Document ID: EPA-HQ-OPP-2005-0297-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-06-07T04:00Z

UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
September
3,
2002
MEMORANDUM
SUBJECT:
Fenarimol.
Updated
HED
Human
Health
Assessment
for
the
Tolerance
Reassessment
Eligibility
Decision
(
TRED)
Document.
Chemical
No.
206600.
No
MRID
#.
DP
Barcode
No.
D285162.

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
Amended
&
Revised
Health
Effects
Division's
Tolerance
Reassessment
Eligibility
Decision
(
TRED)
Document
for
fenarimol,
taking
into
consideration
comments
and
additional
information
on
the
aquatic
photodegradates
recieved
from
the
registrant,
Gowan
Company,
and
requirements
of
the
1996
Food
Quality
Protection
Act
(
FQPA).
This
additional
information
prompted
the
Environmental
Fate
and
Effects
Division
(
EFED)
to
reassess
the
drinking
water
exposure
for
fenarimol.
The
updated
drinking
water
assessment
(
July
31,
2002;
D284487)
was
revised
to
include
fenarimol
and
its
aquatic
photodegradates.
The
model
inputs
were
adjusted
so
that
aquatic
concentrations
were
estimated
assuming
no
aqueous
photolysis,
which
appears
to
be
fenarimol's
most
significant
route
of
dissipation
in
the
environment.
The
result
provided
a
screening
level
estimate
of
combined
concentrations
of
fenarimol
and
its
aquatic
degradates
that
is
conservative
and
that
does
not
underestimate
exposure.
Although,
there
is
still
some
uncertainty
as
to
the
identity,
fate,
and
behavior
of
the
photolysis
degradates
of
fenarimol,
data
will
be
required
to
address
this
uncertainty.
Subsequently,
the
HED
FQPA
Safety
Factor
Committee
(
SFC)
met
to
reevaluate
fenarimol.
Based
on
the
updated
drinking
water
assessment
and
the
recent
HIARC
conclusions
regarding
aromatase,
the
FQPA
SFC
recommended
that
the
FQPA
safety
factor
for
fenarimol
be
reduced
from
10x
to
3x.
2
Additionally,
HED
has
been
informed
by
SRRD
that
the
registrant
has
agreed
to
amend
their
product
labels
to
prohibit
residential
use
and
handling
(
i.
e.
mixing,
loading
or
applying)
of
fenarimol
in
residential
settings.
Applications
to
turf
will
be
limited
to
golf
courses,
and
stadium
fields
or
professional
athletic
fields
only.
Additionally,
the
minimum
re­
application
interval
to
turf
will
be
increased
to
30
days.
Therefore,
residential
handler
and
residential
postapplication
exposure
scenarios
should
no
longer
exist.
The
only
non­
occupational
postapplication
exposure
scenario
remaining
to
evaluate
is
short­
term
dermal
exposure
to
adult
golfers.
Applications
to
residential
turf
will
not
be
permitted
by
product
labels
until
such
time
as
additional
toxicity
data
are
submitted
and
reviewed.
Then
the
Agency
will
reevaluate
the
risk
assessment
for
residential
uses.

This
assessment
only
discusses
the
human
health
risks
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:
Fenarimol
­
2nd
Report
of
the
FQPA
Safety
Factor
Committee
(
B.
Tarplee,
8/
13/
01)
Third
Report
of
the
Hazard
Identification
Assessment
Review
Committee
(
J.
Doherty,
7/
29/
02)
Updated
Drinking
Water
Assessment
to
Support
TRED
for
Fenarimol
(
N.
Birchfield,
7/
31/
02)
Fenarimol.
Amendment
to
Revised
HED
Human
Health
Assessment
for
the
Tolerance
Reassessment
Eligibility
Decision
(
TRED)
Document
(
B.
O'Keefe,
8/
1/
02)
Hazard
Identification
Assessment
Review
Committee
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)
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.
3
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.
Only
the
granular
formulation
is
assumed
to
be
applied
by
residents.
However,
HED
has
been
informed
by
SRRD
that
the
registrants
of
fenarimol
have
agreed
to
amend
their
product
labels
to
prohibit
residential
use
and
handling
(
i.
e.
mixing,
loading
or
applying)
of
fenarimol
in
residential
settings.
Applications
to
turf
will
be
limited
to
golf
courses,
and
stadium
fields
or
professional
athletic
fields
only.

