1
TXR
NO.
0050322
December
6,
2001
MEMORANDUM
SUBJECT:
LINURON:
Report
of
the
FQPA
Safety
Factor
Committee.

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

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

TO:
Carol
Christensen,
Risk
Assessor
Registration
Action
Branch
2
Health
Effects
Division
(7509C)

PC
Code:
035506
The
Health
Effects
Division
(HED)
FQPA
Safety
Factor
Committee
met
on
November
26,
2001
to
evaluate
the
hazard
and
exposure
data
for
linuron
and
recommended
that
the
FQPA
safety
factor
(as
required
by
the
Food
Quality
Protection
Act
of
August
3,
1996)
be
retained
when
assessing
the
risks
posed
from
the
use
of
this
pesticide.

I.
HAZARD
ASSESSMENT
2
(Correspondence:
R.
Fricke
to
C.
Christensen,
October
31,
2001)

1.
Adequacy
of
Toxicity
Database
The
toxicology
data
base
for
linuron
is
complete
for
FQPA
assessment.
The
toxicology
data
bases
for
linuron
were
reviewed
by
the
Hazard
Identification
Assessment
Review
Committee
(HIARC)
on
September
13
th
and
27
th
.
Prenatal
developmental
toxicity
studies
in
the
rat
and
rabbit
and
a
two­
generation
reproduction
study
are
available
with
linuron.

2.
Determination
of
Susceptibility
There
is
no
qualitative/
quantitative
evidence
of
increased
susceptibility
in
the
rabbit
developmental
study;
developmental
effects
were
seen
at
a
dose
higher
than
that
causing
maternal
toxicity.
In
the
rat
developmental
study,
increases
in
post­
implantation
losses
and
increases
in
fetal
resorptions/
litter
were
seen
a
dose
that
caused
decreases
in
maternal
body
weight
and
food
consumption.
The
HIARC
determined
that
the
developmental
effects
are
not
a
concern
for
qualitative
evidence
of
susceptibility,
since
increases
in
resorptions
were
marginal
and
there
was
no
change
in
the
number
of
live
fetuses
to
corroborate
the
increases
in
post­
implantation
losses.

There
was
no
quantitative
evidence
of
susceptibility
either
in
the
2­
generation
or
the
3­
generation
reproduction
studies.
In
the
2­
generation
study,
reduced
body
weight
gains
of
pups
were
seen
at
the
same
dose
that
caused
decreases
in
parental
body
weights.
In
the
3­
generation
study,
offspring
effects
(deceased
pup
survival
and
pup
body
weight)
were
seen
a
dose
higher
than
the
dose
that
caused
decreases
in
body
weight
gain
in
the
parental
animals.

In
both
the
2­
generation
and
the
3­
generation
rat
reproductive
toxicity
studies,
testicular
atrophy
was
seen
at
the
same
dose
that
caused
parental/
systemic
toxicity.
However,
the
HIARC
determined
that
these
lesions
were
of
a
concern
and
provide
qualitative
evidence
of
increased
susceptibility
because
in
both
studies
they
were
seen
in
the
F1
males
but
not
in
F0
males.
This
indicates
an
adverse
effect
on
the
male
reproductive
system
of
the
F1
generation.

3.
Requirement
of
a
Developmental
Neurotoxicity
Study
The
HIARC
concluded
that
a
development
neurotoxicity
study
in
the
rat
is
required
by
the
available
evidence.
This
conclusion
is
based
on
the
findings
that
linuron
is
a
potential
endocrine
disruptor,
as
evidenced
by
the
observation
of
increased
testicular
lesions
and
decreased
fertility
in
the
reproduction
studies.

II.
EXPOSURE
ASSESSMENT
AND
RISK
CHARACTERIZATION
3
1.
Dietary
(Food)
Exposure
Considerations
(Correspondence:
J.
Punzi
to
C.
Christensen,
November
15,
2001)

Linuron
is
registered
for
pre­
plant
and
postemergent
use
on
the
following
crops:
asparagus,
carrots,
celery,
corn
(field
&
sweet),
cotton,
parsley,
potato,
sorghum,
soybean,
and
wheat.
The
rates
of
application
range
from
0.5­
4
lb
ai/
A/
yr
and
may
be
applied
1
or
2
times
per
year.
Linuron
is
mainly
early
season
but
a
few
crops
have
short
PHI's
(notably
asparagus
(1
day)
and
carrot
(14
day)).
There
are
no
Codex,
Canadian,
or
Mexican
MRL's
for
this
chemical.

Due
to
the
data
collection
methods,
linuron
and
metabolites
convertible
to
3,4­
dichloroanaline
require
regulation.
Residues
of
linuron
are
systemic,
however,
washing
will
remove
some
of
the
residue
in
some
instances.
Linuron
residues
are
persistent.

Monitoring
data
are
available
for
this
chemical,
however,
both
PDP
and
FDA
look
for
the
parent
only.
In
PDP
data
detection
rates
for
carrots
are
about
35
%
and
residues
frequently
found
at
0.2
and
0.3
ppm.
Field
trial
residue
data
corrected
for
percent
of
crop
treated
will
be
used
to
estimate
exposure.
Residue
reduction
studies
are
available
for
asparagus
(washing,
boiling)
and
carrot
and
potato
(cooking)
and
will
be
used
to
assess
the
dietary
exposure
for
linuron.

