Document ID: EPA-HQ-OPP-2004-0235-0006
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2004-09-22T04:00Z

United
States
Prevention,
Pesticides
September
20,
2004
Environmental
Protection
and
Toxic
Substances
Agency
(
7508C)

Report
of
the
Food
Quality
Protection
Act
(
FQPA)
Tolerance
Reassessment
Progress
and
Risk
Management
Decision
(
TRED)
for
Fluridone
Page
2
of
6
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
CERTIFIED
MAIL
Dear
Registrant:

This
is
the
Environmental
Protection
Agency's
(
hereafter
referred
to
as
EPA
or
the
Agency)
"
Report
of
the
Food
Quality
Protection
Act
(
FQPA)
Tolerance
Reassessment
Progress
and
Risk
Management
Decision
for
Fluridone,"
which
was
approved
on
September
20,
2004.
This
document
is
also
known
as
a
Tolerance
Reassessment
Decision,
or
TRED.
A
Notice
of
Availability
of
this
tolerance
reassessment
decision
will
be
published
shortly.

The
Federal
Food,
Drug
and
Cosmetic
Act
(
FFDCA),
as
amended
by
FQPA,
requires
EPA
to
reassess
all
the
tolerances
for
registered
chemicals
in
effect
on
or
before
the
enactment
of
the
FQPA
on
August
3,
1996.
In
reassessing
these
tolerances,
the
Agency
must
consider,
among
other
things,
aggregate
risks
from
non­
occupational
sources
of
pesticide
exposure,
whether
there
is
increased
susceptibility
to
infants
and
children,
and
the
cumulative
effects
of
pesticides
with
a
common
mechanism
of
toxicity.
Once
a
safety
finding
has
been
made,
the
tolerances
are
considered
reassessed.
Existing
tolerances
associated
with
fluridone
must
be
reassessed
in
accordance
with
FFDCA,
as
amended
by
FQPA.

The
Agency
has
evaluated
all
current
registered
uses
of
fluridone
and
has
determined
that
there
is
a
reasonable
certainty
that
no
harm
to
any
population
subgroup
will
result
from
exposure
when
considering
dietary
exposure
and
all
other
non­
occupational
sources
of
pesticide
exposure
for
which
there
is
reliable
information.
The
food,
drinking
water
and
recreational
swimmer
risks
are
not
of
concern
separately
or
when
aggregated.
Therefore,
no
mitigation
measures
are
needed,
and
the
current
tolerances
established
at
40
CFR
180.420
for
residues
of
fluridone
in/
on
raw
agricultural
commodities
are
now
considered
reassessed
as
safe
under
section
408(
q)
of
the
FFDCA.

Fluridone
is
a
systemic
herbicide
that
is
used
to
manage
aquatic
weeds
in
ponds
and
lakes.
It
is
particularly
useful
for
the
control
of
hydrilla
in
the
southern
states
and
eurasian
milfoil
in
the
northern
states.
It
inhibits
carotene
synthesis
which
causes
the
loss
of
chlorophyll.
It
is
typically
applied
to
the
whole
water
body
because
it
requires
a
contact
time
of
45
days
to
be
effective.
The
labels
permit
single
treatments
of
up
to
90
ppb
for
whole
lake
treatments
and
150
ppb
for
partial
lake
treatments,
with
a
maximum
cumulative
application
of
150
ppb
per
growth
cycle.
There
are
no
direct
food
uses
for
fluridone,
however,
water
from
areas
treated
with
fluridone
can
be
used
for
the
irrigation
of
crops
and
pastures.
Page
3
of
6
Fluridone
is
a
Toxicity
Category
III
for
acute
dermal
and
eye
irritation,
and
Toxicity
Category
IV
for
acute
oral,
acute
inhalation
and
dermal
irritation.
It
is
not
a
dermal
sensitizer.
There
was
no
indication
of
reproductive
or
neurotoxicant
effects
from
fluridone
in
the
reviewed
studies.
Fluridone
is
classified
as
not
likely
to
be
carcinogenic
to
humans.

Residential
Margin
of
Exposures
(
MOEs)
greater
than
100
are
not
of
concern
to
the
Agency.
The
MOE
of
100
is
based
on
the
standard
safety
factor
of
10X
for
intraspecies
variability
(
i.
e.
differences
among
humans)
and
10X
for
interspecies
variability
(
differences
between
humans
and
animals).
Additional
factors
for
database
uncertainties
were
not
required
because
the
database
was
considered
complete
and
there
were
no
datagaps.

The
FQPA
Safety
Factor
was
reduced
to
1X,
based
on
the
available
hazard
and
exposure
data.
It
is
applicable
to
all
population
subgroup
and
exposure
scenarios.
There
was
no
evidence
of
pre­
or
post­
natal
susceptibility
from
in
utero
or
postnatal
exposure
to
fluridone
and
there
are
no
residual
uncertainties.

