Page
1
of
76
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
MEMORANDUM
Date:
09/
28/
05
SUBJECT:
Endothall:
Revised
HED
Chapter
of
the
Reregistration
Eligibility
Decision
Document
(
RED).
PC
Codes:
038901,038904,
and
038905.

FROM:
Robert
P.
Zendzian
PhD,
Risk
Assessor
Senior
Pharmacologist
Toxicology
Branch
Health
Effects
Division
(
7509C)

THROUGH:
Louis
Scarano
PhD
Chief
Toxicology
Branch
Health
Effects
Division
(
7509C)

TO:
Mika
J.
Hunter
Chemical
Review
Manager
Special
Review
Branch
Special
Review
and
Reregistration
Division
(
7508C)
Page
2
of
76
Table
of
Contents
1.0
Executive
Summary
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5
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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12
2.3
Physical
and
Chemical
Properties
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14
3.0
Metabolism
Assessment
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15
3.1
Comparative
Metabolic
Profile
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15
3.2
Nature
of
the
Residue
in
Foods
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15
3.2.1.
Description
of
Primary
Crop
Metabolism
.
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15
3.2.2
Description
of
Livestock
Metabolism
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16
3.2.3
Description
of
Rotational
Crop
Metabolism,
including
identification
of
major
metabolites
and
specific
routes
of
biotransformation
.
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16
3.3
Environmental
Degradation
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16
3.4
Tabular
Summary
of
Metabolites
and
Degradates
.
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16
3.5
Toxicity
Profile
of
Major
Metabolites
and
Degradates
.
.
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18
3.6
Summary
of
Residues
for
Tolerance
Expression
and
Risk
Assessment
.
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18
3.6.1
Tabular
Summary
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20
3.6.2
Rationale
for
Inclusion
of
Metabolites
and
Degradates
.
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20
4.0
Hazard
Characterization/
Assessment
.
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21
4.1
Hazard
and
Dose
Response
Characterization
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21
4.2
FQPA
Hazard
Considerations
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29
4.2.1
Adequacy
of
the
Toxicity
Data
Base
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29
4.2.2
Evidence
of
Neurotoxicity
.
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29
4.2.3
Developmental
Toxicity
Studies
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29
4.2.4
Reproductive
Toxicity
Study
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29
4.2.5
Additional
Information
from
Literature
Sources
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30
4.2.6
Pre­
and/
or
Postnatal
Toxicity
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30
4.2.6.1
Determination
of
Susceptibility
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30
4.2.6.2
Degree
of
Concern
Analysis
and
Residual
Uncertainties
for
Pre
and/
or
Post­
natal
Susceptibility
.
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30
4.3
Recommendation
for
a
Developmental
Neurotoxicity
Study
.
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30
4.3.1
Evidence
that
supports
requiring
a
Developmental
Neurotoxicity
study
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30
4.3.2
Evidence
that
supports
not
requiring
for
a
Developmental
Neurotoxicity
study
.
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30
4.4
Hazard
Identification
and
Toxicity
Endpoint
Selection
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31
4.4.1
Acute
Reference
Dose
(
aRfD)
­
Females
age
13­
49
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31
4.4.2
Acute
Reference
Dose
(
aRfD)
­
General
Population
.
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31
4.4.3
Chronic
Reference
Dose
(
cRfD)
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31
4.4.4a
Incidental
Oral
Exposure
(
Short
Term)
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32
Page
3
of
76
4.4.4b
Incidental
Oral
Exposure
(
Intermediate
Term)
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32
4.4.5
Dermal
Absorption
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32
4.4.6
Dermal
Exposure
(
Short,
Intermediate
and
Long
Term)
.
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33
4.4.7a
Inhalation
Exposure
(
Short
Term)
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33
4.4.7b
Inhalation
Exposure
(
Intermediate
and
Long
Term)
.
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33
4.4.8
Margins
of
Exposure
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34
4.4.9
Recommendation
for
Aggregate
Exposure
Risk
Assessments
.
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34
4.4.10
Classification
of
Carcinogenic
Potential
.
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35
4.5
Special
FQPA
Safety
Factor
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37
4.6
Endocrine
disruption
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37
5.0
Public
Health
Data
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37
5.1
Incident
Reports
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37
5.2
Other
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39
6.0
Exposure
Characterization/
Assessment
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39
6.1
Dietary
Exposure/
Risk
Pathway
.
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39
6.1.1
Residue
Profile
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39
6.1.2
Acute
and
Chronic
Dietary
Exposure
and
Risk
.
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39
6.1.2.
a.
Acute
Dietary
Exposure
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39
6.1.2.
b.
Chronic
Dietary
Exposure
(
Food
Only)
.
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39
6.1.2.
c
Chronic
Dietary
Exposure
(
Water
Only)
.
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42
6.1.2.
d
Chronic
Dietary
Exposure
(
Food
+
Water)
.
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42
6.2
Water
Exposure/
Risk
Pathway
.
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44
6.2.1
Aquatic
Uses
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44
6.2.2
Terrestrial
Uses
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45
6.3
Residential
and
Other
Non­
Occupational
Exposures
and
Risks
.
.
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46
6.3.1
Residential
Handler
Exposures
and
Risks
.
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46
6.3.1.1
Handler
Exposure
Scenarios
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46
6.3.1.2
Data
and
Assumptions
For
Handler
Exposure
Scenarios
.
.
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47
6.3.1.3
Residential
Handler
Exposure
and
Risk
Estimates
.
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48
Risk
Summary:
.
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48
6.3.1.4
Summary
of
Risk
Concerns
and
Data
Gaps
for
Handlers
.
.
.
.
.
48
6.3.1.5
Recommendations
For
Refining
Residential
Handler
Risk
Assessment
.
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49
6.3.2
Residential
Postapplication
Exposures
and
Risks
.
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49
6.3.2.1Residential
Postapplication
Exposure
Scenarios
.
.
.
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.
49
6.3.2.2Residential
Postapplication
Exposure
and
Risk
Estimates
.
.
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.
49
Risk
Summary:
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49
6.3.3
Residential
Risk
Characterization
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50
6.3.3.1Characterization
of
Residential
Handler
Risks
.
.
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.
50
6.3.3.2Characterization
Of
Residential
Postapplication
Risks
.
.
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.
51
7.0
Aggregate
Risk
Assessments
and
Risk
Characterization
.
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51
7.1
Acute
Aggregate
Risk
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51
7.2
Short­
Term
Aggregate
Risk
.
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51
Page
4
of
76
7.3
Intermediate­
Term
Aggregate
Risk
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52
7.4
Long­
Term
Aggregate
Risk
.
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52
7.5
Cancer
Risk
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52
8.0
Cumulative
Risk
Characterization/
Assessment
.
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53
9.0
Occupational
Exposure/
Risk
Pathway
.
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53
9.1
Occupational
Handler
Exposures
and
Risks
.
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53
9.1.1
Data
and
Assumptions
For
Handler
Exposure
Scenarios
.
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.
54
9.1.1.1Assumptions
for
Handler
Exposure
Scenarios
.
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.
54
9.1.1.2Exposure
Data
for
Handler
Exposure
Scenarios
.
.
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.
55
9.1.2
Endothall
Handler
Exposure
Scenarios
.
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58
9.1.3
Endothall
Handler
Exposure
and
Assessment
.
.
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58
9.1.3.1
Endothall
Handler
Exposure
and
Risk
Calculations
.
.
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.
58
9.1.3.2Endothall
Risk
Summary
.
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60
9.1.4
Cancer
Endothall
Handler
Exposure
and
Risk
Assessment
.
.
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.
65
9.1.5
Summary
of
Risk
Concerns
and
Data
Gaps
for
Occupational
Handlers
.
.
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65
9.1.5.1
Summary
of
Data
Gaps
.
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.
65
9.1.6
Recommendations
For
Refining
Occupational
Handler
Risk
Assessment
.
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.
65
9.2
Occupational
Postapplication
Exposures
and
Risks
.
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.
65
10.0
Date
Needs
and
Label
Requirements
.
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66
10.1
Toxicology
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66
10.2
Residue
Chemistry,
Label
Needs,
Tolerance
Reassessment
.
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66
10.3
Occupational
and
Residential
Exposure
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68
References
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70
Appendices
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71
Page
5
of
76
1.0
Executive
Summary
This
assessment
provides
information
to
support
issuance
of
a
risk
management
decision
document
known
as
a
Reregistration
Eligibility
Decision
(
RED)
Document
for
Endothall.
EPA's
pesticide
reregistration
process
provides
for
the
review
of
older
pesticides
(
those
initially
registered
prior
to
November
1984)
under
the
Federal
Insecticide,
Fungicide
and
Rodenticide
Act
(
FIFRA)
to
insure
that
they
meet
current
scientific
and
regulatory
standards.
The
process
considers
the
human
health
and
ecological
effects
of
pesticides
and
incorporates
a
reassessment
of
tolerances
(
pesticide
residue
limits
in
food)
to
insure
that
they
meet
the
safety
standard
established
by
the
Food
Quality
Protection
Act
(
FQPA)
of
1996.

Use
and
usage
information
Endothall
[
7­
oxabicyclo[
2,2,1]
heptane­
2,3­
dicarboxylic
acid]
is
a
selective
contact
herbicide,
defoliant,
desiccant,
and
aquatic
algicide
which
belongs
to
the
dicarboxylic
acid
chemical
class.
Endothall
(
PC
Code
038901)
and
its
dipotassium
(
PC
Code
038904)
and
alkylamine
(
PC
Code
038905)
salts
are
registered
primarily
as
aquatic
herbicides
to
control
a
variety
of
plants
including
plankton,
pondweed,
naiad,
coontail,
milfoil,
elodea,
and
algae
in
water
bodies.
They
are
also
registered
for
desiccation/
defoliation
of
alfalfa/
clover
(
grown
for
seed
only),
cotton,
and
potatoes
prior
to
harvest,
and
for
reduction
of
sucker
branch
growth
in
hops.

Endothall
acid
and
its
dipotassium
and
mono­
N,
N­
dimethylalkylamine
salts
are
FIFRA
List
B
chemicals.
Although
there
are
other
inactive
Endothall
salts
in
Case
2245,
only
the
active
compounds,
endothall
acid
(
PC
038901)
and
it's
dipotassium
(
PC
038904)
and
mono­
N,
Ndimethylalkylamine
(
PC
038905)
salts
are
being
considered
in
this
reregistration.

The
endothall
formulation
classes
which
are
registered
on
food/
feed
crops
include
the
granular
(
G)
and
soluble
concentrate
liquid
(
SC/
L).
The
G
formulations
typically
contain
10.1%,
11.2%,
or
63%
acid
equivalent
(
ae),
and
the
SC/
L
formulations
contain
0.52,
2.0,
or
3.0
lb
ai/
gal.
Both
formulation
classes
may
be
applied
using
waterborne,
ground
or
aerial
equipment.
The
maximum
treatment
rate
of
endothall,
when
applied
on
aquatic
areas
(
including
irrigation
and
drainage
canals,
lakes,
and
ponds
where
water
may
be
used
as
potable
water)
is
5
ppm.
When
applied
on
agricultural
crops,
the
maximum
registered
seasonal
rates
range
from
0.10
to
2.0
lb
ae/
A
with
preharvest
intervals
of
3
to
85
days.

Endothall
is
applied
as
a
spray
with
aerial
and
groundboom
equipment
when
used
as
a
harvest­
aid
agent
and
when
used
as
a
sucker
suppressant
on
hops,
endothall
is
applied
with
ground
equipment
only.
When
used
as
an
aquatic
herbicide,
a
variety
of
equipment
may
be
used.
Boats
used
to
treat
aquatic
weeds
are
normally
designed
to
apply
sprays
and
granular
applications
from
the
bow.
For
occupational
applications
of
liquid
formulations
to
water,
endothall
may
be
sprayed
onto
the
water
surface
using
hand­
held
or
boat­
mounted
equipment
similar
to
handgun
sprayers
(
for
smaller­
scale
applications).
Endothall
may
also
be
directly
metered
into
the
suction
side
of
a
pump
and
injected
below
the
surface
of
the
water.
This
technique
is
the
only
method
of
application
to
flowing
waters,
but
is
also
used
for
applications
to
quiescent
waters.
For
occupational
applications
of
granular
formulations
to
water,
ground
boom
data
from
PHED
data
base
is
used.
For
Residential
applications
of
granular
formulations
to
water,
HED
assumes
that
a
belly­
grinder­
type
granular
spreader
is
used
Page
6
of
76
Hazard
Profile
The
toxicology
data
base
for
Endothall
is
complete
except
for
a
developmental/
teratology
study
in
the
nonrodent
(
rabbit)
and
a
28­
day
inhalation
toxicity
study.
All
studies
on
hand
have
been
reviewed
and/
or
had
their
review
updated.

Endothall
is
a
caustic
chemical
with
toxicity
being
the
result
of
a
direct
degenerative
effect
on
tissue.
Dermally,
it
destroys
the
stratum
corneum
and
then
the
underlying
viable
epidermis.
Orally,
it
attacks
the
digestive
tract.
The
dog
is
particularly
sensitive
to
endothall
toxicity.
Orally,
it
attacks
the
canine
digestive
tract
at
relatively
low
doses
and
then
the
liver
and
kidneys
at
lethal
doses.
The
rabbit
is
strangely
sensitive
to
ocular
instillation
of
endothall.
In
the
eye
irritation
study,
Endothall
technical
was
extremely
irritating
to
the
eye
as
expected
but
was
also
lethal
to
4/
6
rabbits
tested.

Endothall
is
an
extreme
irritant
by
the
dermal,
oral,
and
ocular
routes
of
administration
(
category
I),
and
is
a
skin
sensitizer.
By
dermal
application
and
inhalation,
it
has
mild
toxicity
(
category
III).

Endothall
is
not
a
neurotoxicant,
nor
does
it
induce
developmental
toxicity
in
the
rat
developmental
toxicity,
or
in
the
2­
generation
reproduction
studies.
Endothall
is
classified
as
"
not
likely
to
be
carcinogenic
to
humans"
based
on
lack
of
evidence
of
carcinogenicity
in
mice
or
rats.
It
has
no
mutagenic
potential.

In
metabolism
studies,
endothall
was
excreted
unchanged
in
the
feces
and
urine.
In
the
dermal
absorption
study,
the
dose
related
pattern
of
absorption
was
typical
of
a
chemical
which
directly
damages
the
skin
destroying
its
barrier
function.
That
is,
the
percent
of
dose
absorbed
increased
with
increasing
dose.

Hazard
Identification
and
Food
Quality
Protection
Act
(
FQPA)
Decision
The
Hazard
Identification
Assessment
Review
Committee
(
HIARC)
dated
June
14,
2004
selected
the
following
endpoints
for
exposure
risk
assessment:

Dermal
No
dermal
endpoint
was
selected
because
the
dermal
irritation
observed
in
a
repeated­
dose
study
is
considered
self­
limiting.
Current
product
labels
recommend
protective
clothing
(
rubber
gloves,
face
shields
or
goggles)
when
handling
liquid
formulations.

Inhalation
The
short­
term
inhalation
risk
assessment
for
endothall
is
based
on
a
NOAEL
of
9.4
mg/
kg/
day
based
on
decreased
pup
body
weight
(
both
sexes)
on
Day
0
F
1
and
F
2
generations
in
a
2­
generation
rat
reproduction
(
oral
feeding)
study.
HED's
level
of
concern
(
LOC)
for
short­
term
occupational
inhalation
risk
is
100
(
i.
e.,
an
MOE
less
than
100,
exceeds
HED's
level
of
concern)
and
the
LOC
for
short­
term
residential
inhalation
risk
is
100
(
i.
e.,
an
MOE
less
than
100,
exceeds
HED's
level
of
concern).
The
intermediate­
term
inhalation
risk
assessment
for
endothall
is
based
on
an
LOAEL
of
2
mg/
kg/
day
and
is
based
on
proliferative
lesions
of
the
Page
7
of
76
gastric
epithelium
(
both
sexes)
in
a
2­
generation
rat
reproduction
(
oral
feeding)
study.
HED's
level
of
concern
(
LOC)
for
intermediate­
term
occupational
and
residential
inhalation
risks
is
300.
Another
3X
is
added
to
account
for
the
lack
of
a
NOAEL.
Long­
term
exposures
to
endothall
(
i.
e.
greater
than
6
months)
are
not
expected
for
current
registered
uses.

Oral
The
short­
term
oral
risk
assessment
for
endothall
is
based
on
a
NOAEL
of
9.4
mg/
kg/
day
based
on
decreased
pup
body
weight
(
both
sexes)
on
Day
0
F
1
and
F
2
generations
in
a
2­
generation
rat
reproduction
(
oral
feeding)
study.

An
acute
dietary
hazard
value
was
not
identified
for
the
general
population
or
for
females
of
child­
bearing
age
(
13­
49
years
old).
This
is
because
there
is
no
appropriate
endpoint
attributable
to
a
single
dose
in
any
of
the
studies
submitted.

Finally,
in
deriving
uncertainty
for
use
in
the
risk
assessment,
the
conventual
10x
factor
for
interspecies
extrapolation
and
10x
for
intraspecies
extrapolation
were
used
for
all
scenarios.
The
data
base
was
complete
enough
and
there
was
no
evidence
of
pre­
or
post­
natal
susceptibility
in
the
studies
submitted
and
evaluated
to
date.
Therefore,
the
FQPA
10X
factor
was
reduced
to
1x.
The
exposure
scenarios
in
which
the
hazard
value
was
based
on
a
LOAEL
(
intermediate
term
inhalation
for
both
occupational
and
residential
settings)
an
additional
uncertainty
factor
of
3x
was
used
to
approximate
a
NOAEL.

Residential
and
Occupational
Exposure
For
agricultural
uses,
HED
relied
almost
completely
on
surrogate
data
from
the
Pesticide
Handlers
Exposure
Database
(
PHED)
Version
1.1.
For
aquatic
uses
data
from
the
Pesticide
Handlers
Exposure
Database
(
PHED)
and
ORETF
were
used.
For
residential
handler
exposure
HED
used
the
ORETF
study
data
and
the
Residential
SOPs.

The
short­
term
inhalation
handler
risk
assessments
for
endothall
agricultural
crop
applications
indicate
no
risk
concerns
(
MOEs

100)
at
baseline
(
i.
e.,
no
respirator)
for
most
scenarios.
For
aerial
applications,
there
are
no
risk
concerns
(
MOEs

100)
with
engineering
controls.
The
short­
term
inhalation
handler
risk
assessments
for
endothall
aquatic
applications
indicate
no
risks
concerns
(
MOEs

100)
at
baseline
(
i.
e.,
no
respirator)
for
all
scenarios.
For
mixing/
loading/
applying
liquid
formulations
with
direct
metering,
there
is
no
risk
of
concern
(
MOEs

100)
with
closed
system
engineering
controls.

For
most
of
the
agricultural
crop
scenarios,
the
intermediate­
term
inhalation
MOEs
for
handlers
are
greater
than
300
at
baseline
(
i.
e.,
no
respirator).
The
intermediate­
term
inhalation
handler
risk
assessments
for
endothall
aquatic
applications
indicate
no
risks
concerns
(
MOEs

300)
with
closed
system
engineering
controls
for
mixing/
loading/
applying
liquid
formulations
through
direct
metering
to
lakes/
ponds.

For
residential
handlers,
short­
term
inhalation
MOEs
are
not
of
concern
for
the
pond
scenarios,
because
they
do
not
exceed
the
Agency's
uncertainty
factor
(
i.
e.,
MOE

100)
for
risk
Page
8
of
76
assessments
in
nonoccupational
settings.
For
treating
ponds,
the
inhalation
MOEs
range
from
470
to
1900.
Short­
term
inhalation
risks
to
residential
handlers
are
not
a
concern
for
treating
garden
pools,
the
inhalation
MOE
is
2,700.

