
rate
of
0.51
lbs
ai/
acre
was
used.
Incidental
oral
doses
were
calculated
using
formulas
presented
in
the
Residential
SOPs
(
updated
1999­
2000).

Short­
and
intermediate­
term
doses
were
calculated
using
the
following
formulas:

(
1)
Hand­
to­
mouth
oral
dose
to
children
on
the
day
of
treatment
(
mg/
kg/
day)
=
[
application
rate
(
lb
ai/
acre)
x
fraction
of
residue
dislodgeable
from
potentially
wet
hands
(
5%)
x
11.2
(
conversion
factor
to
convert
lb
ai/
acre
to

g/
cm2)]
x
median
surface
area
for
1­
3
fingers
(
20
cm2/
event)
x
hand­
to­
mouth
rate
(
20
events/
hour)
x
exposure
time
(
2
hr/
day)
x
0.001
mg/
µ
g]
x
50%
extraction
by
saliva
/
bw
(
15
kg
child
1­
6
yrs).
This
formula
is
based
on
proposed
changes
to
the
December
1999
Residential
SOPs.
[
Note:
The
intermediate­
term
estimates
used
10
events
per
hour.]

(
2)
Turf
mouthing
oral
dose
to
child
on
the
day
of
treatment
(
mg/
kg/
day)
=
[
application
rate
(
lb
ai/
acre)
x
fraction
of
residue
dislodgeable
from
potentially
wet
hands
(
20%)
x
11.2
(
conversion
factor
to
convert
lb
ai/
acre
to

g/
cm2)
x
ingestion
rate
of
grass
(
25
cm2/
day)
x
0.001
mg/
µ
g]
/
bw
(
15
kg
child
1­
6
yrs).

(
3)
Soil
ingestion
oral
dose
to
child
on
the
day
of
treatment
(
mg/
kg/
day)
=
[(
application
rate
(
lb
ai/
acre)
x
fraction
of
residue
retained
on
uppermost
1
cm
of
soil
(
100%
or
1.0/
cm)
x
4.54e+
08

g/
lb
conversion
factor
x
2.47e­
08
acre/
cm2
conversion
factor
x
0.67
cm3/
g
soil
conversion
factor)
x
100
mg/
day
ingestion
rate
x
1.0e­
06
g/

g
conversion
factor]
/
bw
(
15
kg;
child
1­
6
yrs).
Short
term
dose
based
residue
on
the
soil
on
day
of
application.

(
4)
Granular
pellet
ingestion
(
mg/
kg/
day)
oral
dose
to
child
=
[
granule
ingestion
rate
(
300
mg/
day)
x
fraction
of
ai
of
granule
formulations
(
0.0078)]
/
bw
(
15
kg
child
1­
6
yrs).

b
Short­
term
MOE
=
LOAEL
(
35
mg/
kg/
day)
/
Oral
Dose
(
mg/
kg/
day).
LOAEL
from
a
rat
cross
fertility
study;
target
MOE
of
3000,
because
a
NOAEL
was
not
established.
Intermediate­
term
MOE
=
NOAEL
(
0.6
mg/
kg/
day)
/
Oral
dose
(
mg/
kg/
day).
NOAEL
from
a
two
generation
rat
reproduction
study;
target
MOE
of
1000.

c
Combined
MOEs
=
LOAEL
/
[
sum
of
incidental
oral
doses],
with
a
target
MOEs
of
3000
&
1000
for
short­
&
intermediate­
term,
respectively.

d
Combined
Dermal
+
Incidental
Oral
MOEs
=
1/
[
1/
MOEdermal
+
1/
MOEoral
];
see
Table
6
for
dermal
MOE
for
high­
contact
short­
term
activity
(
MOE
=
660)

and
intermediate­
term
activity
(
MOE
=
1000)
on
turf
.
39
Table
13.
Residential
Exposure
Scenario
Descriptions,
Assumptions,
and
Data
Sources
for
the
Use
of
Fenarimol
Exposure
Scenario
(
Number)
Data
Source
Standard
Assumptionsa
Commentsb
Loading/
Applying
with
a
Push­
type
Granular
Spreader
(
1)
ORETF
Study
­
OMA003
MRID
449722­
01
0.5
acres
Baseline:
Hand,
dermal,
and
inhalation
(
30
replicates
each)
data
used
to
establish
exposure
values.
Average
laboratory
and
field
recoveries
were
within
guideline
parameters;
data
of
acceptable
quality
(
AB
grade).

Loading/
Applying
Granular
with
a
Belly
grinder
(
2)
SOPs
for
Residential
Exposure
Assessments
(
12/
97)
0.5
acres
­
turf;
or
0.025
acres
(
1,000
ft2)
for
turf
spot
treatment
Baseline:
Dermal
(
20­
45
replicates)
and
hand
(
23
replicates)
exposure
values
are
based
on
ABC
grade
data.
Inhalation
(
40
replicates)
exposure
value
is
based
on
AB
grade
data.
Medium
confidence
in
dermal/
hand
data
and
high
confidence
in
inhalation
data.

Applying
Granular
by
Hand
(
3)
SOPs
for
Residential
Exposure
Assessments
(
12/
97)
0.025
acres
(
1,000
ft2)
for
spot
treatment
Baseline:
Dermal.
hand,
inhalation
(
each
16
replicates)
exposure
values
are
based
on
ABC
grade
data.
Medium
confidence
in
all
data.
"
No
gloved"
hand
exposure
was
back
calculated
applying
a
90
percent
protection
factor
to
"
gloved"
hand
exposure
data;
therefore
a
10x
FQPA
safety
factor
has
been
applied
to
the
hand
exposure.

a
Standard
Assumptions
based
on
HED
estimates.

b
"
Best
Available"
grades
are
defined
by
HED
SOP
for
meeting
Subdivision
U
Guidelines.
Best
available
grades
are
assigned
as
follows:
matrices
with
grades
A
and
B
data
and
a
minimum
of
15
replicates;
if
not
available,
then
grades
A,
B
and
C
data
and
a
minimum
of
15
replicates;
if
not
available,
then
all
data
regardless
of
the
quality
and
number
of
replicates.
Data
confidence
are
assigned
as
follows:

High
=
grades
A
and
B
and
15
or
more
replicates
per
body
part
Medium
=
grades
A,
B,
and
C
and
15
or
more
replicates
per
body
part
Low
=
grades
A,
B,
C,
D
and
E
or
any
combination
of
grades
with
less
than
15
replicates
