Document ID: EPA-HQ-OPP-2002-0250-0008
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2002-09-24T04:00Z

UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
August
1,
2002
MEMORANDUM
SUBJECT:
Fenarimol.
Amendment
to
Revised
HED
Human
Health
Assessment
for
the
Tolerance
Reassessment
Eligibility
Decision
(
TRED)
Document.
Chemical
No.
206600.
DP
Barcode
No.
D284644.

FROM:
Barry
O'Keefe,
Risk
Assessor
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
describes
amendments
to
the
Revised
Health
Effects
Division's
(
HED's)
Tolerance
Reassessment
Eligibility
Decision
(
TRED)
Document
for
fenarimol
(
June
7,
2002;
D283429)
taking
into
consideration
recent
decisions
from
the
HED's
Food
Quality
Protection
Act
(
FQPA)
Safety
Factor
Committee
(
SFC).
Previously,
the
FQPA
SFC
recommended
that
the
FQPA
safety
factor
for
protection
of
infants
and
children
should
be
retained
at
10x
for
fenarimol
based
on
the
following:

1)
a
developmental
neurotoxicity
study
with
fenarimol
is
required
to
determine
if
the
potential
effects
elicited
by
inhibition
of
aromatase
will
result
in
effects
in
the
offspring;
and
2)
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,
the
drinking
water
assessment
may
underestimate
exposure.

The
FQPA
SFC
reevaluated
fenarimol
because
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
2
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

g/
L
for
surface
water,
and
from
14
to
16

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.
On
May
23,
2002,
the
HED
Hazard
Identification
Assessment
Review
Committee
(
HIARC)
met
and
reassessed
the
need
for
a
developmental
neurotoxicity
study
with
fenarimol.
The
HIARC
concluded
(
July
29,
2002;
TXR
No.
0050977)
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.
Given
this
reduction
in
the
FQPA
safety
factor,
the
target
margins
of
exposure
(
MOEs)
for
fenarimol
are
therefore
reduced;
i.
e.
for
residential
short­
term
handler
and
postapplication
exposures
the
target
MOE
is
reduced
from
3000
to
900,
and
for
residential
intermediate­
term
handler
and
postapplication
exposures
the
target
MOE
is
reduced
from
1000
to
300.
The
MOEs
(
i.
e.
risk
estimates)
for
each
exposure
scenario
remain
unchanged.
Based
on
these
reductions
in
target
MOEs,
risk
estimates
for
several
short­
and
intermediate­
term
handler
and
postapplication
exposure
scenarios
still
exceed
the
Agency's
level
of
concern.
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.
Additionally,
the
registrants
have
agreed
to
extend
the
re­
application
interval
to
turf
to
30
days;
thereby
eliminating
any
residential
intermediate­
term
exposure
scenarios.
If
these
label
changes
are
made,
then
the
only
exposure
scenarios
that
still
exceed
the
Agency's
level
of
concern
are
the
following
short­
term
postapplication
scenarios
to
turf,
affecting
only
toddlers:
1)
high
contact
dermal
activities
(
MOE
=
660),
incidental
oral
hand­
to­
mouth
activities
(
MOE
=
860).
Additionally,
the
combined
risk
estimates
for
short­
term
postapplication
exposures
to
turf
for
toddlers
also
still
exceed
the
Agency's
level
of
concern;
i.
e.,
for
the
following
combinations:
1)
all
combined
incidental
oral
non­
dietary
exposures
to
toddlers
(
except
episodic
ingestion
of
fenarimol
granules)
(
MOE
=
690);
and
2)
combined
dermal
and
all
incidental
oral
non­
dietary
exposures
to
toddlers
(
except
episodic
ingestion
of
fenarimol
granules)
(
MOE
=
340).

Aggregate
Risk
Assessment
Based
on
agreements
with
the
registrant
regarding
amendments
to
product
labels
as
described
above,
HED
anticipates
neither
residential
handler
nor
intermediate­
term
residential
exposures.
Consequently,
HED
has
not
estimated
aggregate
risks
for
these
scenarios.
Because
several
of
the
risk
estimates
for
short­
term
oral
incidental
and
dermal
postapplication
exposures
exceed
HED's
level
of
concern
for
children,
aggregation
of
these
exposures
with
food
and
drinking
water
exposures
would
result
in
risk
estimates
that
further
exceed
HED's
level
of
concern.
HED
has
however
estimated
aggregate
risks
for
chronic
exposures
to
residues
of
fenarimol
in
food
and
drinking
water,
and
for
short­
term
postapplication
dermal
food
and
water
exposures
for
adults
golfing.
3
The
reduction
in
the
FQPA
safety
factor
also
affects
the
aggregate
risk
assessment
for
chronic
exposure
to
fenarimol
in
surface
and
ground
water,
resulting
in
increased
drinking
water
levels
of
concern
(
DWLOCs).
Table
1
summarizes
the
changes
in
the
DWLOCs.

Table
1.
Summary
of
Chronic
DWLOC
Calculations
Population
Subgroup
cPAD
(
mg/
kg/
day
)
Food
Exposure
(
mg/
kg/
day)
Available
Water
Exposure
(
mg/
kg/
day)
Chronic
DWLOC
(

g/
L)
EFED
Generated
EECs
(
Chronic)

Surface
Water
(
FIRST)
(

g/
L)
Ground
Water
(
SCI­
GROW)
(

g/
L)

U.
S.
Population
a
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
0.001998
20
All
Infants
0.000001
0.001999
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
EECs
are
based
on
a
tier
1
model
(
FIRST)
for
a
turf
use
scenario
with
maximum
application
rates.
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
4
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.

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.

Short­
term
dermal
postapplication
exposures
for
adults
golfing
were
combined
with
average
dietary
(
food
&
water)
exposures
in
a
short­
term
aggregate
risk
assessment.
The
aggregate
risk
estimate
for
the
postapplication
short­
term
dermal
exposure
scenario
of
golfing
did
not
exceed
the
Agency's
level
of
concern.
The
exposure
from
food
is
zero
for
adults;
therefore,
the
aggregate
risk
estimates
include
only
dermal
and
water
exposures.
Table
2
presents
the
aggregate
risk
estimates
for
adult
males
and
females,
calculated
using
HED
SOP
99.5.
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.
5
Table
2.
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
(

g/
L)
Surface
Water
EEC6
(

g/
L)
Short­
Term
DWLOC7
(

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
(

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/

g]