Document ID: EPA-HQ-OPP-2005-0056-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-04-12T04:00Z

Page
1
of
55
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
March
3,
2006
MEMORANDUM
SUBJECT:
Pendimethalin:
REVISED
HED
Human
Health
Risk
Assessment
to
Support
Section
3
Registration
for
use
on
Carrots,
Mint,
Citrus,
and
Tree
Nuts.
PC
Code:
108501;
DP
Barcode
No.:
D3125176.

Regulatory
Action:
Section
3
Registration
Risk
Assessment
Type:
Single
Chemical
Aggregate
FROM:
Margarita
Collantes
Registration
Action
Branch
2
Health
Effects
Division
(
7509C)

AND
Zaida
Figueroa
Karlyn
Bailey
Christina
Swartz
Registration
Action
Branch
2
Health
Effects
Division
(
7509C)

THROUGH:
Richard
A.
Loranger,
Ph.
D.,
Branch
Senior
Scientist
Registration
Action
Branch
2
Health
Effects
Division
(
7509C)

TO:
Jim
Tompkins
Herbicide
Branch
Registration
Division
(
7505C)
Page
2
of
55
Table
of
Contents
1.0
Executive
Summary
.
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4
2.0
Ingredient
Profile
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11
2.1
Summary
of
Registered/
Proposed
Uses
.
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11
2.2
Structure
and
Nomenclature
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13
2.3
Physical
and
Chemical
Properties
.
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13
3.0
Metabolism
Assessment
.
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14
3.1
Comparative
Metabolic
Profile
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14
3.2
Nature
of
the
Residue
in
Foods
.
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14
3.2.1.
Description
of
Primary
Crop
Metabolism
.
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14
3.2.2
Description
of
Livestock
Metabolism
.
.
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15
3.2.3
Description
of
Rotational
Crop
Metabolism,
including
identification
of
major
metabolites
and
specific
routes
of
biotransformation
.
.
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15
3.3
Environmental
Degradation
.
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15
3.4
Toxicity
Profile
of
Major
Metabolites
and
Degradates
.
.
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15
3.5
Summary
of
Residues
for
Tolerance
Expression
and
Risk
Assessment
.
.
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.
16
3.5.1
Tabular
Summary
.
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16
4.0
Hazard
Characterization/
Assessment
.
.
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16
4.1
Hazard
Characterization
.
.
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16
4.2
FQPA
Hazard
Considerations
.
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22
4.2.1
Adequacy
of
the
Toxicity
Data
Base
.
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22
4.2.2
Evidence
of
Neurotoxicity
.
.
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23
4.2.3
Developmental
Toxicity
Studies
.
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23
4.2.4
Reproductive
Toxicity
Study
.
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23
4.2.5
Additional
Information
from
Literature
Sources
.
.
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24
4.2.6
Pre­
and/
or
Postnatal
Toxicity
.
.
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24
4.2.6.1
Determination
of
Susceptibility
.
.
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.
24
4.2.6.2
Degree
of
Concern
Analysis
and
Residual
Uncertainties
for
Pre
and/
or
Post­
natal
Susceptibility
.
.
.
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24
4.3
Recommendation
for
a
Developmental
Neurotoxicity
Study
.
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25
4.4
Hazard
Identification
and
Toxicity
Endpoint
Selection
.
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25
4.4.1
Acute
Reference
Dose
(
aRfD)
­
Females
age
13­
49
.
.
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25
4.4.2
Acute
Reference
Dose
(
aRfD)
­
General
Population
.
.
.
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.
25
4.4.3
Chronic
Reference
Dose
(
cRfD)
.
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25
4.4.4
Incidental
Oral
Exposure
(
Short
and
Intermediate
Term)
.
.
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.
26
4.4.5
Dermal
Absorption
.
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26
4.4.6
Dermal
Exposure
(
Short,
Intermediate
and
Long
Term)
.
.
.
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.
.
.
26
4.4.7
Inhalation
Exposure
(
Short,
Intermediate
and
Long
Term)
.
.
.
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26
4.4.8
Margins
of
Exposure
.
.
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26
4.4.9
Recommendation
for
Aggregate
Exposure
Risk
Assessments
.
.
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.
27
4.4.10
Classification
of
Carcinogenic
Potential
.
.
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27
4.5
Special
FQPA
Safety
Factor
.
.
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.
29
Page
3
of
55
4.6
Endocrine
disruption
.
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29
5.0
Public
Health
Data
.
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30
5.1
Incident
Reports
.
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30
6.0
Exposure
Characterization/
Assessment
.
.
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30
6.1
Dietary
Exposure/
Risk
Pathway
.
.
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30
6.1.1
Residue
Profile
.
.
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30
6.1.2
Acute
and
Chronic
Dietary
Exposure
and
Risk
.
.
.
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.
31
6.2
Water
Exposure/
Risk
Pathway
.
.
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32
6.3
Residential
(
Non­
Occupational)
Exposure/
Risk
Pathway
.
.
.
.
.
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33
6.3.1
Home
Uses
.
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33
6.3.1.1
Residential
Handler
.
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33
6.3.1.2
Residential
Postapplication
.
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33
6.3.1.2.1
Dermal
Exposure
.
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34
6.3.1.2.2
Inhalation
Exposure
.
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35
6.3.1.2.3
Oral
Exposure
.
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35
6.3.1.2.4
Aggregate
Residential
Exposure
.
.
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37
6.3.2
Recreational
Uses
.
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39
6.3.3
Other
(
Spray
Drift,
etc.)
.
.
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39
7.0
Aggregate
Risk
Assessments
and
Risk
Characterization
.
.
.
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39
7.1
Acute
Aggregate
Risk
.
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40
7.2
Short­
Term
Aggregate
Risk
.
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40
7.3
Intermediate­
Term
Aggregate
Risk
.
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42
7.4
Long­
Term
Aggregate
Risk
.
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42
7.5
Cancer
Risk
.
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43
8.0
Cumulative
Risk
Characterization/
Assessment
.
.
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43
9.0
Occupational
Exposure/
Risk
Pathway
.
.
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43
9.1
Agricultural
and
Commercial
Handler
Risk
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43
9.2
Agricultural
Postapplication
Risk
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45
9.3
Commercial
Postapplication
Risk
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45
10.0
Data
Needs
and
Label
Requirements
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49
10.1
Toxicology
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49
10.2
Residue
Chemistry
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49
10.3
Occupational
and
Residential
Exposure
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49
References:
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50
Appendices
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51
Page
4
of
55
1.0
Executive
Summary
A
human
health
risk
assessment
has
been
conducted
to
support
a
proposed
Section
3
registration
and
associated
tolerances
for
the
herbicide
pendimethalin
on
carrots,
mint,
citrus
and
tree
nuts.
Pendimethalin
is
a
selective
herbicide
registered
for
control
of
broadleaf
weeds
and
grassy
weed
species
on
a
variety
of
agricultural
crops,
turf
and
ornamentals.
It
is
a
meristematic
inhibitor
that
interferes
with
the
plant's
cellular
division
of
mitosis,
and
is
generally
applied
early
in
the
growing
season.

Toxicology
The
toxicology
database
is
adequate
to
support
the
proposed
uses
for
pendimethalin.
The
scientific
quality
of
the
database
for
pendimethalin
is
relatively
high
and
the
toxicity
profile
can
be
characterized
for
a
wide
range
of
effects,
including
potential
developmental,
reproductive
and
neurotoxic
effects.
However,
HED
has
requested
a
developmental
thyroid
assay
to
characterize
thyroid
effects
in
developing
offspring,
which
are
not
typically
tested
in
guideline
studies.

The
database
characterizes
pendimethalin
as
having
low
acute
oral,
dermal,
and
inhalation
toxicity.
It
is
classified
in
Toxicity
Category
IV
for
acute
dermal
toxicity,
acute
inhalation
toxicity,
and
primary
dermal
irritation;
Toxicity
Category
III
for
acute
oral
and
primary
eye
irritation;
it
is
not
a
dermal
sensitizer.

The
thyroid
is
a
target
organ
for
pendimethalin.
Thyroid
toxicity
in
chronic
and
subchronic
rat
and
mouse
studies
was
manifested
as
alterations
in
thyroid
hormones
(
decreased
Total
T4,
and
T3,
increased
percent
of
free
T4
and
T3),
increased
thyroid
weight,
and
microscopic
thyroid
lesions.

No
appropriate
endpoint
attributable
to
a
single
exposure
was
identified
from
the
oral
toxicity
studies
including
developmental
toxicity
studies
in
rats
and
rabbits.
Therefore,
an
acute
reference
dose
(
aRfD)
was
not
established.
The
following
three
studies:
92­
day
thyroid
function
in
rats,
56­
day
thyroid
function
in
rats
and
14­
day
intra­
thyroid
metabolism
study
in
rats
were
considered
together
to
select
the
dose
and
endpoint
for
establishing
the
chronic
reference
dose
(
cRfD)
of
0.03
mg/
kg/
day.
The
cRfD
is
derived
from
the
NOAEL
of
10
mg/
kg/
day
for
thyroid
effects
based
on
hormonal
and
histological
changes
in
the
thyroid
observed
at
the
LOAEL
of
31
mg/
kg/
day
and
a
combined
uncertainty
factor
of
300.

The
same
three
studies
conducted
in
rats
were
used
for
dose
and
endpoint
selection
for
all
durations
of
dermal
and
inhalation
exposure,
with
a
NOAEL
of
10
mg/
kg/
day,
and
a
LOAEL
of
31
mg/
kg/
day.
Furthermore,
these
three
studies
were
considered
appropriate
for
dose
and
endpoint
selection
for
incidental
oral
exposures
to
infants
and
children
following
application
of
pendimethalin
in
residential
settings
(
turf).
A
dermal
absorption
factor
of
3%
and
an
inhalation
absorption
factor
of
100%
were
used.
Since
both
dermal
and
inhalation
endpoints
were
based
on
the
same
toxicological
effects,
these
route­
specific
Margins
of
Exposure
(
MOEs)
were
combined
Page
5
of
55
into
a
total
MOE.

Pendimethalin
is
classified
as
a
"
Group
C",
possible
human
carcinogen,
chemical
based
on
a
statistically
significant
increased
trend
and
pair­
wise
comparison
between
the
high
dose
group
and
controls
for
thyroid
follicular
cell
adenomas
in
male
and
female
rats.
A
non­
quantitative
approach
(
i.
e.,
non­
linear,
RfD
approach)
was
recommended
by
the
Cancer
Peer
Review
Committee
since
mode
of
action
studies
are
available
that
demonstrate
that
the
thyroid
tumors
are
due
to
a
thyroidpituitary
imbalance.

There
are
no
neurotoxicity
studies
available
for
pendimethalin;
however,
there
are
no
neurotoxic
clinical
signs,
changes
in
brain
weight,
or
histopathology
of
the
nervous
system
in
any
study
with
pendimethalin.
Neurotoxicity
studies
for
pendimethalin
are
not
required
based
on
the
chemical
characteristics.

Both
the
rat
and
rabbit
developmental
toxicity
studies
indicated
no
maternal
or
developmental
toxicity
at
the
highest
doses
tested,
500
mg/
kg/
day
in
the
rat
and
60
mg/
kg/
day
in
the
rabbit.
In
a
2­
generation
rat
reproduction
study
with
pendimethalin,
there
was
no
evidence
of
susceptibility
to
offspring,
with
similar
parental
systemic
and
reproductive/
offspring
NOAELs
(
25
mg/
kg/
day)
and
LOAELs
(
125
mg/
kg/
day).
Systemic
parental
effects
included
decreased
body
weight
gain
and
food
consumption,
and
reproductive/
offspring
effects
included
decreases
in
the
number
of
pups
born
and
pup
body
weights.

There
are
acceptable
studies
to
satisfy
the
initial
mutagenicity
testing
requirements
for
all
three
categories
(
gene
mutations,
structural
chromosomal
aberrations,
and
other
genotoxic
effects).
The
positive
Salmonella
results
in
one
study
indicated
that
pendimethalin
may
have
potential
genotoxic
activity.
However,
subsequent
assays
for
germ
cell
effects
(
Chinese
hamster
ovary
cells
and
rat
testicular
cells)
and
additional
Salmonella
assays
submitted
to
address
this
concern
were
all
negative.
Pendimethalin
is
not
considered
to
be
mutagenic.

There
were
no
appropriate
dermal
absorption
data
available
for
pendimethalin;
therefore,
based
on
data
from
stucturally
similar
active
ingredients
which
indicated
a
maximum
dermal
absorption
of
2.8%,
an
estimate
of
3%
was
assumed
when
calculating
dermal
risks.

FQPA
and
Uncertainty
Factor
Concerns
Although
it
was
not
possible
to
determine
the
potential
for
susceptibility
from
the
rat
and
rabbit
developmental
studies
(
no
adverse
effects
observed
at
doses
tested),
these
studies
were
considered
adequate,
and
no
additional
developmental
toxicity
studies
are
required.
There
was
no
evidence
of
qualitative
or
quantitative
susceptibility
in
a
2­
generation
reproduction
study
conducted
in
the
rat,
and
there
was
no
evidence
of
neurotoxicity
in
the
submitted
studies.
Therefore,
HED
has
recommended
the
10X
special
FQPA
safety
factor
be
removed
(
reduced
to
1X).
Page
6
of
55
Hormonal
changes
(
alterations
in
thyroid
weights
and
histopathological
lesions)
were
observed
in
several
studies
following
oral
administration
of
pendimethalin
and
it
is
likely
that
these
changes
may
cause
disruption
in
the
endocrine
system.
There
is
concern
that
perturbation
of
thyroid
homeostasis
may
lead
to
hypothyroidism,
and
possibly
result
in
adverse
effects
on
the
developing
nervous
system.
Consequently,
HED
has
recommended
that
a
developmental
thyroid
assay
be
conducted
to
evaluate
the
impact
of
pendimethalin
on
thyroid
hormones,
structure,
and/
or
thyroid
hormone
homeostasis
during
development.
Furthermore,
HED
has
recommended
that
a
10X
database
uncertainty
factor
(
UF
DB
)
be
retained
pending
receipt
of
the
study.

The
standard
10X
intraspecies
uncertainty
factor
and
a
3X
interspecies
factor
are
applicable
to
pendimethalin
risk
assessments.
The
interspecies
uncertainty
factor
of
10X
was
reduced
to
3X
due
to
the
greater
sensitivity
of
the
adult
rat
to
thyroid
effects
compared
to
the
adult
humans.
Because
of
toxicodynamic
differences
in
adult
thyroid
function
that
result
in
greater
sensitivity
of
the
adult
rat
to
hypothyroidism
compared
to
adult
humans,
the
3x
(
3.16)
toxicodynamic
part
of
the
10X
can
be
removed
leaving
the
3X
(
3.16)
portion
for
toxicokinetic
interspecies
differences
(
Interim
Guidance
on
Thyroid
Disrupting
Pesticides,
dated
11/
1/
05).
Thus,
the
usual
100X
uncertainty
factor
for
intra­
and
interspecies
differences
is
reduced
to
30X.
A
10X
database
uncertainty
factor
(
UF
DB
)
was
retained
pending
submission
of
the
developmental
thyroid
toxicity
study.
The
level
of
concern
(
target
MOE)
for
occupational
exposure
is
30X,
while
the
target
MOE
for
residential
exposure
is
300X.

Residue
Chemistry
The
nature
of
the
residue
in
plants,
livestock
and
rotational
crops
is
adequately
understood.
Residues
of
concern
in
plants
for
tolerance
enforcement
and
risk
assessment
purposes
are
the
parent
pendimethalin
and
its
3,5­
dinitrobenzyl
alcohol
metabolite;
in
peanut
hulls,
the
residue
of
concern
also
includes
2,4­
dinitrobenzyl
alcohol
metabolite.
The
residue
of
concern
in
drinking
water
is
pendimethalin,
per
se.
The
Agency
has
determined
that
there
is
no
reasonable
expectation
of
finite
pendimethalin
residues
of
concern
in
animal
commodities
(
40
CFR
§
180.6(
a)(
3)).
Tolerances
for
pendimethalin
residues
of
concern
in
animal
commodities
are
not
needed.

In
general,
adequate
field
trials,
storage
stability
data,
analytical
methods
and
processing
studies
are
available
to
support
the
proposed
uses
on
citrus,
mint,
tree
nuts
and
carrots.
In
addition,
adequate
enforcement
methods
are
available.
Additional
field
trial
data
for
citrus
are
required
as
a
condition
of
registration.
In
general,
residue
data
indicate
that
pendimethalin
and
metabolite
residues
are
low
or
nondetectable;
however,
concentration
has
been
observed
in
processed
commodities.

Dietary
Exposure
Dietary
risk
assessments
were
conducted
using
the
Dietary
Exposure
Evaluation
Model
(
DEEMFCID
 
)
and
the
LifeLine
 
Model,
both
of
which
use
food
consumption
data
from
the
USDA's
Page
7
of
55
Continuing
Surveys
of
Food
Intakes
by
Individuals
(
CSFII)
from
1994­
1996
and
1998.
For
both
the
DEEM­
FCID
 
and
LifeLine
 
assessments,
tolerance­
level
residues
were
assumed
for
all
food
commodities
with
current
and
proposed
pendimethalin
tolerances,
and
it
was
assumed
that
all
of
the
crops
included
in
the
analyses
were
treated
(
i.
e.
100%
crop
treated).

The
two
models
provided
similar
estimates
of
chronic
dietary
exposure
and
risk.
The
most
highly
exposed
population
subgroup
was
children
1­
2
years
old.
The
chronic
exposure
estimate
of
approximately
0.002
mg/
kg/
day
corresponds
to
6%
cPAD.
Risks
for
the
general
US
population
and
all
other
population
subgroups
were
lower.
Acute
dietary
exposure
estimates
were
not
generated,
due
to
a
lack
of
an
acute
dietary
endpoint
and
dose
for
risk
assessment.