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
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
4
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,
the
environmental
fate
database
is
incomplete
for
the
aquatic
photolytic
degradate
of
fenarimol,
4­
chloro­
2­(
5­
pyrimidyl)­
2'­
chlorobenzophenone.
Previously,
the
Environmental
Fate
and
Effects
Division
(
EFED)
determined
that
a
screening
level
drinking
water
assessment,
including
this
degradate
of
potential
toxicological
concern,
was
not
possible
at
that
time.
Therefore,
based
on
residual
uncertainties
regarding
the
toxicology
database
and
exposure
considerations,
the
FQPA
committee
determined
that
the
10x
FQPA
factor
should
be
retained
for
all
fenarimol
risk
assessments.
However,
EFED
has
recently
received
additional
information
on
this
aquatic
photo­
degradate
of
concern,
and
subsequently
revised
the
drinking
water
assessment
for
fenarimol.
The
updated
drinking
water
assessment
(
July
31,
2002;
D284487)
was
revised
to
include
fenarimol
and
its
aquatic
photodegradates.
The
model
inputs
were
adjusted
so
that
aquatic
concentrations
were
estimated
assuming
no
aqueous
photolysis,
which
appears
to
be
fenarimol's
most
significant
route
of
dissipation
in
the
environment.
The
result
provides
a
screening
level
estimate
of
combined
concentrations
of
fenarimol
and
its
aquatic
degradates
that
is
conservative
and
that
does
not
underestimate
exposure.
5
As
a
result
of
this
reassessment
the
chronic
EECs
increased
from
59
to
84
µ
g/
L
for
surface
water,
and
from
14
to
16
µ
g/
L
for
ground
water.
Although,
there
is
still
some
uncertainty
as
to
the
identity,
fate,
and
behavior
of
the
photolysis
degradates
of
fenarimol,
data
will
be
required
to
address
this
uncertainty.
Therefore,
the
FQPA
Safety
Factor
Committee
met
on
July
29,
2002,
to
reevaluate
fenarimol.
The
committee
also
reassessed
the
uncertainty
surrounding
the
potential
effects
elicited
by
inhibition
of
aromatase
by
fenarimol.
The
FQPA
SFC
agreed
with
the
HIARC
conclusion
that
a
special
developmental
toxicity
study
to
assess
for
hormonal
effects
is
required
for
fenarimol,
and
a
database
uncertainty
factor
of
3x
is
required
until
the
data
are
received
and
reviewed.
Based
on
the
updated
drinking
water
assessment
and
the
recent
HIARC
conclusions
regarding
aromatase,
the
FQPA
SFC
recommended
that
the
FQPA
safety
factor
for
fenarimol
be
reduced
from
10x
to
3x.

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
0.002
mg/
kg/
day.
The
cPAD
is
the
RfD
divided
by
the
FQPA
safety
factor
(
3X).
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
to
300
does
not
exceed
HED's
level
of
concern
for
intermediate­
term
risk
assessments.
A
MOE
of
greater
than
or
equal
to
300
is
required
for
these
intermediate­
term
exposure
scenarios
because
of
the
10x
interspecies
factor,
the
10x
intraspecies
factor
and
the
10x
3X
FQPA
factor.
Because
the
same
endpoint
was
used
for
all
intermediate­
term
exposure
assessments,
the
risk
6
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
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
an
additional
3x
uncertainty
factor
was
applied.
Therefore,
a
MOE
greater
than
900
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
7
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.

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
ground
water
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
ground
water,
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.

Initially,
the
drinking
water
assessment
did
not
include
the
water
degradate
of
concern,
because
the
environmental
fate
database
is
incomplete
for
the
aquatic
photo­
degradate
of
fenarimol,
4­
chloro­
2­
(
5­
pyrimidyl)­
2'­
chlorobenzophenone.
Consequently,
there
was
some
residual
uncertainty
thatthe
drinking
water
assessment
may
underestimate
exposure.
However,
recently,
the
Environmental
Fate
and
Effects
Division
(
EFED)
received
additional
information
on
the
aquatic
photo­
degradate
and
revised
the
drinking
water
assessment.
The
updated
drinking
water
assessment
(
July
31,
2002;
D284487)
includes
fenarimol
and
its
aquatic
photodegradates.
The
model
inputs
were
adjusted
so
that
aquatic
concentrations
were
estimated
assuming
no
aqueous
photolysis,
which
appears
to
be
fenarimol's
most
significant
route
of
dissipation
in
the
environment.
Minor
model
input
corrections
were
also
made
to
the
application
rate
and
interval.
The
result
provides
a
screening
level
estimate
of
combined
concentrations
of
fenarimol
and
its
aquatic
degradates
that
is
conservative
and
that
does
not
underestimate
exposure.
As
a
result
of
this
reassessment
the
chronic
EECs
increased
from
59
to
84
µ
g/
L
for
surface
water,
and
from
14
to
16
µ
g/
L
for
ground
water.
Although,
there
is
still
some
uncertainty
as
to
the
identity,
fate,
and
behavior
of
the
photolysis
degradates
of
fenarimol,
data
will
be
required
to
address
this
uncertainty.

The
EEC
for
ground
water
is
less
than
all
DWLOCs;
therefore,
there
is
no
concern
for
aggregate
chronic
exposure
to
fenarimol
and
its
degradates
from
food
and
ground
water.
The
EEC
for
surface
water
is
greater
than
all
DWLOCs;
therefore,
there
is
a
potential
concern
for
aggregate
chronic
exposures
to
fenarimol
from
food
and
surface
water.
However,
the
estimated
EEC
for
surface
water
is
a
very
conservative
estimate.
It
represents
the
1­
in­
10
year
mean
yearly
surface
water
concentration.
EFED's
surface
water
modeling
for
drinking
water
uses
a
default
percent
cropped
area
factor
(
PCA)
for
turf,
which
represents
the
fraction
of
the
watershed
that
is
cropped
and
treated
with
the
pesticide
being
modeled.
In
the
absence
of
a
crop­
specific
PCA
factor,
a
default
PCA
of
8
0.87
is
used.
The
0.87
factor
represents
the
maximum
fraction
of
a
watershed
in
the
US
that
is
agriculturally
cropped.
This
default
PCA
was
used
for
fenarimol
modeling
on
turf.
EFED
is
currently
attempting
to
develop
PCA
factors
specific
for
turf
scenarios,
and
recognizes
that
it
is
unlikely
that
87%
of
a
watershed
used
for
drinking
water
would
be
grown
to
turf
and
treated
with
fenarimol
at
the
maximum
rate
allowed
only
for
turf
applications.

