TXR
NO.
0050466
February
12,
2002
MEMORANDUM
SUBJECT:
TEBUTHIURON­
Report
of
the
FQPA
Safety
Factor
Committee.

FROM:
Carol
Christensen,
Acting
Executive
Secretary
FQPA
Safety
Factor
Committee
Health
Effects
Division
(7509C)

THROUGH:
Ed
Zager,
Chairman
FQPA
Safety
Factor
Committee
Health
Effects
Division
(7509C)

TO:
Paula
Deschamp,
Risk
Assessor
Reregistration
Branch
II
Health
Effects
Division
(7509C)

PC
Code:
105501
The
Health
Effects
Division
(HED)
FQPA
Safety
Factor
Committee
met
on
February
4
th
,
2002
to
evaluate
the
hazard
and
exposure
data
for
tebuthiuron.
The
Committee
recommend
that
the
FQPA
Safety
Factor
(as
required
by
the
FQPA)
be
reduced
to
3x
when
assessing
the
exposure
and
risks
of
this
chemical
to
human
health.
2
I.
HAZARD
ASSESSMENT
(Correspondence:
R.
Fricke
to
C.
Christensen
dated
January
31,
2002)

A.
Adequacy
of
Database
The
Hazard
Identification
Assessment
Review
Committee
(HIARC)
met
on
December
13
th
,
2001
and
on
January
7
th
,
2002
to
review
the
toxicological
database
of
tebuthiuron.
The
toxicological
database
is
adequate
for
FQPA
assessment,
however
there
are
significant
data
gaps.
The
developmental
toxicity
study
in
the
rabbit
is
unacceptable
for
the
determination
of
susceptibility
to
the
fetuses
due
to
in
utero
tebuthiuron
exposure.
However,
there
is
an
adequate
developmental
toxicity
study
in
the
rat
and
a
twogeneration
reproductive
toxicity
study
in
the
rat
to
assess
the
susceptibility
of
fetuses/
offspring
to
tebuthiuron.
The
Committee
reserved
the
requirement
of
a
developmental
neurotoxicity
study
due
to
the
data
gap
for
a
developmental
toxicity
study
in
rabbits.

B.
Determination
of
Susceptibility
There
is
no
qualitative/
quantitative
evidence
of
increased
susceptibility
in
the
2­
generation
reproduction
study
in
the
rat
or
the
developmental
toxicity
study
in
the
rat.
In
the
developmental
toxicity
study
in
the
rabbit,
no
maternal
or
developmental
toxicity
was
observed
at
the
highest
dose
tested.
Because
there
was
no
toxicity
observed
at
the
highest
dose
tested,
susceptibility
could
not
be
ascertainted
and
the
HIARC
concluded
that
a
new
developmental
toxicity
in
the
rabbit
is
needed.

II.
EXPOSURE
ASSESSMENT
(Correspondence:
S.
Piper
to
C.
Christensen
dated
January
31,
2002)

A.
Dietary
Exposure
Considerations
Tebuthiuron
is
an
herbicide
registered
for
use
on
pastures
and
rangeland.
The
chemical
is
registered
for
a
single
broadcast
application
to
rangeland
and
forage
grasses
by
ground
or
air
equipment
with
an
application
rate
of
0.75­
4.00
lb
ai/
A.
The
recommended
timing
of
application
is
prior
to
the
resumption
of
active
seasonal
growth
in
the
spring
or
before
expected
seasonal
rainfall.
Tolerances
range
from
0.8­
5.0
ppm
for
secondary
residues
and
10
ppm
for
forage.
There
are
no
Codex
MRLs
established
or
proposed
for
residues
of
tebuthiuron.
Therefore,
issues
of
compatibility
with
respect
to
U.
S.
tolerances
and
Codex
MRLs
do
not
exist.

The
qualitative
nature
of
the
residue
in
grasses
is
adequately
understood.
The
residues
of
concern
are
the
parent
compound
and
its
metabolites
103(
OH),
104,
and
109.
The
terminal
residues
of
concern
in
fat,
meat,
kidney,
and
liver
are
tebuthiuron
and
its
metabolites
104,
106,
108
and
109;
the
terminal
residues
of
concern
in
milk
are
3
tebuthiuron
and
metabolites
104,
104(
OH),
106,
109
and
109(
OH).
Tebuthiuron
is
a
systemic
soil
herbicide
that
is
absorbed
mainly
by
the
roots,
with
ready
translocation.

There
are
no
monitoring
data
(PDP
or
FDA)
for
Tebuthiuron.
Percent
of
crop
treated
information
is
available
for
use
in
the
assessment.
A
DEEM
Tier
II
analysis
will
likely
be
used
to
assess
dietary
exposure
to
this
chemical
using
the
results
of
field
trial
studies
and
percent
of
crop
treated
data.

The
Committee
recognizes
that
further
refinement
to
the
dietary
food
exposure
analyses
may
be
required
as
the
risk
assessment
is
developed.
Therefore,
provided
the
final
dietary
food
exposure
assessment
includes
the
metabolites
of
toxicological
concern
and
does
not
underestimate
the
potential
risk
for
infants
and
children,
the
safety
factor
recommendations
of
this
Committee
stand.