Drinking
Water
Exposure
The
Environmental
Fate
and
Effects
Division
(
EFED)
performed
a
drinking
water
assessment
for
pendimethalin,
based
on
the
proposed
uses
considered
in
this
assessment,
as
well
as
additional
proposed
uses
for
which
residue
chemistry
data
have
been
submitted
but
not
reviewed.
It
was
determined
that
the
parent
pendimethalin
is
the
only
significant
non­
volatile
residue,
therefore,
the
estimated
drinking
water
concentrations
(
EDWCs)
were
calculated
for
parent
pendimethalin
only.
For
surface
water
sources
of
drinking
water,
the
acute
(
peak)
water
concentration
is
38.8
parts
per
billion
(
ppb),
4.8
ppb
for
chronic
(
non­
cancer)
and
3.8
ppb
for
cancer.
The
groundwater
screening
concentration
was
0.024
ppb.

Residential
(
non­
occupational)
Exposure
This
residential
exposure
assessment
will
only
re­
evaluate
exposure
resulting
from
residential
turf/
lawn
uses.
A
complete
residential
exposure
assessment
for
pendimethaline
was
previously
performed
in
the
1996
reregistration
eligibility
decision
(
RED)
document
(
J.
Leahy,
D221532,
February
20,
1996).
The
MOEs
for
residential
handlers
wearing
baseline
attire
were
all
greater
then
the
level
concern
(
MOE
=
300).

Handlers
Since
the
pendimethalin
RED
was
issued
labels
for
use
of
pendimethalin
on
residential
turf
have
been
revised.
All
turf
(
ornamental,
landscape,
golf
course,
non­
cropland)
labels
appear
to
be
for
commercial
use
only
based
on
the
contents
(
i.
e.
requiring
mixing
tanks,
ground
equipment
for
application,
personal
protective
equipment
and
restricted
entry
intervals).
However
labels
do
not
indicate
for
use
by
licenced
chemical
operator
only.
The
Registration
Division
should
confirm
that
proper
language
clarifying
that
these
products
are
to
be
applied
only
by
commercial
or
licensed
operators.

Postapplication
A
revised
dermal
postapplication
exposure
assessment
was
conducted
using
the
turf
transferable
Page
8
of
55
residue
data
(
TTR's)
from
three
test
sites
(
CA,
PA,
and
FL)
identified
in
the
TTR
study.
The
children's
and
adult's
short­
term
dermal
MOEs
are
all
greater
than
the
level
of
concern
of
300.
All
oral
(
hand­
to­
mouth,
object­
to­
mouth,
and
soil
ingestion)
exposure
MOEs
were
calculated
using
both
the
TTR
data
and
chemical
specific
hand
press
data.
All
oral
MOEs
were
greater
than
the
level
of
concern
of
300.

Ingestion
of
pendimethalin
granules
is
also
a
potential
source
of
exposure
because
children
can
eat
them
if
they
are
found
in
treated
lawns
or
gardens.
This
scenario
is
considered
an
episodic
scenario
by
the
Agency
(
i.
e.,
acute
oral
endpoints
would
be
used
to
estimate
the
risk).
A
risk
assessment
for
this
exposure
scenario
for
children
was
not
conducted
since
an
acute
oral
toxicological
endpoint
of
concern
was
not
identified
for
this
pesticide.

Residential
Aggregate
In
evaluating
the
residential
uses
of
pendimethalin,
HED
has
combined
all
non­
dietary
sources
of
postapplication
exposure
to
obtain
an
estimate
of
potential
aggregate
exposure.
These
scenarios
are
short­
term
in
duration
and
consist
of
dermal
(
adults
and
children)
and
oral
(
hand­
to­
mouth,
object­
to­
mouth
and
soil
ingestion
­
children
only)
exposure.
HED
combines
risk
values
resulting
from
separate
exposure
scenarios
when
it
is
likely
they
can
occur
simultaneously
based
on
the
usepattern
and
the
behavior
associated
with
the
exposed
population.

The
level
of
concern
for
oral,
dermal
and
inhalation
exposure
is
300.
The
aggregate
exposure
estimate
for
adults
(
consisting
of
dermal
exposure
only)
resulted
in
a
total
MOE
of
740
and
therefore
not
of
concern.
The
aggregate
residential
exposure
for
children
resulted
in
a
total
MOE
(
dermal
+
oral)
of
410
at
an
application
rate
of
2
lb
ai/
acre
and
a
MOE
of
400
for
an
application
rate
of
3
lb
ai/
acre.
Residential
aggregate
exposure
was
not
of
concern.

Aggregate
Risk
Estimates
In
the
current
aggregate
assessment,
HED
has
considered
occupational,
dietary
(
food
and
drinking
water)
and
non­
occupational,
non­
dietary
postapplication
exposures,
including
incidental
oral
and
dermal
exposures.
Only
dietary
and
non­
occupational
exposure
and
risk
have
been
included
in
the
aggregate
risk
assessment.
Since
no
toxic
effects
attributable
to
a
single
dose
were
identified
for
pendimethalin,
an
acute
aggregate
risk
assessment
was
not
warranted.
In
estimating
short­
term
aggregate
risk,
HED
combined
the
chronic
dietary
(
food)
exposure
estimate
and
the
total
non­
dietary
exposure
estimates
for
adults
and
children
and
used
the
DWLOC
(
drinking
water
level
of
comparison)
approach
to
determine
aggregate
risk.

For
all
population
subgroups,
the
short­
term
DWLOCs
range
from
666
ppb
(
general
U.
S.
population)
to
72
ppb
(
children
1­
2
years
old),
which
are
greater
than
the
chronic
ground
(
0.024
ppb)
and
surface
water
(
5
ppb)
EDWCs.
Therefore,
aggregate
short­
term
exposure
to
pendimethalin
is
not
of
concern.
The
chronic
aggregate
exposure
estimate
included
dietary
exposure
only
(
food
+
water).
The
chronic
DWLOCs
range
from
423
ppb
(
children
1­
2
years)
to
Page
9
of
55
1029
ppb
(
adults
50+
years)
and
are
greater
then
the
ground
(
0.024
ppb)
and
surface
water
(
5
ppb)
EDWCs,
and
are
therefore
not
of
concern.

Occupational
Exposure
Agricultural
Handler
No
chemical­
specific
data
for
assessing
handler
exposures
were
submitted
to
the
Agency
in
support
of
the
proposed
uses;
therefore,
surrogate
data
from
the
Pesticide
Handlers
Exposure
Data
Base
(
PHED)
Version
1.1,
the
Outdoor
Residential
Exposure
Task
Force
(
ORETF)
and
standard
values
established
by
the
Health
Effects
Division
(
HED)
Science
Advisory
Council
for
Exposure
were
used
for
acres
treated
per
day,
body
weight
and
the
level
of
personal
protective
equipment
worn
by
handlers.

Since
both
dermal
and
inhalation
toxicological
endpoints
were
the
same
for
short­
term
duration,
the
route
specific
MOEs
were
combined
and
compared
to
the
NOAEL
(
10
mg/
kg/
day).
The
total
MOEs
for
short­
term
mixing/
loading
scenarios,
ranged
from
50
at
baseline
to
1,200
using
PPE
level
of
mitigation
(
single
layer
and
gloves),
and
did
not
exceed
HED's
level
of
concern
(
MOEs
<
30).
The
total
MOEs
for
short­
term
applicator
and
flagger
scenarios,
at
baseline
level
of
mitigation
and
engineering
controls
for
aerial
application,
range
from
1,000
to
9,100
and
do
not
exceed
HED's
level
of
concern
(
MOEs
<
30).

Commercial
Handlers
Commercial
handler
exposure
estimates
of
applying
pendimethalin
to
ornamentals,
turf
(
golf
courses)
and
right­
of­
ways
turf
resulted
in
MOEs
greater
than
30
wearing
either
baseline
attire
or
with
the
addition
of
gloves.
Therefore,
commercial
handler
scenarios
were
not
of
concern
to
HED.

Agricultural
Postapplication
Since
these
products
are
herbicides
used
mainly
to
control
pre­
emergent
weeds,
and
not
applied
directly
to
foliage,
postapplication
exposure
is
expected
to
be
minimal.
Based
on
this
information
an
occupational
postapplication
exposure
assessment
was
neither
required
nor
performed.

Commercial
Postapplication
As
indicated
previously,
In
the
1996
RED,
the
following
two
representative
post­
application
commercial
scenarios
were
assessed:
1)
maintenance
worker
exposure
to
golf
course
turf,
and
2)
harvesting
turfgrass
from
a
sod
farm.
Calculations
of
postapplication
exposure
resulted
in
acceptable
MOEs
and
therefore
were
not
of
concern.

Restricted
Entry
Interval
(
REI)
Page
10
of
55
The
restricted
entry
interval
(
REI)
is
based
on
the
acute
toxicity
of
pendimethalin
technical
material
which
is
classified
as
Category
III
and
IV
for
acute
dermal,
dermal
irritation
and
eye
irritation
(
HIARC
Doc.
No.
014116,
April
18,
2000).
Acute
toxicity
Category
III
and
IV
chemicals
for
these
potential
hazards
require
a
12­
hour
REI.
Based
on
the
acute
toxicity
categories
for
this
chemical,
HED
recommends
that
the
current
product
labels
provide
a
12­
hour
REI.

Recommendation
HED
recommends
in
favor
of
the
proposed
uses
of
pendimethalin
on
citrus,
mint,
tree
nuts
and
carrots.
However,
HED
recommends
that
the
registration
be
made
conditional
upon
submission
of
additional
citrus
field
trial
data
to
support
the
citrus
crop
group
tolerance.

HED
recommends
40
CFR
§
180.361
be
revised
to
include
tolerances
for
residues
of
pendimethalin
and
its
metabolite
4­[(
1­
ethylpropyl)
amino]­
2­
methyl­
3,5­
dinitrobenzyl
alcohol
in
or
on
the
following
commodities:

Commodity
Recommended
Tolerance
(
ppm)
Petition
Mint
0.2
7E4878
Mint
Oil
1.0
7E4878
Citrus
0.1
6E4787
Citrus
Oil
0.5
6E4787
Carrots
0.5
6E4603
Almond
Hulls
0.4
0E6083
Tree
Nuts
0.1
0E6083
Data
Gaps
and
Deficiencies
Toxicology
HED
has
requested
the
submission
of
developmental
thyroid
toxicity
data
for
adult
rats
and
young
rats
following
pre­
and
post­
natal
exposure
to
pendimethalin.
Guidance
for
conducting
developmental
thyroid
assays
has
been
developed
by
HED
(
Guidance
for
Thyroid
Assays
in
Pregnant
Animals,
Fetuses
and
Postnatal
Animals,
and
Adult
animals,
dated
October
24,
2005)
in
cooperation
with
the
registrant.
Currently,
BASF
is
in
the
process
of
conducting
the
requested
thyroid
study.

Residue
Chemistry
Page
11
of
55
Additional
field
trial
data
are
needed
to
support
the
citrus
crop
group
tolerance;
the
proposed
uses
on
citrus
and
associated
tolerances
should
be
made
conditional
pending
receipt
of
the
additional
grapefruit
and
lemon
field
trials.

Occupational
and
Residential
Exposure
The
Agency
reiterates
the
recommendation
that
agricultural
handlers
should
wear
chemical­
resistant
gloves
when
mixing/
loading
liquids,
and
when
mixing/
loading
and
applying
with
a
low
pressure
handwand.

2.0
Ingredient
Profile
Pendimethalin
(
N­(
1­
ethylpropyl)­
3,4­
dimethyl­
2,6­
dinitrobenzenamine)
is
a
herbicide
used
to
control
annual
grass
and
broadleaf
weeds
and
belongs
to
the
dinitroaniline
class
of
herbicides.
As
with
other
chemicals
in
this
class,
pendimethalin
is
a
meristematic
inhibitor
that
interferes
with
the
plant's
cellular
division
or
mitosis,
and
it
is
applied
early
in
the
growing
season.
The
petitioner
is
currently
proposing
food/
feed
uses
on
mint,
carrots,
citrus
fruits
and
tree
nuts
for
two
new
end
­
use
products:
PROWL
®
3.3
EC
and
PROWL
®
H
2
O.

2.1
Summary
of
Registered/
Proposed
Uses
Table
2.1.
Summary
of
Pendimethalin
End­
Use
Products.

Trade
Name
Reg.
No.
ai
(%
of
Formulation
Formulation
Type
Target
Crop
Target
Pests
Label
Date
Proposed
Uses
Prowl
®
3.3
EC.
241­
337
37.4
liquid
mint,
carrots,
citrus
fruit
and
tree
nuts
annual
grasses
and
broadleaf
weeds
Feb
11,
1999
PROWL
®
H2O
241­
418
38.7
Mar
26,
2003
Registered
Uses
Pendulum
3.3
EC
241­
241
emulsified
conc.
turf
grass
annual
grasses
and
broadleaf
weeds
Pendulum
WDG
241­
340
60
WDG
Pendulum
2G
241­
375
2
granular
Page
12
of
55
Table
2.2.
Summary
of
Directions
for
Use
of
Pendimethalin.

Trade
Name
Applic.
Type,
and
Equip.
Target
Crop
Applic.
Rate
(
lb
ai/
A)
Max.
No.
Applic.
per
Season
Max.
Seasonal
Applic.
Rate
(
lb
ai/
A)
PHI
(
days)
Use
Directions
and
Limitations
Proposed
Uses
Prowl
®
3.3
EC.

ground,
aerial
and
chemigation
mint
0.743­
1.98
2
1.98
90
24
hour
REI
carrots
1.0
1
1.0
60
apply
as
pre­
emergent
within
2
days
after
planting
;
24
hr
REI
citrus
1.98­
3.96
2
3.96
60
24­
hour
REI
tree
nuts
60­
120
PROWL
®
H2O
ground,
aerial
and
chemigation
mint
0.713­
1.9
2
1.9
90
24­
hour
REI
carrots
0.95
1
0.95
60
apply
as
pre­
emergent
within
2
days
after
planting;
24
hr
REI
citrus
1.9­
3.8
2
3,8
60
24­
hour
REI
tree
nuts
60­
120
Registered
Uses
Pendulum
3.3
EC
turf
grass,
sod
farm,
golf
course
2.0­
3.0
2
3.0
Turf
grass
may
be
treated
at
3.0
lb
ai/
acre
in
spring
prior
to
germination
and
then
repeated
6­
8
weeks
later.
Additional
applications
may
be
made
in
late
summer
or
early
fall.
Pendulum
WDG
Pendulum
2G
Page
13
of
55
NO
2
O
2
N
CH
3
CH
3
N
H
CH
3
C
2
H
5
2.3
Structure
and
Nomenclature
TABLE
2.3.
Test
Compound
Nomenclature
Chemical
Structure
Empirical
Formula
C13H19N3O4
Common
name
pendimethalin
Company
experimental
name
n/
a
IUPAC
name
N­(
1­
ethylpropyl)­
2,6­
dinitro­
3,4­
xylidine
CAS
name
N­(
1­
ethylpropyl)­
3,4­
dimethyl­
2,6­
dinitrobenzenamine
CAS
Registry
Number
40487­
42­
1
End­
use
product/
EP
Chemical
Class
dinitroaniline
herbicide
Known
Impurities
of
Concern
nitrosamines
[
product
chemistry
data
indicate
these
impurities
are
not
present
at
levels
that
are
of
concern].

2.4
Physical
and
Chemical
Properties
Pendimethalin
is
an
orange­
yellow
crystalline
solid
with
a
melting
point
of
54­
58
C.
It
is
soluble
in
chlorinated
hydrocarbons
and
aromatic
solvents
such
as
methylene
chloride,
acetone,
and
xylene,
but
only
soluble
in
water
at
<
0.5
ppm
at
20
C.
Pendimethalin
is
stable
under
acidic
and
alkaline
conditions.
Page
14
of
55
TABLE
2.4.
Physicochemical
Properties
Parameter
Value
Reference
Molecular
Weight
281.3
www.
hclrss.
demon.
co.
uk/

Melting
point/
range
57.7
­
58C
EC
7477/
VI/
98­
final,
1/
13/
2003
pH
4.5­
7
www.
aje.
cc/
e_
about_
aje.
htm
Density
0.85
g/
ml
at
25C
EC
7477/
VI/
98­
final,
1/
13/
2003
Water
solubility
(
20
C)
pH4:
0.54
mg/
l
pH7:
0.33
mg/
l
pH10:
0.44
mg/
l
EC
7477/
VI/
98­
final,
1/
13/
2003
Solvent
solubility
(
temperature
not
specified)
n­
Hexane
=
48.98
g/
l
n
 
Octanol
=
66.08
g/
l
Dichloromethane
>
800
g/
l
Xylene
>
800
g/
l
Ethylacetate
>
800
g/
l
Acetone
>
800
g/
l
EC
7477/
VI/
98­
final,
1/
13/
2003
Vapor
pressure
(
25
C)
1.94
x
10­
3
Pa
EC
7477/
VI/
98­
final,
1/
13/
2003
Dissociation
constant,
pKa
2.8
EC
7477/
VI/
98­
final,
1/
13/
2003
Octanol/
water
partition
coefficient,
logPOW
(
25
C)
5.2
EC
7477/
VI/
98­
final,
1/
13/
2003
UV/
visible
absorption
spectrum
238
nm
=
28775
425
nm
=
5490
EC
7477/
VI/
98­
final,
1/
13/
2003
3.0
Metabolism
Assessment
3.1
Comparative
Metabolic
Profile
Following
administration
to
rats,
70%
of
the
radioactivity
was
excreted
in
the
feces
and
20%
in
the
urine
within
24
hours.
The
major
portion
of
the
radioactivity
that
was
excreted
in
the
feces
was
identified
as
the
parent
compound.
Pendimethalin
is
metabolized
in
rats
mainly
through
oxidation
of
the
4­
methyl
group
attached
to
the
benzene
ring
as
well
as
oxidation
of
the
alkyl
side
chain
of
the
N­
substituted
dinitroaniline
compound.
Plant
and
livestock
metabolism
data
indicate
there
are
no
significant
metabolites
that
have
not
been
accounted
for
in
the
rat
metabolism
study.