The
default
PCA
factor
assumed
and
used
in
fenarimol
modeling
is
most
likely
overestimated
and
adds
to
the
conservatism
of
the
assessment.
Given
the
relatively
low
usage
of
fenarimol
across
the
country
it
is
highly
unlikely
that
the
amount
applied
to
the
watershed
in
the
model
will
be
concentrated
in
any
real
watershed
used
to
derive
drinking
water.

In
summary,
the
surface
water
EEC
is
not
likely
to
underestimate
exposure
to
fenarimol
and
its
degradates
based
on
the
conservative
inputs
to
the
model
(
i.
e.,
default
PCA,
no
decay
via
the
major
degradation
pathway,
and
the
concentrated
application
scenario
modeled
is
unlikely
to
occur
in
a
real
watershed
where
drinking
water
is
derived).
The
uncertainties
related
to
the
aqueous
photoproducts
would
likely
be
addressed
through
completion
of
a
satisfactory
guideline
aqueous
photolysis
study.
Other
uncertainties
would
likely
be
addressed
through
the
satisfactory
completion
of
other
outstanding
guideline
studies,
as
detailed
by
EFED.

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).
However,
HED
has
been
informed
by
SRRD
that
the
registrants
have
agreed
to
amend
their
product
labels
to
prohibit
residential
use
and
handling
(
i.
e.
mixing,
loading
or
applying)
of
fenarimol
in
residential
settings.
Applications
to
turf
will
be
limited
to
golf
courses,
and
stadium
fields
or
professional
athletic
fields
only.
Therefore,
residential
handler
and
residential
postapplication
exposure
scenarios
should
no
longer
exist.
The
only
non­
occupational
postapplication
exposure
scenario
remaining
to
evaluate
is
short­
term
dermal
exposure
to
adult
golfers.
Applications
to
residential
turf
will
not
be
permitted
by
products
labels
until
such
time
as
additional
toxicity
data
are
submitted
and
reviewed.
Then
the
Agency
will
reevaluate
the
risk
assessment
for
residential
uses.

Residential
exposures
have
been
estimated
based
on
label
application
rates
and
frequency,
and
the
persistence
of
fenarimol.
Several
post­
application
exposure
scenarios
following
application
to
turf
are
anticipated;
however,
if
registrants
amend
their
product
labels
to
prohibit
residential
use
and
handling
of
fenarimol
in
residential
settings,
as
they
have
agreed
to
do,
then
the
only
non­
occupational
postapplication
exposure
scenario
remaining
to
evaluate
is
short­
term
dermal
exposure
to
adult
golfers.
The
updated
Residential
SOPs
were
used
to
address
the
exposures
of
adult
golfers
contacting
treated
turf.
The
SOPs
for
turf
use
transfer
coefficients
based
on
mowing
studies.
Chemical
specific
data
from
a
turf
transferable
residue
(
TTR)
study
were
available;
however,
these
TTR
data
were
unacceptable
for
use
in
postapplication
exposure
assessment.
Therefore,
default
assumptions
from
the
SOPs
were
used.
Risk
estimates
for
short­
term
dermal
contact
with
treated
turf
during
the
low
contact
activity
of
golfing
resulted
in
a
margin
of
exposure
(
MOE)
of
14,000,
which
does
not
exceed
the
level
of
concern,
a
MOE
of
900.
9
N
N
OH
Cl
Cl
Based
upon
the
slow
dissipation
rate
of
fenarimol
and
the
possibility
of
multiple
applications
to
turf,
intermediate­
term
exposures
of
adult
golfers
are
possible.
However,
if
registrants
amend
their
product
labels
to
increase
the
minimum
re­
application
interval
to
turf
to
30
days,
as
they
have
agreed
to
do,
then
intermediate­
term
exposures
should
no
longer
exist.

Mitigating
circumstances
for
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.
When
fenarimol
is
applied
to
stadium
or
professional
athletic
fields,
applicators
should
water­
in
product
immediately
after
application,
or
do
not
enter
or
allow
others
to
enter
treated
area
for
24­
hours
after
application.
If
product
is
watered­
in
after
treatment,
do
not
enter
or
allow
other
persons
to
enter
until
area
has
dried.

Aggregate
Exposure
and
Risk
Estimates
Because
no
acute
toxicity
endpoint
was
identified
for
risk
assessment,
an
aggregate
acute
risk
assessment
was
not
conducted.
Short­
term
dermal
postapplication
exposures
for
adults
golfing
were
combined
with
average
dietary
(
food
&
water)
exposures
in
a
short­
term
aggregate
risk
assessment.
This
aggregate
risk
estimate
did
not
exceed
the
Agency's
level
of
concern.
The
exposure
from
food
is
insignificant
(<
1%
cPAD)
for
adults;
therefore,
the
aggregate
risk
estimates
include
only
dermal
and
water
exposures.
The
short­
term
DWLOCs
for
adults
are
well
above
the
estimated
EECs
for
ground
and
surface
water,
and
indicate
that
combined
short­
term
dietary
(
food
&
water)
and
dermal
exposures
do
not
exceed
the
Agency's
level
of
concern.
Risk
estimates
for
chronic
aggregate
exposures
to
fenarimol
in
food
and
water
do
not
exceed
levels
of
concern.