N­
methyl
Formamide
(
NMF)
is
the
major
degradate
when
fluridone
is
applied
to
water
bodies.
A
limited
number
of
studies
have
been
conducted
under
field
conditions
and
these
studies
suggest
that
NMF
is
undetectable
in
water
bodies
treated
with
fluridone
at
the
maximum
application
rate.
The
toxicology
database
for
NMF
is
limited
to
one
developmental
study
that
was
reported
in
the
literature.
NMF
is
not
a
metabolite
in
foods.

Fluridone
acute
and
chronic
dietary
exposure
assessments
were
conducted
using
the
Dietary
Exposure
Evaluation
Model
software
with
the
Food
Commodity
Intake
Database
(
DEEM­
FCIDtm,
Version
1.30)
and
the
Lifeline
Model
Version
2.0
which
uses
food
consumption
data
from
USDA's
Continuing
Surveys
of
Food
Intakes
by
Individuals
(
CSFII)
from
1994­
1996
and
1998.
The
acute
dietary
risk
estimates
were
calculated
only
for
females
of
child­
bearing
age
(
13­
49),
as
an
appropriate
endpoint
for
the
general
population
was
not
identified.
The
acute
dietary
exposure
estimates
are
less
than
1%
of
the
aPAD.
For
the
acute
dietary
exposure
assessment
a
developmental
no
observed
adverse
effect
level
(
NOAEL)
of
125
mg/
kg/
day
was
selected
from
a
developmental
toxicity
study
in
rabbits
in
which
increased
incidences
of
abortions
was
observed
at
the
lowest
observed
adverse
effect
level
(
LOAEL)
of
300
mg/
kg/
day.
The
chronic
dietary
risk
estimates
were
calculated
for
all
population
subgroups.
The
chronic
dietary
exposure
estimates
ranged
from
1%
of
the
cPAD
for
the
general
U.
S.
population
to
3.6%
of
the
cPAD
for
children
ages
1­
2.
For
the
chronic
dietary
exposure
assessment
a
NOAEL
of
15
mg/
kg/
day
was
selected
from
a
2­
year
carcinogenicity
study
in
mice
in
which
increased
alkaline
phosphatase
activity
and
hepatocellular
hyperplasia
was
observed
at
the
LOAEL
of
50
mg/
kg/
day.
All
acute
and
chronic
dietary
exposure
estimates
from
fluridone
are
less
than
3.6%
of
the
PAD
and
are
below
the
Agency's
level
of
concern.

The
drinking
water
risk
were
calculated
for
both
fluridone
and
its
major
degradate
NMF
because
fluridone
degrades
to
NMF
in
water.
The
drinking
water
MOEs
for
fluridone
are

7500
and
exceed
the
target
MOE
of
100.
All
drinking
water
exposures
are
below
the
Agency's
level
of
concern.
Page
4
of
6
There
is
a
possibility
that
swimmer
exposures
could
occur
following
fluridone
applications
to
recreational
lakes.
The
recreational
swimmer
exposure
estimates
were
evaluated
using
the
SWIMODEL
and
standard
assumptions
from
the
residential
SOPs.
The
swimmer
MOEs
are

4,800
and
exceed
the
target
MOE
of
100.
All
swimmer
exposure
estimates
are
below
the
Agency's
level
of
concern.

Aggregate
risk
has
been
calculated
for
fluridone
and
the
degradate
NMF
by
combining
the
food,
drinking
water,
and
residential
exposures
(
recreation
swimmers).
The
acute
aggregate
exposures
for
food,
drinking
water
and
recreational
swimmers
were
calculated
only
for
females
because
the
acute
dietary
endpoint
is
based
on
developmental
effects
and
only
applies
to
females.
Short­
and
intermediate­
term
aggregate
exposures
for
food,
drinking
water
and
recreational
swimmers
were
calculated
for
adults
and
children
ages
1
to
6.
Chronic
aggregate
exposures
were
calculated
for
food
and
drinking
water
for
all
population
sub­
groups
because
the
swimmer
exposure
does
not
occur
on
a
long
term
basis.
All
of
the
aggregate
risks
from
dietary,
drinking
water
including
metabolites,
and
recreational
exposures
to
fluridone
are
below
the
Agency's
level
of
concern
and
no
risk
mitigation
is
required.

FQPA
requires
that
EPA
consider
"
available
information"
concerning
the
cumulative
effects
of
a
particular
pesticide's
residues
and
"
other
substances
that
have
a
common
mechanism
of
toxicity."
The
Agency
considers
other
substances
because
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.