B.
Drinking
Water
Exposure
Considerations
The
environmental
fate
database
is
essentially
complete
for
parent
tebuthiuron.
Tebuthiuron
water
degradate
104
was
detected
at
6.9%
and
rising
by
the
end
of
the
study.
The
HED
Metabolism
Assessment
and
Review
Committee
(MARC)
recommended
degradate
104
be
included
in
the
water
exposure
and
risk
assessment.
Based
on
the
available
data,
the
parent
and
degradate
104
are
persistent
and
mobile.
The
quickest
observed
route
of
tebuthiuron
degradation
in
laboratory
studies
was
soil
photolysis
halflife
39.7
days.)

Tebuthiuron
has
been
assessed
through
a
combination
of
modeling
and
analysis
of
surface
water
and
ground
water
monitoring
data.
Drinking­
water
monitoring
results
are
not
available
for
the
chemical
for
direct
quantitative
incorporation
into
the
exposure
and
risk
assessment.
Therefore,
drinking
water
exposure
assessments
are
supplemented
with
modeling
predictions.
Surface
water
concentrations
of
tebuthiuron
were
modeled
using
the
PRZM/
EXAMS
(Tier
II)
programs
for
pasture/
rangeland
using
EFED's
standard
scenario
for
alfalfa
in
Texas.
Groundwater
concentrations
were
modeled
using
the
SCIGROW
program.
Input
parameters
used
Tier
II
(PRZM
version
3.12/
EXAMS
version
2.97.5)
modeling
were
selecting
using
Agency
guidance
and
EFED
calculated
degradation
rate
constants
from
review
of
registrant
submitted
environmental
fate
studies.
This
assessment
strategy
was
designed
to
assess
concentrations
of
the
parent
compound.

In
order
to
account
for
the
degradate
of
toxicological
concern,
EFED
will
complete
modeling
of
the
degradate
using
the
total
residue
approach.
Total
residues
(parent
plus
all
degradates
of
toxicological
concern)
are
summed
from
fate
studies.
In
this
case
fate
parameters
are
estimated
for
total
residues
for
aerobic
soil
metabolism,
aerobic
aquatic
metabolism,
anaerobic
soil
metabolism,
and
photolysis.
Other
required
fate
parameters
are
conservatively
estimated
as
stable
in
accordance
with
EFED
guidance.
This
method
4
provides
conservative
estimates
of
total
residues
(parent
plus
degradates)
in
surface
and
ground
water.
Drinking
water
monitoring
data
support
the
results
of
the
drinking
water
models.

The
FQPA
Safety
Factor
Committee
recognizes
that
further
refinement
to
the
dietary
water
exposure
analyses
may
be
required
as
the
risk
assessment
is
developed.
Therefore,
provided
the
final
dietary
water
exposure
assessment
includes
the
metabolite
of
toxicological
concern
and
does
not
underestimate
the
potential
risk
for
infants
and
children,
the
safety
factor
recommendations
of
this
Committee
stand.

C.
Residential
Exposure
Considerations
There
are
no
registered
residential
uses
for
tebuthiuron.

III.
RISK
CHARACTERIZATION
A.
FQPA
Safety
Factor
Recommendation
The
Committee
recommended
that
the
FQPA
Safety
factor
for
enhanced
sensitivity
to
infants
and
children
(as
required
by
FQPA)
should
be
reduced
(3x).

A.
Rationale
for
Reducing
the
FQPA
Safety
Factor
The
Committee
concluded
that
the
safety
factor
could
be
reduced
for
Tebuthiuron
because:

1.
There
is
no
indication
of
quantitative
or
qualitative
increased
susceptibility
of
rats
to
in
utero
exposure;
2.
There
is
no
indication
of
quantitative
or
qualitative
increased
susceptibility
of
rat
offspring
seen
in
the
two­
generation
reproductive
toxicity
study;
3.
The
dietary
(food
and
drinking
water)
exposure
assessments
will
not
underestimate
the
potential
exposures
for
infants
and
children.

However,
the
Committee
decided
that
a
factor
is
needed
(3x)
because
of
the
data
gap
for
a
developmental
toxicity
study
in
the
rabbit.
5
C.
Application
of
the
FQPA
Safety
Factor:

Acute
Dietary
Exposure
(Females
13­
50):
When
assessing
acute
dietary
exposure
to
females
13­
50,
the
reduced
FQPA
safety
factor
of
3x
will
be
used.
This
is
because
there
is
a
data
gap
for
assessing
susceptibility
of
fetuses
following
in
utero
exposure
to
tebuthiuron.

Chronic
Dietary
Exposure
(General
Population):
When
assessing
chronic
dietary
exposure
to
the
general
population,
the
FQPA
safety
factor
will
be
removed
(1x).
This
is
because
there
was
no
susceptibility
identified
in
the
2­
generation
rat
reproduction
study
(a
long­
term
study).