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:

Empirical
Formula:
C
17
H
12
Cl
2
N
2
O
10
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.
11
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
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
12
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
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.
13
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
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
Third
Report
of
the
HIARC
(
J.
Doherty,
7/
29/
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.
14
Table
2.
Toxicology
Profile
for
Fenarimol.

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
15
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
16
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
17
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
µ
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
µ
g/
mL.
The
100
µ
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
18
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.
The
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
HIARC
confirmed
this
decision
on
May
23,
2002
during
a
revisit
of
the
issue
in
response
to
comments
received
on
4/
11/
02,
Gowan
Company
requesting
that
the
HED
re­
evaluate
the
need
for
a
developmental
neurotoxicity
(
DNT)
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
(
July
29,2002;
TXR
No.
0050977)
that
a
Database
Uncertainty
Factor
of
3X
is
required
until
the
data
are
received
and
evaluated.
Evidence
suggesting
a
special
developmental
toxicity
study
to
assess
hormonal
effects
is
needed
is
given
below.

<
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
19
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.

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.

Based
on
the
HIARC
determinations,
the
FQPA
Safety
Factor
Committee
(
SFC)
initially
recommended
that
the
10x
Safety
Factor
should
be
retained
at
10x
for
all
populations
and
all
fenarimol
risk
assessments
fenarimol
due
to
the
following
data
gaps
(
B.
Tarplee,
9/
28/
01):

<
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.
Consequently,
the
photolytic
degradate
was
not
included
in
the
assessment
and
there
was
residual
uncertainty
that
the
drinking
water
assessment
may
underestimate
exposure.

In
a
revisit
meeting
on
July
29,
2002,
the
FQPA
SFC
reevaluated
fenarimol
because
the
Environmental
Fate
and
Effects
Division
(
EFED)
received
additional
information
on
the
aquatic
photo­
degradate
of
concern,
and
subsequently
revised
the
drinking
water
assessment
for
fenarimol.
The
updated
drinking
water
assessment
(
July
31,
2002;
D284487)
was
revised
to
include
fenarimol
and
its
aquatic
photodegradates.
The
model
inputs
were
adjusted
so
that
aquatic
concentrations
were
estimated
assuming
no
aqueous
photolysis,
which
appears
to
be
fenarimol's
most
significant
route
of
dissipation
in
the
environment.
Minor
model
input
corrections
were
also
made
to
the
application
rate
and
interval.
The
result
provides
a
screening
level
estimate
of
combined
concentrations
of
fenarimol
and
its
aquatic
degradates
that
is
conservative
and
that
does
not
underestimate
exposure.
As
a
result
of
this
reassessment
the
chronic
EECs
increased
from
59
to
84
µ
g/
L
for
surface
water,
and
from
14
to
16
µ
g/
L
for
ground
water.
Although,
there
is
still
some
uncertainty
as
to
the
identity,
fate,
and
behavior
of
the
photolysis
degradates
of
fenarimol,
data
will
be
required
to
address
this
uncertainty.

The
FQPA
SFC
also
reassessed
the
uncertainty
surrounding
the
potential
effects
elicited
by
inhibition
of
aromatase
by
fenarimol.
The
FQPA
SFC
agreed
with
the
HIARC
conclusion
that
a
special
developmental
toxicity
study
to
assess
for
hormonal
effects
is
required
for
fenarimol,
and
a
database
uncertainty
factor
of
3x
is
required
until
the
data
are
received
and
reviewed.
Based
on
the
updated
drinking
water
assessment
and
the
recent
HIARC
conclusions
regarding
aromatase,
the
FQPA
SFC
recommended
that
the
FQPA
safety
factor
for
fenarimol
be
reduced
from
10x
to
3x.

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
20
the
dose
levels
for
use
in
risk
assessment
(
HIARC
document
of
9/
5/
01).
The
recently
updated
HIARC
report
(
July
29,2002;
TXR
No.
0050977)
did
not
change
any
toxicity
endpoints
or
dose
levels
for
use
in
risk
assessment.
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
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.
The
HED
calculated
a
chronic
Population
Adjusted
Dose
(
cPAD)
of
0.002
mg/
kg/
day.
The
cPAD
is
the
RfD
divided
by
the
FQPA
safety
factor
(
3X).
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
300
does
not
exceed
HED's
level
of
concern
for
IT
risk
assessments.
An
MOE
of
greater
than
300
is
required
because
of
the
10x
interspecies
factor,
the
10x
intraspecies
factor
and
the
3x
FQPA
factor.
However,
HED
has
been
informed
by
SRRD
that
the
registrant
has
agreed
to
amend
their
product
labels
to
extend
the
re­
application
interval
to
turf
to
30
days;
thereby
eliminating
any
residential
intermediate­
term
exposure
scenarios.
Given
these
label
changes,
intermediate­
term
scenarios
and
risks
should
no
longer
exist.
Refer
to
the
previous
HED
TRED
chapter
for
risk
estimates
involving
such
scenarios
(
i.
e.,
"
Fenarimol.
Revised
HED
Human
Health
Assessment
for
the
Tolerance
Reassessment
Eligibility
Decision
(
TRED)
Document.
Chemical
No.
206600.
No
MRID
#.
DP
Barcode
No.
D283429",
dated
June
7,
2002).