3.2
Nature
of
the
Residue
in
Foods
3.2.1.
Primary
Crop
Metabolism
The
qualitative
nature
of
the
residue
in
plants
is
understood
based
on
adequate
studies
conducted
with
[
14C]
pendimethalin
on
potatoes
and
sweet
corn.
The
results
of
these
studies
are
supported
by
additional
corn,
cotton,
dry
bean,
lima
bean,
peanut,
potato,
red
table
beet,
rice,
snap
bean,
soybean,
sugarcane,
and
wheat
metabolism
data.
Pendimethalin
per
se
and
its
3,5­
dinitrobenzyl
Page
15
of
55
alcohol
metabolite
are
the
residues
of
concern
(
for
risk
assessment
and
tolerance
enforcement)
in
plants,
with
the
exception
of
peanut
hulls,
which
also
include
the
2,4­
dinitrobenzyl
alcohol
metabolite.

3.2.2
Livestock
Metabolism
Adequate
goat
and
poultry
metabolism
studies
are
available.
The
Agency
has
determined
that
there
is
no
reasonable
expectation
of
finite
pendimethalin
residues
of
concern
in
animal
commodities
(
40
CFR
§
180.6(
a)(
3)).
No
additional
animal
metabolism,
analytical
methods,
storage
stability,
and
magnitude
of
the
residue
data
are
required.
Tolerances
for
pendimethalin
residues
of
concern
in
livestock
commodities
are
not
needed.

3.2.3
Rotational
Crop
Metabolism
An
acceptable
confined
rotational
crop
study
was
submitted
and
reviewed
in
conjunction
with
the
pendimethalin
RED
document
(
1996).
The
study
indicates
pendimethalin
residues
in
rotational
crop
matrices
are
extensively
metabolized.
Only
radioactive
residues
of
pendimethalin
per
se
exceeded
0.01
ppm
in/
on
any
of
the
mature
RACs
studied.
Limited
field
rotational
crop
studies
are
not
needed
provided
labels
indicate
a
90­
day
plantback
interval
(
PBI)
for
cereal
grains,
and
a
270­
day
PBI
for
all
other
crops.

3.3
Environmental
Degradation
Pendimethalin
dissipates
in
the
environment
through
binding
to
soil,
microbial
metabolism
and
volatilization.
In
both
laboratory
and
field
studies,
pendimethalin
residues
are
tightly
bound
to
soil
and
sediment
particles.
Pendimethalin
is
stable
to
sterile
hydrolysis,
soil
photolysis,
and
anaerobic
soil
metabolism,
but
degrades
slowly
under
aqueous
photolysis.
Pendimethalin
forms
many
minor
(<
10%
of
applied)
degradates
that
consist
primarily
of
an
intact
benzene
ring
with
rearranged
alkyl
groups.
Parent
pendimethalin
is
the
only
significant
non­
volatile
residue
expected
in
ground
and
surface
water
sources
of
drinking
water.

3.4
Toxicity
Profile
of
Major
Metabolites
and
Degradates
There
are
no
toxicity
data
available
for
pendimethalin
metabolites.
For
the
purpose
of
risk
assessment,
the
3,5­
dinitrobenzyl
metabolite
has
been
considered
toxicologically
equivalent
to
the
parent.
That
is,
for
dietary
risk
assessment,
combined
residues
of
pendimethalin
and
metabolites
were
compared
to
the
NOAEL
for
pendimethalin,
per
se.
Page
16
of
55
3.5
Summary
of
Residues
for
Tolerance
Expression
and
Risk
Assessment
3.5.1
Tabular
Summary
Table
3.5.
Summary
of
Pendimethalin
Metabolites
and
Degradates
to
be
included
in
the
Risk
Assessment
and
Tolerance
Expression
Matrix
Residues
included
in
Risk
Assessment
Residues
included
in
Tolerance
Expression
Plants
Primary
Crops
Pendimethalin
3,5­
dinitrobenzyl
alcohol
Pendimethalin
3,5­
dinitrobenzyl
alcohol
Peanut
Hulls
Pendimethalin
3,5­
dinitrobenzyl
alcohol
2,4­
dinitrobenzyl
alcohol
N/
A
Rotational
Crop
N/
A
N/
A
Livestock
Ruminant
Not
applicable
­
there
is
no
reasonable
expectation
of
finite
residues
in
livestock.
Poultry
Drinking
Water
Pendimethalin
Not
Applicable
4.0
Hazard
Characterization/
Assessment
4.1
Hazard
Characterization
The
toxicity
database
for
pendimethalin
is
adequate
for
the
purpose
of
characterizing
potential
toxic
effects
following
acute,
short­
term
and
long­
term
exposures
via
oral,
dermal
and
inhalation
routes
of
exposure.

The
database
adequately
characterizes
pendimethalin
as
having
low
acute
oral,
dermal,
and
inhalation
toxicity.
Pendimethalin
is
classified
in
Toxicity
Category
IV
for
acute
dermal
toxicity,
acute
inhalation
toxicity,
and
primary
dermal
irritation;
Toxicity
Category
III
for
acute
oral
and
primary
eye
irritation;
it
is
not
a
dermal
sensitizer.
The
acute
toxicity
is
summarized
in
Table
4.1.
a.

The
thyroid
is
a
target
organ
for
pendimethalin.
Thyroid
toxicity
in
chronic
and
subchronic
rat
and
mouse
studies
was
manifested
as
alterations
in
thyroid
hormones
(
decreased
Total
T4,
and
T3,
increased
percent
of
free
T4
and
T3),
increased
thyroid
weight,
and
microscopic
thyroid
lesions
(
including
increased
thyroid
follicular
cell
height,
follicular
cell
hyperplasia,
as
well
as
follicular
cell
adenomas).

The
toxicology
database
for
pendimethalin
is
complete
with
regard
to
pre­
natal
developmental
Page
17
of
55
toxicity
in
rats
and
rabbits;
the
studies
are
both
classified
as
acceptable.
However,
a
developmental
thyroid
study
has
been
requested
to
provide
additional
information
to
evaluate
thyroid
toxicity
in
the
developing
fetus
following
pre­
and
post­
natal
exposure.
The
available
data
provided
no
indication
of
qualitative
or
quantitative
susceptibility
following
pre­
natal
and
postnatal
exposure
in
a
2­
generation
reproduction
study
in
rats.

In
a
combined
chronic/
carcinogenicity
study
in
rats,
the
LOAEL
of
250
mg/
kg/
day
is
based
on
decreased
survival,
body
weight
gain
and
food
consumption,
increased
gamma
glutamyl
transferase
and
cholesterol,
increase
in
absolute
and/
or
relative
liver
weight,
generalized
icterus,
dark
adipose
tissue
in
females,
diffusely
dark
thyroids
and
follicular
cell
hyperplasia
of
the
thyroid.
Thyroid
tumors
were
observed
in
both
male
and
female
rats.
In
the
carcinogenicity
study
in
mice,
the
LOAEL
of
622.1/
806.99
mg/
kg/
day
(
M/
F)
is
based
on
increased
mortality
in
females,
decreased
body
weight
in
females,
increased
absolute
thyroid,
liver
and
gall
bladder
weights
and/
or
relative
body
and
brain
weight
ratios
in
males
and
females
as
well
as
amyloidosis
in
males.
There
were
no
tumors
observed
in
mice.

Pendimethalin
is
classified
as
a
"
Group
C",
possible
human
carcinogen,
chemical
based
on
a
statistically
significant
increased
trend
and
pair­
wise
comparison
between
the
high
dose
group
and
controls
for
thyroid
follicular
cell
adenomas
in
male
and
female
rats.
A
non­
quantitative
approach
(
i.
e.,
non­
linear,
RfD
approach)
was
recommended
by
the
Cancer
Peer
Review
Committee
since
mode
of
action
studies
are
available
that
demonstrate
that
the
thyroid
tumors
are
due
to
a
thyroidpituitary
imbalance,
and
also
since
pendimethalin
was
shown
to
be
non­
mutagenic
in
mammalian
somatic
cells
and
germ
cells.

Rat
metabolism
data
indicated
pendimethalin
is
rapidly
eliminated
from
the
body
with
70%
being
excreted
in
the
feces,
primarily
unchanged
as
parent
compound,
and
20%
in
the
urine
within
24
hours.
It
is
mainly
metabolized
through
oxidation
of
the
4­
methyl
group
on
the
benzene
ring
and
the
alkyl
side
chain.

There
were
no
appropriate
dermal
absorption
or
toxicity
studies
available
to
allow
an
estimation
of
the
dermal
absorption
by
a
route­
to­
route
comparison
of
toxicity.
In
a
previous
risk
assessment,
dermal
absorption
was
estimated
to
be
no
greater
than
10%.
This
was
based
on
structurally
related
chemicals
(
oryzalin,
trifluralin
and
ethalfluralin)
with
dermal
absorption
studies
(
in
monkeys)
indicating
absorption
rates
of
2.3%,
~
1%,
and
2.8%,
respectively.
The
solubilities
(
water)
for
pendimethalin
and
these
related
chemicals
are
also
similar
at
0.5
ppm,
2.5
ppm,
0.3
ppm
and
<
1
ppm,
respectively.
The
upper­
bound
value
of
10%
previously
estimated
for
pendimethalin
is
considered
very
conservative.
Therefore,
for
risk
characterization
purposes,
a
more
appropriate
estimate
of
3%
was
applied.
This
absorption
rate
is
comparable
to
those
identified
for
related
chemicals.
Page
18
of
55
Table
4.1a
Acute
Toxicity
Profile
­
Pendimethalin
Guideline
No.
Study
Type
MRID(
s)
Results
Toxicity
Category
870.1100
Acute
oral
[
Rat]
00026657
LD50=
1250
mg/
kg
(
m)
=
1050
mg/
kg
(
f)
III
870.1200
Acute
dermal
[
Rabbit]
00026657
LD50
=
>
5000
mg/
kg
IV
870.1300
Acute
inhalation
[
Rat]
00073342
LC50
=
32
mg/
L
IV
870.2400
Acute
eye
irritation
[
Rabbit]
00026657
slight
conjunctival
irritation
III
870.2500
Acute
dermal
irritation
[
Rabbit]
00026657
no
dermal
irritation
IV
870.2600
Skin
sensitization
[
Guinea
pig
]
00153767
non­
sensitizer
­

Table
4.1b
Subchronic,
Chronic
and
Other
Toxicity
Profile
for
Pendimethalin.

Guideline
No.
Study
Type
MRID
No./
Classification
Dose
Levels
Results
870.3100
Subchronic
oral
rat
(
30­
day)
000106754
Supplementary
ppm
=
0,
800,
1600,
3200
mg/
kg/
day
=
0,
80,
160,
320
NOAEL
=
160
mg/
kg/
day
LOAEL
=
320
mg/
kg/
day
based
on
increased
liver
weight.

870.3100
Subchronic
oral
rat
(
13­
week)
00156081
ppm
=
0,
100,
500,
5000
mg/
kg/
day
=
0,
10,
50,
500
NOAEL
=
50
mg/
kg/
day
LOAEL
=
500
mg/
kg/
day
based
on
decreased
body
weight
gain
and
food
consumption,
decreased
hematocrit
and
hemoglobin
w/
increases
in
platelets
in
males,
increased
liver
weight,
red
thyroids,
and
hypertrophy
of
the
liver.

870.3100
Subchronic
oral
rat
(
13­
week)
00059468
Supplementary
ppm
=
0,
25,
50,
100,
500,
2500
mg/
kg/
day
=
0,
2.5,
5,
10,
50,
250
NOAEL
=
250
mg/
kg/
day
LOAEL
was
not
determined
870.3100
Subchronic
oral
rat
(
13
week)
00059469
Supplementary
ppm
=
0,
2500
mg/
kg/
day
=
0,
250
NOAEL
=
250
mg/
kg/
day
LOAEL
was
not
determined
870.3100
Subchronic
oral
rat
(
92­
day)
42054601
ppm
=
0,
100,
5000
mg/
kg/
day
=
0,
4.98,
245.4
NOAEL
=
4.98
mg/
kg/
day
LOAEL
=
245.4
mg/
kg/
day
based
on
thyroid
effects
Table
4.1b
Subchronic,
Chronic
and
Other
Toxicity
Profile
for
Pendimethalin.

Guideline
No.
Study
Type
MRID
No./
Classification
Dose
Levels
Results
Page
19
of
55
870.3100
Subchronic
oral
rat
(
56­
day)
43135001
ppm
=
0,
500,
5000
mg/
kg/
day
=
0,
31,
292
NOAEL
was
not
determined
LOAEL
=
31
mg/
kg/
day
based
on
thyroid
effects
870.3100
Subchronic
oral
rat
(
14­
day)
43135003
ppm
=
0,
100,
500
mg/
kg/
day
=
0,
10,
500
NOAEL
=
10
mg/
kg/
day
LOAEL
=
500
mg/
kg/
day
based
on
thyroid
effects
870.3100
Subchronic
oral
dog
(
90­
day)
00026672
Supplementary
mg/
kg/
day
=
0,
62.5,
250,
1000
NOAEL
=
62.5
mg/
kg/
day
LOAEL
=
250
mg/
kg/
day
based
on
body
weight
loss
870.3150
Subchronic
oral
mouse
(
30­
day)
000106754
Supplementary
ppm
=
0,
500,
1000,
2000
mg/
kg/
day
=
0,
75,
150,
300
NOAEL
=
300
mg/
kg/
day
LOAEL
was
not
determined
870.3200
21­
Day
dermal
toxicity
(
rat)
00026663
mg/
kg/
day
=
0,
250,
500,
1000
NOAEL
=
1000
mg/
kg/
day
LOAEL
was
not
determined
870.3700a
Prenatal
Developmental
Toxicity
(
Rat)
00025752
Supplementary;
but
satisfactory
when
considered
w/
rabbit
developmental
mg/
kg/
day
=
0,
125,
250,
500
Maternal
NOAEL
=
500
mg/
kg/
day
(
highest
dose
tested)
Maternal
LOAEL
was
not
determined
Developmental
NOAEL
=
500
mg/
kg/
day
(
highest
dose
tested)
Developmental
LOAEL
was
not
determined
870.3700b
Prenatal
Developmental
Toxicity
(
Rabbit)
00117444
Supplementary;
Upgradeable
mg/
kg/
day
=
0,
15,
30,
60
Maternal
NOAEL
=
60
mg/
kg/
day
(
highest
dose
tested)
Maternal
LOAEL
was
not
determined
Developmental
NOAEL
=
60
mg/
kg/
day
(
highest
dose
tested)
Developmental
LOAEL
was
not
determined
Note:
range
finding
study
indicated
doses
$
125
mg/
kg/
day
associated
with
increased
mortality
Table
4.1b
Subchronic,
Chronic
and
Other
Toxicity
Profile
for
Pendimethalin.

Guideline
No.
Study
Type
MRID
No./
Classification
Dose
Levels
Results
Page
20
of
55
870.3800
Reproduction
and
fertility
effects
(
2­
Generation
Reproduction
in
Rats)
41725203
ppm
=
0,
500,
2500,
5000
mg/
kg/
day
(
M/
F)
=
0,
34/
43,
172/
216,
346/
436
HED
RED
mg/
kg/
day
=
0,
25,
125,
250
HIARC
Document
Note:
Doses
were
obtained
from
a
HED
pendimethalin
RED
and
a
HIARC
document
(
4/
18/
2000)
which
resulted
in
different
dose
calculations
for
mg/
kg/
day.
Consequently,
doses
are
given
as
a
range,
based
on
calculations
from
actual
chemical
intake
and
a
generic
ratio
(
1:
20)
of
dietary
intake.
Parental/
Systemic
NOAEL
=
25­
34/
43
(
M/
F)
mg/
kg/
day
(
500
ppm)
Parental
/
Systemic
LOAEL
=
125­
172/
216
(
M/
F)
mg/
kg/
day
(
2500
ppm)
based
on
decreased
body
weight
gain
and
food
consumption.

Reproductive/
Offspring
NOAEL
=
25­
34/
43
(
M/
F)
mg/
kg/
day
(
500
ppm)
Reproductive/
Offspring
LOAEL
=
125­
172/
216
(
M/
F)
mg/
kg/
day
(
2500
ppm)
based
on
decreases
in
the
number
of
pups
born
and
pup
weights.

870.3800
Reproduction
and
fertility
effects
3­
Generation
Reproduction
in
Rats
00026671,
0040304,
00059470
ppm
=
0,
500,
5000
mg/
kg/
day
=
0,
25,
250
Parental/
Systemic
NOAEL
=
25
mg/
kg/
day.
Parental/
Systemic
LOAEL
=
250
mg/
kg/
day
based
on
decreased
body
weight.

Reproductive/
Offspring
NOAEL
=
25
mg/
kg/
day
Reproductive/
Offspring
LOAEL
=
250
mg/
kg/
day
based
on
decreased
pup
body
weight
gain
and
possible
decreased
pups
born
alive
and
pup
survival.
Table
4.1b
Subchronic,
Chronic
and
Other
Toxicity
Profile
for
Pendimethalin.

Guideline
No.
Study
Type
MRID
No./
Classification
Dose
Levels
Results
Page
21
of
55
870.4100a
Chronic
toxicity
(
Mouse)
40909901
ppm
=
0,
100,
500,
5000
mg/
kg/
day
(
M/
F)
=
0,
12.3/
15.6,
62.3/
78.3,
622.1/
806.9
NOAEL
=
62.3/
78.3
mg/
kg/
day
LOAEL
=
622.1/
806.99
mg/
kg/
day
based
on
mortality,
body
weight
decrease,
organ
weight
changes
and
amyloidosis.

870.4100b
Chronic
toxicity
(
2­
year
Oral
Dog)
00058657
mg/
kg/
day
=
0,
12.5,
50,
200
NOAEL
=
12.5
mg/
kg/
day
LOAEL
=
50
mg/
kg/
day
based
on
increased
SAP,
liver
weights
and
pathology.