The
overall
results
indicate
that
the
Agency
has
no
risk
concerns
for
most
endothall
use­
patterns
involving
agricultural
crops,
aquatic
and
residential
uses.

Dietary
Exposure
The
endothall
formulation
classes
which
are
registered
on
food/
feed
crops
include
the
granular
(
G)
and
soluble
concentrate
liquid
(
SC/
L).
The
G
formulations
typically
contain
10.1%,
11.2%,
or
63%
acid
equivalent
(
ae),
and
the
SC/
L
formulations
contain
0.52,
2.0,
or
3.0
lb
ae/
gal.
Both
formulation
classes
may
be
applied
using
ground
or
aerial
equipment.
When
applied
on
agricultural
crops,
the
maximum
registered
seasonal
rates
range
from
0.10
to
2.0
lb
ae/
A
with
preharvest
intervals
of
3
to
85
days.
The
maximum
treatment
rate
of
endothall,
when
applied
on
aquatic
areas
(
including
irrigation
and
drainage
canals,
lakes,
and
ponds
where
water
may
be
used
as
potable
water)
is
5
ppm.

The
qualitative
nature
of
the
residue
in
plants
and
animals
is
adequately
understood.
The
Endothall
reregistration
team
has
determined
that
the
residue
of
concern
for
risk
assessment
in
plants
and
livestock
and
fish
is
endothall
and
its
monomethyl
ester.
The
residue
to
be
measured
for
tolerance
enforcement
in
plants,
animals
and
fish
is
also
the
combined
residues
of
endothall
and
its
monomethyl
ester,
which
can
be
measured
after
an
hydrolysis
step.
The
residues
of
concern
in
water
is
only
endothall,
per
se.

Tolerances
for
residues
of
endothall,
from
use
of
the
mono­
N,
N­
dimethylalkylamine
salt,
in/
on
plant
commodities
should
be
revised
to
be
expressed
in
terms
of
endothall
per
se
and
its
monomethyl
ester
[
40
CFR
§
180.293].
Tolerances
are
established
for
residues
in/
on
undelinted
cottonseed
(
0.1
ppm),
hops
(
0.1
ppm),
potato
(
0.1
ppm),
and
rice
grain
and
straw
(
0.05
ppm
each)
and
will
not
change
in
value.
An
interim
tolerance
of
0.2
ppm
has
been
established
for
residues
of
endothall
in
potable
water.
This
tolerance
should
be
revoked.
A
Maximum
Contaminant
Level
(
MCL)
has
been
established
for
endothall
of
100
ug/
L.
Under
40
CFR
§
180.319,
an
interim
tolerance
exists
for
residues
of
endothall
in/
on
sugar
beets
at
0.2
ppm.
EPA
recommends
that
this
interim
tolerance
should
be
continued
to
cover
uses
of
endothall
in
irrigation
water.
No
endothall
tolerances
have
been
established
for
livestock
commodities.
The
available
ruminant
and
poultry
metabolism
studies
suggest
that
detectable
residues
of
endothall
are
likely
to
be
transferred
to
meat,
milk,
poultry
and
eggs
as
a
result
of
registered
uses
on
feedstuffs.
Thus,
the
registrant
has
been
required
to
conduct
animal
(
ruminant
and
poultry)
feeding
studies
which
will
be
used
to
determine
the
levels
of
secondary
residues
in
meat,
milk,
poultry,
and
eggs
in
order
to
set
appropriate
tolerances.
Data
have
been
submitted
to
support
tolerances
in
fin
fish.
These
fish
tolerances
may
be
acceptable
if
the
data
are
supported
by
a
radiovalidated
enforcement
method
and
stability
study.

GC
method
with
microcoulometric
nitrogen
detection
is
listed
as
Method
I
in
the
Pesticide
Analytical
Manual
(
PAM,
Volume
II)
for
the
determination
of
endothall
residues
in/
on
crop
commodities.
An
improved
HPLC­
MSD
method
has
been
submitted
as
a
confirmatory
enforcement
method
for
plants
and
fish.
Data
collection
and
regulatory
analytical
methods
for
Page
9
of
76
animal
commodities
are
currently
not
available
and
are
required
for
reregistration.

The
submitted
magnitude
of
the
residue
studies
for
alfalfa
seed,
and
cottonseed
have
been
reviewed
and
were
deemed
inadequate
to
satisfy
reregistration
requirements
mainly
because
of
insufficient
geographic
representation
of
data.
The
submitted
magnitude
of
the
residue
study
for
potatoes
has
been
reviewed
and
was
deemed
inadequate
because
the
potatoes
were
treated
at
2
quarts
ai/
A
(
2
lbs
ai/
A
or
2x)
in
these
field
trials
(
and
yielded
residues
above
the
current
tolerance),
while
the
current
label
rate
is
1
quart/
A
(
1
lb
ae/
A).
The
submitted
data
for
hops
supports
the
national
section
3
labels,
but
does
not
support
the
section
24(
c)
local
uses
because
a
different
PHI
was
used.

The
submitted
residue
data
for
irrigated
cabbage,
celery,
grapefruit,
pepper,
and
turnip
have
been
deemed
inadequate,
pending
additional
information,
because
in
multiple
applications
the
individual
water
treatment
rate
used
was
3
ppm
ae,
applied
5
times,
while
the
maximum
labeled
individual
treatment
rate
is
5
ppm
ae
in
the
water.
Because
it
is
unclear
how
often
the
5
ppm
rate
would
be
applied
in
a
season,
a
maximum
seasonal
rate
must
be
proposed
for
the
label
before
it
can
be
determined
if
these
studies
adequately
reflect
labeled
treatment
rates.
In
addition,
these
five
crops
do
not
adequately
cover
all
irrigated
crops
that
will
need
tolerances.
Discussions
between
HED
and
the
registrant
are
needed
to
decide
which
additional
crops
can
best
fulfill
those
needs.

A
submitted
confined
rotational
crop
study
has
been
deemed
inadequate
because
an
unknown
that
constituted
the
largest
portion
of
the
TRR
was
not
identified,
however
HED
concedes
that
the
only
residues
of
concern
that
could
be
in
rotational
crops
are
endothall
and
its
monomethyl­
and
dimethyl­
ethers.
So
a
new
confined
rotational
crop
study
is
needed.
In
lieu
of
repeating
the
confined
rotational
crop
study
the
registrant
may
perform
the
full
battery
of
limited
field
trials
(
on
the
grounds
that
TRR
for
some
commodities
from
all
crops
exceeded
0.01
ppm
at
all
post
treatment
intervals
in
the
existing
confined
rotational
crop
study)
so
long
as
endothall
and
its
monomethyl­
and
dimethyl­
esters
are
analyzed
in
these
field
trials.

The
submitted
processing
studies
on
cotton
and
potatoes
are
acceptable,
and
the
results
of
these
studies
show
that
endothall
does
not
concentrate
in
the
processed
fractions
of
cotton
and
potatoes.
The
registrant
has
also
submitted
a
sugar
beet
processing
study
which
was
deemed
inadequate,
in
part
because
the
results
are
not
supported
by
storage
stability
data
(
processed
samples
were
stored
for
4.5
years
without
supporting
data).

Chronic
Dietary
Exposure
(
Food
Only)
Results
and
Characterization
Endothall
has
uses
for
direct
application
to
crops
and
also
has
aquatic
uses
to
treat
water
that
may
subsequently
be
used
to
irrigate
crops.
To
assess
food
only
residues
from
these
uses,
two
assessments
were
performed
for
dietary
exposure
to
endothall.
One
assessment
was
based
solely
upon
residues
in/
on
crops
directly
treated
with
endothall.
Another
assessment
incorporated
both
residues
from
directly
treated
crops
and
from
crops
irrigated
with
water
containing
endothall.

The
results
of
the
DEEMTM
analysis
based
upon
directly
treated
crops
only
were
1.2%
of
the
cPAD
(
0.000084
mg/
Kg/
day)
for
the
general
population.
The
most
highly
exposed
population
Page
10
of
76
subgroup
was
children
3­
5
at
3%
cPAD
(
0.000211
mg/
Kg/
day).
These
results
were
based
upon
tolerances
(
and
hops
were
assumed
to
be
100%
crop
treated)
and
so
should
be
somewhat
conservative.

The
results
of
the
DEEMTM
analysis,
for
food
only,
based
upon
both
directly
treated
crops
and
crops
that
may
have
been
irrigated
with
endothall
treated
water
were
2.7%
of
the
cPAD
(
0.000189
mg/
Kg/
day)
for
the
general
population.
The
most
highly
exposed
population
subgroup
was
children
1­
2
at
7.8%
cPAD
(
0.000544
mg/
Kg/
day).

Conservative
assumptions
were
used
in
estimating
residues
in
the
various
specific
irrigated
crops.
These
assessments
also
began
with
an
assumption
that
all
crops
are
100%
irrigated
with
water
containing
endothall.
Subsequently,
the
total
portion
of
the
exposure
from
crops
that
may
be
irrigated
with
endothall
was
adjusted
by
a
factor
of
0.01.
The
factor
of
0.01
was
determined
by
an
estimate
that
not
more
than
about
0.024%
of
all
crops
in
the
entire
U.
S.
were
likely
to
be
treated
with
endothall.
The
value
of
0.024%
was
conservatively
rounded
up
to
1%
to
account
for
variations
amongst
individual
crops,
regions,
etc;
and
the
1%
was
then
applied
to
the
entire
anticipated
exposure
through
crops
from
irrigated
water.
This
approach
was
necessitated
because
the
DEEMTM
and
LifelineTM
models
are
designed
to
estimate
exposure
using
crop
by
crop
information,
but
no
crop
by
crop
data
were
available
on
the
percent
of
each
crop
that
is
irrigated
with
endothall
containing
water.

Chronic
Dietary
Exposure
(
Water
Only)

Exposures
based
on
drinking
water
from
aquatic
uses
were
also
calculated
in
DEEMTM.
The
results
were
30%
of
the
cPAD
(
0.002108
mg/
Kg/
day)
for
the
general
population.
The
most
highly
exposed
population
subgroup
was
infants
(<
1
year
old)
at
99%
cPAD
(
0.006910
mg/
Kg/
day).

Chronic
Dietary
Exposure
(
Food
Plus
Water)

Exposures
based
on
treated
crops,
irrigated
crops
and
drinking
water
from
aquatic
uses
were
also
calculated
in
DEEMTM.
The
results
for
directly
treated
crops
plus
water
were
31%
of
the
cPAD
(
0.002191
mg/
Kg/
day)
for
the
general
population.
The
most
highly
exposed
population
subgroup
was
infants
(<
1
year
old)
at
100%
cPAD
(
0.007017
mg/
Kg/
day).
The
results
for
food
from
both
directly
treated
crops,
and
irrigated
crops,
plus
water
were
33%
of
the
cPAD
(
0.002297
mg/
Kg/
day)
for
the
general
population.
The
most
highly
exposed
population
subgroup
was
infants
at
103%
cPAD
(
0.007234
mg/
Kg/
day).

Aggregate
Exposure
Assessment
Because
residential
exposures
are
short­
term
in
nature,
only
a
short­
term
aggregate
risk
assessment
was
conducted.
For
adults,
estimated
dietary
exposures
via
food
and
drinking
water
were
combined
with
inhalation
exposures
during
application
to
a
pond
or
lake
and
potential
postapplication
exposures
during
swimming.
HED
notes
the
handler
scenario
aggregated
for
adults
is
the
exposure
scenario
resulting
in
the
lowest
MOE
(
highest
risk
estimate)
for
residential
handlers.
For
children,
estimated
dietary
exposures
via
food
and
drinking
water
were
combined
with
Page
11
of
76
potential
post­
application
exposures
during
swimming.
The
short­
term
aggregate
risk
estimate
(
MOE)
for
adults
is
310,
for
children,
it
is
250.
MOEs
greater
than
100
are
not
a
risk
concern.
Therefore,
there
are
no
short­
term
aggregate
(
food
+
drinking
water
+
residential)
risk
concerns
for
endothall
Page
12
of
76
2.0
Ingredient
Profile
2.1
Summary
of
Registered/
Proposed
Uses
Table
2.1.
Registered
Food/
Feed
Use
Patterns
of
Endothall
(
PC
Code
038901).

Site
Application
Timing
Application
Type
Application
Equipment
Formulatio
n
[
EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ae
Maximum
Number
of
Applicatio
ns
Per
Season
Maximum
Seasonal
Rate,
ae
Preharv
est
Interval,
Days
Use
Directions
and
Limitations
Alfalfa
(
Grown
for
Seed)
and
Clover
(
including
Crimson,
Alsike,
Ladino,
Red,
Sweet,
and
White
Types
of
Clover
Grown
for
Seed)

Preharvest
dessication
Foliar
Ground
and
aerial
0.52
lb
ae/
gal
SC/
L
[
4581­
206]
0.65
lb/
A
when
applied
2x
per
season
or
0.78
lb/
A
when
applied
once
per
season
1
or
2
1.30
lb/
A
when
applied
2x
per
season
5
Use
limited
to
crops
grown
for
seed.
Apply
in
8­
9
gal
of
water
per
acre
or
GPA
(
aerial)
or
in
15­
20
GPA
(
ground).
Treated
plants
must
be
harvested
by
mechanical
means
only.
When
to
combine
is
dependent
on
the
weather
but
usually,
the
desiccated
alfalfa
or
clover
is
ready
to
combine
5­
10
days
after
treatment.
Seed
crops
should
not
be
sprayed
until
the
seed
is
mature,
and
the
plants
have
lost
moisture
normally
following
the
end
of
the
irrigation
season.

Cotton
Preharvest
defoliation
or
dessication
Foliar
Aerial
0.52
lb
ae/
gal
SC/
L
[
4581­
284]
0.10
lb/
A
not
specified
not
specified
not
specifie
d
Apply
in
a
minimum
of
3
GPA
of
water
using
aerial
equipment.
Application
through
any
type
of
irrigation
equipment
in
prohibited.
Apply
when
fiber
quality
of
the
top
bolls
will
not
be
damaged
by
loss
of
the
top
leaves
which
feed
these
bolls.
Top
bolls
should
be
firm
to
thumb
pressure
or
difficult
to
cut
with
knife.
May
be
applied
as
a
tank
mix
with
other
registered
cotton
defoliants
or
desiccants
including
tribufos
(
Def
®
and
Folex
®
)
,
dimethipin
(
Harvade
®
)
,
paraquat
(
Starfire
®
and
Cyclone
Max
®
)
,
thidiazuron
(
Dropp
®
)
,
sodium
chlorate,
cacodylic
acid,
ethephon
(
Prep
®
and
Cottonquick
®
)
,
and
glyphosate
(
Roundup
®
)
.
Table
2.1.
Registered
Food/
Feed
Use
Patterns
of
Endothall
(
PC
Code
038901).

Site
Application
Timing
Application
Type
Application
Equipment
Formulatio
n
[
EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ae
Maximum
Number
of
Applicatio
ns
Per
Season
Maximum
Seasonal
Rate,
ae
Preharv
est
Interval,
Days
Use
Directions
and
Limitations
Page
13
of
76
O
OH
O
O
OH
Hops
Preharvest
dessication
Basal
directed
Ground
0.52
lb
ae/
gal
SC/
L
[
4581­
206]
[
OR03003
6]
1.0
lb/
A
2
2.0
lb/
A
(
implied)
85
[
4581­
206]
or
28
[
OR030
036]
For
use
in
hops
sucker
suppression.
Not
for
use
in
CA.
Make
first
application
when
main
bines
are
2­
3
feet
tall.
Subsequent
applications
may
be
made
7­
14
days
later
when
hops
suckers
are
1­
2
feet
long.
Avoid
spraying
main
bine
within
1­
2
feet
of
growing
point.
Apply
in
15­
40
GPA
of
water
using
ground
equipment
only.

Potato
Preharvest
vine
desiccation
Foliar
Ground
and
aerial
0.52
lb
ae/
gal
SC/
L
[
4581­
206]
1.0
lb/
A
2
2.0
lb/
a
10
Treated
plants
must
be
harvested
by
mechanical
means
only.
Culling
of
harvested
potatoes
is
allowed.
May
be
applied
using
aerial
(
5­
10
GPA)
or
ground
(
20­
100
GPA)
equipment.
For
exceptionally
heavy
vines,
apply
0.52
lb
ae/
A
in
5
gal
of
water
per
acre
in
one
direction
followed
immediately
by
a
similar
amount
applied
at
right
angles
to
the
first
set
of
swaths.
The
addition
of
diesel
oil
or
paraffin
base
herbicide
oil
may
increase
speed
and
overall
vine
kill.

2.2
Structure
and
Nomenclature
TABLE
2.2.
Endothall
and
Salts
Nomenclature
Chemical
Structure
Common
name
Endothall
Molecular
Formula
C8H10O5
Molecular
Weight
186.16
TABLE
2.2.
Endothall
and
Salts
Nomenclature
Page
14
of
76
O
O
O
O
O
K
+

K
+

O
O
O
O
O
[
NH(
CH
3)
2(
CH
2)
n(
CH
3)]+

n=
7­
17
IUPAC
name
7­
oxabicyclo[
2.2.1]
heptane­
2,3­
dicarboxylic
acid
CAS
name
7­
oxabicyclo[
2.2.1]
heptane­
2,3­
dicarboxylic
acid
CAS
#
145­
73­
3
PC
Code
038901
Current
Food/
Feed
Site
Registration
Cotton,
hops,
potato,
alfalfa
grown
for
seed
Chemical
Structure
Common
name
Endothall,
dipotassium
salt
Molecular
Formula
C8H8K2O5
Molecular
Weight
262.33
IUPAC
name
Not
available
CAS
name
Not
available
CAS
#
2164­
07­
0
PC
Code
038904
Current
Food/
Feed
Site
Registration
Cotton,
hops,
potato,
alfalfa
grown
for
seed,
aquatic
uses
Chemical
Structure
Common
name
Endothall,
mono­
N,
N­
dimethyl
alkyl
amine
salt
Molecular
Formula
Not
available
Molecular
Weight
Average:
422
IUPAC
name
7­
oxabicyclo[
2.2.1]
heptane­
2,3­
dicarboxylic
acid,
compound
with
N,
Ndimethylcocoamine
CAS
name
Not
available
CAS
#
66330­
88­
9
PC
Code
038905
Current
Food/
Feed
Site
Registration
Cotton,
hops,
potato,
alfalfa
grown
for
seed,
aquatic
uses
Page
15
of
76
2.3
Physical
and
Chemical
Properties
TABLE
2.3.
Physicochemical
Properties
of
Endothall
and
Salts
Parameter
Value
Reference
Endothall
(
acid)

Melting
point
108­
110

C
D187593,
D187590,
and
D187588,
5/
5/
93,
K.
Dockter
pH
2.7
at
25

C
(
1%
solution)
D187593,
D187590,
and
D187588,
5/
5/
93,
K.
Dockter
Density,
bulk
density,
or
specific
gravity
0.481
g/
cm3
(
bulk)
at
25

C
D187593,
D187590,
and
D187588,
5/
5/
93,
K.
Dockter
Water
solubility
at
25

C
109.8
g/
L
13.1
g/
100
mL
in
water,
pH
5
12.7
g/
100
mL
in
water,
pH
7
12.5
g/
100
mL
in
water,
pH
9
D166798,
7/
2/
92,
K.
Dockter
D207011,
9/
30/
94,
F.
Toghrol
Solvent
solubility
at
25

C
3.4
g/
100
mL
in
acetonitrile
2.4
g/
100
mL
in
n­
octanol
16.0
g/
100
mL
in
tetrahydrofuran
D207011,
9/
30/
94,
F.
Toghrol
Vapor
pressure
3.92
x
10­
5
mm
Hg
at
24.3

C
D166798,
7/
2/
92,
K.
Dockter
Dissociation
constant,
pKa
4.32
for
Step
1
and
6.22
for
Step
2
at
20