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
900
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.
21
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
=
3X
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
=
0.002
mg/
kg/
day
Incidental
Oral,
Short­
Term
LOAEL=
35
UF
=
300X
FQPA
=
3X
Decreased
fertility
and
dystocia
an
indication
of
hormonal
effects.
Special
reproduction
study
MRID
#
0084968
Incidental
Oral,
Intermediate­
Term
NOAEL=
0.6
UF
=
100X
FQPA
=
3X
Decreased
liveborn
litter
size.
LOAEL
=
1.2
mg/
kg/
day
Rat
reproduction
MRID
#
00235175
Dermal,
Short­
Term
Oral
LOAEL=
35
UF
=
300X
FQPA
=
3X
Decreased
fertility
and
dystocia
an
indication
of
hormonal
effects.
Special
reproduction
study
MRID
#
0084968
Dermal,
Intermediate­
Term
Oral
NOAEL=
0.6
UF
=
100X
FQPA
=
3X
Decreased
liveborn
litter
size.
LOAEL
=
1.2
mg/
kg/
day
Rat
reproduction
MRID
#
00235175
Dermal,
Long­
Term
Oral
NOAEL=
0.6
UF
=
100X
FQPA
=
3X
Decreased
liveborn
litter
size.
LOAEL
=
1.2
mg/
kg/
day
Rat
reproduction
MRID
#
00235175
Inhalation,
Short­
Term
Oral
LOAEL
=
35
UF
=
300X
FQPA
=
3X
Decreased
fertility
and
dystocia
an
indication
of
hormonal
effects
Special
reproduction
study
MRID
#
0084968
Inhalation,
Intermediate­
Term
Oral
NOAEL=
0.6
UF
=
100X
FQPA
=
3X
Decreased
liveborn
litter
size.
LOAEL
=
1.2
mg/
kg/
day
Rat
reproduction
MRID
#
00235175
Inhalation,
Long­
Term
Oral
NOAEL=
0.6
UF
=
100X
FQPA
=
3X
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
22
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
Rubigan
 
,
and
this
formulation
is
typically
applied
using
ground
equipment.
HED
has
been
informed
by
SRRD
that
the
registrant
has
agreed
to
amend
their
product
labels
to
limit
applications
to
turf
to
golf
courses
and
professional
playing
fields
only.
Applications
to
residential
turf
will
not
be
permitted
on
products
labels
until
such
time
as
additional
data
are
submitted,
reviewed,
found
acceptable,
and
warrant
these
uses
to
be
reinstated
on
product
labels.

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
23
N
N
OH
Cl
Cl
N
H
N
OH
Cl
Cl
N
NH
Cl
Cl
OH
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.

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.
24
4.2.2
Dietary
Exposure
Risk
from
Food
Sources
HED
conducts
dietary
risk
assessments
using
the
Dietary
Exposure
Evaluation
Model
(
DEEM
 
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
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);
see
Table
4.

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
Population
Subgroup
Exposure
(
mg/
kg/
day)
%
cPAD1
25
Males
20+
years
0.000000
<
1
Seniors
55+
0.000000
<
1
1
cPAD
=
0.0006
mg/
kg/
day
4.3
Water
Exposure
Pathway
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
three
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
ground
water
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
ground
water
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
ground
water
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
ground
water
concentrations.

Since
the
last
version
of
this
HED
TRED
(
June
7,
2002),
the
Environmental
Fate
and
Effects
Division
(
EFED)
received
additional
information
on
the
aquatic
photo­
degradate
(
i.
e.
4­
chloro­
2­(
5­
pyrimidyl)­
2'­
clorobenzophenone)
and
has
subsequently
revised
the
drinking
water
assessment.
The
26
updated
drinking
water
assessment
(
N.
Birchfield;
July
31,
2002;
D284487)
was
revised
to
include
fenarimol
and
its
aquatic
photodegradates.
The
previous
drinking
water
assessment
(
L.
Liebelo,
August
6,
2001;
D276622)
did
not
attempt
to
account
for
possible
photo­
degradates
of
concern.
In
the
new
updated
drinking
water
assessment,
the
model
inputs
were
adjusted
so
that
aquatic
concentrations
were
estimated
assuming
no
aqueous
photolysis,
which
appears
to
be
fenarimol's
most
significant
route
of
dissipation
in
the
environment.
Minor
model
input
corrections
were
also
made
to
the
application
rate
and
interval.
The
result
provides
a
screening
level
estimate
of
combined
concentrations
of
fenarimol
and
its
aquatic
degradates
that
is
conservative
and
that
does
not
underestimate
exposure.
The
EECs
for
surface
and
ground
water
are
summarized
in
Table
5.
As
a
result
of
this
reassessment,
the
surface
water
acute
EEC
increased
from
242
to
261
µ
g/
L,
and
the
chronic
EECs
increased
from
59
to
84
µ
g/
L
for
surface
water,
and
from
14
to
16
µ
g/
L
for
ground
water.
These
surface
water
EEC
values
represent
the
maximum
surface
water
concentration
(
acute
EEC),
and
the
mean
yearly
concentration
(
chronic
EEC),
respectively,
resulting
from
fenarimol
use
on
turf.
The
ground
water
screening
concentration,
calculated
using
SCI­
GROW,
represents
a
90­
day
average
concentration
value.
This
value
should
be
used
for
both
chronic
and
acute
ground
water
estimates.
Although,
there
is
still
some
uncertainty
as
to
the
identity,
fate,
and
behavior
of
the
photolysis
degradates
of
fenarimol,
data
will
be
required
to
address
this
uncertainty.

Table
5.
Modeling
Results
(
Estimated
Environmental
Concentrations
(
EECs))
for
Application
of
Fenarimol
to
Turf.