870.4200
Chronic
Toxicity/
Carcinogenicity
(
2­
year
Oral
Rat)
40174401
ppm
=
0,
100,
500,
5000
mg/
kg/
day
=
0,
5,
25,
250
NOAEL
=
25
mg/
kg/
day
LOAEL
=
250
mg/
kg/
day
based
on
decreased
survival,
body
weight
gain
and
decreased
food
consumption,
increased
gamma
glutamyl
transferase,
cholesterol
and
liver
weights
and
thyroid
effects.

870.4200
Chronic
Toxicity
(
2­
year
Oral
Rat)
42027802
ppm
=
0,
1250,
2500,
3750,
5000
mg/
kg/
day
=
0,
51,
103,
154,
213
NOAEL
was
not
determined
LOAEL
=
51
mg/
kg/
day
based
on
non­
neoplastic
thyroid
follicular
cell
changes.

870.4300
Carcinogenicity
(
18­
month
Oral
Mouse)
40909901
ppm
=
0,
100,
500,
5000
mg/
kg/
day
(
M/
F)
=
0,
12.3/
15.6,
62.3/
78.3,
622.1/
806.9
NOAEL
=
62.3/
78.3
mg/
kg/
day
LOAEL
=
622./
806.9
mg/
kg/
day
based
on
mortality,
body
weight
decrease,
organ
weight
changes
and
amyloidosis.

870.5100
Reverse
Gene
Mutation
Assay
in
Bacteria
strains
of
S.
typhimurium
00153768
50,
158,
500,
1581,
5000
µ
g/
plate
Positive
Evidence
of
a
2­
fold
increase
in
number
of
induced
mutant
colonies
over
background
at
all
doses
from
50
to
5000
µ
g/
plate
870.5100
Reverse
Gene
Mutation
Assay
in
Escherichia
coli
WP2
43177801
25,
50,
100,
250,
500,
750
µ
g/
plate
Negative
Table
4.1b
Subchronic,
Chronic
and
Other
Toxicity
Profile
for
Pendimethalin.

Guideline
No.
Study
Type
MRID
No./
Classification
Dose
Levels
Results
Page
22
of
55
870.5100
Reverse
Gene
Mutation
Assay
in
Escherichia
coli
WP2
43135005
50,
158,
500,
1581,
5000
µ
g/
plate
or
1000
µ
g/
paper
disk/
plate
Negative
870.5100
Reverse
Gene
Mutation
Assay
in
Escherichia
coli
WP2
43135006
50,
100,
250,
500,
750
µ
g/
plate
Negative
870.5300
Mammalian
Cell
Gene
Mutation
in
Chinese
hamster
ovary
43177802
1,
5,
7.5,
10,
20,
30,
40,
50
µ
g/
ml
(­
S9)

10,
25,
50,
75,
100,
125,
150,
175
µ
g/
ml
(+
S9)
Negative
870.5375
Chromosomal
Aberration
(
CHO)
00153770
Doses
ranging
from
5­
50
µ
g/
ml
Negative
870.5395
Mouse
Micronucleus
Study
42027801
313,
625,
1250
mg/
kg
Negative
870.5550
Alkaline
Elution
Assay
in
Rats
43135007
1250,
2500,
5000
mg/
kg/
bw
Negative
870.7485
Metabolism
and
pharmacokinetics
in
Rat
00046275
n/
a
Pendimethalin
is
eliminated
from
body
with
70%
being
excreted
in
feces
primarily
parent
compound
and
20%
in
urine
within
24
hours.

C
Some
of
the
LOAELs/
NOAELS
in
Table
4.1b
were
previously
denoted
as
LOELs/
NOELS
in
Data
Evaluation
Records
(
DERs),
the
language
was
updated
to
comply
with
current
standards
without
reexamining
effects.
As
new
uses
for
pendimethalin
are
submitted,
DERs
will
be
re­
reviewed
and
updated.

4.2
FQPA
Hazard
Considerations
4.2.1
Adequacy
of
the
Toxicity
Data
Base
The
toxicology
database
for
pendimethalin
is
adequate
and
complete.
However,
based
on
the
hormonal
changes
(
alterations
in
thyroid
weights
and
histopathological
lesions)
observed
in
several
studies
following
oral
administration
of
pendimethalin,
it
is
likely
that
pendimethalin
may
cause
disruption
in
the
endocrine
system.
There
is
concern
that
perturbation
of
thyroid
homeostasis
may
lead
to
hypothyroidism,
and
possibly
result
in
adverse
effects
on
the
developing
Page
23
of
55
nervous
system.
Consequently,
HED
has
recommended
that
a
developmental
thyroid
assay
be
conducted
to
evaluate
the
impact
of
pendimethalin
on
thyroid
hormones,
structure,
and/
or
thyroid
hormone
homeostasis
during
development.
Furthermore,
HED
has
recommended
that
a
10X
database
uncertainty
factor
(
UF
DB
)
of
10X
be
retained
pending
receipt
of
the
required
study.

4.2.2
Evidence
of
Neurotoxicity
There
were
no
neurotoxicity
studies
available
for
pendimethalin.
Furthermore,
there
was
no
evidence
of
neurotoxic
clinical
signs,
changes
in
brain
weight,
or
histopathology
of
the
nervous
system
in
any
study
with
pendimethalin.
Neurotoxicity
studies
for
pendimethalin
are
not
required
based
on
the
chemical
characteristics.

4.2.3
Developmental
Toxicity
Studies
In
the
rat,
the
pendimethalin
NOAELs
for
developmental
and
maternal
toxicity
are
both
500
mg/
kg/
day
(
highest
dose
tested).
There
were
no
maternal
or
developmental
effects
noted
at
any
dose
level
tested.
However,
the
study
is
considered
adequate,
and
a
new
study
is
not
required
because
in
other
rat
studies,
thyroid
toxicity
was
seen
at
significantly
lower
doses
(
31
mg/
kg/
day)
than
the
highest
dose
tested
in
this
study,
and
because
if
thyroid
parameters
had
been
measured,
maternal
toxicity
would
likely
have
been
demonstrated.

A
rabbit
toxicity
study
with
pendimethalin
did
not
demonstrate
maternal
toxicity
at
doses
up
to
60
mg/
kg/
day
(
highest
dose
tested).
The
NOAEL
for
developmental
toxicity
was
60
mg/
kg/
day
(
HDT).
Since
neither
maternal
nor
developmental
toxicity
was
seen
at
the
highest
dose
tested,
potential
for
increased
sensitivity
of
the
offspring
could
not
be
determined.

4.2.4
Reproductive
Toxicity
Study
A
2­
generation
reproduction
study
(
MRID#
41725203)
with
pendimethalin
was
reviewed
by
HED.
The
pendimethalin
RED
and
the
Data
Evaluation
Report
(
DER),
concluded
that
the
parental
systemic
NOAEL
was
172
mg/
kg/
day
[
M]
and
216
mg/
kg/
day
[
F]
(
2500
ppm),
based
on
decreased
body
weight
gain
and
food
consumption
at
the
LOAEL
of
346
mg/
kg/
day
[
M]
and
436
mg/
kg/
day
[
F]
(
5000
ppm).
The
reproductive/
offspring
NOAEL
was
172
mg/
kg/
day
[
M]
and
216
mg/
kg/
day
[
F]
(
2500
ppm),
based
on
decreased
pup
weight
at
the
LOAEL
of
346
mg/
kg/
day
[
M]
and
436
mg/
kg/
day
[
F]
(
5000
ppm).
The
mg/
kg/
day
were
calculated
from
actual
intake
of
chemical
specific
data
in
the
DER.

Conclusions
for
the
same
2­
generation
reproduction
study
(
MRID#
41725203)
with
pendimethalin
in
the
HIARC
(
4/
18/
2000)
indicated
that
the
parental
systemic
NOAEL
was
25
mg/
kg/
day
(
500
ppm),
based
on
decreased
body
weight
gain
and
food
consumption
at
the
LOAEL
of
125
mg/
kg/
day
(
2500
ppm).
The
reproductive/
offspring
NOAEL
is
25
mg/
kg/
day
(
500
ppm),
based
on
decreases
in
the
number
of
pups
born
and
pup
weight
at
the
LOAEL
of
125
mg/
kg/
day
(
2500
ppm).
Parental
and
reproductive
NOAELs
and
LOAELs
were
based
on
a
Page
24
of
55
generic
ratio
(
1:
20)
of
dietary
intake
of
chemical.

4.2.5
Additional
Information
from
Literature
Sources
There
was
no
additional
information
available
from
the
literature.

4.2.6
Pre­
and/
or
Postnatal
Toxicity
HED
has
concluded
there
is
potential
for
pre­
and/
or
postnatal
toxicity
(
thyroid)
in
developing
offspring
resulting
from
exposure
to
pendimethalin.

4.2.6.1
Determination
of
Susceptibility
There
was
no
indication
of
pre­/
or
postnatal
qualitative
or
quantitative
increased
susceptibility
in
the
developmental
studies
in
rats
and
rabbits
or
the
2­
generation
reproduction
studies
in
rats.
However,
because
developmental
LOAELs
could
not
be
determined
in
the
developmental
studies,
HED
has
requested
developmental
thyroid
toxicity
data,
in
order
to
determine
potential
thyroid
toxicity
following
pre­
and/
or
post­
natal
exposure
to
pendimethalin.

4.2.6.2
Degree
of
Concern
Analysis
and
Residual
Uncertainties
for
Pre
and/
or
Post­
natal
Susceptibility
HED
performed
a
Degree
of
Concern
Analysis
because
the
developmental
studies
were
not
adequate
to
fully
address
the
potential
for
susceptibility.
The
purpose
of
the
Degree
of
Concern
analysis
is
(
1)
to
determine
the
level
of
concern
for
the
effects
observed
when
considered
in
the
context
of
all
available
toxicity
data;
and
(
2)
identify
any
residual
uncertainties
after
establishing
toxicity
endpoints
and
traditional
uncertainty
factors
to
be
used
in
the
risk
assessment.

If
residual
uncertainties
are
identified,
then
HED
determines
whether
these
residual
uncertainties
can
be
addressed
by
a
special
FQPA
safety
factor
and,
if
so,
the
size
of
the
factor
needed.

In
the
case
of
pendimethalin,
the
developmental
studies
in
rats
and
rabbits
were
acceptable
but
not
adequate
to
determine
the
potential
for
thyroid
toxicity
during
development.
Consequently,
there
is
concern
for
potential
increased
sensitivity
or
susceptibility
in
offspring
regarding
thyroid
effects.
A
developmental
thyroid
toxicity
study
has
been
required,
and
the
registrant
has
met
with
the
Agency
to
discuss
the
conduct
of
the
ongoing
study.
Pending
receipt
of
the
study,
a
10X
database
uncertainty
factor
(
UF
DB
)
has
been
retained.
The
10X
special
FQPA
Factor
has
been
reduced
to
1X,
however,
since
thyroid
effects
serve
as
the
basis
for
endpoints
for
risk
assessment
for
pendimethalin,
since
there
were
no
developmental
effects
observed
in
the
rat
and
rabbit
developmental
toxicity
studies,
and
since
the
10X
UF
DB
has
been
retained
for
the
lack
of
data
in
the
developing
thyroid.
Page
25
of
55
4.3
Recommendation
for
a
Developmental
Neurotoxicity
Study
Because
there
is
no
concern
for
neurotoxicity
following
exposure
to
pendimethalin,
a
developmental
neurotoxicity
study
is
not
needed.

4.4
Hazard
Identification
and
Toxicity
Endpoint
Selection
4.4.1
Acute
Reference
Dose
(
aRfD)
­
Females
age
13­
49
The
developmental
toxicity
rat
and
rabbit
studies
and
the
2­
generation
rat
reproduction
study
did
not
demonstrate
developmental,
reproductive,
or
offspring
acute
toxicity.
Therefore,
there
is
not
a
concern
for
prenatal
exposure
to
pendimethalin
following
a
single
dose.
A
separate
aRfD
for
women
of
childbearing
age
is
not
required.

4.4.2
Acute
Reference
Dose
(
aRfD)
­
General
Population
No
appropriate
endpoint
attributable
to
a
single
exposure
(
dose)
was
identified
from
the
oral
toxicity
studies
including
developmental
toxicity
studies
in
rats
and
rabbits.
Therefore,
an
acute
RfD
for
the
general
population
was
not
established.

4.4.3
Chronic
Reference
Dose
(
cRfD)

The
following
three
studies:
92­
day
thyroid
function
in
rats,
56­
day
(
28­
day
treatment
period)
thyroid
function
in
rats
and
14­
day
intra­
thyroid
metabolism
study
in
rats
were
considered
together
to
select
the
dose
and
endpoint
for
establishing
the
cRfD
of
0.03
mg/
kg/
day.
The
cRfD
is
derived
from
the
14­
day
NOAEL
of
10
mg/
kg/
day
which
is
based
on
hormonal
and
histological
changes
in
the
thyroid.
On
this
basis,
the
56­
day
LOAEL
of
31
mg/
kg/
day
was
established;
the
cRfD
includes
the
combined
uncertainty
factor
of
300X,
based
on
a
3X
interspecies
extrapolation
and
a
10X
for
intraspecies
variability
(
see
section
4.4.8),
as
well
as
the
10X
UF
DB
for
the
lack
of
a
developmental
thyroid
toxicity
study.

Note:
Subchronic
exposure
to
Pendimethalin
for
28
days
resulted
in
a
LOAEL
of
500
ppm
(
31
mg/
kg/
day)
based
on
several
hormonal
and
histologic
thyroid
changes
observed
throughout
the
28
day
treatment
period
(
TSH
and
organ
weights
showed
no
overt
changes
at
this
dose).
The
NOAEL
in
the
92­
day
study
was
100
ppm
(
4.98
mg/
kg/
day)
while
the
5000
ppm
group
exhibited
thyroid
hormonal,
histologic
and
organ
weight
changes.
The
NOAEL
in
the
14­
day
intrathyroidal
study
was
100
ppm
(
10
mg/
kg/
day)
with
thyroid
hormonal,
histologic
and
organ
weight
changes
also
observed
at
5000
ppm.
The
difference
in
the
NOAELs
of
4.98
mg/
kg/
day
and
10
mg/
kg/
day
(
both
based
on
dietary
concentrations
of
100
ppm)
is
due
to
the
time
weighted
average
of
compound
intake.
For
the
14
day
study,
the
rats
received
a
higher
dose
of
the
compound
than
older
rats
due
to
increased
body
weight.
The
14­
day
NOAEL
of
10
mg/
kg/
day,
accurately
reflects
a
true
NOAEL
for
thyroid
effects
since
these
effects
have
been
demonstrated
to
have
an
early
onset
(
before
14
days).
The
three
studies
were
considered
together
when
establishing
the
Page
26
of
55
LOAEL
at
31
mg/
kg/
day
and
the
NOAEL
at
10
mg/
kg/
day.

4.4.4
Incidental
Oral
Exposure
(
Short
and
Intermediate
Term)

The
same
three
oral
rat
studies
used
to
select
endpoints
and
doses
for
risk
assessment
for
chronic
dietary,
dermal
and
inhalation
routes
of
exposure
(
all
durations)
are
considered
applicable
to
endpoint
selection
for
incidental
oral
exposure,
since
thyroid
toxicity
was
observed
after
3
days
of
dosing
in
the
14­
day
study.
A
NOAEL
of
10
mg/
kg/
day
was
selected
for
all
durations
of
oral
exposure.
The
LOAEL
of
31
mg/
kg/
day
was
based
on
several
hormonal
and
histological
thyroid
changes.

4.4.5
Dermal
Absorption
There
were
no
appropriate
dermal
absorption
or
toxicity
studies
available
to
allow
an
estimation
of
the
dermal
absorption
by
a
route­
to­
route
comparison
of
toxicity.
In
a
previous
risk
assessment
(
HIARC
doc.
4/
18/
2000),
dermal
absorption
was
estimated
to
be
no
greater
than
10%.
This
was
based
on
structurally
related
chemicals
(
oryzalin,
trifluralin
and
ethalfluralin)
with
dermal
absorption
studies
(
in
monkeys)
indicating
absorption
rates
of
2.3%,
~
1%,
and
2.8%,
respectively.
The
solubilities
(
water)
for
pendimethalin
and
these
related
chemicals
are
also
similar
at
0.5
ppm,
2.5
ppm,
0.3
ppm
and
<
1
ppm,
respectively.
The
upper­
bound
value
of
10%
previously
estimated
for
pendimethalin
is
considered
very
conservative.
Therefore,
for
risk
characterization
purposes,
a
more
appropriate
estimate
of
3%
was
applied.
This
absorption
rate
is
comparable
to
those
identified
for
related
chemicals.

4.4.6
Dermal
Exposure
(
Short,
Intermediate
and
Long
Term)

The
dermal
endpoint
and
dose
were
selected
considering
three
studies:
92­
day
thyroid
function
in
rats,
56­
day
thyroid
function
in
rats
and
14­
day
intra­
thyroid
metabolism
study
in
rats.
A
NOAEL
of
10
mg/
kg/
day
was
selected
for
all
durations
of
dermal
exposure.
The
LOAEL
of
31
mg/
kg/
day
was
based
on
several
hormonal
and
histological
thyroid
changes.
Since
the
dermal
endpoint
was
based
on
oral
studies,
an
absorption
factor
of
3%
was
applied.

4.4.7
Inhalation
Exposure
(
Short,
Intermediate
and
Long
Term)

The
inhalation
endpoint
and
dose
was
selected
considering
three
studies:
92­
day
thyroid
function
in
rats,
56­
day
thyroid
function
in
rats
and
14­
day
intra­
thyroid
metabolism
study
in
rats.
A
NOAEL
of
10
mg/
kg/
day
was
selected
for
all
durations
of
inhalation
exposure.
The
LOAEL
of
31
mg/
kg/
day
was
based
on
several
hormonal
and
histological
thyroid
changes.
Since
the
inhalation
endpoint
was
based
on
oral
studies
an
inhalation
absorption
factor
of
100%
was
applied.