C
(
0.2%
solution
in
20%
basic
ethanol);
dissociation
rate
1.8­
2.3
x
103

mho
within
3­
5
minutes
at

25

C,
by
conductivity
meter
D188708,
5/
3/
93,
K.
Dockter
Octanol/
water
partition
coefficient
Not
applicable
to
endothall
acid
D166798,
7/
2/
92,
K.
Dockter
UV/
visible
absorption
spectrum
Not
available
Endothall,
dipotassium
salt
Melting
point
>
360

C
D187593,
D187590,
and
D187588,
5/
5/
93,
K.
Dockter
pH
9.1
at
25

C
(
1%
solution)
D187593,
D187590,
and
D187588,
5/
5/
93,
K.
Dockter
Density,
bulk
density,
or
specific
gravity
0.766
g/
cm3
(
bulk)
at
25

C
D187593,
D187590,
and
D187588,
5/
5/
93,
K.
Dockter
Water
solubility
>
65
g/
100
mL
in
water,
pH
5,
pH
7,
and
pH
9
D214691,
6/
7/
95,
D.
Hrdy
Solvent
solubility
<
0.001
g/
100
mL
in
acetonitrile,
n­
octanol,
and
tetrahydrofuran
D214691,
6/
7/
95,
D.
Hrdy
Vapor
pressure
Not
applicable.
An
organic
acid
K
salt
is
anticipated
to
have
an
insignificant
vapor
pressure.
D178085,
6/
18/
92,
S.
Funk
Dissociation
constant,
pKa
4.16
for
Step
1
and
6.14
for
Step
2
at
20

C
in
water;
dissociation
complete
at

5
mins
(
13.6
x
103

mho)
D304027,
6/
10/
2004,
D.
Soderberg
TABLE
2.3.
Physicochemical
Properties
of
Endothall
and
Salts
Parameter
Value
Reference
Page
16
of
76
Octanol/
water
partition
coefficient
KOW
<
0.02
and
<
0.3
at
concentrations
of
9
x
10­
3
M
and
9
x
10­
4
M,
respectively,
at
25

C
D210814,
8/
9/
95,
S.
Knizner
UV/
visible
absorption
spectrum
Not
available
Endothall,
mono­
N,
N­
dimethyl
alkyl
amine
salt
Boiling
point
Not
available
pH
5.2
at
25

C
(
1%
solution)
D187593,
D187590,
and
D187588,
5/
5/
93,
K.
Dockter
Density,
bulk
density,
or
specific
gravity
1.028
g/
mL
at
25

C
D187593,
D187590,
and
D187588,
5/
5/
93,
K.
Dockter
Water
solubility
at
25

C

49.2
g/
100mL
in
water,
pH
5

51.6
g/
100
mL
in
water,
pH
7

49.8
g/
100
mL
in
water,
pH
9
D210814,
8/
9/
95,
S.
Knizner
Solvent
solubility
at
25

C

102.5
g/
100mL
in
acetonitrile

95.4
g/
100
mL
in
n­
octanol

104.3
g/
100
mL
in
tetrahydrofuran
D210814,
8/
9/
95,
S.
Knizner
Vapor
pressure
2.09
x
10­
5
mm
Hg
at
25

C
(
calculated;
mixed
mono­
and
dialkylamine
(
C8­
C20))
D206344,
9/
22/
94,
F.
Toghrol
Dissociation
constant,
pKa
4.24
for
Step
1
and
6.07
for
Step
2
at
20

C
for
mixed
mono­
and
dialkylamine
(
C8­
C20)
in
acidified
ethanol/
water;
dissociation
complete

17
minutes
(
1.7
x
103

mho)
at
25

C
D198885,
4/
7/
94,
F.
Toghrol
Octanol/
water
partition
coefficient
KOW
2.097
at
concentrations
of
8.9
x
10­
3
M
and
8.9
x
10­
4
M,
at
25

C
D209995,
1/
20/
95,
L.
Edwards
UV/
visible
absorption
spectrum
Not
available
3.0
Metabolism
Assessment
3.1
Comparative
Metabolic
Profile
The
metabolism
in
plants
and
animals
is
very
similar.
Endothall,
per
se,
remains
the
major
residue.
The
major
metabolite
in
both
is
the
monomethyl
ester
with
minor
formation
of
the
dimethyl
ester.
Upon
further
metabolism
endothall
is
rapidly
broken
down
and
incorporated
into
tissues
as
natural
constituents.
By
combining
information
from
soil
and
water
metabolism
there
is
sufficient
information
on
rotated
crops
to
conclude
that
the
residues
of
concern
remain
the
same
in
rotated
crops.

3.2
Nature
of
the
Residue
in
Foods
3.2.1.
Description
of
Primary
Crop
Metabolism
The
metabolism
of
endothall
in
crops
is
adequately
understood.
Endothall
is
the
major
residue
Page
17
of
76
with
some
formation
of
the
monomethyl
ester.
These
are
the
residues
of
concern
for
risk
assessment
and
to
be
used
for
the
tolerance
expression.
It
appears
that
once
metabolic
changes
are
initiated
the
bicyclic
structure
of
endothall
is
rapidly
broken
up
and
endothall
fragments
become
incorporated
into
natural
constituents.
Page
18
of
76
3.2.2
Description
of
Livestock
Metabolism
The
metabolism
of
endothall
in
livestock
is
adequately
understood.
Endothall
and
its
monomethyl
ester
are
the
major
residues.
In
livestock
endothall
predominates.
In
poultry
tissue
the
monomethyl
ester
is
the
predominant
residue.
Thus
the
residues
of
concern
for
risk
assessment
and
to
be
used
for
the
tolerance
expression
is
endothall
and
its
monomethyl
ester.
It
appears
that
once
metabolic
changes
are
initiated
the
bicyclic
structure
of
endothall
is
rapidly
broken
up
and
endothall
fragments
become
incorporated
into
natural
constituents.

3.2.3
Description
of
Rotational
Crop
Metabolism,
including
identification
of
major
metabolites
and
specific
routes
of
biotransformation
An
adequate
confined
rotational
crop
study
has
not
been
submitted,
however,
by
comparing
existing
rotational
crop
information
with
plant
metabolism
information
and
soil
and
water
metabolism
data
it
is
possible
to
conclude
that
the
only
possible
residues
of
concern
in
rotated
crops
are
endothall
and
it
monomethyl­
and
dimethyl­
ester
metabolites.

3.3
Environmental
Degradation
Endothall,
per
se,
is
the
residue
of
concern
for
drinking
water.

3.4
Tabular
Summary
of
Metabolites
and
Degradates
Table
3.4.
Summary
of
Metabolites
and
Degradates
Chemical
Name
(
other
names
in
parenthesis)
Commodity
Percent
TRR
(
PPM)
1
Structure
Matrices
­
Major
Residue
(>
10%
TRR)
Matrices
­
Minor
Residue
(<
10%
TRR)

Endothall
Alfalfa
Forage
98%
TRR
Alfalfa
Seed
84%
TRR
Cotton
88%
TRR
Sugarbeet
Top
64%
TRR
Sugarbeet
Root
37%
TRR
Rotational
Crops
No
Data
No
Data
Goat
Kidney
51%
TRR
Goat
Liver
60%
TRR
Goat
Muscle
No
Residue
Goat
Fat
No
Residue
Milk
No
Residue
Chicken
Kidney
13%
TRR
Chicken
Liver
5%
TRR
Chicken
Muscle
No
Residue
Chicken
Skin
13%
TRR
Egg
White
No
Residue
Egg
Yolk
30%
TRR
Rat
Table
3.4.
Summary
of
Metabolites
and
Degradates
Chemical
Name
(
other
names
in
parenthesis)
Commodity
Percent
TRR
(
PPM)
1
Structure
Matrices
­
Major
Residue
(>
10%
TRR)
Matrices
­
Minor
Residue
(<
10%
TRR)

Page
19
of
76
Water
100%

Endothall
monomethyl
ester
Alfalfa
Forage
<
10%
TRR
Alfalfa
Seed
<
10%
TRR
Cotton
<
10%
TRR
Sugarbeet
Top
1.2%
TRR
Sugarbeet
Root
22%
TRR
Rotational
Crops
No
Data
No
Data
Goat
Kidney
26%
TRR
Goat
Liver
­­

Goat
Fat
No
Residue
Goat
Muscle
No
Residue
Milk
No
Residue
Chicken
Kidney
74%
TRR
Chicken
Liver
54%
TRR
Chicken
Skin
54%
TRR
Chicken
Muscle
No
Residue
Egg
White
No
Residue
Egg
Yolk
9%
TRR
Rat
Water
None
Endothall
dimethyl
ester
Alfalfa
Forage
<
10%
TRR
Alfalfa
Seed
<
10%
TRR
Cotton
<
10%
TRR
Sugarbeet
Top
3.4%
TRR
Sugarbeet
Root
0%
TRR
Rotational
Crops
No
Data
No
Data
Goat
Kidney
4%
TRR
Goat
Liver
­­

Moat
Fat
No
Residue
Goat
Muscle
No
Residue
Milk
No
Residue
Chicken
Kidney
0
Chicken
Liver
0
Chicken
Skin
0
Chicken
Muscle
No
Residue
Egg
White
No
Residue
Egg
Yolk
0
Rat
Water
None
Table
3.4.
Summary
of
Metabolites
and
Degradates
Chemical
Name
(
other
names
in
parenthesis)
Commodity
Percent
TRR
(
PPM)
1
Structure
Matrices
­
Major
Residue
(>
10%
TRR)
Matrices
­
Minor
Residue
(<
10%
TRR)

Page
20
of
76
The
final
row
of
the
table
should
have
a
concise
summary
of
relevant
parameters.
Alfalfa;
MRID
42619201,
0.65
lbs
ae/
A;
3X
rate,
near
maturity/
seed
pods
dying;
9
days
PHI
Cotton;
MRID
42619202,
0.1
lb
ae/
A;
1X;
maturity;
before
and
4
and
14
days
PHI.
Sugarbeet;
MRID
42619203;
1.5
lbs
ae/
A;
2,
48
and
132
days
PHI.
Goats;
MRID
42792701;
13.5
and
10.4
ppm
x
5
days,
4­
5X
Chickens;
MRID
42816601;
9.7
ppm
x
14
days,
30X
Rotational
Crops;
MRID
43300701;
D205980
Rat
;
MRID
42169502;
oral
0.9,
4.5
or
9.0
mg/
kg
single
dose
0.9
or
9.0
mg/
kc/
day
15
day.

3.5
Toxicity
Profile
of
Major
Metabolites
and
Degradates
The
1996
MARC
concluded
that
the
monomethyl
and
dimethyl
esters
of
endothall
are
likely
to
have
the
same
toxicity
as
the
parent.
Upon
doing
this
review,
HED
agrees
for
dietary
exposure
because
the
monomethyl
and
dimethyl
esters
can
be
rapidly
converted
back
to
endothall,
per
se,
in
the
gut.

3.6
Summary
of
Residues
for
Tolerance
Expression
and
Risk
Assessment
HED
recommends
that
the
residues
to
be
used
in
the
tolerance
expressions
for
plant
and
animal
commodities
consist
of
endothall
and
its
monomethyl
ester.
While
this
recommendation
represents
a
change
from
language
used
in
the
current
endothall
tolerance
expressions
as
listed
in
40
CFR
§
180.293,
it
does
not
significantly
change
the
actual
residues
subsumed
within
these
tolerance
expressions
and
so
does
not
change
the
tolerances.

Tolerances
Listed
Under
40
CFR
§
180.293
(
a)(
1)

Tolerances
are
established
for
residues
of
endothall
[
7­
oxabicyclo[
2,2,1]
heptane­
2,3­
dicarboxylic
acid]
from
use
of
its
mono­
N,
N­
dimethylalkylamine
salt,
wherein
the
alkyl
group
is
derived
from
the
fatty
acids
of
coconut
oil,
in/
on:
undelinted
cotton
seed,
hop,
potato,
rice
grain,
and
rice
straw.

HED
recommends
for
the
deletion
of
references
to
any
form
of
endothall
salts
in
the
tolerance
expression
since
HED
has
determined
that
the
dipotassium
salt
would
be
expected
to
behave
similarly
to
the
mono­
N,
N­
dimethylalkylamine
salt.
Similar
solubilities
and
transport
properties
are
anticipated
for
the
two
salts.

The
tolerances
for
"
cotton,
undelinted
seed",
"
hop",
and
"
potato"
could
not
be
reassessed
at
this
time
because
additional
data
are
required.
Although
there
are
presently
no
registered
uses
on
rice,
HED
recommends
for
the
retention
of
tolerances
for
"
rice,
grain"
and
"
rice,
straw"
until
the
registrant
has
submitted
the
requested
irrigation
crop
data
which
should
include
data
for
rice
commodities.
Page
21
of
76
Tolerance
Listed
Under
40
CFR
§
180.293
(
a)(
2)

An
interim
tolerance
of
0.2
ppm
is
established
for
residues
of
endothall
in
potable
water
from
use
of
its
potassium,
sodium,
di­
N,
N­
dimethylalkylamine,
and
mono­
N­
N­
dimethylalkylamine
salts
as
algicides
or
herbicides
to
control
aquatic
plants
in
canals,
lakes,
ponds,
and
other
potential
sources
of
potable
water.

This
interim
tolerance
should
be
revoked.
OPP
no
longer
establishes
tolerances
in
drinking
water.
EPA's
Office
of
Water
has
established
an
MCL
for
endothall
at
0.10
ppm.

Tolerance
Listed
Under
40
CFR
§
180.319
An
interim
tolerance
exists
for
residues
of
endothall
in/
on
sugar
beets
at
0.2
ppm.
Although
there
are
presently
no
registered
uses
on
sugar
beets,
HED
recommends
for
the
retention
of
the
interim
tolerance
for
sugar
beet,
as
"
beet,
sugar,
root,"
until
the
registrant
has
submitted
the
requested
irrigation
crop
data
which
should
include
data
for
sugar
beet
root
and
tops.
The
registrant
will
need
to
propose
a
tolerance
for
sugar
beet
tops
when
the
requested
data
have
been
received
and
evaluated.

Tolerances
to
be
Proposed
40
CFR
§
180.293
A
tolerance
for
cotton,
gin
byproducts
will
need
to
be
proposed
when
requested
cotton
field
trials
have
been
received
and
evaluated.

Tolerances
for
animal
commodities
will
need
to
be
proposed
when
the
requested
animal
feeding
studies
have
been
received
and
evaluated.

Tolerances
for
processed
commodities
may
be
needed
if
the
levels
of
endothall
residues
expected
in
processed
commodities
are
found
to
be
significantly
higher
than
the
RACs.

Tolerances
that
have
been
proposed
for
fish
and
shellfish
may
become
acceptable
after
the
appropriate
stability
data
and
independently
validated
enforcement
method
have
been
submitted.
(
An
ILV
has
been
submitted
as
MRID
46421403
and
is
currently
under
review.)

A
summary
of
metabolites
and
degradates
to
be
included
in
the
risk
assessment
and
tolerance
expression
are
presented
in
Table
3.6.1.
Page
22
of
76
3.6.1
Tabular
Summary
Table
3.6.
Summary
of
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
Crop
Endothall
and
its
Monomethyl
Ester
Endothall
and
its
Monomethyl
Ester
Rotational
Crop
TBD
TBD
Livestock
Ruminant
Endothall
and
its
Monomethyl
Ester
Endothall
and
its
Monomethyl
Ester
Poultry
Endothall
and
its
Monomethyl
Ester
Endothall
and
its
Monomethyl
Ester
Fish
Endothall
and
its
Monomethyl
Ester
Endothall
and
its
Monomethyl
Ester
Drinking
Water
Endothall
Not
Applicable
3.6.2
Rationale
for
Inclusion
of
Metabolites
and
Degradates
Other
than
binding
of
radioactive
residues
of
endothall
into
natural
tissue
constituents,
the
monomethyl
and
dimethyl
esters
of
endothall
are
the
only
metabolites
shown
to
have
been
formed
in
crops,
livestock
or
fish.
The
dimethyl
ester
has
only
been
found
in
trace
amounts.
In
some
cases
the
monomethyl
ester
is
a
very
significant
metabolite
or
can
even
predominate
over
endothall
as
the
major
residue.
Page
23
of
76
4.0
Hazard
Characterization/
Assessment
4.1
Hazard
and
Dose
Response
Characterization
Table
4.1a
Acute
Toxicity
Profile
­
Endothall
Guideline
No./
Study
Type
MRID
No.
Results
Toxicity
Category
870.1100
Acute
oral
toxicity
42289201
LD
50
=
50.2/
44.4[
m/
f]
mg/
kg
I
870.1200
Acute
dermal
toxicity
42289202
LD
50
=
>
2000[
m/
f]
mg/
kg
III
870.1300
Acute
inhalation
toxicity
42169501
LC
50
=
1.27/
2.20[
m/
f]
mg/
L
III
870.2400
Acute
eye
irritation
42289203
severe
irritant
lethal
4/
6
rabbits
I
870.2500
Acute
dermal
irritation
42289204
unacceptable
study
I
a
870.2600
Skin
sensitization
41871901
sensitizer
N/
A
a
Endothall
has
been
shown
to
be
a
skin
irritant
in
a
preliminary
range
finding
study
of
the
dermal
absorption
study
(
MRID
42169503)
at
doses
of
50
ug/
cm2
and
higher
and
in
the
21­
day
dermal
toxicity
study
(
MRID
43465201)
after
one
application
at
doses
of
30
mg/
kg
or
higher.
This
information
is
considered
sufficient
to
classify
Endothall
as
a
severe
dermal
irritant
Page
24
of
76
Table
4.1b
Subchronic,
Chronic
and
Other
Toxicity
Profile
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
870.3100
90­
Day
oral
toxicity
rodents
(
rat)
43480810(
1994)
Acceptable/
guideline
0,
150,
600,
1800
ppm
M:
0,
10,
39,
118
mg/
kg/
d
F:
0,
12,
51,
153
mg/
kg/
d
NOAEL
=
39
mg/
kg/
day
LOAEL
=
118
mg/
kg/
day
based
on
treatment
related
deficits
in
body
weight.

870.3150
13
week
oral
toxicity
in
nonrodents
(
dog)
43480802
(
1994)
Acceptable/
guideline
0,
100,
400,
1000
ppm
M:
0,
3.2,
11.7,
27.5
mg/
kg/
d
F:
0,
3.2,
13.0,
28.9
mg/
kg/
day
NOAEL
=
11.7
mg/
kg/
day
LOAEL
=
27.5
mg/
kg/
day
based
on
decreases
in
body
weight
gain.

870.3200
21­
Day
dermal
toxicity
(
rat)
range­
finding
42814101
(
1992)
Acceptable/
nonguide
­
line
0,
80,
200,
500
mg/
kg/
d
NOAEL
=
not
determined
LOAEL
=
80
mg/
kg/
day
based
systemic
toxicity
(
death)
LOAEL
=
80
mg/
kg/
day
based
on
dermal
irritation
870.3250
21­
Day
dermal
toxicity
(
rat)
43465201(
1994)
Acceptable/
guideline
0,
30,
100,
300
mg/
kg/
d
NOAEL
=
not
determined
LOAEL
=
30
mg/
kg/
d
based
on
decreased
body
weight
gains.
LOAEL
=
30
mg/
kg/
d
based
on
dermal
irritation
870.3700a
Prenatal
developmental
in
rodents
(
rat)
42776301
(
1993)
Acceptable/
guideline
0,
6.25,
12.5,
25.0
mg/
kg/
d
Maternal
NOAEL
=
12.5
mg/
kg/
day
LOAEL
=
25
mg/
kg/
day
based
on
decreased
body
weight
gain.
Developmental
NOAEL
=>
25
mg/
kg/
day
LOAEL
=
not
determined
HDT.
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
Page
25
of
76
870.3800
Reproduction
and
fertility
effects
43152101
(
1993)
43629301
(
1995)
Acceptable/
guideline
0,
30,
150,
900
ppm
M:
0,
2,
10.2,
64
mg/
kg/
d
F:
0,
1.8,
9.4,
60
mg/
kg/
d
premating
0,
3.1,
17.3,
104.7
mg/
kg/
d
lactation
Parental/
Systemic
NOAEL
=
not
established
LOAEL
=
2
mg/
kg/
day
based
on
proliferative
lesions
gastric
epithelium
both
sexes.
Reproductive
NOAEL
=
9.4
mg/
kg/
day
LOAEL
=
60.0
mg/
kg/
day
based
on
decreased
pup
body
weights
Reproductive
Offspring
NOAEL
=
9.4
mg/
kg/
day
LOAEL
=
60.0
mg/
kg/
day
based
on
decreased
pup
body
weights.