Model
Concentrationa
FIRST
Peak
Day
(
Acute)
Surface
Water
261
µ
g/
L
FIRST
Annual
Average
(
Chronic)
Surface
Water
84
µ
g/
L
SCI­
GROW
Ground
Water
Value
16
µ
g/
L
a
EECs
are
for
parent
fenarimol
and
the
aqueous
photolytic
degradate.

4.4
Residential
Exposure
Potential
residential
exposures
were
possible
as
a
result
of
applications
of
fenarimol
to
residential
lawns
or
turf
by
residents
and
by
professional
lawn
care
operators
(
LCOs).
However,
as
mentioned
above,
HED
has
been
informed
by
SRRD
that
the
registrant
has
agreed
to
amend
their
product
labels
to
limit
applications
to
turf
to
golf
courses
and
professional
playing
fields
only.
Applications
to
residential
turf
will
not
be
permitted
on
products
labels
until
such
time
as
additional
data
are
submitted,
reviewed,
found
acceptable,
and
warrant
these
uses
to
be
reinstated
on
product
labels.
Therefore,
the
only
residential/
recreational
exposure
scenario
to
evaluate
is
adult
golfers.
These
residential/
recreational
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,
but
were
not
used
to
estimate
the
short­
term
postapplication
risk
to
golfers,
because
of
several
limitations
of
the
day
zero
TTR
data.
As
a
result
of
uses
on
golf
courses
and
professional
playing
fields,
the
HED
has
concerns
for
potential
exposures
to
adults.

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
27
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
Current
product
labels
indicate
that
residential
handler
exposure
could
occur
from
handling
the
granular
fenarimol
product.
However,
HED
has
been
informed
by
SRRD
that
the
registrant
has
agreed
to
amend
their
product
labels
to
prohibit
handling
(
i.
e.
mixing,
loading
or
applying)
of
fenarimol
by
residents.
Therefore,
residential
handler
exposure
scenarios
should
no
longer
exist.
Refer
to
the
previous
HED
TRED
chapter
for
risk
estimates
involving
such
scenarios
(
i.
e.,
"
Fenarimol.
Revised
HED
Human
Health
Assessment
for
the
Tolerance
Reassessment
Eligibility
Decision
(
TRED)
Document.
Chemical
No.
206600.
No
MRID
#.
DP
Barcode
No.
D283429",
dated
June
7,
2002).

4.4.1.2
Postapplication
Exposure
Current
product
labels
indicate
that
several
post­
application
exposure
scenarios
following
application
to
turf
are
anticipated.
However,
since
the
registrant
has
agreed
to
amend
their
product
labels
to
prohibit
use
of
fenarimol
in
residential
settings
and
to
increase
the
re­
application
interval
to
30
days,
then
the
only
remaining
postapplication
residential/
recreational
exposure
scenario
to
evaluate
is
shortterm
exposure
to
adult
golfers.

The
short­
term
postapplication
dermal
exposure
and
risk
estimates
for
adult
golfers
are
presented
in
Table
6.
Margins
of
Exposure
(
MOEs)
greater
than
900
do
not
exceed
HED's
level
of
concern.
For
adult
golfers,
a
MOE
of
14,000
is
estimated
for
short­
term
postapplication
dermal
exposure,
and
does
not
exceed
HED's
level
of
concern.

Table
6:
Residential
Postapplication
Activities
on
Treated
Turf:
Dermal
Exposure
and
Non­
Cancer
Risk
Estimates
Short­
term
Risk
Estimates
at
DAT
0
Activity
DAT0
TTR
(
µ
g/
cm2)
(
a)
Transfer
Coefficient
(
cm2/
hr)
(
b)
Dermal
Dose
(
mg/
kg/
day)
(
c)
MOE
(
d)

golf
course
reentry
by
adults
1.53
500
0.0026
14,000
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
µ
g
for
the
DFR
value
(
4.54E8
µ
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
µ
g/
lb
x
24.7E­
9
acre/
cm2
=
1.53
µ
g/
cm2.
b
Transfer
coefficient
from
the
Residential
SOP's
(
02/
01).
c
Dermal
Dose
=
TTR
(
µ
g/
cm2)
x
TC
(
cm2/
hr)
x
conversion
factor
(
1
mg/
1,000
µ
g)
x
exposure
time
(
4
hrs
golfing)
x
Dermal
Absorption
Factor
(
5/
100)/
body
weight
(
60
kg
adult).
Short­
term
MOEs
were
calculated
using
DAT
0
residue
values.
28
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.
TTR
=
turf
transferable
residue
DAT
=
days
after
treatment
Uncertainties
Residential
SOPs
were
utilized
to
estimate
initial
residues
(
i.
e.
DAT
0
residues)
based
on
application
rate
and
to
estimate
contact
rates
with
turf.
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.
A
dissipation
rate
of
8%
(
daily)
was
derived
from
these
data.
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.

The
exposure
estimates
generated
for
the
golfing
turf
use
using
the
Draft
SOPs
is
based
on
some
upper­
percentile
assumptions
(
i.
e.,
duration
of
exposure
and
maximum
application
rate
for
this
shortterm
assessment)
and
is
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
estimate
is
believed
to
be
a
reasonable
and
protective
estimate,
that
is
based
on
Agency
residential
SOPs.
Therefore,
the
level
of
confidence
is
fairly
high,
and
does
not
under
estimate
risk.