Unlike
other
pesticides
for
which
EPA
has
followed
a
cumulative
risk
approach
based
on
a
common
mechanism
of
toxicity,
EPA
has
not
made
a
common
mechanism
of
toxicity
finding
as
to
fluridone
and
any
other
substances
and
fluridone
does
not
appear
to
produce
a
toxic
metabolite
produced
by
other
substances.
For
the
purposes
of
this
tolerance
action,
therefore,
EPA
has
not
assumed
that
fluridone
has
a
common
mechanism
of
toxicity
with
other
substances.
For
information
regarding
EPA's
efforts
to
determine
which
chemicals
have
a
common
mechanism
of
toxicity
and
to
evaluate
the
cumulative
effects
of
such
chemicals,
see
the
policy
statements
released
by
EPA's
Office
of
Pesticide
Programs
concerning
common
mechanism
determinations
and
procedures
for
cumulating
effects
from
substances
found
to
have
a
common
mechanism
on
EPA's
website
at:
http://
www.
epa.
gov/
pesticides/
cumulative/.

EPA
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
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
Page
5
of
6
resources
allow,
screening
of
additional
hormone
systems
may
be
added
to
the
Endocrine
Disruptor
Screening
Program
(
EDSP).

In
the
available
toxicity
studies
on
fluridone,
there
were
no
estrogen,
androgen
and/
or
thyroid
mediated
toxicity.
When
the
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency's
EDSP
have
been
developed,
fluridone
may
be
subjected
to
additional
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.

Tolerance
Reassessment
All
of
the
existing
fluridone
tolerances
established
at
40
CFR
180.420
are
adequately
supported
and
are
considered
reassessed
by
the
Agency.
These
tolerances
are
listed
in
Table
1.

Table
1.
Reassessed
Tolerances
for
Fluridone
That
Were
Included
in
the
Dietary
Risk
Assessments
Commodity
Tolerance
(
ppm)
Commodity
Tolerance
(
ppm)

Avocado
0.1
Hog,
Meat
by­
products
0.05
Cattle,
Fat
0.05
Hops
0.1
Cattle,
Kidney
0.1
Horse,
Fat
0.05
Cattle,
Liver
0.1
Horse,
Kidney
0.1
Cattle,
Meat,
except
Kidney
and
Liver
0.05
Horse,
Liver
0.1
Cattle,
Meat
by­
products
0.05
Horse,
Meat,
except
Kidney
and
Liver
0.05
Citrus
0.1
Horse,
Meat
by­
products
0.05
Cotton,
Undelinted
Seed
0.1
Leafy
vegetables
0.1
Crayfish
0.5
Legume,
forage
0.15
Cucurbit
vegetables
group
0.1
Milk
0.05
Egg
0.05
Nut
0.1
Fish
0.5
Poultry,
Fat
0.05
Fruit,
Pome
0.1
Poultry,
Kidney
0.01
Fruit,
Stone
0.1
Poultry,
Liver
0.01
Goat,
Fat
0.05
Poultry,
Meat,
except
Kidney
and
Liver
0.05
Goat,
Kidney
0.1
Poultry,
Meat
by­
products
0.05
Goat,
Liver
0.1
Root
Crop
Vegetables
0.1
Goat,
Meat,
except
Kidney
and
Liver
0.05
Seed
and
Pod
Vegetables
0.1
Goat,
Meat
by­
products
0.05
Sheep,
Fat
0.05
Grain,
crop
0.1
Sheep,
Kidney
0.1
Grass,
Forage
0.15
Sheep,
Liver
0.1
Hog,
Fat
0.05
Sheep,
Meat,
except
Kidney
and
Liver
0.05
Hog,
Kidney
0.1
Sheep,
Meat
by­
products
0.05
Hog,
Liver
0.1
Small
Fruit
0.1
Hog,
Meat,
except
Kidney
and
Liver
0.05
Vegetables,
fruiting
0.1
Page
6
of
6
This
document
summarizes
the
Agency's
decision
on
the
tolerance
reassessment
for
fluridone.
Please
contact
Wilhelmena
Livingston
of
my
staff
with
any
questions
regarding
this
decision;
she
may
be
reached
by
phone
at
(
703)
308­
8025
or
by
e­
mail
at
livingston.
wilhelmena@
epa.
gov.

Sincerely,

Debbie
Edwards,
Ph.
D.
Director
Special
Review
and
Reregistration
Division
Enclosures:
Human
Health
Risk
Assessment
for
Fluridone
TRED.

Fluridone
and
its
Major
Degradate,
N­
methyl
formamide
 
Drinking
Water
Assessment
for
the
Health
Effects
Division
(
HED)
Reregistration
Eligibility
Decision
Document.

Fluridone:
Toxicology
Chapter
for
TRED.

Fluridone
Acute
and
Chronic
Dietary
Exposure
Assessments
for
the
Reregistration
Eligibility
Decision.