4.4.8
Margins
of
Exposure
HED
has
recommended
retaining
a
10X
UF
DB
for
pendimethalin
to
account
for
the
lack
of
a
Page
27
of
55
developmental
thyroid
toxicity
study.
The
standard
10X
intraspecies
uncertainty
factor
and
a
3X
interspecies
factor
are
applicable
to
pendimethalin
risk
assessments.
The
interspecies
uncertainty
factor
of
10X
was
reduced
to
3X
due
to
the
greater
sensitivity
of
the
adult
rat
to
thyroid
effects
compared
to
the
adult
humans.
Because
of
toxicodynamic
differences
in
adult
thyroid
function
that
result
in
greater
sensitivity
of
the
adult
rat
to
hypothyroidism
compared
to
adult
humans,
the
3x
(
3.16)
toxicodynamic
part
of
the
10X
can
be
removed
leaving
the
3X
(
3.16)
portion
for
toxicokinetic
interspecies
differences
(
Interim
Guidance
on
Thyroid
Disrupting
Pesticides,
dated
11/
1/
05).
Thus,
the
usual
100X
uncertainty
factor
for
intra­
and
interspecies
differences
is
reduced
to
30X.
Therefore,
the
level
of
concern
(
target
MOE)
for
occupational
exposure
is
30X,
while
the
target
MOE
for
residential
exposure
is
300X
because
the
additional
10X
UF
DB
has
been
included
for
the
lack
of
a
developmental
thyroid
toxicity
study.

4.4.9
Recommendation
for
Aggregate
Exposure
Risk
Assessments
In
accordance
with
the
requirements
of
the
FQPA
(
1996),
HED
has
considered
the
potential
for
concurrent
exposure
to
pendimethalin
via
oral,
dermal
and
inhalation
routes.
HED
estimates
aggregate
exposure
when
exposure
via
different
routes
produces
the
same
toxicological
effects.
Short­
term
oral,
dermal
and
inhalation
exposures
are
being
regulated
based
on
the
same
effects
seen
in
the
same
three
oral
studies
(
92­
day
thyroid
function
in
rats,
56­
day
thyroid
function
in
rats
and
14­
day
intra­
thyroid
metabolism
study
in
rats).
The
use
of
these
same
studies
to
evaluate
multiple
routes
of
exposure
implicitly
assumes
that
different
routes
of
exposure
will
result
in
the
same
toxicological
effects
and
should,
therefore,
be
aggregated.

4.4.10
Classification
of
Carcinogenic
Potential
The
HED
Cancer
Peer
Review
Committee
classified
pendimethalin
(
3/
18/
92
and
re­
affirmed
11/
1/
99)
as
a
"
Group
C",
possible
human
carcinogen,
chemical
based
on
a
statistically
significant
increased
trend
and
pair­
wise
comparison
between
the
high
dose
group
and
controls
for
thyroid
follicular
cell
adenomas
in
male
and
female
rats.
The
Committee
recommended
a
non­
quantitative
approach
(
i.
e.,
non­
linear,
RfD
approach)
since
mode
of
action
studies
are
available
that
demonstrate
that
the
thyroid
tumors
are
due
to
a
thyroid­
pituitary
imbalance,
and
also
since
pendimethalin
was
shown
to
be
non­
mutagenic
in
mammalian
somatic
cells
and
germ
cells.
Page
28
of
55
Table
4.4.
Toxicological
Doses
and
Endpoints
for
Pendimethalin
Human
Health
Risk
Assessments
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Dietary
Exposure
Acute
Dietary
(
Females
13­
49)
(
General
US
Pop.)
NA
NA
No
appropriate
acute
endpoint
identified
for
these
groups.
There
were
no
toxic
effects
attributable
to
a
single
dose.

Chronic
Dietary
(
all
populations)
NOAEL
=
10
mg/
kg/
day
UF
=
10X
(
intraspecies)
3X
(
interspecies)
10X
(
database
UF)

Total
UF
=
300X
Chronic
RfD=
0.03
mg/
kg/
day
FQPA
SF
=
1X
cPAD
=
Chronic
RfD
FQPA
SF
cPAD
=
0.03
mg/
kg/
day
92­
day
thyroid
function
study
in
rats;
56­
day
thyroid
study
in
rats;
14­
day
intra
thyroid
metabolism
study
in
rats.

LOAEL=
31
mg/
kg/
day
based
on
hormonal
and
histopathological
changes
in
the
thyroid.

Incidental
Oral
Exposure
Incidental
Oral
Short­
Term
(
1
­
30
days)

Intermediate­
Term
(
1
­
6
months)
NOAEL
=
10
mg/
kg/
day
UF
=
10X
(
intraspecies)
3X
(
interspecies)
10X
(
database
UF)

Total
UF
=
300X
FQPA
SF
=
1X
Residential
LOC
=
300
Occupational
LOC
=
30
92­
day
thyroid
function
study
in
rats;
56­
day
thyroid
study
in
rats;
14­
day
intra
thyroid
metabolism
study
in
rats.

LOAEL=
31
mg/
kg/
day
based
on
hormonal
and
histopathological
changes
in
the
thyroid.

Dermal
Exposure
Dermal
Short­
Term
(
1
­
30
days)

Intermediate­
Term
(
1
­
6
months)

Long­
Term
(>
6
months)
NOAEL
=
10
mg/
kg/
day
UF
=
10X
(
intraspecies)
3X
(
interspecies)
10X
(
database
UF)

Total
UF
=
300X
Dermal
Absorption
=
3%
FQPA
SF
=
10X
Residential
LOC
=
300
Occupational
LOC
=
30
92­
day
thyroid
function
study
in
rats;
56­
day
thyroid
study
in
rats;
14­
day
intra
thyroid
metabolism
study
in
rats.

LOAEL=
31
mg/
kg/
day
based
on
hormonal
and
histopathological
changes
in
the
thyroid.

Inhalation
Exposure
Table
4.4.
Toxicological
Doses
and
Endpoints
for
Pendimethalin
Human
Health
Risk
Assessments
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Page
29
of
55
Inhalation
Short­
Term
(
1
­
30
days)

Intermediate­
Term
(
1
­
6
months)

Long­
Term
(>
6
months)
NOAEL
=
10
mg/
kg/
day
UF
=
10X
(
intraspecies)
3X
(
interspecies)
10X
(
database
UF)

Total
UF
=
300X
Inhalation
Absorption
=
100%
FQPA
SF
=
10X
Residential
LOC
=
300
Occupational
LOC
=
30
92­
day
thyroid
function
study
in
rats;
56­
day
thyroid
study
in
rats;
14­
day
intra
thyroid
metabolism
study
in
rats..

LOAEL=
31
mg/
kg/
day
based
on
hormonal
and
histopathological
changes
in
the
thyroid.

Cancer
Cancer
(
oral,
dermal,
inhalation)
Pendimethalin
is
considered
to
be
a
possible
human
carcinogen;
quantitative
estimate
of
cancer
risk
is
not
required.
2­
year
chronic/
carcinogenicity
study
in
rats
UF
=
uncertainty
factor,
FQPA
SF
=
Special
FQPA
safety
factor,
NOAEL
=
no
observed
adverse
effect
level,
LOAEL
=
lowest
observed
adverse
effect
level,
PAD
=
population
adjusted
dose
(
a
=
acute,
c
=
chronic)
RfD
=
reference
dose,
MOE
=
margin
of
exposure,
LOC
=
level
of
concern,
NA
=
Not
Applicable
*
Refer
to
Section
4.5
4.5
Special
FQPA
Safety
Factor
HED
has
reduced
the
Special
FQPA
Safety
Factor
of
10X
for
pendimethalin
to
1X.
Hormonal
changes
(
alterations
in
thyroid
weights
and
histopathological
lesions)
were
observed
in
several
studies
following
oral
administration
of
pendimethalin
and
it
is
likely
that
pendimethalin
may
cause
disruption
in
the
endocrine
system.
There
is
concern
that
perturbation
of
thyroid
homeostasis
may
lead
to
hypothyroidism,
and
possibly
result
in
adverse
effects
on
the
developing
nervous
system.
HED
has
recommended
that
a
developmental
thyroid
assay
be
conducted
to
evaluate
the
impact
of
pendimethalin
on
thyroid
hormones,
structure,
and/
or
thyroid
hormone
homeostasis
during
development.

Since
there
was
no
evidence
of
quantitative
or
qualitative
susceptibility
in
the
submitted
studies,
and
since
a
10X
database
uncertainty
factor
has
been
retained
for
pendimethalin
pending
receipt
of
the
required
developmental
thyroid
toxicity
study,
HED
reduced
the
10X
Special
FQPA
Safety
Factor
to
1X.

4.6
Endocrine
disruption
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
recommendations
of
Page
30
of
55
its
Endocrine
Disruptor
and
Testing
Advisory
Committee
(
EDSTAC),
EPA
determined
that
there
was
a
scientific
basis
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
resources
allow,
screening
of
additional
hormone
systems
may
be
added
to
the
Endocrine
Disruptor
Screening
Program
(
EDSP).

Based
on
the
hormonal
changes
(
alterations
in
thyroid
weights
and
histopathological
lesions)
observed
in
several
studies
following
oral
administration
of
pendimethalin,
it
is
likely
that
pendimethalin
may
cause
disruption
in
the
endocrine
system.
Therefore,
when
additional
appropriate
screening
and/
or
testing
protocols
have
been
developed,
it
is
recommended
that
pendimethalin
be
tested
to
better
characterize
effects
related
to
endocrine
disruption.

5.0
Public
Health
Data
5.1
Incident
Reports
A
search
in
the
Office
of
Pesticide
Programs'
Incident
Data
System
(
2/
28/
96)
indicated
12
reports
with
3
of
these
involving
5
humans
(
the
remainder
concern
fish,
wildlife
or
domestic
animals).
The
symptoms
included
signs
of
systemic
illness:
vomiting,
diarrhea,
chills
and
shakiness.
Three
people
were
hospitalized
when
they
were
exposed
to
a
mixture
of
pesticides
including
pendimethalin
and
nitrogen.
The
database
does
not
indicate
the
associated
use
patterns
or
activities
in
which
the
poisoned
individuals
were
involved.

The
California
Pesticide
Illness
Surveillance
Program
for
1982­
1992
contained
six
reports.
In
three
the
effects
were
systemic
(
vomiting,
diarrhea,
etc.),
two
had
skin
effects,
and
one
involved
eye
effects.

Pendimethalin
ranked
41st
on
a
list
of
the
top
200
active
ingredients
for
which
the
National
Pesticide
Telecommunications
Network
(
NPTN)
received
calls
during
1982­
1991.
There
were
682
calls,
with
91
concerning
human
poisoning
due
to
pendimethalin.
HED
has
requested
more
details
on
the
NPTN
reports
for
review.

6.0
Exposure
Characterization/
Assessment
6.1
Dietary
Exposure/
Risk
Pathway
6.1.1
Residue
Profile
Page
31
of
55
Tolerances
are
established
for
the
combined
residues
of
the
herbicide
pendimethalin
[
N­(
1­
ethylpropyl)­
3,4­
dimethyl­
2,6­
dinitrobenzenamine]
and
its
metabolite
4­[(
1­
ethylpropyl)
amino]­
2­
methyl­
3,5­
dinitrobenzyl
alcohol
in
or
on
a
variety
of
raw
agricultural
commodities,
including
bean,
lima,
seed;
bean,
lima,
succulent;
bean,
forage;
bean,
hay;
corn,
field,
forage;
corn,
field,
grain;
corn,
field,
stover;
corn,
pop,
grain;
corn,
sweet,
forage;
corn,
sweet,
kernel
plus
cob
with
husks
removed;
corn,
sweet,
stover;
cotton,
undelinted
seed;
garlic;
onion,
dry
bulb;
pea,
succulent;
peanut;
peanut,
hay;
potato;
rice,
grain;
rice,
straw;
sorghum,
forage;
sorghum,
grain;
grain;
sorghum,
grain,
stover;
soybean,
forage;
soybean,
hay;
soybean,
seed;
sugarcane,
cane;
and
sunflower,
seed
[
all
at
0.1
ppm].

The
residue
chemistry
database
to
support
reregistration
of
agricultural
uses
of
pendimethalin,
with
respect
to
the
nature
of
the
residue
in
plants,
livestock
and
rotational
crops;
residues
to
be
regulated
in
plants
for
both
risk
assessment
and
tolerance
enforcement;
storage
stability;
processing
studies
and
residue
analytical
methods
were
summarized
in
the
1996
residue
chemistry
chapter
of
the
pendimethalin
RED.

The
residue
chemistry
data
submitted
to
support
the
proposed
uses
(
and
associated
tolerances)
on
citrus,
mint,
carrots
and
tree
nuts
are
generally
adequate
with
respect
to
field
trials,
analytical
methods,
storage
stability
data
and
processing
studies.
Additional
field
trial
data
to
support
the
proposed
crop
group
tolerance
on
citrus
are
conditionally
required.
Required
additional
field
trial
data
for
carrots
grown
in
CA
are
considered
adequate.
In
general,
residue
data
indicate
combined
residues
of
parent
pendimethalin
and
its
3,5­
dinitrobenzyl
alcohol
metabolite
are
very
low
or
nondetectable.
However,
residues
concentrate
in
some
processed
commodities,
including
citrus
oil
and
mint
oil.

6.1.2
Acute
and
Chronic
Dietary
Exposure
and
Risk
(
Pendimethalin:
Chronic
Dietary
Exposure
Assessment
to
Support
Proposed
Section
3
Registration
on
Citrus,
Mint,
Carrots
and
Tree
Nuts.
Christina
Swartz,
2006;
DP
Document
Pending)

A
chronic
dietary
risk
assessment
was
conducted
using
the
Dietary
Exposure
Evaluation
Model
(
DEEM­
FCID
 
,
Version
2.03),
which
use
the
most
recent
food
consumption
data
from
USDA
(
CSFII,
1994­
1996
and
1998).

Tolerance­
level
residues
were
assumed
for
all
food
commodities
with
current
and
proposed
pendimethalin
tolerances,
and
it
was
assumed
that
all
of
the
crops
included
in
the
analysis
were
treated
(
i.
e.,
100
%
crop
treated).
These
assumptions
result
in
highly
conservative
estimates
of
dietary
exposure
and
risk.
In
calculating
dietary
risk
estimates,
HED
has
compared
the
chronic
population­
adjusted
dose
(
cPAD)
to
the
estimated
dietary
exposure
from
DEEM­
FCID.
Typically,
HED
has
concerns
regarding
dietary
risk
when
the
exposure
estimates
exceed
100%
of
the
cPAD.
Even
with
the
conservative
assumptions
noted
above,
risk
estimates
associated
with
dietary
exposure
to
pendimethalin
are
significantly
below
HED's
level
of
concern.

The
most
highly
exposed
population
subgroup
was
children
1­
2
years
old.
The
chronic
exposure
estimate
of
approximately
0.002
mg/
kg/
day
corresponds
to
6
%
cPAD.
Risks
for
the
general
US
Page
32
of
55
population
and
all
other
population
subgroups
were
lower.

Table
6.1
Summary
of
Chronic
Dietary
Exposure
and
Risk
for
Pendimethalin.

Population
Subgroup
cPAD,
mg/
kg/
day
DEEM­
FCIDTM
Exposure
mg/
kg/
day
%
cPAD
General
U.
S.
Population
0.03
0.000710
2.4
All
Infants
(<
1
yr)
0.03
0.001295
4.3
Children
1­
2
yrs
0.03
0.001787
6
Children
3­
5
yrs
0.03
0.001608
5.4
Children
6­
12
yrs
0.03
0.001105
3.7
Youth
13­
19
yrs
0.03
0.000742
2.5
Adults
20­
49
yrs
0.03
0.000558
1.9
Adults
50+
yrs
0.03
0.000473
1.6
Females
13­
49
yrs
0.03
0.000556
1.9
C
The
values
for
the
population
with
the
highest
risk
for
each
type
of
risk
assessment
are
bolded.

6.2
Water
Exposure/
Risk
Pathway
(
Drinking
Water
Assessment
for
Pendimethalin
for
Bearing
Citrus,
Fruit
and
Nut
Trees,
Onion
and
Mint,
James
Breithaupt,
12/
22/
04,
D310591)

Pendimethalin
dissipates
in
the
environment
by
binding
to
soil,
metabolizing
by
microbes,
and
by
volatilizing
into
air.
Persistence
decreased
with
increased
temperature,
increased
moisture
and
decreased
soil
organic
carbon.
Pendimethalin
residues
in
laboratory
and
field
studies
are
tightly
bound
to
soil
and
sediment
particles,
which
is
consistent
with
the
laboratory
mobility
studies.

EFED
estimated
concentrations
in
drinking
water
using
Tier
II
screening
level
surface
water
modeling
(
PRZM­
EXAMS)
for
surface
water
and
Tier
I
modeling
(
SCI­
GROW2)
for
ground
water.
These
Estimated
Drinking
Water
Concentrations
(
EDWCs)
may
be
used
for
acute,
chronic
(
non­
cancer),
and
chronic
(
cancer)
exposure
assessments.
The
PRZM­
EXAMS
concentrations
to
be
used
for
drinking
water
ranged
from
2.2
to
38.8
ug/
L
for
peak
values,
0.1
to
4.8
ug/
L
for
chronic
(
non­
cancer),
and
0.1
to
3.8
ug/
L
for
chronic
(
cancer)
exposures
as
summarized
in
Table
6.2.

The
1
in
10
year
annual
peak
(
acute),
1
in
10
year
annual
mean
(
non­
cancer
chronic),
and
36­
year
annual
mean
concentrations
(
cancer
chronic)
were
derived
from
modeling
pendimethalin
on
the
Pennsylvania
apple
scenario.

Based
on
SCI­
GROW
modeling,
the
acute
and
chronic
pendimethalin
concentrations
are
not
expected
to
exceed
0.024
:
g/
L
(
ppb)
from
one
application
of
4
lbs
ai/
A.
The
estimated
concentrations
of
up
to
0.024
ug/
L
were
actually
lower
than
the
detected
concentrations
in
ground
water,
ranging
from
0.2
to
0.9
ppb.
However,
EFED
does
not
consider
pendimethalin
to
Page
33
of
55
be
a
likely
ground
water
contaminant
in
most
environments
based
on
its
environmental
fate
property
of
tight
sorption
to
soil.