HED
assumes
that
the
general
public's
exposure
on
a
golf
course
will
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.
When
fenarimol
is
applied
to
stadium
or
professional
athletic
fields,
applicators
should
water­
in
product
immediately
after
application,
or
do
not
enter
or
allow
others
to
enter
treated
area
for
24­
hours
after
application.
If
product
is
watered­
in
after
treatment,
do
not
enter
or
allow
other
persons
to
enter
until
area
has
dried.

4.4.2
Spray
Drift
29
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.

5.2
Short­
and
Intermediate­
Term
Aggregate
Risk
Assessment
Based
on
agreements
with
the
registrant
regarding
amendments
to
product
labels
as
described
above,
HED
does
not
anticipate
any
intermediate­
term
exposure,
nor
any
residential
handler
or
postapplication
exposures,
other
than
those
from
uses
on
golf
course
and
professional
playing
fields.
Short­
term
dermal
postapplication
exposures
for
adults
golfing
were
combined
with
average
dietary
(
food
&
water)
exposures
in
a
short­
term
aggregate
risk
assessment.
This
aggregate
risk
estimate
did
not
exceed
the
Agency's
level
of
concern.
The
exposure
from
food
is
insignificant
for
adults;
therefore,
the
aggregate
risk
estimates
include
only
dermal
and
water
exposures.
Table
7
presents
the
aggregate
risk
estimates
for
adult
males
and
females,
calculated
using
HED
SOP
99.5.
The
shortterm
DWLOCs
for
adults
are
well
above
the
estimated
EECs
for
ground
and
surface
water,
and
indicate
that
combined
short­
term
dietary
(
food
&
water)
and
postapplication
dermal
exposures
do
not
exceed
the
Agency's
level
of
concern.
30
Table
7.
Short­
Term
Aggregate
Risk
and
DWLOC
Calculations
(
Oral/
Dermal
Endpoints
and
NOAELs
the
Same)

Population
Short­
Term
Scenario
NOAEL
mg/
kg/
day
Target
MOE1
Max
Exposure2
mg/
kg/
day
Average
Food
Exposure
mg/
kg/
day
Residential
Exposure3
mg/
kg/
day
Aggregate
MOE
(
food
and
residential)
4
Max
Water
Exposure5
mg/
kg/
day
Ground
Water
EEC6
(
µ
g/
L)
Surface
Water
EEC6
(
µ
g/
L)
Short­
Term
DWLOC7
(
µ
g/
L)

Adult
Male
35
900
0.0388
0.0
0.0026
13460
0.0362
16
84
1267
Adult
Female
35
900
0.0388
0.0
0.0026
13460
0.0362
16
84
1086
1
Target
MOE
=
10x
uncertainty
factor
(
UF)
for
intra­
species
variability,
a
10x
UF
for
inter
species
extrapolation,
a
3x
UF
for
lack
of
a
NOAEL
in
the
study
used
as
the
basis
of
the
endpoint,
and
an
FQPA
Safety
Factor
of
3x
2
Maximum
Exposure
(
mg/
kg/
day)
=
NOAEL/
Target
MOE
3
Residential
Exposure
=
Dermal
Exposure
for
Adults
Golfing
4
Aggregate
MOE
=
[
NOAEL
÷
(
Avg
Food
Exposure
+
Residential
Exposure)]

5
Maximum
Water
Exposure
(
mg/
kg/
day)
=
Target
Maximum
Exposure
­
(
Food
Exposure
+
Residential
Exposure)

6
The
crop
producing
the
highest
level
was
used.

7
DWLOC
(
µ
g/
L)
=
[
maximum
water
exposure
(
mg/
kg/
day)
x
body
weight
(
kg)]
Male
body
weight
=
70
kg;
Female
body
weight
=
60
kg;
water
consumption
=
2
L
[
water
consumption
(
L)
x
10­
3
mg/
µ
g]
31
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
EEC
for
surface
water
exceeds
the
chronic
DWLOCs
for
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
ground
water
which
are
presented
in
Table
8.
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
DEEM
 
)
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.
The
EECs
are
based
on
tier
1
models
(
FIRST
for
surface
water;
SCI­
GROW
for
ground
water)
for
a
turf
use
scenario
with
maximum
application
rates.
Initially,
the
drinking
water
assessment
did
not
include
the
water
degradate
of
concern,
because
the
environmental
fate
database
is
incomplete
for
the
aquatic
photodegradate
of
fenarimol,
4­
chloro­
2­(
5­
pyrimidyl)­
2'­
chlorobenzophenone.
Consequently,
the
drinking
water
assessment
may
underestimate
exposure.
Recently,
the
Environmental
Fate
and
Effects
Division
(
EFED)
received
additional
information
on
the
aquatic
photo­
degradate
and
revised
the
drinking
water
assessment.
The
updated
drinking
water
assessment
(
July
31,
2002;
D284487)
was
revised
to
include
fenarimol
and
its
aquatic
photodegradates.
The
model
inputs
were
adjusted
so
that
aquatic
concentrations
were
estimated
assuming
no
aqueous
photolysis,
which
appears
to
be
fenarimol's
most
significant
route
of
dissipation
in
the
environment.
Minor
model
input
corrections
were
also
made
to
the
application
rate
and
interval.
The
result
provides
a
screening
level
estimate
of
combined
concentrations
of
fenarimol
and
its
aquatic
degradates
that
is
conservative
and
that
does
not
underestimate
exposure.
As
a
result
of
this
reassessment
the
chronic
EECs
increased
from
59
to
84
µ
g/
L
for
surface
water,
and
from
14
to
16
µ
g/
L
for
ground
water.
Although,
there
is
still
some
uncertainty
as
to
the
identity,
fate,
and
behavior
of
the
photolysis
degradates
of
fenarimol,
data
will
be
required
to
address
this
uncertainty.
32
Table
8.
Fenarimol
­
Summary
of
Chronic
DWLOC
Calculations
Population
Subgroup
cPAD
(
mg/
kg/
day
)
Food
Exposure
(
mg/
kg/
day)
Available
Water
Exposure
(
mg/
kg/
day)
Chronic
DWLOC
(
µ
g/
L)
EFED
Generated
EECs
(
Chronic)