870.4100b
Chronic
toxicity
dogs
40745202
(
1987)
supplementary/
guideli
ne
0,
150,
450,350
ppm.
high
dose
lowered
to
1000
ppm
at
the
7th
M:
0,
5.7,
17
or
40
mg/
kg/
d
F:
0,
6.5,
18,
33
mg/
kg/
d
52
weeks.
NOAEL
=
not
determined
LOAEL
(
LDT)
=
6.5
mg/
kg/
d
based
on
gastric
epithelial
hyperplasia.

870.4200b
Carcinogenicity
mice
40685301
(
1988)
supplementary/
guideli
ne
0,
50,
100,
300
ppm
0,
7.5,
15,
45
mg/
kg/
d
21
months
NOAEL
=
15
mg/
kg/
day
LOAEL
=
45
mg/
kg/
day
based
on
decreased
body
weight
gain
and
microscopic
findings
in
male
kidney.
no
evidence
of
carcinogenicity
870.4200b
Carcinogenicity
mice
43608301(
1995)
acceptable/
guideline
0,
750,
1500
ppm
M:
01,
124,
258
mg/
kg/
d
F:
0,
152,
319
mg/
kg/
d
79
weeks
NOAEL
=
not
determined
LOAEL
=
124
mg/
kg/
day
based
on
decreased
body
weight
gain
in
males.
no
evidence
of
carcinogenicity
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
Page
26
of
76
870.4300
chronic/
onco
rat
41040301(
1989)
acceptable
0,
150,
300,
900,
1800ppm
M:
0,
6,
12,
37,
80
mg/
kg/
d
F:
0,
8,
16,
49,
110
mg/
kg/
d
NOAEL
=
8
mg/
kg/
day
LOAEL
=
16
mg/
kg/
day
based
on
decreased
body
weight
and
body
weight
gain.
no
evidence
of
carcinogenicity
Gene
Mutation
Guideline
#
OPPTS
870.5300
[
§
84­
2];
OECD
476,
study
type
In
vitro
Mammalian
Cell
Gene
Mutation
Assay
43437801
(
1993)
classification
Acceptable
equivalent
=
11.6%)
Dosed
in
(
DMSO)
at
concentrations
of
0.0116,
0.0580,
0.116,
0.580,
1.16,
2.32,
2.9,
3.48,
4.06,
and
4.64

g/
mL
(
all
concentrations
expressed
as
active
ingredient)
without
metabolic
activation
or
at
0.116,
0.58,
1.16,
5.8,
11.6,
17.4,
20.3,
21.8,
23.2
and
26.1

g/
mL
with
metabolic
activation
(
Initial
Trial).
For
the
confirmatory
trial,
levels
of
0.0116,
0.0580,
0.116,
0.580,
1.16,
2.32,
2.90,
3.48.
4.06.
4.64,
5.22
and
5.80

g/
mL
­
S9
or
0.116,
0.580,
1.16,
5.80,
11.6,
17.4,
23.2,
26.1
and
29

g/
mL
+
S9
were
processed.
Negative
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
Page
27
of
76
Gene
Mutation
Guideline
#
Bacterial
Gene
Mutation
Assay
(
Salmonella
typhimurium)/
O
PPTS
870.5100/[
§
84­
2]
OECD
471
43154801
(
1993).
Unacceptable
in
dimethyl
sulfoxide
(
DMSO)
(
equivalent
to
1.93,
5.80,
19.3,
58.0,
116
or
193

g/
plate
active
ingredient)
with
or
without
S9
activation.
Negative
Cytogenetics
In
vivo
Mammalian
Cytogenetics
­
Micronucleus
Assay
in
Mice/
OPPTS
870.5395/[
§
84­
2]
43157401
(
1994)
Acceptable
mice
were
administered
0.464,
0.928
and
1.86
mg/
kg
Endothall
Technical
amine
salt
(
1.5:
1
amine
:
salt
ratio;
Batch
No.
B46­
44­
1;
endothall
amine
30.3%;
endothall
acid
equivalent
=
11.6%)
via
intraperitoneal
injection
(
IP)
in
deionized
water;
Negative
Cytogenetics
In
vivo
Mammalian
Cytogenetics
­
Micronucleus
Assay
in
Mice/
OPPTS
870.5395/[
§
84­
2]
41700301
(
1989)
Acceptable
mice
were
administered
2,10
or
50
mg/
kg
Endothall
Negative
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
Page
28
of
76
Cytogenetics
In
vitro
Mammalian
Cytogenetics
OPPTS
870.5375
[
§
84­
2];
OECD
473
41700302
(
1989)
Acceptable
in
dimethyl
sulfoxide
(
DMSO)
at
concentrations
of
2.5,
10.0,
20.0
and
40.0

g/
mL
without
metabolic
activation
or
were
exposed
for
3
hours
to
15.0,
60.0,
120.0
or
240.0

g/
mL
with
metabolic
activation
Negative
870.7485
Metabolism
and
pharmacokinetic
s
42169502
(
1990),
acceptable
a
single
i.
v.
dose
at
0.9
mg/
kg,
a
single
oral
dose
at
0.9,
4.5
or
9.0
mg/
kg
and
as
a
15
day
multiple
dose
at
0.9
and
9.0
mg/
kg/
day.
Intravenous
administration
of
0.9
mg/
kg
resulted
in
excretion
mainly
by
the
urine
(
69%)
and
feces.
At
an
oral
0.9
mg/
kg
dose,
blood
half­
life
elimination
­
1.8
hrs
in
males,
2.5
hrs
females.
At
4.5
mg/
kg
half­
life
­
13.9
hours
in
males;
the
half­
life
in
females
could
not
be
calculated
because
of
a
double
blood
peak.
Multiple
oral
or
single
administration
indicated
that
the
test
material
was
rapidly
absorbed
and
excreted
in
the
feces
(
89­
98%)
and
urine
(
5­
9%).
The
compound
did
not
bioaccumulate.
At
24
hours
tissue
distribution
of
the
compound
was
extensive
but
low,
the
highest
amount
(<
10%)
being
found
in
the
gastrointestinal
tract.
By
48
hours,
the
compound
was
mostly
undetectable
in
the
tissue.
Bile
elimination
was
only
of
minor
importance.
Absorbed
or
unabsorbed
test
compound
in
all
groups
was
excreted
mainly
as
chemically
unchanged
Endothall
in
the
feces
and
urine.
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
Page
29
of
76
870.7485
Metabolism
and
pharmacokinetic
s
44263501
(
1997)
acceptable
administered
to
10
Sprague
Dawley
rats
(
5/
sex/
dose)
in
distilled
water
by
gavage
at
a
dose
9
mg/
kg.
Animals
were
sacrificed
after
24
hours.
Following
a
single
oral
administration
of
[
14C}­
Endothall
to
male
and
female
rats
(
approximately
9
mg/
kg),
the
majority
of
the
radioactivity
(
70.8%
males,
71.2%
females)
was
excreted
within
the
0­
24
hour
time
period,
with
most
of
the
radioactivity
being
present
in
the
feces
(
47.6%
males,
47.5%
females)
At
24
hours
after
dosing,
less
than
0.21%
of
the
dose
was
found
in
the
stomach
(+
contents),
small
intestine
(+
contents)
and
pancreas
and
very
little
detected
in
the
blood
(
below
15
ng
eq/
g).
Higher
levels
of
radioactivity
were
found
in
the
caecum
(
3.0%
males,
6.
1
%
females)
and
the
large
intestine
(
3.2%
males,
8.2%
females).

Analysis
of
extracts
of
the
urine,
feces,
caecum
and
large
intestine
of
both
male
and
female
rats
gave
a
single
radioactive
component
corresponding
to
unchanged
Endothall
which
accounted
for
>
86,
>
96,
>
74
and
>
69%
of
total
recovery
from
the
respective
extracts.

870.7600
Dermal
penetration
42169503
(
1990)
acceptable
Dose
levels
were
0.0125
mg/
cm2
(
0.3
mg/
rat),
0.0625
mg/
cm2
(
1.5
mg/
rat)
and
0.125
mg/
cm2
(
3.0
mg/
rat)
respectively.
Five
(
5)
animals
per
time
period
(
0..
5,
1,
2,
4,
10
or
24
hours)
in
each
dose
Approximately
55
to
82%
of
the
applied
dermal
dose
was
washed
from
the
application
site.
The
rest
of
the
[
14C]­
Endothall
equivalents
was
contained
in
the
application
site
skin.
Urinary
excretion
of
[
14C]­
Endothall
equivalents
increased
in
a
dose
related
manner
at
10
and
24
hours
to
a
maximum
of
2.3%
of
the
applied
dose
at
the
0.125
mg/
cm2
(
3.0
mg/
rat)
dose
level.
Fecal
excretion
amounted
to
<
0.1%
at
all
dose
levels.
At
the
0.0125
mg/
cm2
(
0.3
mg/
rat),
0.0625
mg/
cm2
(
1.5
mg/
rat)
and
0.125
mg/
cm2
(
3.0
mg/
rat)
dose
levels,
systemic
bioavailability
(
absorption)
of
3.9%,
2.2%
and
7.3%,
respectively,
were
noted
at
24
hours.
A
time
related
increase
in
systemic
bioavailability
occurred
only
at
the
1.5%
dose
level.
The
dose
related
pattern
of
absorption
was
typical
of
a
chemical
which
directly
damages
the
skin.
The
percent
of
dose
absorbed
increased
with
increasing
dose.
The
total
percent
recovery
of
[
14C]­
Endothall
equivalents
was
97.7
to
101.1%
of
the
administered
dose
throughout
the
24
hour
period.
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
Page
30
of
76
Special
studies
none
Page
31
of
76
4.2
FQPA
Hazard
Considerations
4.2.1
Adequacy
of
the
Toxicity
Data
Base
The
HIARC
concluded
that
the
toxicology
database
for
Endothall
is
incomplete
for
FQPA
assessment.
A
rabbit
(
non­
rodent)
developmental
toxicity
study
is
not
available
4.2.2
Evidence
of
Neurotoxicity
The
HIARC
concluded
that
there
is
not
a
concern
for
neurotoxicity
resulting
from
exposure
to
Endothall.
No
clinical
signs
or
symptoms
of
neurotoxicity
were
detected
in
any
of
the
available,
guideline
studies.

4.2.3
Developmental
Toxicity
Studies
In
a
developmental
toxicity
study
(
MRID
42776301)
Groups
of
pregnant
Crl:
CD
BR
rats
(
25/
dose)
were
administered
endothall
(
19.2%
a.
i.
Batch
#
CAF
21C901)
via
gavage
at
dose
levels
of
0,
6.25,
12.5,
or
25.0
mg/
kg/
day
during
gestation
Days
6­
15.
Maternal
toxicity
was
observed
at
the
highest
dose
tested
as
indicated
by
decreases
in
body
weight
gain.
Endothall
did
not
induce
developmental
toxicity
at
any
of
the
doses
tested.

4.2.4
Reproductive
Toxicity
Study
In
a
2­
generation
reproduction
study
(
MRIDs
43152101
and
43629301),
Endothall
Turf
Herbicide
(
disodium
salt
of
Endothall,
19.9%
ai)
was
administered
continuously
in
the
diet
to
Sprague
Dawley
CD
rats
(
26/
sex/
dose)
at
concentrations
of
0,
30,
150
or
900
ppm
(
a.
i.)
for
two
successive
generations
(
1
litter
P
1
generation,
2
litters
F
1
generation).
The
dose
levels
were
equivalent
to
0,
2,
10.2,
or
64
mg/
kg/
day
for
males
and
0,
2.3,
11.7,
or
78.7
mg/
kg/
day
for
females
during
the
premating
period;
0,
1.8,
9.4
or
60
mg/
kg/
day
during
the
gestation
period;
and
0,
3.1,
17.3,
or
104.7
mg/
kg/
day
during
the
lactation
period.

Under
conditions
of
this
study,
a
NOAEL
for
parental
systemic
toxicity
was
not
established;
the
LOAEL
was
estimated
to
be
30
ppm
(
2
mg/
kg/
day
for
males
and
2.3
mg/
kg/
day
for
females)
based
on
proliferative
lesions
of
the
gastric
epithelium
(
both
sexes).
The
NOAEL
for
offspring
toxicity
was
150
ppm
(
9.4
mg/
kg/
day)
and
the
LOAEL
was
900
ppm
(
60.0
mg/
kg/
day)
based
on
decreased
pup
body
weights
(
both
sexes)
at
Day
0
of
the
F
1
and
F
2a
generations.
Page
32
of
76
4.2.5
Additional
Information
from
Literature
Sources
Open
literature
searches
identified
no
additional
information
4.2.6
Pre­
and/
or
Postnatal
Toxicity
The
HIARC
concluded
that
there
is
not
a
concern
for
pre­
and/
or
postnatal
toxicity
resulting
from
exposure
to
Endothall
in
rats
(
rabbit
­
not
yet
determined).

4.2.6.1
Determination
of
Susceptibility
There
was
no
quantitative
or
qualitative
evidence
of
increased
susceptibility
following
prenatal
exposure
to
rats
in
the
developmental
toxicity
study
and
pre­/
postnatal
exposure
to
rats
in
the
2­
generation
reproduction
study.
Due
to
the
lack
of
a
prenatal
developmental
study
in
rabbits,
susceptibility
could
not
be
ascertained
in
a
second
(
non­
rodent)
species.

4.2.6.2
Degree
of
Concern
Analysis
and
Residual
Uncertainties
for
Pre
and/
or
Post­
natal
Susceptibility
There
are
no
concerns
for
residual
uncertainty
for
prenatal
toxicity
in
the
available
developmental
study,
or
the
2­
generation
rat
toxicity
study.
In
evaluating
the
toxicological
database
for
endothall,
the
primary
effects
are
the
point
of
entry
effects
(
i.
e.,
dermal).
In
addition,
the
weight
of
evidence
suggests
that
endothall
will
be
of
no
developmental
concern.
The
rabbit
developmental
study
is
being
required
as
a
confirmatory
study.

4.3
Recommendation
for
a
Developmental
Neurotoxicity
Study
The
HIARC
concluded
that
there
is
not
a
concern
for
developmental
neurotoxicity
resulting
from
exposure
to
Endothall.

4.3.1
Evidence
that
supports
requiring
a
Developmental
Neurotoxicity
study
None.

4.3.2
Evidence
that
supports
not
requiring
for
a
Developmental
Neurotoxicity
study
No
clinical
signs
or
symptoms
of
neurotoxicity
/
neuropathology
were
detected
in
any
of
the
available,
guideline
studies.
Page
33
of
76
4.4
Hazard
Identification
and
Toxicity
Endpoint
Selection
4.4.1
Acute
Reference
Dose
(
aRfD)
­
Females
age
13­
49
An
acute
RfD
was
not
established
for
any
population
subgroup
because
an
appropriate
endpoint
attributable
to
a
single
dose
was
not
available
from
any
study,
including
the
prenatal
developmental
toxicity
study
in
rats.
The
most
sensitive
indicator
of
oral
toxicity
in
the
rat
was
direct
damage
to
the
stomach.
The
maternal
stomach
was
not
examined
for
toxicity
in
the
prenatal
developmental
toxicity
study
in
rats.
Therefore,
this
study
could
not
be
used
for
an
acute
reference
dose.

4.4.2
Acute
Reference
Dose
(
aRfD)
­
General
Population
An
acute
RfD
was
not
established
for
any
population
subgroup
because
an
appropriate
endpoint
attributable
to
a
single
dose
was
not
available
from
any
study,
including
the
prenatal
developmental
toxicity
study
in
rats.
The
most
sensitive
indicator
of
oral
toxicity
in
the
rat
was
direct
damage
to
the
stomach.
The
maternal
stomach
was
not
examined
for
toxicity
in
the
prenatal
developmental
toxicity
study
in
rats.
Therefore,
this
study
could
not
be
used
for
an
acute
reference
dose.

4.4.3
Chronic
Reference
Dose
(
cRfD)

Study
Selected:
2­
Generation
Reproduction
Toxicity
Study
in
Rats
(
MRID
Nos:
43152101
and
43629301
Dose
and
Endpoint
for
Establishing
cRfD:
The
LOAEL
=
2
mg/
kg/
day
for
males
and
2.3
mg/
kg/
day
for
females)
based
on
proliferative
lesions
of
the
gastric
epithelium
in
both
sexes.

Uncertainty
Factor(
s):
300.
This
includes
the
10X
for
interspecies
extrapolation
and
10X
for
intraspecies
variation,
and
an
additional
3X
for
the
lack
of
a
NOAEL
in
the
study
used
for
endpoint
selection.
A
3x
factor
was
used
to
extrapolate
from
a
LOAEL
to
a
NOAEL
for
the
following
reasons:
1)
the
gastric
lesions
were
not
observed
in
the
Fo
parental
animals;
2)
the
lesions
were
observed
in
the
F
1
parental
animals
only;
and
3)
the
incidence
and
severity
of
the
lesions
did
not
increase
dramatically
across
the
dose
groups
(
all
were
classified
as
"
moderate"
in
severity);
2/
3
males
and
1/
2
females
{
low
dose};
2/
2
females
{
mid
dose}
and
3/
3
males
{
high
dose}.

Comments
about
Study/
Endpoint:
This
dose
and
endpoint
is
appropriate
with
respect
to
the
route
and
duration
of
this
exposure
scenario.

Chronic
RfD
=
2
mg/
kg/
day
(
LOAEL)
=
0.007
mg/
kg/
day
300
(
UF)
Page
34
of
76
4.4.4a
Incidental
Oral
Exposure
(
Short
Term)

Study
Selected:
2­
Generation
Reproduction
Toxicity
Study
in
Rats
MRID
Nos:
43152101
and
43629301
Dose
and
Endpoint
for
Risk
Assessment:
Offspring
NOAEL
=
9.4
mg/
kg/
day
based
on
decreased
pup
body
weights
in
both
sexes
at
Day
0
of
the
F
1
and
F
2a
generations
Comments
about
Study/
Endpoint:
This
endpoint
is
appropriate
with
respect
to
the
duration
and
population
of
concern
(
i.
e.,
hand­
to­
mouth
behavior
in
infants
and
children)

Uncertainty
Factor
(
MOEs)

See
MOE
Table
Sec
4.4.8
4.4.4b
Incidental
Oral
Exposure
(
Intermediate
Term)

Study
Selected:
Rat
2­
Generation
Reproduction
Toxicity
Study
(
MRID
Nos:
43152101
and
43629301
Dose
and
Endpoint
for
Risk
Assessment:
The
parental
systemic
toxicity
LOAEL
was
estimated
to
be
30
ppm
(
2
mg/
kg/
day
for
males
females)
based
on
proliferative
lesions
of
the
gastric
epithelium
(
both
sexes).

Comments
about
Study/
Endpoint:
This
endpoint
is
appropriate
with
respect
to
the
population
of
concern
(
i.
e.,
hand­
to­
mouth
behavior
in
infants
and
children)
and
the
duration
of
exposure
(
1­
6
months)
since
stomach
lesions
were
seen
at
the
end
of
this
study
which
is
approximately
13­
weeks
in
duration.