Parent
pendimethalin
is
the
only
significant
non­
volatile
residue,
therefore,
the
EDWCs
were
calculated
for
parent
pendimethalin
only.

Table
6.2.
Summary
of
Estimated
Surface
and
Ground
Water
Concentrations
for
Pendimethalin.

Exposure
Duration
Pendimethalin,
per
se
Surface
Water
Conc.,
ppb
Ground
Water
Conc.,
ppb
Acute
38.8
0.024
Chronic
(
non­
cancer)
4.8
0.024
Chronic
(
cancer)
3.8
NA
6.3
Residential
(
Non­
Occupational)
Exposure/
Risk
Pathway
(
Occupational
and
Residential
Exposure
for
the
Use
of
Pendimethalin
Proposed
Section
3
Registration
for
Use
on
Mint,
Citrus
Fruits,
Tree
Nuts,
and
Carrots;
PC
Code:
108501;
DP
Barcode
D310952;
M.
Collantes
and
Z.
Figueroa;
3/
09/
05)

6.3.1
Home
Uses
6.3.1.1
Residential
Handler
Residential
handler
exposure
estimates
of
applying
pendimethalin
to
residential
turf
were
previously
assessed
in
the
1996
re­
registration
eligibility
decision
(
RED)
document
for
pendimethalin
(
J.
Leahy,
D221532,
February
20,
1996).
The
MOEs
for
residential
handlers
wearing
baseline
attire
were
all
greater
then
the
level
of
concern.
Since
that
time
registered
labels
for
use
of
pendimethalin
on
turf
have
been
revised.
All
turf
(
ornamental,
landscape,
golf
course,
non­
cropland)
labels
appear
to
be
for
commercial
use
only
based
on
the
contents
(
i.
e.
requiring
mixing
tanks,
ground
equipment
for
application,
personal
protective
equipment
and
restricted
entry
intervals).
However
labels
do
not
indicate
for
use
by
licenced
chemical
operator
only.
The
Registration
Division
should
confirm
that
proper
language
clarifying
that
products
are
to
be
applied
only
by
commercial
or
licensed
operators.
A
revised
residential
handler
exposure
assessment
for
applying
pendimethalin
to
residential
turf
was
not
performed.

6.3.1.2
Residential
Postapplication
In
the
1996
RED,
the
following
three
representative
post­
application
scenarios
were
assessed:
1)
toddler
exposure
to
residential
turf;
2)
maintenance
worker
exposure
to
golf
course
turf;
and
3)
harvesting
turfgrass
from
a
sod
farm.
Of
these
three
scenarios,
toddler
exposure
to
residential
turf
grass
is
the
only
scenario
considered
as
residential
exposure.
This
scenario
was
representative
of
the
worst
case
postapplication
exposure
to
residential
populations,
including
children,
following
Page
34
of
55
applications
to
residential
and
recreational
turf
areas
or
ornamental
plantings.
Based
on
postapplication
calculations
using
surrogate
data,
HED
concluded
that
the
MOEs
were
unacceptable
at
the
3
lb
a.
i./
acre
rate
and
required
a
reduction
in
maximum
use
rate
from
3
to
2
lb
a.
i./
acre
on
residential
and
recreational
area
turf
grass.
Since
that
time,
application
rates
have
been
reduced
to
2
lb.
a.
i./
acre
for
residential
turf.
Furthermore
chemical­
specific
turf
transferable
residue
(
TTR)
and
hand
press
data
have
been
submitted
to
the
Agency
and
reviewed
in
support
of
the
use
of
pendimethalin
on
residential
lawns.
HED
has
provided
the
following
revised
postapplication
exposure
assessment
for
use
of
pendimethalin
on
residential
lawns.

6.3.1.2.1
Dermal
Exposure
and
Risk
Chemical­
specific
WDG
turf
transferable
residue
(
TTR)
data
have
been
submitted
to
the
Agency
and
reviewed
in
support
of
assessing
dermal
exposure
to
adults
and
children.

The
level
of
concern
for
non­
occupational
dermal
exposure
is
300.
Using
the
TTR
data
for
the
Pendulum
WDG
formulation,
children's
short­
term
dermal
MOEs
calculated
at
a
rate
of
3.0
lb
ai/
A
ranged
from
440
to
910.
For
adults,
short­
term
dermal
MOEs
ranged
from
740
to
1500.
All
dermal
short­
term
MOEs
were
greater
than
300
and
therefore
did
not
exceed
HED's
level
of
concern
(
LOC).
A
summary
of
the
dermal
exposure
and
MOEs
are
included
as
Tables
6.3a
and
b.

Table
6.3
a:
Summary
Table
of
Short­
term
Dermal
Exposure
for
Children
(
Tier
1)

State
TTR
1
(
µ
g/
cm2)
(
mg/
µ
g)
TC
2
(
cm2/
hr)
ET
3
(
hrs)
Dermal
Absorption
BW
(
kg)
Daily
Dose
4
(
mg/
kg/
day)
NOAEL
(
mg/
kg/
day)
MOE
5
CA
1.1
0.001
5200
2
0.03
15
0.0228
10
440
PA
0.756
0.0157
640
FL
0.538
0.011
910
1.
TTR
=
transferable
residues
based
on
Pendulum
WDG
TTR
study
(
MRID
449699­
01)
2.
Tc
=
transfer
coefficient
based
on
HED
Residential
SOPs
3.
ET
=
exposure
time
based
on
HED
Residential
SOPs
4.
Dose
=
TTR
(
ug/
cm2)
x
0.001
(
mg/
ug)
x
Tc
(
cm2/
hr)
x
ET
(
hrs/
day)
x
dermal
absorp
BW
5.
Dermal
MOE
=
Short­
term
NOAEL
(
10
mg/
kg/
day)
Daily
Dose
Page
35
of
55
Table
6.3b:
Summary
Table
of
Short­
term
Dermal
Exposure
for
Adults
(
Tier
1)

State
TTR
1
(
µ
g/
cm2)
(
mg/
µ
g)
TC
2
(
cm2/
hr)
ET
3
(
hrs)
Dermal
Absorption
BW
(
kg)
Dose
4
(
mg/
kg/
day)
NOAEL
(
mg/
kg/
day)
MOE
5
CA
1.1
0.001
14500
2
0.03
70
0.0136
10
740
PA
0.756
0.009
1100
FL
0.538
0.00668
1500
1.
TTR
=
transferable
residues
based
on
Pendulum
WDG
TTR
study
(
MRID
449699­
01)
2.
Tc
=
transfer
coefficient
based
on
HED
Residential
SOPs
3.
ET
=
exposure
time
based
on
HED
Residential
SOPs
4.
Dose
=
TTR
(
ug/
cm2)
x
0.001
(
mg/
ug)
x
Tc
(
cm2/
hr)
x
ET
(
hrs/
day)
x
dermal
absorp
(
mg/
kg/
day)
BW
5.
MOE
=
Short­
term
NOAEL
(
10
mg/
kg/
day)
Daily
Dose
6.3.1.2.2
Inhalation
Exposure
Since
there
are
no
indoor
residential
uses
and
only
outdoor
turf
uses
associated
with
these
products,
inhalation
exposure
resulting
from
outdoor
uses
is
expected
to
be
negligible.
Therefore,
a
postapplication
inhalation
exposure
assessment
was
not
required.

6.3.1.2.3
Oral
Exposure
and
Risk
The
NOAEL
of
10
mg/
kg/
day
was
used
to
calculate
MOEs
for
children's
oral
exposure
for
handto
mouth,
object­
to­
mouth,
and
soil
ingestion.
To
further
refine
oral
exposure
estimates,
HED
used
hand­
press
residue
data
to
estimate
oral
MOEs.
The
level
of
concern
for
non­
occupational
oral
exposure
is
300.

All
oral
(
hand­
to­
mouth,
object­
to­
mouth,
and
soil
ingestion)
exposures
were
greater
than
300
and
therefore
are
not
of
concern
to
HED.
The
MOEs
calculated
for
hand­
to­
mouth
exposures
using
the
rate
of
2.0
lb
ai/
A
resulted
in
an
MOE
of
7,700.
The
MOEs
for
object­
to­
mouth
and
soil
ingestion
exposure
were
130,000
and
100,000
respectively.
MOEs
calculated
for
hand­
tomouth
exposures
using
the
rate
of
3.0
lb
ai/
A
resulted
in
an
MOE
of
5,300.
The
MOEs
for
object­
to­
mouth
and
soil
ingestion
exposure
were
85,000
and
67,000
respectively.
A
summary
of
the
oral
MOEs
is
provided
in
Table
6.3c.

Ingestion
of
pendimethalin
granules
is
also
a
potential
source
of
exposure
because
children
can
eat
them
if
they
are
found
in
treated
lawns
or
gardens.
This
scenario
is
considered
to
be
episodic,
and
therefore
acute
oral
endpoints
would
be
used
to
estimate
the
risk.
A
risk
assessment
for
this
exposure
scenario
for
children
was
not
conducted
since
an
acute
oral
toxicological
endpoint
of
concern
was
not
identified
for
pendimethalin.
Page
36
of
55
Table
6.3c:
Summary
of
Oral
Exposure
for
Pendimethalin
(
Tier
1)
Hand­
to­
Mouth
1
Rate
(
lbai/
A
)
SR
0
TTR
a
(
µ
g/
cm2)
Grt
a
(
µ
g/
cm2)
Srt
a
(
µ
g/
g)
(
mg/
µ
g)
b
or
(
g/
ug)
c
SA
(
cm2/
event)
IgR
(
cm2/
day)

d
or
(
mg/
day)
e
FQ
(
events/
hr
)
SEF
ET
(
hrs)
BW
(
kg)
Dose
f
(
mg/
kg/
day)
MOE
2.0
22.4
0.049
NA
NA
1E­
3
b
20
NA
20
0.5
2
15
0.0013
7700
3.0
33.6
0.74
0.0019
5300
Object­
to­
Mouth
2
2.0
NA
NA
0.0471
NA
1E­
3
b
NA
25
NA
NA
NA
15
0.0000785
130,000
3.0
0.07
0.0001178
85,000
Soil
Ingestion
3
2.0
NA
NA
NA
15
1E­
6
c
NA
100
NA
NA
NA
15
0.0001
100,000
3.0
22.5
0.00015
67,000
Total
Oral
Dose
5
and
MOE
6
2.0
0.001479
6800
3.0
0.00217
4600
Notes:

0.
SR
=
Surface
Residue
=
2
lb
ai/
A
x
11.2
=
22.4
1a.
TTR
=
application
rate
(
2
lb
ai/
A)
x
conversion
factor
(
11.22
µ
g/
cm2
)
x
%
transferability
(
0.0022)
for
gauze
wipe
1f.
Hand­
to­
mouth
Dose
=
TTR
t
(
ug/
cm2)
x
SA
(
cm2/
event)
x
SEF
x
FQ
(
events/
hr)
x
1.0E­
3
mg/
ug
x
ET
(
hrs/
day)

Body
Weight
(
kg)

2a.
GRt
=
application
rate
(
2
lb
ai/
A)
x
(
11.22
µ
g/
cm2
)
x
%
transferability
(
0.0021)
aerosol
OT
solution
sample
2f.
Object­
to­
mouth
Dose
=
GR
t
(
ug/
cm2)
x
IgR
(
cm2/
day)
x
1.0E­
3
mg/
ug
Body
Weight
(
kg)

3a.
Srt
=
application
rate
(
2
lb
ai/
A)
x
(
11.22
µ
g/
cm2
)
x
%
transferability
(
1.0)
x
0.67
cm2/
g
soil
3f
Oral
Dose
t
=
SR
t
(
ug/
g)
*
IgR
(
100
mg/
day)
*
CF1(
10­
3
g/
mg)
x
(
10­
3
mg/
ug)

Body
Weight
(
kg)

4.
TTR,
Grt,
and
Srt
values
are
cited
from
2001
ORE
memo
for
Pendimethalin
(
D270528)

5.
Total
Dose
=
Hand­
to­
mouth
dose
+
Object­
to­
mouth
dose
+
Soil
ingestion
dose
6.
Total
Oral
MOE
=_
1
Or
NOAEL
(
10
mg/
kg/
day)

1
1
1
Hand­
to­
Mouth
Dose
+
Object­
to
Mouth
Dose
+
Soil
Ingestion
Dose
Hand­
to­
Mouth
MOE
+
Object­
to­
Mouth
MOE
+
Soil
Ingestion
MOE
Page
37
of
55
6.3.1.2.4
Aggregate
Residential
Exposure
In
evaluating
the
residential
uses
of
pendimethalin,
HED
has
combined
all
non­
dietary
sources
of
postapplication
exposure
to
obtain
an
estimate
of
potential
aggregate
exposure.
These
scenarios
are
short­
term
in
duration
and
consist
of
dermal
(
adults
and
children)
and
oral
(
hand­
to­
mouth,
object­
to­
mouth
and
soil
ingestion
­
children
only)
exposure.
HED
combines
risk
values
resulting
from
separate
exposure
scenarios
when
it
is
likely
they
can
occur
simultaneously
based
on
the
usepattern
and
the
behavior
associated
with
the
exposed
population.

A
Tier
1
aggregate
exposure
estimate
for
adults
(
consisting
of
dermal
exposure
only)
resulted
in
a
total
MOE
of
740
which
is
greater
than
the
level
of
concern
of
300
and
therefore
not
of
concern
(
Table
6.3d).
The
adult
total
MOE
of
740
was
based
on
using
the
TTR
from
California
test
site
and
3%
dermal
absorption
factor.
Since
the
California
test
site
resulted
in
the
lowest
dermal
MOE,
it
was
determined
to
represent
the
worst
case
scenario.
In
assessing
the
aggregate
residential
exposure
for
children,
HED
also
used
the
California
TTR
data,
hand
press
data
and
3%
dermal
absorption
factor
for
determining
dermal
exposure
to
children.
This
resulted
in
a
total
MOE
(
dermal
+
oral)
of
410
for
an
application
rate
of
2
lb
ai/
acre
and
400
for
an
application
rate
of
3
lb
ai/
acre,
both
of
which
are
greater
than
300
and
therefore
not
of
concern.
This
information
is
also
summarized
in
Table
6.3d.
Page
38
of
55
Table
6.3d:
Aggregate
Risk
Resulting
from
Residential
Exposure
to
Pendimethalin
(
Tier
1)

Exposure
Scenario
Population
TTR
((
ug/
cm2)
1
Dermal
Dose
2
(
mg/
kg/
day)
Dermal
MOE
3
Inhalation
MOE
Total
Oral
Dose4
(
mg/
kg/
day)
Oral
MOE3
Total
Dose
Total
MOE
4
Turf
Grass
adults
1.1
0.0136
a
740
NA
NA
NA
0.0136
740
children
0.0228
b
440
NA
0.0015
6800
0.0243
410
0.0022
4600
0.025
400
Notes:

1.
TTR
values
based
on
Pendulum
WDG
TTR
study
(
MRID
449699­
01)

2a.
See
Table
4
2b.
See
Table
5
3.
Dermal
MOE
=
Average
of
dermal
MOEs
for
adults
and
children
calculated
from
TTR
data
from
CA,
PA
and
FL
(
see
Tables
4
and
5)

4.
Oral
Dose
=
Hand­
to­
mouth
dose
+
Object­
to­
mouth
dose
+
Soil
ingestion
dose
(
See
Table
6)

5.
Oral
MOE
=
_
1
Hand
to
Mouth
MOE
+
Object­
to­
Mouth
MOE
+
Soil
Ingestion
MOE
6.
Total
MOE
=
_
1
OR
NOAEL
(
10
mg/
kg/
day)

____
1______
+
1
Dermal
Dose
+
Total
Oral
Dose
(
Hand
to
Mouth
Dose
+
Object­
to­
Mouth
Dose
+
Soil
Ingestion
Dose)

Dermal
MOE
Oral
MOE
Page
39
of
55
6.3.2
Recreational
Uses
In
the
1996
RED,
handler
and
postapplication
exposures
were
assessed
for
maintenance
worker
exposure
to
golf
course
turf.
As
indicated
previously,
children's
exposure
to
residential
turfgrass
was
also
assessed
and
determined
to
represent
the
worst
case
exposure
resulting
from
residential
populations,
including
children,
following
applications
to
residential
and
recreational
turf
areas
or
ornamental
plantings.
Therefore
a
residential
exposure
assessment
for
golf
course
exposures
has
not
been
included
in
this
assessment.

6.3.3
Other
(
Spray
Drift,
etc.)

Spray
drift
is
always
a
potential
source
of
exposure
to
residents
nearby
to
spraying
operations.
This
is
particularly
the
case
with
aerial
application,
but,
to
a
lesser
extent,
could
also
be
a
potential
source
of
exposure
from
the
ground
application
method
employed
for
pendimethalin.
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.
On
a
chemical
by
chemical
basis,
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
with
specific
products
with
significant
risks
associated
with
drift.

7.0
Aggregate
Risk
Assessments
and
Risk
Characterization
In
accordance
with
the
FQPA,
HED
must
consider
and
aggregate
(
add)
pesticide
exposures
and
risks
from
three
major
sources:
food,
drinking
water,
and
residential
exposures.
In
an
aggregate
assessment,
exposures
from
relevant
sources
are
added
together
and
compared
to
quantitative
estimates
of
hazard
(
e.
g.,
a
NOAEL
or
PAD),
or
the
risks
themselves
can
be
aggregated.
When
aggregating
exposures
and
risks
from
various
sources,
HED
considers
both
the
route
and
duration
of
exposure.

In
evaluating
the
proposed
uses
of
pendimethalin,
HED
has
combined
dietary
(
food)
and
nondietary
(
turf
grass)
sources
of
exposure
to
obtain
an
estimate
of
potential
aggregate
exposure.
The
non­
dietary
scenarios
in
the
aggregate
assessment
include
dermal
exposure
for
adults
and
children
as
well
as
incidental
oral
exposures
(
hand­
and
object­
to­
mouth
transfer
of
residues
and
ingestion
of
soil)
for
children
only.