Carrots,
meats,
and
milk
will
contribute
significantly
to
the
diet.
Feeding
studies
indicate
tolerances
are
needed
for
meats
and
milk,
linuron
is
registered
on
many
feed
crops.
The
dietary
exposure
assessment
is
considered
Tier
3.
It
will
include
field
trial
data
corrected
for
percent
of
crop
treated
and
the
translation
of
cooking
studies
to
various
foods.

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
regulatory
concern
and
does
not
underestimate
the
potential
risk
for
infants
and
children,
the
safety
factor
recommendations
of
this
Committee
stand.

2.
Dietary
(Drinking
Water)
Exposure
Considerations
(Correspondence:
I.
Abdel­
Saheb
to
C.
Christensen,
dated
November
20,
2001)

The
environmental
fate
data
base
for
parent
linuron
is
complete
for
FQPA
assessment.
Parent
linuron
appears
to
be
moderately
persistent
and
relatively
immobile.
Information
on
the
persistence,
mobility
and
dissipation
pathways
of
several
degradates
of
linuron
is
limited.
However,
EFED
believes
that
there
is
no
reason
to
believe
that
the
EECs
produced
for
the
drinking
water
for
linuron
will
underestimate
the
risk
from
its
major
degradates.
Estimate
are
conservative
because
the
metabolites
are
formed
under
aerobic
soil
metabolism
conditions
at
low
percentages
and,
therefore,
no
significant
changes
to
the
parent
water
numbers
would
result
due
to
degradation.
4
A
combination
of
modeling
and
monitoring
data
were
used
in
the
assessment.
The
Tier
II
screening
models
PRZM­
EXAMS
with
the
Index
Reservoir
and
Percent
Crop
Area
adjustment
(IR­
PCA
PRZM/
EXAMS)
were
used
to
determine
estimated
surface
water
concentrations
of
linuron.
The
Screening
Concentration
in
Groundwater
(SCI­
GROW)
model
was
used
to
estimate
groundwater
concentrations
for
linuron.
However,
because
SCI­
GROW
estimated
concentrations
of
linuron
were
less
than
those
from
monitoring
data,
EFED
recommends
using
monitoring
results
in
the
groundwater
drinking
water
assessment.

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
adequately
assesses
for
metabolites
of
concern
in
drinking
water
and
does
not
underestimate
the
potential
risk
for
infants
and
children,
the
safety
factor
recommendations
of
this
Committee
stand.

3.
Residential
Exposure
Considerations
There
are
no
registered
residential
uses
of
linuron.
5
III.
SAFETY
FACTOR
RECOMMENDATION
AND
RATIONALE
1.
FQPA
Safety
Factor
Recommendation
The
Committee
recommended
that
the
FQPA
safety
factor
for
protection
of
infants
and
children
(as
required
by
FQPA)
should
be
retained.

2.
Rationale
for
Requiring
the
FQPA
Safety
Factor
The
FQPA
SFC
concluded
that
a
safety
factor
is
required
because:

1.
A
qualitative
increase
in
susceptibility
seen
in
the
F1
males
in
the
rat
reproductive
toxicity
study;
and
2.
A
developmental
neurotoxicity
study
in
rats
is
required
for
the
chemical
because
linuron
is
a
potential
endocrine
disruptor
and
there
is
evidence
for
testicular
lesions
and
decreased
fertility
in
the
rat
reproductive
toxicity
study.

However,
the
Committee
concluded
that
the
safety
factor
could
be
reduced
to
3x
for
linuron
because:

1.
The
toxicology
database
is
complete;
2.
The
dietary
(food
and
water)
exposure
assessments
will
not
underestimate
the
potential
exposures
for
infants,
children,
and/
or
women
of
childbearing
age;
and,
3.
There
are
no
residential
uses.

3.
Application
of
the
Safety
Factor
­
Population
Subgroups
/
Risk
Assessment
Scenarios
Females
13­
50
Population
Subgroup:
When
assessing
Acute
Dietary
exposure,
the
safety
factor
should
be
reduced
to
3x
since
the
developmental
neurotoxicity
study
in
rats
is
required.
The
developmental
neurotoxicity
study
may
further
define
the
neurotoxic
(neuro­
endocrine)
potential
observed
in
rats
that
were
exposed
in
pre­
and
post­
natal
time
periods.

All
Population
Subgroups:
When
assessing
Chronic
Dietary,
the
safety
factor
should
be
Retained
at
10x
since
there
is
concern
for
the
qualitative
increase
in
susceptibility
observed
in
the
rat
reproductive
toxicity
study,
and,
since
the
developmental
neurotoxicity
study
in
rats
is
required.
The
developmental
neurotoxicity
study
may
further
define
the
neurotoxic
(neuro­
endocrine)
potential
observed
in
rats
due
to
pre­
and
post­
natal
exposure.