Uncertainty
Factor
(
MOEs)

See
MOE
Table
Sec
4.4.8
4.4.5
Dermal
Absorption
Dermal
Absorption
Factor:
7.3%
at
24
hours.

Selected
Study:
Dermal
Absorption
Study
in
Rats
MRID:
42169503
Page
35
of
76
4.4.6
Dermal
Exposure
(
Short,
Intermediate
and
Long
Term)

The
RARC
recommended
that
no
dermal
assessments
be
conducted,
since
endothall
is
so
toxic
at
the
portals
of
entry
and
is
therefore
self­
limiting.
In
the
21­
day
dermal
toxicity
study
(
MRID43465201),
in
addition
to
weight
loss,
severe
dermal
effects
were
observed
at
30
mg/
kg/
day
(
the
lowest
dose
tested).
The
NOAEL
for
dermal
irritation
was
not
established
due
to
erythema,
edema,
and
fissuring
and
sloughing
off
of
the
skin
at
the
dose
site
at
the
lowest
tested
dose
of
30
mg/
kg/
d.
The
only
systemic
toxicity
observed
at
this
same
dose
of
30
mg/
kg/
d
was
slight
(
3.3%
­
nonsignificant
body
weight
losses
in
females
on
day
20.
Total
body
weight
gains
were
inhibited
(­
27%
for
males
and
­
85%
for
females)
when
compared
to
controls.

4.4.7a
Inhalation
Exposure
(
Short
Term)

Study
Selected:
2­
Generation
Reproduction
Toxicity
Study
in
Rats
MRID
No.
43152101
and
43629301
Dose/
Endpoint
for
Risk
Assessment:
Offspring
NOAEL
=
9.4
mg/
kg/
day
based
on
decreased
pup
body
weight
at
Day
0
of
the
F
1
and
F
2
generations
Comments
about
Study/
Endpoint:.
In
the
absence
of
a
repeated
dose
inhalation
study,
an
oral
study
was
selected.
Absorption
via
the
inhalation
route
is
presumed
to
be
equivalent
to
oral
absorption
(
i.
e.,
100%).

Uncertainty
Factor
(
MOEs)

See
MOE
Table
Sec
4.4.8
4.4.7b
Inhalation
Exposure
(
Intermediate
and
Long
Term)

Study
Selected:
2­
Generation
Reproduction
Toxicity
Study
in
Rats
MRID
Nos:
43152101
and
43629301
Dose/
Endpoint
for
Risk
Assessment:
The
parental/
systemic
toxicity
LOAEL
=
2
mg/
kg/
day
based
on
proliferative
lesions
of
the
gastric
epithelium
in
both
sexes.

Comments
about
Study/
Endpoint:
In
the
absence
of
a
repeated
dose
inhalation
study,
an
oral
study
was
selected.
Absorption
via
the
inhalation
route
is
presumed
to
be
equivalent
to
oral
absorption
(
i.
e.,
100%).

Uncertainty
Factor
(
MOEs)
Page
36
of
76
See
MOE
Table
Sec
4.4.8
4.4.8
Margins
of
Exposure
Summary
of
target
Margins
of
Exposure
(
MOEs)
for
risk
assessment.

Route
Duration
Short­
Term
(
1­
30
Days)
Intermediate­
Term
(
1
­
6
Months)
Long­
Term
(>
6
Months)

Occupational
(
Worker)
Exposure
Dermal
N/
A
N/
A
N/
A
Inhalation
100
300
300
Residential
(
Non­
Dietary)
Exposure
Oral
100
300
N/
A
Dermal
N/
A
N/
A
N/
A
Inhalation
100
300
300
Occupational
Exposure:
For
Short­
term
Inhalation
exposure
assessments,
an
MOE
of
100
is
required
based
on
the
conventional
100X
(
10X
for
intraspecies
extrapolation
and
10X
for
interspecies
variation);

For
Intermediate­
and
Long­
term
Inhalation,
an
MOE
of
300
is
required
based
on
the
conventional
100X
(
10X
for
intraspecies
extrapolation
and
10X
for
interspecies
variation),
and
an
additional
3X
for
the
lack
of
a
NOAEL
in
the
study
used
for
endpoint
selection.
.

Residential
Exposure:
For
Short­
term
Incidental
Oral
and
Inhalation,
an
MOE
of
100
is
required
based
on
the
conventional
100X
(
10X
for
intraspecies
extrapolation
and
10X
for
interspecies
variation).

For
Intermediate­
term
Incidental
Oral
­
all
durations,
and
Intermediate­
and
Long­
term
Inhalation,
an
MOE
of
300
is
required
based
on
the
conventional
100X
(
10X
for
intraspecies
extrapolation
and
10X
for
interspecies
variation),
and
an
additional
3X
for
the
lack
of
a
NOAEL
in
the
study
used
for
endpoint
selection.

4.4.9
Recommendation
for
Aggregate
Exposure
Risk
Assessments
As
per
FQPA,
1996,
when
there
are
potential
residential
exposures
to
Page
37
of
76
the
pesticide,
aggregate
risk
assessment
must
consider
exposures
from
three
major
sources:
oral,
dermal
and
inhalation
exposures.
The
toxicity
endpoints
selected
for
these
routes
of
exposure
may
be
aggregated
as
follows:

Short
Term:
Combine
oral,
and
inhalation
(
endpoint
is
based
on
body
weight
changes)

Intermediate
Term:
Combine
oral
and
inhalation
(
endpoint
is
based
on
stomach
lesions)

4.4.10
Classification
of
Carcinogenic
Potential
In
accordance
with
the
1999
Draft
Guidelines
for
Cancer
Risk
Assessment,
the
HIARC
classified
Endothal
as
"
not
likely
to
be
carcinogenic
to
humans"
based
on
the
lack
of
evidence
of
carcinogenicity
in
mice
or
rats.

Table
4.4.
Summary
of
Toxicological
Doses
and
Endpoints
for
Chemical
for
Use
in
Human
Risk
Assessments
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
(
General
population
including
infants
and
children)
(
Females
13­
50
years
of
age
An
appropriate
endpoint
attributable
to
a
single
dose
was
not
available
from
any
study,
including
the
prenatal
developmental
toxicity
study
in
rats.
An
acute
RfD
was
not
established.

Chronic
Dietary
(
All
populations)
LOAEL=
2
mg/
kg/
day
UF
=
300]
Chronic
RfD
=
0.007
mg/
kg/
day
(
MRID
43152101)
FQPA
SF
=
1
cPAD
=
chronic
RfD
FQPA
SF
=
0.007
mg/
kg/
day
Rat
2­
generation
reproduction
study
LOAEL
2
mg/
kg/
day
based
on
proliferative
lesions
of
the
gastric
epithelium
(
both
sexes)

Short­
Term
Incidental
Oral
(
1­
30
days)
Offspring
NOAEL
=
9.4
mg/
kg/
day
(
MRID
43152101)
Residential
LOC
for
MOE
=
100
Occupational
=
NA
Rat
2­
generation
reproduction
study
LOAEL
60
mg/
kg/
day
based
on
decreased
pup
body
weight
(
both
sexes)
on
Day
0
F1and
F2
generations
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Page
38
of
76
Intermediate­
Term
Incidental
Oral
(
1­
6
months)
LOAEL=
2
mg/
kg/
day
(
MRID
43152101)
Residential
LOC
for
MOE
=
300
Occupational
=
NA
Rat
2­
generation
reproduction
study
LOAEL
2
mg/
kg/
day
based
on
proliferative
lesions
of
the
gastric
epithelium
(
both
sexes)

Short­
Term
Dermal
(
1
to
30
days)
The
RARC
recommended
that
no
dermal
assessments
be
conducted,
since
endothall
is
so
toxic
at
the
portals
of
entry.
In
the
21­
day
dermal
toxicity
study
(
MRID43465201),
in
addition
to
weight
loss,
severe
dermal
effects
were
observed
at
30
mg/
kg/
day
(
the
lowest
dose
tested).

Intermediate­
Term
Dermal
(
1
to
6
months)
The
RARC
recommended
that
no
dermal
assessments
be
conducted,
since
endothall
is
so
toxic
at
the
portals
of
entry.
In
the
21­
day
dermal
toxicity
study
(
MRID43465201),
in
addition
to
weight
loss,
severe
dermal
effects
were
observed
at
30
mg/
kg/
day
(
the
lowest
dose
tested).

Long­
Term
Dermal
(>
6
months)
NA
no
exposure
under
use
pattern
Residential
NA
Occupational
NA
NA
Short­
Term
Inhalation
(
1
to
30
days)
Offspring
NOAEL
=
9.4
mg/
kg/
day
(
inhalation
absorption
rate
=
100%)
(
MRID
43152101)
Residential
LOC
for
MOE
=
100
Occupational
LOC
for
MOE
=
100
Rat
2­
generation
reproduction
study
LOAEL
60
mg/
kg/
day
based
on
decreased
pup
body
weight
(
both
sexes)
on
Day
0
F1and
F2
generations
Intermediate­
Term
Inhalation
(
1
to
6
months)
and
Long­
Term
Inhalation
(>
6
months)
LOAEL=
2
mg/
kg/
day
(
MRID
43152101)
Residential
LOC
for
MOE
=
300
Occupational
LOC
for
MOE
=
300
Rat
2­
generation
reproduction
study
LOAEL
2
mg/
kg/
day
based
on
proliferative
lesions
of
the
gastric
epithelium
(
both
sexes)
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Page
39
of
76
Cancer
(
oral,
dermal,
inhalation)
NA
(
MRID
41040301)

(
MRID
40685301&
43608301)
NA
Chronic/
Onco
Rat
Negative
for
carcinogenicity
Carcinogenicity
Mice
Negative
for
carcinogenicity
Not
likely
carcinogenic
to
humans
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
Based
on
the
above
data
base
(
which
is
considered
adequate),
no
special
FQPA
safety
factor
(
i.
e
1X)
is
required
since
there
are
no
residual
uncertainties
for
prenatal
toxicity.

In
deriving
uncertainty
for
use
in
the
risk
assessment,
the
conventional
10x
factor
for
interspecies
extrapolation
and
10x
for
intraspecies
extrapolation
were
used
for
all
scenarios.
The
data
base
was
complete
enough
and
there
was
no
evidence
of
pre­
or
postnatal
susceptibility
in
the
studies
submitted
and
evaluated
to
date.
Therefore,
the
FQPA
10X
factor
was
reduced
to
1x.
The
exposure
scenarios
in
which
the
hazard
value
was
based
on
a
LOAEL
(
intermediate
term
inhalation
for
both
occupational
and
residential
settings)
an
additional
uncertainty
factor
of
3x
was
used
to
approximate
a
NOAEL.

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
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).
Page
40
of
76
In
the
available
toxicity
studies
on
Endothall,
there
was
no
estrogen,
androgen,
and/
or
thyroid
mediated
toxicity.

5.0
Public
Health
Data
5.1
Incident
Reports
Incident
reporting
data
and
case
reports
of
human
toxicity
have
been
reviewed
by
HED
(
memorandum
from
Jerry
Blondell
and
Monica
Hawkins
to
Seyed
Tadayon,
DP
Barcode
DP304467).
The
following
databases
were
reviewed
and
findings
are
summarized
for
each:

1)
OPP
Incident
Data
System
(
IDS)
­
reports
of
incidents
from
various
sources,
including
registrants,
other
federal
and
state
health
and
environmental
agencies
and
individual
consumers,
submitted
to
OPP
since
1992.
Reports
submitted
to
the
Incident
Data
System
represent
anecdotal
reports
or
allegations
only,
unless
otherwise
stated.
Typically
no
conclusions
can
be
drawn
implicating
the
pesticide
as
a
cause
of
any
of
the
reported
health
effects.
Nevertheless,
sometimes
with
enough
cases
and/
or
documentation
risk
mitigation
measures
may
be
suggested.

Findings:
Five
incidents
were
reported,
one
in
each
of
the
following
five
years:
1995,
1997,
1998,
2000,
and
2003.
Three
cases
involved
accidental
splashing
of
an
endothall
product
into
the
eyes;
all
of
which
resulted
in
eye
irritation/
pain
at
the
time
of
the
accident.
One
case
involved
a
twenty­
four
year
old
man
who
got
some
product
on
unprotected
wrists
and
knees
which
resulted
in
a
rash
later
treated
by
a
physician.
The
fifth
case
was
not
likely
to
be
associated
with
the
single
reported
exposure
because
the
report
was
based
on
a
seizure
one
month
after
exposure
and
the
individual
was
identified
as
being
addicted
to
drugs.

2)
Poison
Control
Centers
­
as
the
result
of
a
data
purchase
by
EPA,
OPP
received
Poison
Control
Center
data
covering
the
years
1993
through
1998
for
all
pesticides.
Most
of
the
national
Poison
Control
Centers
(
PCCs)
participate
in
a
national
data
collection
system,
the
Toxic
Exposure
Surveillance
System
which
obtains
data
from
about
65­
70
centers
at
hospitals
and
universities.
PCCs
provide
telephone
consultation
for
individuals
and
health
care
providers
on
suspected
poisonings,
involving
drugs,
household
products,
pesticides,
etc.

Findings:
Comparisons
were
made
between
endothall­
related
products
and
all
pesticides
cases
reported
for
percent
cases
with
symptomatic
outcomes
and
degree
of
severity
of
the
outcome,
and
the
percent
resulting
in
a
visit
to
a
health
care
facility
and
of
those,
the
percentage
resulting
in
hospitalization
or
requiring
intensive
care.
Separate
comparisons
were
made
for
occupational
cases
(
15
exposures),
non­
occupational
cases
for
adults
and
older
children
(
75
exposures)
and
non­
occupational
cases
for
children
under
six
years
of
age
(
16
exposures).
Too
few
cases
were
reported
among
workers
or
children
under
age
six
to
draw
any
firm
conclusions.
Among
all
occupational
and
non­
occupational
reports,
the
leading
symptoms
were
eye
and
skin
irritation/
pain
reported
by
15,
and
13
persons,
respectively.
Comparisons
of
the
data
indicated
that
relative
to
all
pesticides,
endothall­
related
products
were
in
general
approximately
equal
to
result
in
symptomatic
outcomes
of
any
severities
(
67%
for
endothall
and
69%
for
all
pesticides)
and
for
outcomes
of
moderate
severity
(
14%
vs.
11%).
Health­
care
facility
visits
were
slightly
higher
for
endothall
(
24%)
vs.
all
pesticides
(
17%).
Importantly,
none
of
the
endothall
exposures
Page
41
of
76
resulted
in
life­
threatening
situations
(
0%
vs.
0.4%
for
all
pesticides)
or
hospitalizations
(
0%
vs.
6%
for
all
pesticides).

3)
California
Department
of
Pesticide
Regulation
­
California
has
collected
uniform
data
on
suspected
pesticide
poisonings
since
1982.
Physicians
are
required
by
statute
to
report
to
their
local
health
officer
all
occurrences
of
illness
suspected
of
being
related
to
exposure
to
pesticides.
The
majority
of
the
incidents
involve
workers.
Information
on
exposure
(
worker
activity),
type
of
illness
(
systemic,
eye,
skin,
eye/
skin
and
respiratory),
likelihood
of
a
causal
relationship,
and
number
of
days
off
work
and
in
the
hospital
are
provided.

Findings:
From
1982
to
2002,
19
cases
were
submitted
to
the
California
Pesticide
Surveillance
Program
and
in
11
of
them
endothall
was
used
alone
or
was
judged
to
be
responsible
for
the
health
effects.
Endothall
ranked
205th
as
a
cause
of
systemic
poising
in
California
during
this
20­
year
reporting
period.
Five
of
the
11
cases
included
eye
effects,
five
skin
effects,
and
one
systemic
(
not
defined).
Six
of
the
11
cases
were
associated
with
applicator
activities.
None
ot
these
cases
required
hospitalization.

4)
National
Pesticide
Information
Center
(
NPIC)
­
NPIC
is
a
toll­
free
information
service
supported
by
OPP.
A
ranking
of
the
top
200
active
ingredients
for
which
telephone
calls
were
received
during
calendar
years
1984­
1991,
inclusive
has
been
prepared.
The
total
number
of
calls
was
tabulated
for
the
categories
human
incidents,
animal
incidents,
calls
for
information,
and
others.

Findings:
On
the
list
of
the
top
200
chemicals
for
which
NPIC
received
calls
from
1984­
1991
inclusively,
endothall
was
ranked
148th
with
19
incidents
in
humans
reported
and
three
in
animals
(
mostly
pets).

5.2
Other
The
memo
cited
above
(
Blondell
and
Hawkins)
also
discussed
case
reports
of
poisonings
from
the
literature.
The
only
citation
in
the
literature
addressing
health
effects
of
endothall
to
humans
is
a
case
history
of
a
21­
year
old
male
suicide
victim
who
ingested
7­
8
grams
of
endothall
in
solution
(
about
100
mg
endothall
ion/
kg).
Effects
included
repeated
voliting,
hemorrhages
and
edema
in
the
lungs
and
gross
hemorrhages
of
the
gastrointestinal
tract.

In
summary,
relatively
few
incidents
of
illness
have
been
reported
due
to
endothall.
In
general
reports
are
of
irritative
effects
to
the
eye
and
skin.
No
endothall
related
hospitalizations
have
been
reported
due
to
pesticidal
use.
No
recommendation
are
made
based
on
the
very
limited
incident
data
available
for
this
pesticide.

6.0
Exposure
Characterization/
Assessment
6.1
Dietary
Exposure/
Risk
Pathway
6.1.1
Residue
Profile
Page
42
of
76
Endothall
metabolism
leads
either
to
the
monomethyl
ester
(
and
some
small
amount
of
the
dimethyl
ester),
or
to
complete
decomposition
and
uptake
of
the
radioactive
residues
into
natural
constituents
of
plant
and
animal
tissues.
The
residues
of
concern
in
plants
and
animals
are
therefore
endothall
and
its
monomethyl
ester.

6.1.2
Acute
and
Chronic
Dietary
Exposure
and
Risk
A
dietary
exposure
assessment
for
endothall
has
been
performed
and
is
reported
in
D296790.
DRS
This
assessment
addressed
only
chronic
exposure.
Endothall
is
applied
to
hops,
cotton,
and
potatoes,
and
has
interim
tolerances
on
sugar
beets
and
rice.
Endothall
is
also
used
to
treat
water
that
may
be
used
to
irrigate
crops,
so
HED
recommends
retaining
the
tolerances
for
sugar
beets
and
rice
to
cover
possible
inadvertent
residues
from
treated
irrigation
water.
In
addition,
tolerances
exist
for
livestock,
poultry,
milk
and
egg.

6.1.2.
a.
Acute
Dietary
Exposure
No
toxicological
endpoint
was
identified
for
acute
oral
exposure.
Therefore
no
acute
dietary
exposure
assessment
was
performed.

6.1.2.
b.
Chronic
Dietary
Exposure
(
Food
Only)

Endothall
has
uses
for
direct
application
to
crops,
as
described
above,
and
also
has
aquatic
uses
to
treat
water
that
may
subsequently
be
used
to
irrigate
crops.
To
assess
food
only
residues
from
these
uses,
two
assessments
were
performed
for
dietary
exposure
to
endothall.
One
assessment
was
based
solely
upon
residues
in/
on
crops
directly
treated
with
endothall.
Another
assessment
incorporated
both
residues
from
directly
treated
crops
and
from
crops
irrigated
with
water
containing
endothall.
The
results
of
these
two
assessments
are
summarized
in
Tables
6.1.2.
b.
1.
and
6.1.2.
b.
2.

The
results
of
the
DEEMTM
analysis
based
upon
directly
treated
crops
only
were
1.2%
of
the
cPAD
(
0.000084
mg/
Kg/
day)
for
the
general
population.
The
most
highly
exposed
population
subgroup
was
children
3­
5
at
3.0%
cPAD
(
0.000211
mg/
Kg/
day).
These
results
were
based
upon
tolerances
(
and
hops
were
assumed
to
be
100%
crop
treated)
and
so
should
be
somewhat
conservative.