HED
acknowledges
that
the
aggregate
exposure
and
risk
estimates
for
children
are
likely
to
overestimate
actual
exposures
since
our
estimates
assume
simultaneous,
constant
exposures
from
dietary
and
non­
dietary
sources.
An
assessment
that
takes
into
account
the
timing
of
source
Page
40
of
55
specific
exposures
and
the
likelihood
of
their
co­
occurring
would
be
expected
to
produce
more
realistic
and
lower
exposure
and
risk
estimates.

For
most
pesticide
active
ingredients,
water
monitoring
data
are
considered
inadequate
to
determine
surface
and
ground
water
drinking
water
exposure
estimates,
so
model
estimates
have
been
used
to
estimate
residues
in
drinking
water
(
EDWCs).
In
order
to
determine
if
aggregate
risks
are
of
concern,
HED
then
calculates
drinking
water
levels
of
comparison,
or
DWLOCs.
The
DWLOC
is
the
maximum
amount
of
a
pesticide
in
drinking
water
that
would
be
acceptable
in
light
of
combined
exposure
from
food
and
residential
pathways.
The
calculated
DWLOCs
are
then
compared
to
the
EDWCs
provided
by
EFED;
if
model­
derived
EDWCs
exceed
the
DWLOCs
for
surface
or
ground
water,
there
may
be
a
concern
for
dietary
exposure
to
residues
in
drinking
water,
and
monitoring
data
may
be
required.

7.1
Acute
Aggregate
Risk
No
toxic
effects
attributable
to
a
single
dose
were
identified
for
pendimethalin.
Therefore,
an
acute
risk
assessment
is
not
warranted
for
this
chemical.

7.2
Short­
Term
Aggregate
Risk
In
estimating
short­
term
aggregate
risk,
HED
combined
the
chronic
dietary
(
food)
exposure
estimate
and
the
total
non­
dietary
(
residential)
exposure
estimate
for
adults
and
children.
The
chronic
dietary
exposure
estimate
reflects
average
dietary
exposure
and
serves
as
an
estimate
of
dietary
exposure
that
co­
occurs
with
potential
short­
term
non­
dietary
exposure
to
adults
and
children.
The
short­
term
aggregate
exposures
for
adults
and
children
at
application
rates
of
3
and
2
lb
ai/
acre
were
greater
than
the
EDWC
for
groundwater
or
surface
water
and
therefore,
were
not
of
concern.
Short­
term
aggregate
risk
estimates
for
pendimethalin
are
summarized
in
Table
7.2.
Page
41
of
55
Table
7.2.
Short­
Term
and/
or
Intermediate­
Term
Aggregate
Risk
and
DWLOC
Calculations
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
EDWC6
(
ppb)
Surface
Water
EDWC6
(
ppb)
Short­

Term
DWLOC7
(
µ
g/
L)

Adult
Male
(
U.
S.
Population)
10
300
0.0333333
0.000710
0.014
699
0.019023
0.024
5
666
Adult
Female
(
Females
13+)
10
300
0.0333333
0.000473
0.016
607
0.016860
506
Child
(
1­
2
yrs)
10
300
0.0333333
0.001787
0.024
383
0.007246
72
0.025
370
0.006300
95
1
Target
MOE
=
300
based
on
a
total
UF
of
100
(
10X
intraspecies,
3X
interspecies,
10X
Database).

2
Maximum
Exposure
(
mg/
kg/
day)
=
NOAEL/
Target
MOE
3
Residential
Exposure
=
[
Oral
exposure
+
Dermal
exposure
+
Inhalation
Exposure]

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)]

[
water
consumption
(
L)
x
10­
3
mg/
µ
g]

Body
Weight
=
70
kg
for
adults,
10
Kg
for
children;
Water
consumption
=
2L
for
adults,
1L
for
children.

8Exposure
refers
to
the
highest
dietary
exposure.
Page
42
of
55
7.3
Intermediate­
Term
Aggregate
Risk
Based
on
the
currently
requested
uses,
there
are
no
scenarios
that
are
likely
to
result
in
intermediate­
term
exposure
(
30­
180
days,
continuous).
Therefore,
HED
has
not
conducted
an
intermediate­
term
risk
assessment
for
pendimethalin.

7.4
Long­
Term
Aggregate
Risk
The
dietary
exposure
(
food)
pathway
is
the
only
source
of
exposure
to
pendimethalin
that
is
expected
to
be
long­
term
(
180
­
365
days).
Therefore,
the
long
term
aggregate
exposure
and
risk
estimates
are
equivalent
to
the
chronic
dietary
exposure
and
risk
estimates
discussed
in
Section
6.1.2.
The
chronic
aggregate
exposure
is
provided
in
Table
7.4
for
convenience.
For
all
population
subgroups,
the
chronic
DWLOC
is
greater
than
the
chronic
ground
and
surface
water
EDWC;
therefore,
aggregate
chronic
exposure
to
pendimethalin
is
not
expected
to
exceed
HED's
level
of
concern.

Table
7.4.
Aggregate
Risk
Assessment
for
Chronic
(
Non­
Cancer)
Exposure
to
Pendimethalin.

Population
Subgroup
Chronic
Scenario
cPAD
mg/
kg/
day
Chronic
Food
Exp
mg/
kg/
day
Max
Chronic
Water
Exp
mg/
kg/
day1
Ground
Water
EDWC
(
ppb)
2
Surface
Water
EDWC
(
ppb)
2
Chronic
DWLOC
(
ppb)
3
U.
S.
Population
0.03
0.000710
0.02929
0.024
4.8
1025
All
Infants
(<
1
year
old)
0.0001295
0.02987
448
Children
1­
2
years
0.001787
0.028213
423
Children
3­
5
years
0.001608
0.0284
426
Children
6­
12
0.001105
0.028895
433
Youth
13­
19
0.000742
0.02926
1024
Adults
20­
49
0.000558
0.029442
1030
Females
13+
0.000473
0.0295
885
Adults
50+
years
0.000556
0.0294
1029
1Maximum
Chronic
Water
Exposure
(
mg/
kg/
day)
=
[
Chronic
PAD
(
mg/
kg/
day)
­
Chronic
Dietary
Exposure
(
mg/
kg/
day)]
2
See
Table
6.2­
Estimated
Surface
and
Groundwater
Concentrations
3
Chronic
DWLOC(
µ
g/
L)
=
[
maximum
chronic
water
exposure
(
mg/
kg/
day)
x
body
weight
(
kg)]
[
water
consumption
(
L)
x
10­
3
mg/
µ
g]
body
weights
(
70
kg
adult
male;
60
kg
adult
female;
10
kg
child)
Page
43
of
55
7.5
Cancer
Aggregate
Risk
The
HED
Cancer
Peer
Review
Committee
classified
pendimethalin
as
a
"
Group
C",
possible
human
carcinogen
based
on
thyroid
follicular
cell
adenomas
in
the
rats.
The
committee
recommended
a
non­
quantitative
approach
(
i.
e.,
non­
linear,
RfD
approach)
therefore,
a
quantitative
cancer
aggregate
risk
assessment
was
not
required.

8.0
Cumulative
Risk
Characterization/
Assessment
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
pendimethalin
and
any
other
substances
and
pendimethalin
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
pendimethalin
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/.

9.0
Occupational
Exposure/
Risk
Pathway
(
Occupational
and
Residential
Exposure
for
the
Use
of
Pendimethalin
Proposed
Section
3
Registration
for
Use
on
Mint,
Citrus
Fruits,
Tree
Nuts,
and
Carrots;
PC
Code:
108501;
DP
Barcode
D310952;
M.
Collantes
and
Z.
Figueroa;
3/
09/
05)

9.1
Agricultural
and
Commercial
Handlers
The
following
two
agricultural
(
PROWL
®
3.3
EC
and
PROWL
®
H
2
O)
and
commercial
(
Pendulum
3.3
EC
and
Pendulum
AquaCap)
products
have
been
assessed
for
occupational
exposure.

PROWL
®
3.3
EC
contains
37.4%
of
the
active
ingredient
(
a.
i.)
pendimethalin,
while
PROWL
®

H
2
O
Herbicide
contains
38.7%
active
ingredient.
Both
products
are
formulated
as
liquids,
used
as
an
agricultural
herbicide
on
mint,
citrus
fruits,
tree
nuts,
and
carrots
and
applied
by
chemigation,
ground
and
aerial
equipment.
The
proposed
application
rates
for
PROWL
®
3.3
EC
range
from
0.743
to
3.96
lbs
active
ingredient
(
ai)
per
acre.
A
maximum
seasonal
application
rates
are
also
specified
as
1.98
lb
a.
i./
A/
season
for
mint,
1.0
lb
a.
i./
A/
season
for
carrots,
and
3.96
lb
a.
i./
A/
season
for
citrus
fruits
and
tree
nuts.
The
proposed
application
rates
for
Prowl
®
H
2
O
range
from
0.713
to
3.80
lbs
active
ingredient
(
ai)
per
acre.
The
maximum
seasonal
application
rates
are
also
specified
as
1.90
lb
a.
i./
A/
season
for
mint,
0.95
lb
a.
i./
A/
season
for
carrots,
and
3.80
lb
a.
i./
A/
season
for
citrus
fruits
and
tree
nuts.

Pendulum
3.3
EC
herbicide
contains
37.4%
of
the
active
ingredient
(
a.
i.)
pendimethalin,
while
Page
44
of
55
Pendulum
AquaCap
herbicide
contains
38.7
%
pendimethalin.
Both
products
are
formulated
as
liquids,
used
to
control
weeds
in
turfgrass,
ornamentals,
landscape,
ground
maintenance,
golf
courses,
sod
farms
and
noncrop
land
areas.
Both
products
are
applied
by
ground
equipment,
backpack
and
hand­
gun
sprayers
applied
at
a
maximum
rate
of
3
lbs
a.
i.
per
acre.

Based
on
the
number
of
seasonal
applications
indicated
on
these
product
labels,
and
information
provided
by
the
registrant,
handler
exposures
are
expected
to
be
short­
term
in
duration.

Chemical­
specific
data
for
assessing
exposure
during
pesticide
handling
activities
were
not
submitted
to
the
Agency
in
support
of
this
Section
3
application.
It
is
HED
policy
to
use
data
from
the
Pesticide
Handlers
Exposure
Database
(
PHED)
Version
1.1
to
assess
handler
exposures
for
regulatory
actions
when
chemical­
specific
data
are
not
available
(
HED
Science
Advisory
Council
for
Exposure,
SOP
Number
.007,
January
1999).

Occupational
handler
exposure
assessments
were
completed
by
HED
using
baseline
and
single
layer
of
personal
protective
equipment
(
PPE).
The
baseline
clothing
level
for
occupational
exposure
scenarios
is
generally
an
individual
wearing
long
pants,
a
long­
sleeved
shirt,
no
chemical­
resistant
gloves,
and
no
respirator.
The
first
level
of
mitigation
generally
applied
is
PPE.
As
reflected
in
the
calculations
included
herein,
PPE
may
involve
the
use
of
single
layer
of
clothing,
chemical­
resistant
gloves,
and
no
respirator.

9.1.2
Exposure
and
Risk
Summaries
of
the
non­
cancer
(
MOEs)
short­
term
risks
for
handlers
at
the
baseline
and
PPE
levels
are
included
in
Table
9.
Calculations
for
handler
exposure
were
performed
for
the
highest
application
rate
per
crop
to
represent
the
worst
case
scenario.
Since
both
dermal
and
inhalation
toxicological
endpoints
were
the
same
for
the
short­
term
duration,
the
route­
specific
MOEs
were
combined
and
compared
to
the
NOAEL
(
10
mg/
kg/
day).
The
total
MOEs
for
short­
term
mixing/
loading
scenarios
ranged
from
50
at
baseline
to
1,200
using
PPE
(
single
layer
and
gloves),
and
did
not
exceed
HED's
level
of
concern
(
MOEs
<
30).
The
total
MOEs
for
short­
term
applicator
and
flagger
scenarios,
at
baseline
level
of
mitigation
and
engineering
controls
for
aerial,
range
from
1,000
to
9,100
and
do
not
exceed
HED's
level
of
concern
(
MOEs
<
30).
The
total
MOEs
for
short­
term
mixer/
loader/
applicator
using
PPE
(
single
layer
clothes
and
gloves)
ranged
from
40
to
2,800
and
did
not
exceed
HED's
level
of
concern
(
MOEs
<
30).

The
handler
exposure
estimates
in
this
assessment
are
based
on
a
central
tendency
estimate
of
unit
exposure
and
an
upper­
percentile
assumption
for
the
application
rate,
and
are
assumed
to
be
representative
of
high­
end
exposures.
The
uncertainties
associated
with
this
assessment
stem
from
the
use
of
surrogate
exposure
data
(
e.
g.,
differences
in
use
scenario
and
data
confidence)
and
assumptions
regarding
the
amount
of
chemical
handled.
The
estimated
exposures
are
believed
to
be
reasonable
high­
end
estimates
based
on
observations
from
field
studies
and
professional
judgement.
It
should
be
noted
that
for
mixing/
loading
scenarios,
gloves
are
requested.
Page
45
of
55
9.2
Agricultural
Postapplication
No
postapplication
data
were
submitted
in
support
of
this
registration
action.
Based
on
the
number
of
seasonal
applications
indicated
on
the
proposed
product
labels,
and
information
provided
by
the
registrant,
postapplication
exposures
are
expected
to
be
short­
term
in
duration
for
all
agricultural
crops.
Furthermore,
since
these
products
are
herbicides
used
to
mainly
control
pre­
emergent
weeds,
and
not
applied
directly
to
foliage,
postapplication
exposure
is
expected
to
be
minimal.
Based
on
this
information
a
postapplication
exposure
assessment
was
neither
required
nor
performed.

9.3
Commercial
Postapplication
The
following
two
representative
post­
application
commercial
scenarios:
1.)
maintenance
worker
exposure
to
golf
course
turf,
and
2.)
harvesting
turfgrass
from
a
sod
farm
were
assessed
in
the
1996
RED.
Surrogate
Foliar
Dislodgeable
Residue
(
FDR)
data
were
used
to
assess
golf
course
and
sod
farm
turf
postapplication
exposure.
Calculations
of
postapplication
exposure
resulted
in
acceptable
MOEs
and
therefore
were
not
of
concern
to
HED.

Restricted
Entry
Interval
(
REI)
The
restricted
entry
interval
(
REI)
is
based
on
the
acute
toxicity
of
pendimethalin
technical
material
which
is
classified
as
Category
III
and
IV
for
acute
dermal,
dermal
irritation
and
eye
irritation
(
HIARC
Doc.
No.
014116,
April
18,
2000).
Acute
toxicity
Category
III
and
IV
chemicals
for
these
potential
hazards
require
a
12­
hour
REI.
Based
on
the
acute
toxicity
categories
for
this
chemical,
HED
recommends
that
the
current
product
labels
provide
a
12­
hour
REI.
Page
46
of
55
Table
9
:
Short­
term
Handler
Exposure
and
Risk
for
Pendimethalin
Exposure
Scenario
Crop
Mitigation
Level
Dermal
Unit
Exposure
(
mg/
lb
ai)
Inhalation
Unit
Exposure
(:
g/
lb
ai)
Application
Rate
(
lb
ai/
A)
Amount
Treated
(
acres/
day)
Dermal
Dose
(
mg/
kg/
day)
a
Inhalation
Dose
b
(
mg/
kg/
day)
Dermal
MOE
c
Inhalation
MOE
d
Total
Dose
e
Total
MOE
f
Mixer/
Loader
Liquid
for
Aerial
application
carrots
Baseline
2.9
1.2
(
0.0012
mg/
lb
ai)
1.0
350
0.435
0.0060
23
1,700
0.441
22
Single
layer,

gloves
0.023
0.00345
0.0060
2900
1,700
0.00945
1100
Liquid
for
Grourndboom
Application
mint
Baseline
2.9
1.2
(
0.0012
mg/
lb
ai)
1.98
80
0.196
0.0027
50
3,700
0.198
50
Liquid
for
Grourndboom
Application
citrus
Baseline
2.9
1.2
(
0.0012
mg/
lb
ai)
3.96
80
0.39
0.0054
25
1,900
0.39
25
Single
layer,

gloves
0.023
0.00312
0.0054
3,200
1,900
0.00852
1200
Liquid
for
Groundboom
Application
carrots
Baseline
2.9
1.2
(
0.0012
mg/
lb
ai)
1.0
80
0.099
0.0014
30
100
0.1
100
Liquid
for
Groundboom
Application
tree
nuts
Baseline
2.9
1.2
(
0.0012
mg/
lb
ai)
3.96
80
.4
0.0054
25
1,900
0.4
25
Single
layer,

gloves
0.023
0.00312
0.0054
3,200
1,900
0.0085
1200
Liquid
for
Groundboom
Application
turfgrass,
sod,
golf
course,
ornamentals,

landscape,
grounds
maintenance,
noncroplands
Baseline
2.9
0.0012
mg/
lb
ai
3.0
200
(
sod
farm)
0.75
0.0103
13
970
0.76
13
Single
layer,

gloves
0.023
0.006
0.0103
1700
970
0.0163
610
Liquid
for
Chemigation
Application
Citurs
Fruits
Baseline
2.9
1.2
(
0.0012
mg/
lb
ai)
3.96
350
1.7
0.024
6
416
1.7
6
Single
layer,

gloves
0.023
0.0136
0.024
740
416
0.037
270
Table
9
:
Short­
term
Handler
Exposure
and
Risk
for
Pendimethalin
Exposure
Scenario
Crop
Mitigation
Level
Dermal
Unit
Exposure
(
mg/
lb
ai)
Inhalation
Unit
Exposure
(:
g/
lb
ai)
Application
Rate
(
lb
ai/
A)
Amount
Treated
(
acres/
day)
Dermal
Dose
(
mg/
kg/
day)
a
Inhalation
Dose
b
(
mg/
kg/
day)
Dermal
MOE
c
Inhalation
MOE
d
Total
Dose
e
Total
MOE
f
Page
47
of
55
Liquid
for
Chemigation
application
carrots
Baseline
2.9
1.2
(
0.0012
mg/
lb
ai)
1.0
350
0.435
0.0060
30
1,700
0.441
22
Single
layer,