Surface
Water
(
FIRST)
(
µ
g/
L)
Ground
Water
(
SCI­
GROW)
(
µ
g/
L)

U.
S.
Populationa
0.002
0.000000
0.002
70
84
16
Females
13­
50
yrs
0.000000
0.002
60
Children
1­
6
yrs
b
0.000002
0.000598
20
All
Infants
0.000001
0.000599
20
EEC
=
Estimated
Environmental
Concentrations
for
fenarimol
and
its
aquatic
photodegradates.

NOAEL
(
No
Observable
Adverse
Effect
Level)
=
0.6
mg/
kg/
day
UF
(
Uncertainty
Factor)
=
100
cRfD
(
Chronic
Reference
Dose)
=
NOAEL
=
0.006
mg/
kg/
day
UF
FQPA
SF
(
Food
Quality
Protection
Act
Safety
Factor)
=
3
cPAD
=
Chronic
Population
Adjusted
Dose
=
cRfD
=
0.002
mg/
kg/
day
FQPA
SF
DWLOCchronic
=
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.

The
EEC
for
ground
water
is
less
than
all
DWLOCs;
therefore,
there
is
no
concern
for
aggregate
chronic
exposure
to
fenarimol
and
its
degradates
from
food
and
ground
water.
The
EEC
for
surface
water
is
greater
than
all
DWLOCs;
therefore,
there
is
a
potential
concern
for
aggregate
chronic
exposures
to
fenarimol
from
food
and
surface
water.
However,
the
estimated
EEC
for
surface
water
is
a
very
conservative
estimate.
It
represents
the
1­
in­
10
year
mean
yearly
surface
water
concentration.
EFED's
surface
water
modeling
for
drinking
water
uses
a
default
percent
cropped
area
factor
(
PCA)
for
turf,
which
represents
the
fraction
of
the
watershed
that
is
cropped
and
treated
with
the
pesticide
being
modeled.
In
the
absence
of
a
crop­
specific
PCA
factor,
a
default
PCA
of
0.87
is
used.
The
0.87
factor
represents
the
maximum
fraction
of
a
watershed
in
the
US
that
is
agriculturally
cropped.
This
default
PCA
was
used
for
fenarimol
modeling
on
turf.
EFED
is
currently
attempting
to
develop
PCA
factors
specific
for
turf
scenarios,
and
recognizes
that
it
is
unlikely
that
87%
of
a
watershed
used
for
drinking
water
would
be
grown
to
turf
and
treated
with
fenarimol
at
the
maximum
rate
allowed
only
for
turf
applications.

The
default
PCA
factor
assumed
and
used
in
fenarimol
modeling
is
most
likely
overestimated
and
adds
to
the
conservatism
of
the
assessment.
Given
the
relatively
low
usage
of
fenarimol
across
the
country
it
is
highly
unlikely
that
the
amount
applied
to
the
watershed
in
the
model
will
be
concentrated
in
any
real
watershed
used
to
derive
drinking
water.
33
In
summary,
the
surface
water
EEC
is
not
likely
to
underestimate
exposure
to
fenarimol
and
its
degradates
based
on
the
conservative
inputs
to
the
model
(
i.
e.,
default
PCA,
no
decay
via
the
major
degradation
pathway,
and
the
concentrated
application
scenario
modeled
is
unlikely
to
occur
in
a
real
watershed
where
drinking
water
is
derived).
The
uncertainties
related
to
the
aqueous
photoproducts
would
likely
be
addressed
through
completion
of
a
satisfactory
guideline
aqueous
photolysis
study
(
Guidelines
161­
2,
835.2240).
Other
uncertainties
would
likely
be
addressed
through
the
satisfactory
completion
of
other
outstanding
guideline
studies;
as
detailed
by
EFED.

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
7.1
Tolerance
Reassessment
Recommendation
Table
9
summarizes
the
tolerance
reassessment
for
fenarimol.

Table
9.
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]
Commodity
Established
Tolerance
(
ppm)
Reassessed
Tolerance
(
ppm)
Comment
[
Correct
Commodity
Definition]

34
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]

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

35
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
10.
Table
10
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.

Table
10.
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
Codex
Reassessed
U.
S.
Tolerance,
ppm
Recommendation
And
Comments
Commodity,
As
Defined
MRL
1
(
mg/
kg)

36
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.

Label
Language:

Mitigating
circumstances
for
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.
When
fenarimol
is
applied
to
stadium
or
professional
athletic
fields,
applicators
should
water­
in
product
immediately
after
application,
or
do
not
enter
or
allow
others
to
enter
treated
area
for
24­
hours
after
application.
If
product
is
watered­
in
after
treatment,
do
not
enter
or
allow
other
persons
to
enter
until
area
has
dried.