Table
6.1.2.
b.
1.
Summary
of
Dietary
Exposure
and
Risk
for
Endothall
From
Directly
Treated
Crops
Only
Population
Subgroup
Chronic
Dietary
DEEM
Dietary
Exposure
(
mg/
kg/
day)
%
cPAD
General
U.
S.
Population
0.000084
1.2
All
Infants
(<
1
year
old)
0.000107
1.5
Population
Subgroup
Chronic
Dietary
DEEM
Dietary
Exposure
(
mg/
kg/
day)
%
cPAD
Page
43
of
76
Children
1­
2
years
old
0.000201
2.9
Children
3­
5
years
old
0.000211
3.0
Children
6­
12
years
old
0.000157
2.2
Youth
13­
19
years
old
0.000081
1.2
Adults
20­
49
years
old
0.000063
0.9
Adults
50+
years
old
0.000053
0.8
Females
13­
49
years
old
0.000062
0.9
The
results
of
the
DEEMTM
analysis,
for
food
only,
based
upon
both
directly
treated
crops
and
crops
that
may
have
been
irrigated
with
endothall
treated
water
were
2.7%
of
the
cPAD
(
0.000189
mg/
Kg/
day)
for
the
general
population.
The
most
highly
exposed
population
subgroup
was
children
1­
2
at
7.8%
cPAD
(
0.000544
mg/
Kg/
day).

Table
6.1.2.
b.
2.
Summary
of
Dietary
Exposure
and
Risk
for
Endothall
Both
From
Directly
Treated
Crops
And
From
Crops
Irrigated
with
5
ppm
Endothall
(
Adjusted
by
0.01
factor)

Population
Subgroup
Chronic
Dietary
DEEM
Dietary
Exposure
(
mg/
kg/
day)
%
cPAD
General
U.
S.
Population
0.000189
2.7
All
Infants
(<
1
year
old)
0.000324
4.6
Children
1­
2
years
old
0.000544
7.8
Children
3­
5
years
old
0.000464
6.6
Children
6­
12
years
old
0.000299
4.3
Youth
13­
19
years
old
0.000154
2.2
Adults
20­
49
years
old
0.000141
2.0
Adults
50+
years
old
0.000141
2.0
Females
13­
49
years
old
0.000144
2.1
Conservative
assumptions
were
used
in
estimating
residues
in
the
various
irrigated
crops.
Because
specific
residue
data
ware
not
available
for
most
crops,
translations
of
residue
data
were
made
from
other
crops.
While
these
translations
of
residues
from
other
crops
may
not
have
been
Page
44
of
76
conservative
in
some
particular
cases,
overall
the
translations
were
conservative.

In
calculating
residues
on
directly
treated
crops
plus
irrigated
crops,
an
assumption
that
all
crops
are
100%
irrigated
with
water
containing
endothall
was
initially
used
directly
in
the
DEEM
program.
This
approach
was
necessitated
because
the
DEEMTM
and
LifelineTM
models
are
designed
to
estimate
exposure
using
crop
by
crop
information,
but
no
crop
by
crop
data
were
available
on
the
percent
of
each
crop
that
is
irrigated
with
endothall
containing
water.
Following
this,
the
residue
data
on
directly
treated
crops
was
subtracted
from
the
combined
residues
for
both
sets
of
crops,
leaving
behind
an
estimate
of
the
residues
on
irrigated
crops
only.
This
estimate
was
then
corrected
by
a
factor
of
0.01.
The
0.01
factor
was
derived
from
an
estimate
of
the
total
pounds
of
endothall
sold
for
irrigation
use
in
the
US
in
a
single
year
compared
to
an
estimate
of
the
total
volume
of
irrigation
water
used
in
the
US
in
a
single
year.
The
result
of
this
calculation
was
that
approximately
0.024%
of
irrigation
water
is
likely
to
be
treated
with
endothall.
To
conservatively
address
errors
in
the
estimation
of
0.024%,
and
to
assure
that
regional
and
crop
differences
in
irrigation,
and
differences
in
consumption
of
different
crops,
were
all
properly
compensated,
this
value
was
conservatively
rounded
up
to
1.0%.
After
this
correction
to
the
residues
on
the
irrigated
crops,
the
residues
for
the
directly
treated
crops
were
added
back
in
to
create
an
estimate
of
the
total
residues
from
both
irrigated
and
directly
treated
crops.
The
results
are
shown
in
table
6.1.2.
b.
2.

6.1.2.
c
Chronic
Dietary
Exposure
(
Water
Only)

Results
for
the
dietary
risk
assessment
based
on
drinking
water
exposures
alone
are
presented
in
Table
6.1.2.
c.
1.
This
assessment
assumes
an
endothall
concentration
of
100
ppb
as
the
average
concentration
in
drinking
water.
This
concentration
is
the
Maximum
Contaminant
Level
(
MCL)
for
endothall.
Refer
to
Section
6.2
(
below)
for
the
rationale
for
the
use
of
the
MCL
in
the
drinking
water
assessment.

Table
6.1.2.
c.
1.
Summary
of
Dietary
Exposure
and
Risk
for
Endothall
From
Drinking
Water
Only
at
the
MCL
of
100
ppb
Population
Subgroup*
Chronic
Dietary
DEEM
Dietary
Exposure
(
mg/
kg/
day)
%
cPAD
General
U.
S.
Population
0.002108
30
All
Infants
(<
1
year
old)
0.006910
99
Children
1­
2
years
old
0.003130
45
Children
3­
5
years
old
0.002930
42
Table
6.1.2.
c.
1.
Summary
of
Dietary
Exposure
and
Risk
for
Endothall
From
Drinking
Water
Only
at
the
MCL
of
100
ppb
Population
Subgroup*
Chronic
Dietary
DEEM
Dietary
Exposure
(
mg/
kg/
day)
%
cPAD
Page
45
of
76
Children
6­
12
years
old
0.002021
29
Youth
13­
19
years
old
0.001524
22
Adults
20­
49
years
old
0.001968
28
Adults
50+
years
old
0.002070
30
Females
13­
49
years
old
0.001960
28
The
results
of
the
DEEMTM
analysis
were
30%
of
the
cPAD
(
0.002108
mg/
Kg/
day)
for
the
general
population.
The
most
highly
exposed
population
subgroup
was
infants
(<
1
year
old)
at
99%
cPAD
(
0.006910
mg/
Kg/
day).

6.1.2.
d
Chronic
Dietary
Exposure
(
Food
+
Water)

Results
for
the
dietary
risk
assessment
based
on
drinking
water
exposures
and
food
exposures
from
directly
treated
crops
are
presented
in
Table
6.1.2.
d.
1.
This
assessment
assumes
an
endothall
concentration
of
100
ppb
as
the
average
concentration
in
drinking
water.
This
concentration
is
the
Maximum
Contaminant
Level
(
MCL)
for
endothall.
Refer
to
Section
6.2
(
below)
for
the
rationale
for
the
use
of
the
MCL
in
the
drinking
water
assessment.

Table
6.1.2.
d.
1.
Summary
of
Dietary
Exposure
and
Risk
for
Endothall
From
Directly
Treated
Crops
Only
Plus
Water
at
the
MCL
of
100
ppb
Population
Subgroup*
Chronic
Dietary
DEEM
Dietary
Exposure
(
mg/
kg/
day)
%
cPAD*

General
U.
S.
Population
0.002191
31
All
Infants
(<
1
year
old)
0.007017
100
Children
1­
2
years
old
0.003331
48
Children
3­
5
years
old
0.003142
45
Table
6.1.2.
d.
1.
Summary
of
Dietary
Exposure
and
Risk
for
Endothall
From
Directly
Treated
Crops
Only
Plus
Water
at
the
MCL
of
100
ppb
Population
Subgroup*
Chronic
Dietary
DEEM
Dietary
Exposure
(
mg/
kg/
day)
%
cPAD*

Page
46
of
76
Children
6­
12
years
old
0.002178
31
Youth
13­
19
years
old
0.001604
23
Adults
20­
49
years
old
0.002031
29
Adults
50+
years
old
0.002123
30
Females
13­
49
years
old
0.002022
29
The
results
of
the
DEEMTM
analysis
were
31%
of
the
cPAD
(
0.002191
mg/
Kg/
day)
for
the
general
population.
The
most
highly
exposed
population
subgroup
was
infants
(<
1
year
old)
at
100%
cPAD
(
0.007017
mg/
Kg/
day).

Results
for
the
dietary
risk
assessment
based
on
drinking
water
exposures
and
food
exposures
from
directly
treated
crops
and
irrigated
crops
are
presented
in
Table
6.1.2.
d.
2.
This
assessment
assumes
an
endothall
concentration
of
100
ppb
as
the
average
concentration
in
drinking
water.
This
concentration
is
the
Maximum
Contaminant
Level
(
MCL)
for
endothall.
Refer
to
Section
6.2
(
below)
for
the
rationale
for
the
use
of
the
MCL
in
the
drinking
water
assessment.

Table
6.1.2.
d.
2.
Summary
of
Dietary
Exposure
and
Risk
for
Endothall
Both
From
Directly
Treated
Crops
And
From
Crops
Irrigated
with
5
ppm
Endothall
(
Adjusted
by
0.01
factor)
Plus
Water
at
the
MCL
of
100
ppb
Population
Subgroup*
Chronic
Dietary
DEEM
Dietary
Exposure
(
mg/
kg/
day)
%
cPAD
General
U.
S.
Population
0.002297
33
All
Infants
(<
1
year
old)
0.007234
103
Children
1­
2
years
old
0.003574
51
Children
3­
5
years
old
0.003395
48
Children
6­
12
years
old
0.002320
33
Youth
13­
19
years
old
0.001677
24
Table
6.1.2.
d.
2.
Summary
of
Dietary
Exposure
and
Risk
for
Endothall
Both
From
Directly
Treated
Crops
And
From
Crops
Irrigated
with
5
ppm
Endothall
(
Adjusted
by
0.01
factor)
Plus
Water
at
the
MCL
of
100
ppb
Population
Subgroup*
Chronic
Dietary
DEEM
Dietary
Exposure
(
mg/
kg/
day)
%
cPAD
Page
47
of
76
Adults
20­
49
years
old
0.002109
30
Adults
50+
years
old
0.002211
32
Females
13­
49
years
old
0.002104
30
The
results
of
the
DEEMTM
analysis
were
33%
of
the
cPAD
(
0.002297
mg/
Kg/
day)
for
the
general
population.
The
most
highly
exposed
population
subgroup
was
infants
(<
1
year
old)
at
103%
cPAD
(
0.007234
mg/
Kg/
day).

6.2
Water
Exposure/
Risk
Pathway
Human
exposure
to
endothall
through
ingestion
of
drinking
water
from
terrestrial
use
on
potatoes,
cotton,
clover
and
alfalfa
for
seed,
hops,
and
aquatic
uses
was
assessed
through
modeling
and
monitoring.
Concentrations
of
endothall
in
drinking
water
were
estimated
for
terrestrial
and
aquatic
uses.
Aquatic
uses
resulted
in
estimated
concentrations
that
were
higher
than
those
from
terrestrial
applications.
Therefore,
concentrations
based
on
aquatic
uses
were
used
for
risk
assessment.
Since
no
degradates
of
concern
have
been
identified,
no
degradates
of
endothall
were
modeled
in
this
assessment.
Should
the
Health
Effects
Division
(
HED)
determine
that
any
of
the
environmental
fate
degradates
are
of
concern,
a
separate
assessment
will
be
conducted.

6.2.1
Aquatic
Uses
Direct
applications
to
water
were
modeled
by
the
Environmental
Fate
and
Effects
Division
(
EFED)
assuming
uniform
application
over
an
entire
reservoir
at
the
maximum
labeled
rate
(
Drinking
Water
Assessment
for
Endothall
for
both
Terrestrial
and
Aquatic
Uses;
05/
05/
04;
James
Breithaupt).
Based
on
these
assumptions,
the
peak
concentration
of
endothall
in
surface
water
was
estimated
to
be
5000
ug/
l,
and
the
annual
mean
(
chronic)
concentration
was
estimated
to
be
545
ug/
l.
EPA
believes
it
is
highly
unlikely
that
concentrations
of
endothall
would
reach
these
levels
in
areas
where
surface
water
is
directly
used
for
drinking
water
for
several
reasons:


The
assumption
that
100%
of
a
water
body
is
treated
with
endothall
at
the
maximum
label
rate
is
conservative
and
highly
unlikely.
Typically,
endothall
is
applied
as
a
peripheral
treatment
around
boat
docks
and
piers,
so
that
only
a
small
percentage
of
the
water
body
is
treated.
Page
48
of
76

Endothall
treatments
are
made
to
the
upper
3
to
5
feet
of
the
water
body,
whereas
drinking
water
intakes
are
typically
located
at
the
deepest
point
in
a
reservoir
where
endothall
concentrations
would
be
expected
to
be
lower.


Monitoring
data
for
endothall
suggest
that
average
concentrations
of
endothall
in
drinking
water
are
well
below
the
modeled
estimates.
Monitoring
data
are
available
from
the
National
Contaminant
Occurrence
Database
(
NCOD)
for
both
surface
and
ground
water.
Detectable
residues
of
endothall
were
found
in
only
7
of
27,494
or
0.025%
of
ground
water
samples
and
8
of
5,112
or
0.15%
of
surface
water
samples.

The
maximum
detected
concentrations
in
ground
and
surface
water
were
4,550
ppb
and
2,900
ppb,
respectively;
and
the
mean
concentration
for
samples
with
detectable
residues
was
670
ppb
in
ground
water
and
865
ppb
in
surface
water.
Although
these
few
values
are
well
above
the
established
Maximum
Contaminant
Level
(
MCL)
for
endothall
of
100
ppb,
the
vast
majority
of
ground
and
surface
water
samples
contained
concentrations
of
endothall
below
the
limit
of
detection
(
10
ppb).
Endothall
may
be
applied
to
water
at
concentrations
up
to
5000
ppb.
It
is
likely
that
the
NCOD
samples
with
high
concentrations
were
taken
at
or
soon
after
application
and
very
near
the
application
site.
As
such,
these
high
values
would
not
be
representative
of
average
concentrations
in
drinking
water.
This
determination
is
further
supported
by
additional
monitoring
data
collected
under
the
Safe
Drinking
Water
Act
(
SDWA).
Data
collected
under
the
Safe
Drinking
Water
Information
System
(
SDWIS)
between
1993
and
2005
indicated
only
2
occurrences
of
endothall
residues
that
exceeded
the
established
MCL
of
100
ppb.
Both
of
these
occurred
in
1994,
with
no
violations
occurring
since
that
time.

For
these
reasons,
EPA
does
not
believe
the
modeled
EECs
are
appropriate
for
use
in
estimating
exposure
to
endothall
in
drinking
water.
As
noted
above,
an
MCL
of
100
ppb
has
been
established
for
endothall.
Although
the
MCL
is
likely
to
overestimate
average
(
i.
e.,
chronic)
residues
of
endothall
in
drinking
water,
EPA
believes
it
provides
a
reasonable
high­
end
estimate
of
potential
drinking
water
concentrations
from
the
aquatic
uses
of
endothall.
Consequently,
the
MCL
of
100
ppb
was
used
in
the
dietary
risk
assessments
(
using
DEEM)
detailed
above.

6.2.2
Terrestrial
Uses
Surface
water
concentrations
from
use
on
terrestrial
crops
were
estimated
using
the
Tier
II
model
PRZM
version
3.12/
EXAMS
version
2.98.04
and
ground
water
concentrations
were
estimated
using
the
Tier
I
model
SCIGROW
version
2.2.
A
total
of
five
scenarios
were
modeled
for
endothall
use
on
terrestrial
crops
based
on
individual
EFED
standard
scenarios.
The
scenarios
modeled
were
cotton
and
alfalfa
in
California,
Oregon
Hops,
and
potatoes
in
Maine
and
Idaho.
These
scenarios
were
chosen
to
estimate
the
concentration
of
endothall
in
surface
drinking
water
over
a
geographically
dispersed
range
of
existing
terrestrial
crop
production
areas
These
scenarios
chosen
for
this
assessment
represent
all
relevant
PRZM/
EXAMS
scenarios
for
the
terrestrial
use
of
endothall.
Endothall
may
be
applied
by
aerial
or
ground
equipment
as
per
the
labels
for
this
product.
All
terrestrial
scenarios
were
modeled
with
aerial
application
which
results
in
the
highest
amount
of
spray
drift,
except
for
hops
which
is
treated
by
ground
equipment.
Page
49
of
76
Based
on
modeling
results,
the
estimated
surface
water
drinking
water
concentrations
for
endothall
are:

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

Exposure
Duration
Endothall
Surface
Water
Conc.,
ppb
Ground
Water
Conc.,
ppb
Acute
7.1
0.086
Chronic
(
non­
cancer)
2.5
0.086
Chronic
(
cancer)
2.4
0.086
These
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
endothall
on
the
labeled
terrestrial
crops
in
Table
1.
The
estimates
of
surface
water
concentrations
ranged
from
0.13
to
7.2.
0.02
to
2.5,
and
0.02
to
2.4
µ
g
/
L
for
the
peak,
annual
mean,
and
overall
means.
For
shallow
ground
water
used
for
drinking
water,
the
SCI­
GROW
model
estimates
are
not
expected
to
exceed
0.086
µ
g
/
L.
These
modeled
concentrations
can
be
considered
as
both
the
acute
and
chronic
value.
As
noted
above,
estimated
concentrations
of
endothall
based
on
aquatic
uses
were
used
in
risk
assessment
rather
than
these
estimated
concentrations
from
terrestrial
uses.

6.3
Residential
and
Other
Non­
Occupational
Exposures
and
Risks
It
has
been
determined
that
there
is
a
potential
for
exposure
in
residential
settings
during
the
application
process
for
homeowners
who
use
endothall
products
to
control
aquatic
weeds
and
algae
in
ponds
and
garden
pools.
There
is
also
a
potential
for
exposure
to
adults
and
children
from
contacting
water
treated
with
endothall
through
swimming,
wading,
water
skiing,
etc.
As
a
result,
risk
assessments
have
been
completed
for
both
residential
handler
and
postapplication
scenarios.

6.3.1
Residential
Handler
Exposures
and
Risks
Residential
handlers
are
addressed
somewhat
differently
by
the
Agency
as
homeowners
are
assumed
to
complete
all
elements
of
an
application
with
little
use
of
protective
equipment.

6.3.1.1
Handler
Exposure
Scenarios
The
purpose
of
this
section
is
to
describe
how
the
exposure
scenarios
were
defined.
Much
of
the
process
for
residential
uses
is
identical
to
that
considered
for
the
occupational
assessment
with
a
few
notable
exceptions
that
include:


Residential
handler
exposure
scenarios
are
only
considered
to
be
short­
term
in
nature
due
to
the
episodic
uses
associated
with
homeowner
products.
Page
50
of
76

A
tiered
approach
for
personal
protection
using
increasing
levels
of
personal
protective
equipment
(
PPE)
is
not
used
in
residential
handler
risk
assessments.
Rather
than
using
PPE,
homeowner
handler
assessments
are
completed
based
on
individuals
using
shorts
and
short­
sleeved
shirts.


Homeowner
handlers
are
expected
to
complete
all
tasks
associated
with
the
use
of
a
pesticide
product
including
loading
as
well
as
the
application.


Label
use
rates
and
use
information
specific
to
residential
products
serve
as
the
basis
for
the
risk
calculations
as
opposed
to
the
rates
used
in
the
occupational
assessment.


Area
treated
per
day
in
the
risk
assessment
is
based
on
Agency
guidance
specific
to
residential
use
patterns.