gloves
0.023
1.0
0.00345
0.0060
2900
1,700
0.00945
1100
Liquid
for
Chemigation
application
tree
nuts
Baseline
2.9
1.2
(
0.0012
mg/
lb
ai)
3.96
350
1.7
0.024
6
416
1.7
6
Single
layer,

gloves
0.023
3.96
0.0136
0.024
740
416
0.037
270
Applicator
Sprays
for
Aerial
application
carrots
Baseline
0.005
0.068
(
0.000068
mg/
lb
ai)
1.0
350
0.00075
0.00034
13,000
29,000
0.0011
9,100
Sprays
for
Groundboom
application
mint
Baseline
0.014
0.74
(
0.00074
mg/
lb
ai)
1.98
80
0.0009
0.0017
11,000
5,900
0.0026
3,800
Sprays
for
Groundboom
application
citrus
fruit
Baseline
0.014
0.74
(
0.00074
mg/
lb
ai)
3.96
80
0.0019
0.0033
5,300
3,000
0.0052
1,900
Sprays
for
Groundboom
application
carrots
Baseline
0.014
0.74
(
0.00074
mg/
lb
ai)
1.0
80
0.00048
0.00085
21,000
12,000
0.00133
7,500
Sprays
for
Groundboom
application
tree
nuts
Baseline
0.014
0.74
(
0.00074
mg/
lb
ai)
3.96
80
0.0019
0.0033
5,300
3,000
0.0052
1,900
Sprays
for
Groundboom
application
turfgrass,
sod,,
golf
course,
ornamentals,

landscape,
grounds
maintenance,
noncroplands
Baseline
0.014
0.00074
mg/
lb
ai
3.0
200
(
sod
farm)
0.0036
0.0063
2800
1600
0.0099
1,000
Flagger
Table
9
:
Short­
term
Handler
Exposure
and
Risk
for
Pendimethalin
Exposure
Scenario
Crop
Mitigation
Level
Dermal
Unit
Exposure
(
mg/
lb
ai)
Inhalation
Unit
Exposure
(:
g/
lb
ai)
Application
Rate
(
lb
ai/
A)
Amount
Treated
(
acres/
day)
Dermal
Dose
(
mg/
kg/
day)
a
Inhalation
Dose
b
(
mg/
kg/
day)
Dermal
MOE
c
Inhalation
MOE
d
Total
Dose
e
Total
MOE
f
Page
48
of
55
Liquid
for
Aerial
application
carrots
Baseline
0.011
0.35
(
0.00035
mg/
lb
ai)
1.0
350
Acres/
day
0.00165
0.00175
6,100
5,700
0.0034
2,900
Mixer/
loader/
Applicator
Backpack
(
PHED)
turfgrass,
sod,,
golf
course,
ornamentals,

landscape,
grounds
maintenance,
noncroplands
resdiental
lawn
Single
layer
and
gloves
2.5
0.03
mg/
lb
ai
3.8
lb
ai/
gal
40
gal/
day
0.16
0.065
63
150
0.225
40
Lawn
Handgun
Sprayer
(
ORETF)
0.5
0.0019
mg/
lb
ai
3
lb
ai/
acre
5
acres
0.0032
0.0004
3,100
25,000
0.0036
2,800
a.
Dermal
Dose
(
mg/
kg/
day)
=
Rate
(
lb
ai/
A)
x
UE
(
mg
/
lb
ai
)
x
DA
(
0.03)
x
Acres
Treated
(
A/
day)
d.
Inhalation
MOE
=
Inhalation
NOAEL
(
10
mg/
kg/
day)

BW
(
70
kg)
Inhalation
Dose
(
mg/
kg/
day)

b.
Inhalation
Dose
(
mg/
kg/
day)
=
Rate
(
lb
ai/
A)
x
UE
(
mg
/
lb
ai
)
x
Acres
Treated
(
A/
day)
e.
Total
Dose
(
mg/
kg/
day)
=
Dermal
Dose
(
mg/
kg/
day)
+
Inhalation
Dose
BW
(
70
kg)

c.
Dermal
MOE
=
Dermal
NOAEL
(
10
mg/
kg/
day)
f.
Total
MOE
=
NOAEL
(
10
mg/
kg/
day)
/
Total
Dose
(
mg/
kg/
day)

Dermal
Dose
(
mg/
kg/
day)
Page
49
of
55
10.0
Data
Needs
and
Label
Requirements
10.1
Toxicology
HED
has
requested
the
submission
of
developmental
thyroid
toxicity
data
for
adult
rats
and
young
rats
following
pre­
and
post­
natal
exposure
to
pendimethalin.

10.2
Residue
Chemistry
Residue
chemistry
data
are
adequate
to
support
the
proposed
uses
on
mint,
tree
nuts
and
carrots;
however,
as
a
condition
of
registration,
additional
residue
data
are
required
to
support
the
proposed
citrus
crop
group
tolerance.
Specifically,
grapefruit
field
trial
data
from
Regions
3,
6
and
10
(
one
test
each),
and
lemon
field
trial
data
from
Region
10
(
two
tests)
are
needed.

10.3
Occupational
and
Residential
Exposure
The
Agency
reiterates
the
recommendation
that
agricultural
handlers
should
wear
chemicalresistant
gloves
when
mixing/
loading
liquids,
and
when
mixing/
loading
and
applying
with
a
low
pressure
handwand.
Page
50
of
55
References
Endpoint
selection
document:

Pendimethalin
­
Revisit
to
HIARC
in
Response
to
Registrant
Rebuttal;
S.
Williams­
Foy;
PC
Code
108501:
HED
DOC
NO.
014116;
April
18,
2000
Dietary
Exposure
Memo:

Pendimethalin:
Chronic
Dietary
Exposure
Assessment
to
Support
Proposed
Section
3
Registration
on
Citrus,
Mint,
Carrots
and
Tree
Nuts;
C.
Swartz,
3/
7/
2005;
PC
Code:
108501,
DP
Number:
D313734.

Residue
Chemistry
Memoranda
Product
and
Residue
Chemistry
Chapters
for
the
Pendimethalin
Reregistration
Eligibility
Decision
(
RED)
Document.
CBRS
No.:
16592
DP
Barcode
No.:
D221531
Chemical
No.:
108501
Reregistration
Case
No.:
0187;
Bonnie
Kohlligian,
12/
12/
95
Residue
Chemistry
Data
Reviews:

PP#
6E4787.
Request
for
the
use
of
Pendimethalin
on
Citrus.
Evaluation
of
Analytical
Method
and
Magnitude
of
the
Residue
Data.
DP
Barcode:
D238469;
W.
D.
Cutchin,
7/
26/
99.

PP#
0E6083.
Request
for
the
use
of
Pendimethalin
on
Tree
Nuts
including
Pistachios.
Evaluation
of
Analytical
Method
and
Magnitude
of
the
Residue
Data.
W.
D.
Cutchin,
9/
1/
2000
Pendimethalin
(
Prowl
®
)
on
Carrots;
N.
Dodd,
3/
26/
1996.

Occupational
and
Residential
Exposure
Memo:

Occupational
and
Residential
Exposure
for
the
Use
of
Pendimethalin
Proposed
Section
3
Registration
for
Use
on
Mint,
Citrus
Fruits,
Tree
Nuts,
and
Carrots;
PC
Code:
108501;
DP
Barcode
D310952;
M.
Collantes
and
Z.
Figueroa;
3/
09/
05
Reregistration
Eligibility
Document
Pendimethalin
Reregistration
Eligibility
Document;
D221532;
J.
Leahy;
02/
20/
96
Page
51
of
55
Appendices
1.0
TOXICOLOGY
DATA
REQUIREMENTS
HED
has
requested
the
submission
of
developmental
thyroid
toxicity
data
for
adult
rats
and
young
rats
following
pre­
and
post­
natal
exposure
to
pendimethalin.

2.0
NON­
CRITICAL
TOXICOLOGY
STUDIES
Refer
to
the
3/
18/
96
HED
RED
Chapter
for
additional
details.

3.0
METABOLISM
CONSIDERATIONS
The
nature
of
the
residue
in
plants,
livestock
and
rotational
crops
is
adequately
understood.
Metabolism
studies
identified
and
discussed
in
the
3/
18/
96
RED
chapter
support
the
currently
proposed
uses
on
carrots,
mint,
tree
nuts,
and
citrus.
Rotational
crop
tolerances
are
not
needed,
provided
labels
specify
rotational
crop
plantback
intervals
of
90­
days
for
cereal
grains,
and
270
days
for
all
other
crops.

4.0
ANALYTICAL
METHODOLOGY
Adequate
methods
are
available
for
data
collection
and
tolerance
enforcement
for
existing
and
proposed
uses
of
pendimethalin.
Methods
I
through
IV
in
PAM
Vol.
II
are
gas
chromatography/
electron
capture
(
GC/
ECD)
methods.
Methods
used
for
data
collection
are
essentially
the
same
as
the
PAM
Vol.
II
methods,
and
have
been
adequately
validated.

The
FDA
PESTDATA
database
(
PAM
Volume
I,
Appendix
I)
indicates
that
pendimethalin
is
completely
recovered
(>
80%)
by
Multiresidue
Methods
Section
302
(
Luke
method;
Protocol
D)
and
303
(
Mills,
Onley,
Gaither
method;
Protocol
E,
nonfatty),
and
partially
recovered
(
50­
80%)
by
Multiresidue
Method
Section
304
(
Mills
fatty
food
method;
Protocol
E,
fatty).

5.0
SUMMARY
OF
MAGNITUDE
OF
RESIDUE
(
MOR)
STUDIES
Magnitude
of
the
residue
data
have
been
submitted
and
reviewed
in
conjunction
with
the
proposed
new
uses.
Adequate
data
support
the
proposed
uses
on
mint,
tree
nuts
and
carrots.
HED
had
required
the
submission
of
an
additional
field
trial
in
CA
to
support
the
use
on
carrots;
the
required
study
has
been
submitted
to
the
Agency,
and
a
preliminary
review
indicates
that
data
are
acceptable,
and
are
consistent
with
the
previously
submitted
studies,
which
support
the
proposed
tolerance
of
0.5
ppm.
Page
52
of
55
Additional
field
trial
data
are
required
to
support
the
proposed
citrus
crop
group
tolerance:
grapefruit
field
trial
data
from
Regions
3,
6
and
10
(
one
test
each),
and
lemon
field
trial
data
from
Region
10
(
two
tests).
These
data
are
considered
confirmatory,
and
a
time­
limited
tolerance
should
be
established
pending
receipt
of
the
data.

In
general,
residue
data
indicate
combined
residues
of
parent
pendimethalin
and
its
3,5­
dinitrobenzyl
alcohol
metabolite
are
very
low
or
nondetectable.
In
nutmeats,
combined
residues
were
<
0.1
ppm,
the
combined
LOQ;
these
data
have
not
been
summarized
in
the
tables
below.

Field
Trial
Data
Results
for
Citrus
Crops
MRID
Location
Application
Data
Residues
(
ppm)

Total
Rate
(
lb
ai/
A)
PHI
Pendimethalin
3,5­
dinitrobenzyl
alcohol
Total
Orange
44103901
FL
6.0
1
<
0.005,
<
0.005
<
0.005,
<
0.005
<
0.010,
<
0.010
44312201
CA
6.0
1
<
0.005,
<
0.005
<
0.005,
<
0.005
<
0.010,
<
0.010
CA
1
<
0.005,
<
0.005
<
0.005,
<
0.005
<
0.010,
<
0.010
50
<
0.005,
<
0.005
<
0.005,
<
0.005
<
0.010,
<
0.010
FL
1
<
0.005,
<
0.005
<
0.005,
<
0.005
<
0.010,
<
0.010
FL
1
<
0.005,
<
0.005
<
0.005,
<
0.005
<
0.010,
<
0.010
FL
6.0
1
<
0.005,
<
0.005
<
0.005,
<
0.005
<
0.010,
<
0.010
5.4
49
<
0.005,
<
0.005
<
0.005,
<
0.005
<
0.010,
<
0.010
FL
6.0
1
<
0.005,
<
0.005
<
0.005,
<
0.005
<
0.010,
<
0.010
FL
1
<
0.005,
<
0.005
<
0.005,
<
0.005
<
0.010,
<
0.010
FL
1
<
0.005,
<
0.005
<
0.005,
<
0.005
<
0.010,
<
0.010
TX
1
<
0.005,
<
0.005
<
0.005,
<
0.005
<
0.010,
<
0.010
44103904
CA
4.0
60
<
0.05
<
0.05
<
0.10
12.0
<
0.005
<
0.005
<
0.010
FL
4.0
58
<
0.05
<
0.05
<
0.10
12.0
<
0.005
<
0.005
<
0.010
Grapefruit
44103902
FL
6.0
1
0.008,
0.007
<
0.005,
<
0.005
0.013,
0.012
44312202
CA
6.0
1
<
0.005,
<
0.005
<
0.005,
<
0.005
<
0.010,
<
0.010
FL
1
<
0.005,
<
0.005
<
0.005,
<
0.005
<
0.010,
<
0.010
44103904
CA
4.0
60
<
0.05
<
0.05
<
0.10
12.0
<
0.05
<
0.05
<
0.10
FL
2.0
+
4.0
<
0.05
<
0.05
<
0.10
6.0
+
6.0
<
0.05
<
0.05
<
0.10
Field
Trial
Data
Results
for
Citrus
Crops
MRID
Location
Application
Data
Residues
(
ppm)

Total
Rate
(
lb
ai/
A)
PHI
Pendimethalin
3,5­
dinitrobenzyl
alcohol
Total
Orange
44103901
FL
6.0
1
<
0.005,
<
0.005
<
0.005,
<
0.005
<
0.010,
<
0.010
Page
53
of
55
TX
2.0
+
4.0
<
0.05
<
0.05
<
0.10
6.0
+
6.0
<
0.05
<
0.05
<
0.10
Lemon
44103903
AZ
6.0
1
0.006,
0.006
<
0.005,
<
0.005
0.011,
0.011
44312203
CA
6.0
1
0.009,
<
0.005
<
0.005,
<
0.005
0.014,
<
0.010
FL
1
0.019,
0.018
<
0.005,
<
0.005
0.024,
0.023
44103904
AZ
4.0
55
<
0.05
<
0.05
<
0.10
12.0
<
0.05
<
0.05
<
0.10
CA
4.0
59
<
0.05
<
0.05
<
0.10
12.0
<
0.005
<
0.005
<
0.010
Field
Trial
Data
Results
for
Mint
Location/
Mint
Variety
Rate
(
lb
ai/
A)
PHI
Residues
(
ppm)

Pendimethalin
3,5­
dinitrobenzyl
alcohol
metabolite
Total
OR
Native
spearmint
2.0
145
0.052,
0.054
<
0.05,
<
0.05
0.10,
0.10
10.0
<
0.05,
<
0.05
<
0.05,
<
0.05
<
0.10,
<
0.10
WA
Black
Mitchum
2.0
124
<
0.05,
<
0.05
<
0.05,
<
0.05
<
0.10,
<
0.10
10.0
<
0.05,
0.076
<
0.05,
<
0.05
<
0.10,
0.13
Page
54
of
55
Field
Trial
Data
Results
for
Almond
Hulls
MRID
Location
Total
Rate
(
lb
ai/
A)
PHI
Residues
(
ppm)

Pendimethalin
3,5­
dinitrobenzyl
alcohol
Total
44983301
CA
5.58
(
0.9x)
128
<
0.05
<
0.05
<
0.1
CA
5.62
(
0.9x)
128
<
0.05
<
0.05
<
0.1
CA
6.01
(
1x)
111
<
0.05
<
0.05
<
0.1
CA
6.01
(
1x)
116
0.11
<
0.05
0.16
CA
5.99
(
1x)
116
0.21
<
0.05
0.26
44983305
CA
4.0
(
0.7x)
60
0.13
<
0.05
0.18
90
0.19
<
0.05
0.24
12.0
(
2x)
60
0.06
<
0.05
0.11
90
0.08
<
0.05
0.13
CA
4.0
(
0.7x)
90
<
0.05
<
0.05
<
0.10
120
0.29
<
0.05
0.34
12.0
(
2x)
90
0.42
<
0.05
0.47
120
0.62
<
0.05
0.67
Field
Trial
Data
Results
for
Carrots
Location
Application
Rate
(
lbs
ai/
A)
PHI
(
days)
Residues
(
ppm)

Pendimethalin
3,5­
dinitrobenzyl
alcohol
Total
WA
1
+
1
2
+
2
59
59
<
0.05
0.080
<
0.05
<
0.05
<
0.1
0.13
MI
1
+
1
2
+
2
61
61
<
0.05
0.064
<
0.05
<
0.05
<
0.1
0.114
MD
1
+
1
2
+
2
46
46
<
0.05
0.088
<
0.05
<
0.05
<
0.1
0.138
NJ
1
+
1
2
+
2
61
61
<
0.05
0.054
<
0.05
<
0.05
<
0.1
0.104
FL
1
+
1
2
+
2
60
60
<
0.05
0.080
0.29
0.44
0.34
0.52
CA
1
+
1
2
+
2
51
51
0.058
0.10
0.096
<
0.05
0.154
0.15
Field
Trial
Data
Results
for
Carrots
Location
Application
Rate
(
lbs
ai/
A)
PHI
(
days)
Residues
(
ppm)

Pendimethalin
3,5­
dinitrobenzyl
alcohol
Total
Page
55
of
55
TX
1
+
1
2
+
2
60
60
0.10
0.16
<
0.05
<
0.05
0.15
0.21
6.0
INTERNATIONAL
CONSIDERATIONS
There
are
no
established
or
proposed
Codex
MRLs
for
pendimethalin
residues.
Therefore,
there
are
no
questions
of
compatibility
with
respect
to
Codex
MRLs
and
U.
S.
tolerances.