It
has
been
determined
that
exposure
to
pesticide
handlers
is
likely
during
the
residential
use
of
endothall
granular
products
in
ponds
and
garden
pools.
The
anticipated
use
patterns
and
current
labeling
indicate
two
likely
residential
exposure
scenarios
 
loading/
applying
granules
with
a
bellygrinder
and
applying
granules
by
hand.
The
quantitative
exposure/
risk
assessment
developed
for
residential
handlers
is
based
on
these
two
scenarios.
[
Note:
The
scenario
numbers
correspond
to
the
tables
of
risk
calculations
included
in
the
occupational
risk
calculation
sections
of
the
appendices.]

(
1)
Granular
formulation:
loading/
applying
with
bellygrinder;
and
(
2)
Granular
formulation:
applying
by
hand.

6.3.1.2
Data
and
Assumptions
For
Handler
Exposure
Scenarios
A
series
of
assumptions
and
exposure
factors
served
as
the
basis
for
completing
the
residential
handler
risk
assessments.
Each
assumption
and
factor
is
detailed
below.
In
addition
to
these
factors,
unit
exposure
values
were
used
to
calculate
risk
estimates.
These
unit
exposure
values
were
taken
from
the
Pesticide
Handlers
Exposure
Database
(
PHED).
[
Note:
Several
of
the
assumptions
and
factors
used
for
the
assessment
are
similar
to
those
used
in
the
occupational
assessment
presented
above.
As
such,
only
factors
that
are
unique
to
the
residential
scenarios
are
presented
below.]

Assumptions
and
Factors:
The
assumptions
and
factors
used
in
the
risk
calculations
include:


The
Agency
always
considers
the
maximum
application
rates
allowed
by
labels
in
its
risk
assessments
to
consider
what
is
legally
possible
based
on
the
label.


Residential
risk
assessments
were
not
based
on
what
could
be
applied
in
a
typical
workday
as
with
the
occupational
risk
assessments
presented
above.
Instead,
the
Agency
based
calculations
on
what
would
reasonably
be
treated
by
homeowners,
such
as
the
size
of
a
pond,
or
the
size
of
a
garden
pool.
This
information
was
used
by
the
Agency
to
define
Page
51
of
76
chemical
throughput
values
for
handlers
which
in
turn
were
coupled
with
unit
exposure
values
to
calculate
risks.
The
daily
area
treated,
based
on
HED's
professional
judgement,
used
in
each
residential
scenario,
include:


typical
pond
application:
rangefinder
calculation
using
1
acre
of
surface
area
and
5­
feet
depth
and
10,000
square
feet
surface
area
and
2­
feet
depth.


typical
garden
pool
application:
1,000
square
feet
of
surface
area
and
2
feet
depth.

Residential
Handler
Exposure
Studies:
The
unit
exposure
values
that
were
used
in
this
assessment
were
based
on
studies
completed
by
the
Pesticide
Handler
Exposure
Database
(
PHED,
Version
1.1
August
1998).

6.3.1.3
Residential
Handler
Exposure
and
Risk
Estimates
The
residential
handler
exposure
and
risk
calculations
are
presented
in
this
section.
Risks
were
calculated
using
the
Margin
of
Exposure
(
MOE)
approach,
with
a
target
MOE
of
100
for
short­
term
risk
assessments.
Much
of
the
process
for
residential
uses
is
identical
to
that
considered
for
the
occupational
assessment
with
a
few
notable
exceptions
(
e.
g.,
all
are
short­
term
exposures
and
assume
homeowners
wear
shorts
and
short­
sleeved
shirts
with
no
gloves).
Residential
exposures
are
expected
to
be
short­
term
only.

Risk
Summary:
The
short
risk
calculations
for
residential
endothall
handlers
are
summarized
below.

Table
6.3
Endothall
Short­
Term
Risks
to
Residential
Handler
Exposure
Scenario
Crop
or
Target
Application
Rate
(
lb
ai/
cubic
feet)
Surface
Area
Treated
Daily
(
square
feet)
Depth
of
Water
(
feet)
Short­
Term
Inhalation
MOE
(
no
respirator)

Mixer/
Loader/
Applicator
Loading/
Applying
Granulars
via
Belly
Grinder
Ponds/
Lakes
0.00022
43,560
2
470
Ponds/
Lakes
0.00022
10,000
2
1900
Applying
Granulars
via
Hand
Garden
pool
0.00022
1,000
2
2700
In
residential
settings,
the
Agency
does
not
use
personal
protective
equipment
(
PPE)
to
limit
exposures,
because
PPE
are
viewed
as
impractical
and
not
enforceable.

For
residential
handlers,
short­
term
inhalation
MOEs
are
not
of
concern
for
any
of
the
scenarios
and
do
not
exceed
the
Agency's
target
MOE
(

100).

6.3.1.4
Summary
of
Risk
Concerns
and
Data
Gaps
for
Handlers
In
summary,
the
assessment
for
residential
handler
exposure
presented
in
this
section
concludes
that
there
are
no
risk
concerns
for
endothall
as
it
is
currently
used
in
a
residential
environment.
Page
52
of
76
6.3.1.5
Recommendations
For
Refining
Residential
Handler
Risk
Assessment
In
order
to
refine
this
residential
risk
assessment,
more
data
on
actual
use
patterns
including
rates,
timing,
and
areas
treated
would
better
characterize
endothall
risks.

6.3.2
Residential
Postapplication
Exposures
and
Risks
6.3.2.1
Residential
Postapplication
Exposure
Scenarios
Postapplication
exposures
to
adults
and
children
are
expected
following
applications
of
endothall
to
ponds
and
lakes.
Of
the
possible
postapplication
exposures,
swimming
in
treated
water
is
considered
by
HED
to
be
worse­
case
and
is
used
as
a
surrogate
for
all
other
possible
postapplication
exposures,
such
as
wading,
water
skiing,
etc.

The
Agency
considered
residential
postapplication
exposure
for
different
segments
of
the
population.
Risks
were
calculated
for
swimming
in
treated
lakes
or
ponds.

6.3.2.2
Residential
Postapplication
Exposure
and
Risk
Estimates
The
residential
postapplication
exposure
and
risk
calculations
are
presented
in
this
section.
Risks
were
calculated
using
the
Margin
of
Exposure
(
MOE)
approach.

Risk
Summary:
The
Agency
has
addressed
residential
postapplication
exposures
to
endothall
using
the
SWIM
model.

The
following
assumptions
have
used
to
assess
postapplication
exposure
to
swimmers.

S
Body
Weights
22kg
for
children
and
70kg
for
adults
S
Body
surface
area
9000
cm2
and
21000
cm2
for
adults
S
Exposure
Time
3hrs/
day
S
Water
Intake
5
liter
or
5000
ml
in
and
out
of
the
mouth
per
hour
S
Water
ingested
0.05
L
or
50
ml
per
hour
S
Application
rate
1
to
5
ppm
or
1
to
5
mg/
L
or
1
to
5
mg/
1000
cm3
S
Permeability
coefficient
K
p
8.82
x10­
7
cm/
hr
S
Octanol/
water
partition
coefficient
K
ow
0.0008
S
Vapor
pressure
3.92x10­
5
mg/
day
Table
6.3.2.2
provides
the
individual
exposure
through
various
routes
based
on
the
standard
factors
and
physical
constant.
The
estimates
provided
by
the
SOP
are
the
absorbed
doses
and
risks
using
endothall
for
recreational
swimming
from
to
all
routes
of
exposure.
Page
53
of
76
Table
6.3.2.2
Summary
of
Endothall
Swimmer
Postapplication
Risk
Exposure
Children
(
6
to
10)
Adult
Daily
Dose
mg/
kg/
day
MOE
Daily
Dose
mg/
kg/
day
MOE
Oral
0.0341
280
0.0107
900
Dermal
NA
NA
NA
NA
Buccal
Insignificant*
NA
Insignificant
NA
Orbital/
Nasal
Insignificant
NA
Insignificant
NA
Total
280
900
*
Dosage
is
insignificant
according
to
the
SOP
because
endothall
is
lipophobic
(
K
OW
=
0.0008)

For
significant
absorption
through
buccal/
sublingual,
orbital
and
nasal
exposure
the
chemical
must
be
lipophilic
with
a
high
K
OW.
Since
endothall
has
a
low
K
ow
Value,
therefore
no
significant
risk
is
expected.
Also
due
to
low
vapor
pressure,
inhalation
exposure
is
expected
to
be
negligible.

Risk
Summary:

The
Agency
considered
one
residential
postapplication
exposure
scenario
 
swimming
 
for
different
segments
of
the
population
including
children,
and
adults.
Risks
were
calculated.
In
residential
settings,
the
Agency
does
not
use
REIs
or
other
mitigation
approaches
to
limit
exposures,
because
they
are
viewed
as
impractical
and
not
enforceable.
As
such,
risk
estimates
on
the
day
of
application
are
the
key
concern.
However,
several
of
the
Special
Local
Needs
labels
do
have
swimming
restrictions
following
commercial
applications
of
endothall.

6.3.3
Residential
Risk
Characterization
6.3.3.1
Characterization
of
Residential
Handler
Risks
The
data
that
were
used
in
the
endothall
residential
handler
assessment
represent
the
best
data
and
approaches
that
are
currently
available.
For
each
use
pattern,
the
Pesticide
Handlers
Exposure
Database
(
PHED)
was
used
to
develop
the
unit
exposure
values.
All
data
that
have
been
used
may
not
be
of
optimal
quality,
but
represent
the
best
available
data.

The
inputs
for
application
rate
and
other
use/
usage
information
(
e.
g.,
area
treated)
used
by
the
Agency
were
supported
by
the
available
endothall
labels.
There
are
also
many
uncertainties
in
the
assessment
that
are
common
with
the
occupational
assessment
as
well.
These
factors
and
their
impacts
on
the
results
should
be
considered
as
well
in
the
interpretation
of
the
results
for
Residential
handlers.

In
summary,
with
respect
to
residential
handler
risks,
the
Agency
believes
that
the
values
presented
in
this
assessment
represent
the
highest
quality
results
that
could
be
produced
given
the
exposure,
use,
and
toxicology
data
that
are
available.
As
calculated
MOE's
>
for
all
exposure
scenarios
Page
54
of
76
Page
55
of
76
6.3.3.2
Characterization
Of
Residential
Postapplication
Risks
The
data
that
were
used
in
the
endothall
residential
postapplication
assessment
represent
the
best
data
and
approaches
that
are
currently
available.

The
Agency
believes
that
the
values
presented
in
this
assessment
represent
the
highest
quality
results
that
could
be
produced
based
on
the
currently
available
postapplication
exposure
data.
The
Agency
believes
that
the
risks
represent
reasonable
worse­
case
estimates
of
exposure
because
maximum
application
rates
are
used
to
define
residue
levels
upon
which
the
calculations
are
based.

7.0
Aggregate
Risk
Assessments
and
Risk
Characterization
7.1
Acute
Aggregate
Risk
Due
to
the
lack
of
an
acute
Rfd
and
acute
dietary
exposure/
risk,
an
acute
aggregate
risk
assessment
was
not
performed.

7.2
Short­
Term
Aggregate
Risk
A
risk
assessment
for
aggregate
exposures
(
food
+
drinking
water
+
residential)
was
conducted
for
the
short
term
exposure
scenario
because
residential
uses
of
endothall
are
expected
to
be
only
episodic.
Food
exposures
are
based
on
treated
crops
and
irrigated
crops.
Drinking
water
exposures
are
based
on
aquatic
uses
of
endothall.
Although
endothall
has
terrestrial
uses
as
well
as
aquatic
uses,
the
aquatic
uses
result
in
the
highest
estimates
of
potential
drinking
water
exposures.
Residential
handler
exposures
for
adults
are
based
on
granular
applications
of
endothall
with
a
belly
grinder
to
lakes
or
ponds.
Residential
post­
application
exposures
for
adults
and
children
are
based
on
swimming.

For
adults,
estimated
dietary
exposures
via
food
and
drinking
water
were
combined
with
inhalation
exposures
during
application
to
a
pond
or
lake
and
potential
post­
application
exposures
during
swimming.
HED
notes
the
handler
scenario
aggregated
for
adults
is
the
exposure
scenario
resulting
in
the
lowest
MOE
(
highest
risk
estimate)
for
residential
handlers.
For
children,
estimated
dietary
exposures
via
food
and
drinking
water
were
combined
with
potential
postapplication
exposures
during
swimming.
The
short
term
aggregate
risk
estimate
(
MOE)
for
adults
is
310,
for
children,
it
is
250.
The
MOEs
are
not
a
risk
concern.
Therefore,
there
are
no
short
term
aggregate
(
food
+
drinking
water
+
residential)
risk
concerns
for
endothall.
Table
7.2
summarizes
the
results
of
the
short­
term
aggregate
risk
assessment.
Page
56
of
76
Table
7.2
Short­
Term
Aggregate
Risk
Population
Short
Term
Scenario
Target
Aggregate
MOE1
MOE
food
+
water2
Residential
Aggregate
MOE
(
food
+
water
and
residential)
6
MOE
oral3
MOE
dermal4
MOE
inhalation5
Child
(
3­
5
years
old)
100
2770
280
N.
A.
N.
A.
250
Adults
(
50+
years
old)
100
4250
900
N.
A.
470
310
1
Target
MOE
of
100
based
on
using
uncertainty
factors
(
UF)
of
10X
for
interspecies
extrapolation
and
10X
for
intraspecies
variability.

2
MOE
food
+
water,
which
incorporated
the
dietary
exposures
for
treated
crops,
irrigated
crops
and
aquatic
uses,
=
[(
short­
term
oral
NOAEL)/(
chronic
dietary
exposure)].
Short­
term
NOAEL
=
9.4
mg/
kg/
day
from
the
2­
generation
reproduction
rat
study,
MRID
43152101;
chronic
dietary
(
food+
water)
exposure
=
0.003395,
Children
3­
5
years
old,
and
0.002211,
Adults
50+
years
old.

3
MOE
oral
=
[(
short­
term
oral
NOAEL)/(
Oral
postapplication
exposure
of
Swimmers)]
Short­
term
NOAEL
=
9.4
mg/
kg/
day
from
the
2­
generation
reproduction
rat
study,
MRID
43152101;
Oral
daily
postapplication
exposure
of
swimmers
=
0.0341
mg/
kg/
day
,
Children
6­
10
years
old;
0.0107
mg/
kg/
day,
Adults
(
see
Table
6.3.2.2).

4
Not
Applicable
(
N.
A.)

5
MOE
inhalation
=
[(
inhalation
NOAEL)/(
high­
end
inhalation
residential
handler
exposure)]
Short­
term
inhalation
NOAEL
=
9.4
mg/
kg/
day
from
the
2­
generation
reproduction
rat
study,
MRID
43152101.

6
Aggregate
MOE
(
food
+
water
and
residential)
=
1
÷
[
[(
1
÷
MOE
food+
water)
+
(
1
÷
MOE
oral)
+
(
1
÷
MOE
dermal)
+
(
1
÷
MOE
inhalation)]]

7.3
Intermediate­
Term
Aggregate
Risk
Due
to
the
episodic
residential
use
of
endothall,
no
intermediate
term
aggregate
(
dietary
+
residential)
risk
assessment
was
performed.

7.4
Long­
Term
Aggregate
Risk
There
are
no
long
term
residential
uses
of
endothall.
Aggregated
chronic
exposures
to
endothall
through
food
plus
drinking
water
were
calculated
in
DEEMTM.
The
results
for
directly
treated
crops,
irrigated
crops
and
drinking
water
from
aquatic
uses
of
endothall
were
33%
of
the
cPAD
(
0.002297
mg/
Kg/
day)
for
the
general
population.
The
most
highly
exposed
population
subgroup
was
infants
at
103%
cPAD
(
0.007234
mg/
Kg/
day).

7.5
Cancer
Risk
Page
57
of
76
Endothall
is
considered
not
likely
to
be
carcinogenic
to
humans.

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
endothall
and
any
other
substances
and
endothall
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
endothall
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
It
has
been
determined
that
there
is
a
potential
for
exposure
to
endothall
in
occupational
scenarios
from
handling
endothall
products
during
the
application
process
(
i.
e.,
mixer/
loaders,
applicators,
flaggers,
and
mixer/
loader/
applicators)
and
a
potential
for
postapplication
worker
exposure
from
entering
into
areas
previously
treated
with
endothall.
As
a
result,
risk
assessments
have
been
completed
for
occupational
handler
scenarios
as
well
as
occupational
postapplication
scenarios.

9.1
Occupational
Handler
Exposures
and
Risks
Tasks
associated
with
occupational
pesticide
use
(
i.
e.,
for
"
handlers")
can
generally
be
categorized
using
one
of
the
following
terms:

Mixers
and/
or
Loaders:
these
individuals
perform
tasks
in
preparation
for
an
application.
For
example,
prior
to
application,
mixer/
loaders
would
mix
the
endothall
and
load
it
into
the
holding
tank
of
the
airplane
or
groundboom
sprayer.


Applicators:
these
individuals
operate
application
equipment
during
the
release
of
a
pesticide
product
into
the
environment.
These
individuals
can
make
applications
using
equipment
such
as
airplanes
or
groundboom.


Mixer/
Loader/
Applicators
and
or
Loader/
Applicators:
these
individuals
are
involved
in
the
entire
pesticide
application
process
(
i.
e.,
they
do
all
job
functions
related
to
a
pesticide
application
event).
These
individuals
would
transfer
endothall
into
the
application
equipment
and
then
also
apply
it.


Occupational
Flaggers:
these
individuals
guide
aerial
applicators
during
the
release
of
a
Page
58
of
76
pesticide
product
onto
an
intended
target.

HED
always
completes
risk
assessments
using
maximum
application
rates
for
each
scenario,
because
what
is
possible
under
the
label
must
be
evaluated,
for
complete
stewardship,
in
order
to
ensure
there
are
no
concerns
for
each
specific
use.

A
chemical
can
produce
different
effects
based
on
how
long
a
person
is
exposed,
how
frequently
exposures
occur,
and
the
level
of
exposure.
It
is
likely
that
endothall
exposures
can
occur
in
a
variety
of
patterns.
HED
believes
that
occupational
endothall
exposures
can
occur
over
a
single
day
or
up
to
weeks
at
a
time
for
many
use­
patterns
and
intermittent
exposures
over
several
weeks
are
also
anticipated.
Some
applicators
may
apply
endothall
over
a
period
of
weeks,
because
they
are
custom
or
commercial
applicators
who
are
completing
a
number
of
applications
for
a
number
of
different
clients.
HED
classifies
exposures
up
to
30
days
as
short­
term
and
exposures
greater
than
30
days
up
to
several
months
as
intermediate­
term.
HED
completes
both
short­
and
intermediate­
term
assessments
for
occupational
scenarios
in
essentially
all
cases,
because
these
kinds
of
exposures
are
likely
and
acceptable
use/
usage
data
are
not
available
to
justify
deleting
intermediate­
term
scenarios.
Long­
term
handler
exposures
are
not
expected
to
occur
for
endothall.
Different
toxicological
endpoints
of
concern
(
from
an
oral
study)
have
been
selected
for
short­
and
intermediate­
term
inhalation
exposures
to
endothall,
therefore
the
risk
results
for
all
inhalation
durations
of
exposure
are
numerically
distinct.

Occupational
handler
exposure
assessments
are
completed
by
HED
using
different
levels
of
personal
protection.
HED
typically
evaluates
all
exposures
with
a
tiered
approach.
The
lowest
tier
is
represented
by
the
baseline
exposure
scenario
(
i.
e.,
long­
sleeve
shirt,
long
pants,
shoes,
and
socks)
followed
by
increasing
the
levels
of
personal
protective
equipment
or
PPE
(
e.
g.,
gloves,
double­
layer
body
protection,
and
respirators)
and
engineering
controls
(
e.
g.,
enclosed
cabs
and
closed
mixing/
loading
systems).
This
approach
is
always
used
by
HED
in
order
to
be
able
to
define
label
language
using
a
risk­
based
approach.
In
addition,
the
minimal
level
of
adequate
protection
for
a
chemical
is
generally
considered
by
HED
to
be
the
most
practical
option
for
risk
reduction
(
i.
e.,
over­
burdensome
risk
mitigation
measures
are
not
considered
a
practical
alternative).

9.1.1
Data
and
Assumptions
For
Handler
Exposure
Scenarios
9.1.1.1
Assumptions
for
Handler
Exposure
Scenarios
A
series
of
assumptions
and
exposure
factors
served
as
the
basis
for
completing
the
occupational
handler
risk
assessments.
Each
assumption
and
factor
is
detailed
below
on
an
individual
basis.
The
assumptions
and
factors
used
in
the
risk
calculations
include:


Occupational
handler
exposure
estimates
were
based
on
surrogate
data
from:
(
1)
the
Pesticide
Handlers
Exposure
Database
(
PHED)
and
(
2)
the
Outdoor
Residential
Exposure
Task
Force
(
ORETF).


The
average
body
weight
of
an
adult
female
handler
(
i.
e.,
60
kilograms)
is
used
for
assessing
inhalation
dose,
because
the
toxicity
endpoint
values
used
for
the
inhalation
Page
59
of
76
assessments
are
from
a
reproductive
study
and,
therefore,
are
female­
specific.


Generic
protection
factors
(
PFs)
were
used
to
calculate
exposures
when
data
were
not
available.
For
example,
an
80
percent
protection
factor
was
assumed
for
the
use
of
a
quarter­
face
dust/
mist
respirator.


Exposure
factors
used
to
calculate
daily
exposures
to
handlers
are
based
on
applicable
data,
if
available.
For
lack
of
appropriate
data,
values
from
a
scenario
deemed
similar
enough
by
the
assessor
might
be
used.
For
the
endothall
handler
exposure
assessment,
the
following
surrogate
data
was
used
for
certain
application
methods,
since
the
nature
of
these
application
methods
are
believed
to
be
similar
enough
to
bridge
the
data:


for
occupational
large
scale
spray
applications
to
water
using
boat­
mounted
boom
sprayers,
PHED
data
for
mixing/
loading
and
applying
with
ground
boom
were
used;


for
occupational
larger­
scale
spray
applications
to
water
using
boat­
mounted
spray
tanks
equipped
with
a
handgun,
ORETF
data
for
loading/
applying
with
handgun
equipment
were
used;


for
occupational
direct
metering
of
liquid
formulations
to
water,
PHED
data
for
mixing/
loading
liquid
formulations
were
used;


for
occupational
boat­
mounted
granular
applications
to
water
using
blower­
type
spreaders,
PHED
data
for
loading
granulars
were
used;
and

for
residential
granular
applications
to
water,
PHED
data
for
loading/
applying
granulars
with
bellygrinder
equipment
were
used.


For
occupational
assessments,
HED
assumes
the
maximum
application
rates
allowed
by
labels
in
its
risk
assessments.


The
average
occupational
workday
is
assumed
to
be
8
hours.
The
daily
areas
treated
were
defined
for
each
handler
scenario
(
in
appropriate
units)
by
determining
the
amount
that
can
be
reasonably
treated
in
a
single
day
(
e.
g.
acres,
square
feet,
cubic
feet,
or
gallons
per
day).
When
possible,
the
assumptions
for
daily
areas
treated
are
taken
from
the
Health
Effects
Division
Science
Advisory
Committee
on
Exposure
SOP
#
9:
Standard
Values
for
Daily
Acres
Treated
in
Agriculture,
which
was
completed
on
July
5,
2000.
However,
no
standard
values
are
available
for
numerous
scenarios.
Assumptions
for
these
scenarios
are
based
on
HED
estimates
and
could
be
further
refined
from
input
from
affected
sectors.

S
Aerial
equipment:
350
acres
for
most
crops
on
which
endothall
is
registered,
except
1200
acres
for
high
acreage
crops
(
i.
e.,
cotton);

S
Groundboom
equipment:
80
acres
for
most
crops
on
which
endothall
is
registered,
except
200
acres
for
high
acreage
crops
(
i.
e.,
cotton)
and
40
acres
for
hops;
 
Flaggers:
350
acres
for
all
crops
on
which
endothall
is
registered;
 
Pond/
Lake
spray
and
granular
applications:
30­
acre
surface
area
and
5­
feet
depth;
 
Canal
spray
and
granular
applications:
10
miles
in
length,
5­
feet
depth,
and
20­
or
5­
feet
width;
and
 
Flowing
water
applications:
5
hours,
if
water
is
flowing
50
cubic
feet
per
second
Page
60
of
76
and
2
hours,
if
water
is
flowing
200
cubic
feet
per
second.

9.1.1.2
Exposure
Data
for
Handler
Exposure
Scenarios
For
endothall
handler
exposure
assessments,
all
analyses
were
completed
using
data
that
were
deemed
to
be
a
source
of
acceptable
surrogate
exposure
data
for
the
scenario
in
question.

HED
uses
a
concept
known
as
unit
exposure
as
the
basis
for
the
scenarios
used
to
assess
handler
exposures
to
pesticides.
Unit
exposures
numerically
represent
the
exposures
one
would
receive
related
to
an
application.
They
are
generally
presented
as
milligrams
of
active
ingredient
exposure
per
pound
of
active
ingredient
handled.
HED
has
developed
a
series
of
unit
exposures
that
are
unique
for
each
scenario
typically
considered
in
our
assessments
(
i.
e.,
there
are
different
unit
exposures
for
different
types
of
application
equipment,
job
functions,
and
levels
of
protection).
The
unit
exposure
concept
has
been
established
in
the
scientific
literature
and
also
through
various
exposure
monitoring
guidelines
published
by
the
U.
S.
EPA
and
international
organizations
such
as
Health
Canada
and
OECD
(
Organization
For
Economic
Cooperation
and
Development).

Pesticide
Handler
Exposure
Database
(
PHED)
Version
1.1
(
August
1998):
PHED
was
designed
by
a
task
force
of
representatives
from
the
U.
S.
EPA,
Health
Canada,
the
California
Department
of
Pesticide
regulation,
and
member
companies
of
the
American
Crop
Protection
Association.
PHED
is
a
software
system
consisting
of
two
parts
­­
a
database
of
measured
exposure
values
for
workers
involved
in
the
handling
of
pesticides
under
actual
field
conditions
and
a
set
of
computer
algorithms
used
to
subset
and
statistically
summarize
the
selected
data.
Currently,
the
database
contains
values
for
over
1,700
monitored
individuals
(
i.
e.,
replicates).

Users
select
criteria
to
subset
the
PHED
database
to
reflect
the
exposure
scenario
being
evaluated.
The
subsetting
algorithms
in
PHED
are
based
on
the
central
assumption
that
the
magnitude
of
handler
exposures
to
pesticides
are
primarily
a
function
of
activity
(
e.
g.,
mixing/
loading,
applying),
formulation
type
(
e.
g.,
wettable
powders,
granulars),
application
method
(
e.
g.,
aerial,
groundboom),
and
clothing
scenarios
(
e.
g.,
gloves,
double
layer
clothing).

Once
the
data
for
a
given
exposure
scenario
have
been
selected,
the
data
are
normalized
(
i.
e.,
divided
by)
by
the
amount
of
pesticide
handled
resulting
in
standard
unit
exposures
(
milligrams
of
exposure
per
pound
of
active
ingredient
handled).
Following
normalization,
the
data
are
statistically
summarized.
The
distribution
of
exposure
values
for
each
body
part
(
e.
g.,
chest
upper
arm)
is
categorized
as
normal,
lognormal,
or
"
other"
(
i.
e.,
neither
normal
nor
lognormal).
A
central
tendency
value
is
then
selected
from
the
distribution
of
the
exposure
values
for
each
body
part.
These
values
are
the
arithmetic
mean
for
normal
distributions,
the
geometric
mean
for
lognormal
distributions,
and
the
median
for
all
"
other"
distributions.
Once
selected,
the
central
tendency
values
for
each
body
part
are
composited
into
a
"
best
fit"
exposure
value
representing
the
entire
body.

The
unit
exposure
values
calculated
by
PHED
generally
range
from
the
geometric
mean
to
the
median
of
the
selected
data
set.
To
add
consistency
and
quality
control
to
the
values
produced
from
this
system,
the
PHED
Task
Force
has
evaluated
all
data
within
the
system
and
has
Page
61
of
76
developed
a
set
of
grading
criteria
to
characterize
the
quality
of
the
original
study
data.
The
assessment
of
data
quality
is
based
on
the
number
of
observations
and
the
available
quality
control
data.
These
evaluation
criteria
and
the
caveats
specific
to
each
exposure
scenario
are
summarized
in
Appendix
A
,
Table
A7
of
the
Occupational
and
Residential
Exposure
Assessment..
While
data
from
PHED
provide
the
best
available
information
on
handler
exposures,
it
should
be
noted
that
some
aspects
of
the
included
studies
(
e.
g.,
duration,
acres
treated,
pounds
of
active
ingredient
handled)
may
not
accurately
represent
labeled
uses
in
all
cases.
HED
has
developed
a
series
of
tables
of
standard
unit
exposure
values
for
many
occupational
scenarios
that
can
be
utilized
to
ensure
consistency
in
exposure
assessments.
Unit
exposures
are
used
which
represent
different
levels
of
personal
protection
as
described
above.
Protection
factors
were
used
to
calculate
unit
exposure
values
for
varying
levels
of
personal
protection
if
data
were
not
available.

ORETF
Handler
Studies
(
MRID
449722­
01):
A
report
was
submitted
by
the
ORETF
(
Outdoor
Residential
Exposure
Task
Force)
that
presented
data
in
which
the
application
of
various
products
used
on
turf
by
homeowners
and
lawncare
operators
(
LCOs)
was
monitored.
All
of
the
data
submitted
in
this
report
were
completed
in
a
series
of
studies.
The
study
that
monitored
LCO
exposure
scenarios
using
a
low
pressure,
high
volume
turf
handgun
(
ORETF
Study
OMA002)
is
summarized
below.

LCO
Handgun
Sprayer:
A
mixer/
loader/
applicator
study
was
performed
by
ORETF
using
Dacthal
as
a
surrogate
compound
to
determine
"
generic"
exposures
to
individuals
applying
a
pesticide
to
turf
with
a
low­
pressure
"
nozzle
gun"
or
"
handgun"
sprayer.
Dermal
and
inhalation
exposures
were
estimated
using
whole­
body
passive
dosimeters
and
breathing­
zone
air
samples
on
OVS
tubes.
Inhalation
exposure
was
calculated
using
an
assumed
respiratory
rate
of
17
liters
per
minute
for
light
work
(
NAFTA,
1999),
the
actual
sampling
time
for
each
individual,
and
the
pump
flow
rate.
All
results
were
normalized
for
pounds
active
ingredient
handled.
A
total
of
90
replicates
were
monitored
using
17
different
subjects.
Four
different
formulations
of
dacthal
[
75%
wettable
powder
(
packaged
in
4
and
24
pound
bags),
75%
wettable
powder
in
water
soluble
bags
(
3
pound
bag),
75%
water
dispersible
granules
(
2
pound
bag)
and
55%
liquid
flowable
(
2.5
gallon
container)]
were
applied
by
five
different
LCOs
to
actual
residential
lawns
at
each
site
in
three
different
locations
(
Ohio,
Maryland,
and
Georgia)
for
a
total
of
fifteen
replicates
per
formulation.
An
additional
ten
replicates
at
each
site
were
monitored
while
they
performed
spray
application
only
using
the
75
percent
wettable
powder
formulation.
A
target
application
rate
of
2
pounds
active
ingredient
was
used
for
all
replicates
(
actual
rate
achieved
was
about
2.2
pounds
active
ingredient
per
acre).
Each
replicate
treated
a
varying
number
of
actual
client
lawns
to
attain
a
representative
target
of
2.5
acres
(
1
hectare)
of
turf.
The
exposure
periods
averaged
five
hours
twenty­
one
minutes,
five
hours
thirty­
nine
minutes,
and
six
hours
twenty­
four
minutes,
in
Ohio,
Maryland
and
Georgia,
respectively.
Average
time
spent
spraying
at
all
sites
was
about
two
hours.
All
mixing,
loading,
application,
adjusting,
calibrating,
and
spill
clean
up
procedures
were
monitored,
except
for
typical
end­
of­
day
clean­
up
activities
(
e.
g.
rinsing
of
spray
tank,
etc).
Dermal
exposure
was
measured
using
inner
and
outer
whole
body
dosimeters,
hand
washes,
face/
neck
washes,
and
personal
air
monitoring
devices.
All
test
subjects
wore
one­
piece,
100
percent
cotton
inner
dosimeters
beneath
100
percent
cotton
long­
sleeved
shirt
and
long
pants,
rubber
boots
and
nitrile
gloves.
Gloves
are
typically
worn
by
most
LCOs,
and
required
by
many
pesticide
labels
for
mixing
and
loading.
Page
62
of
76
Overall,
residues
were
highest
on
the
upper
and
lower
leg
portions
of
the
dosimeters.
In
general,
concurrent
lab
spikes
produced
mean
recoveries
in
the
range
of
78­
120
percent,
with
the
exception
of
OVS
sorbent
tube
sections
which
produced
mean
recoveries
as
low
as
65.8
percent.
Adjustment
for
recoveries
from
field
fortifications
were
performed
on
each
dosimeter
section
or
sample
matrix
for
each
study
participant,
using
the
mean
recovery
for
the
closest
field
spike
level
for
each
matrix
and
correcting
the
value
to
100
percent.
The
unit
exposure
values
are
presented
below.
[
Note
the
data
were
found
to
be
lognormally
distributed.
As
a
result,
all
exposure
values
are
geometric
means.]

Table
9.1.1
Unit
Exposure
Values
Obtained
From
ORETF
LCO
Handgun
Studies
(
MRID
449722­
01)

Application
Method
Inhalation
Unit
Exposure
(

g/
lb
ai)
1
LCO
Handgun
Spray
Mixer/
Loader/
Applicator
Liquid
Flowable3
1.8
1Air
concentration
(
mg/
m3/
lb
ai)
calculated
using
NAFTA
`
99
standard
breathing
rate
of
17
lpm
(
1
m3/
hr).
2Exposure
calculated
using
OPP/
HED
50%
protection
factor
(
PF)
for
cotton
coveralls
on
torso,
arms,
legs.
3All
commercial
handlers
wore
long
pants,
long­
sleeved
shirt,
nitrile
gloves
and
shoes.

9.1.2
Endothall
Handler
Exposure
Scenarios
It
has
been
determined
that
exposure
to
pesticide
handlers
is
likely
during
the
occupational
use
of
endothall
in
two
distinct
occupational
environments
 
applying
endothall
to
crops
as
a
harvest­
aid
and
applying
endothall
to
water
for
aquatic
plant
control.
The
anticipated
use
patterns
and
current
labeling
indicate
several
occupational
exposure
scenarios
based
on
the
types
of
equipment
and
techniques
that
can
potentially
be
used
during
endothall
applications.
The
quantitative
exposure/
risk
assessment
developed
for
occupational
handlers
is
based
on
the
following
scenarios.
[
Note:
The
scenario
numbers
correspond
to
the
tables
of
risk
calculations
included
in
the
occupational
risk
calculation
sections
of
the
appendices.
Endothall
inhalation
exposure
was
estimated
using
PHED
or
ORETF
data.]

Mixer/
Loaders
Supporting
Applications
to
Crops:
(
1a)
Liquids
for
Aerial
Applications;
(
1b)
Liquids
for
Groundboom
Applications;

Applicators
Applying
to
Crops:
(
2)
Aerial
Applications
(
Sprays);
(
3)
Groundboom
Applications;

Flaggers
Supporting
Applications
to
Crops:
(
4)
Flagging
for
Sprays;

Mixer/
Loader/
Applicators
Applying
to
Water:
(
5)
Liquid:
Handgun
Sprayer;
(
6)
Liquid:
Direct
Metering
(
using
data
for
mixing/
loading
liquid
formulations);
(
7)
Granular:
Blower­
type
Spreader
(
using
data
for
loading
granules).

9.1.3
Endothall
Handler
Exposure
and
Assessment
Page
63
of
76
Daily
Exposure
mg
ai
day

Unit
Exposure
mg
ai
lb
ai
handled
x
Application
Rate
lbs
ai
area
x
Daily
Area
Treated
area
day
Average
Daily
Dose
mg
/
kg
/
day

Daily
Exposure
mg
ai
day
x
Absorption
Factor
(%
/
100)
Body
Weight
(
kg)
The
occupational
handler
exposure
and
risk
calculations
are
presented
in
this
section.

9.1.3.1
Endothall
Handler
Exposure
and
Risk
Calculations
Risks
were
calculated
using
the
Margin
of
Exposure
(
MOE)
[
NOAEL/
Exposure].
Daily
dose
values
are
calculated
by
first
calculating
exposures
by
considering
application
parameters
(
i.
e.,
rate
and
area
treated)
along
with
unit
exposure
values.
Exposures
were
then
normalized
by
body
weight
and
adjusted
for
absorption
factors
as
appropriate
to
calculate
dose
levels.
MOEs
then
were
calculated.

Daily
Exposure:
The
daily
exposure
and
daily
dose
to
handlers
were
calculated
as
described
below.
The
first
step
was
to
calculate
daily
exposure
(
inhalation)
using
the
following
formula:

Where:

Daily
Exposure
=
Amount
(
mg
ai/
day)
inhaled
that
is
available
for
inhalation
absorption;
Unit
Exposure
=
Unit
exposure
value
(
mg
ai/
lb
ai)
derived
from
August
1998
PHED
data
and
from
ORETF
data;
Application
Rate
=
Normalized
application
rate
based
on
a
logical
unit
treatment,
such
as
acres,
square
feet,
gallons,
or
cubic
feet.
Maximum
values
are
generally
used
(
lb
ai/
A,
lb
ai/
sq
ft,
lb
ai/
gal,
lb
ai/
cu
ft);
and
Daily
Area
Treated
=
Normalized
application
area
based
on
a
logical
unit
treatment
such
as
acres
(
A/
day),
square
feet
(
sq
ft/
day),
gallons
per
day
(
gal/
day),
or
cubic
feet
(
cu
ft/
day).

Daily
Dose:
Daily
dose
(
inhalation)
was
calculated
by
normalizing
the
daily
inhalation
exposure
value
by
body
weight
and
accounting
for
inhalation
absorption.
For
assessing
an
average
body
weight
of
60
kilograms
was
used
 
representing
the
body
weight
of
an
average
adult
female
handler.
Since
the
inhalation
toxicological
endpoint
of
concern
is
based
on
an
oral
study,
an
inhalation
absorption
rate
is
needed
and
is
assumed
to
be
100
percent.
Daily
dose
was
calculated
using
the
following
formula:

Where:

Average
Daily
Dose
=
Absorbed
dose
received
from
exposure
to
a
pesticide
in
a
given
scenario
(
mg
pesticide
active
ingredient/
kg
body
weight/
day);
Daily
Exposure
=
Amount
(
mg
ai/
day)
inhaled
that
is
available
for
inhalation
absorption;
Absorption
Factor
=
A
measure
of
the
amount
of
chemical
that
crosses
a
biological
boundary
such
as
the
skin
or
lungs
(%
of
the
total
available
absorbed);
and
Page
64
of
76
MOE

NOAEL
mg/
kg/
day
Average
Daily
Dose
mg/
kg/
day
Body
Weight
=
Body
weight
determined
to
represent
the
population
of
interest
in
a
risk
assessment
(
kg).

Margins
of
Exposure:
Finally,
the
calculations
of
daily
inhalation
dose
received
by
handlers
were
then
compared
to
the
appropriate
endpoint
(
i.
e.,
NOAEL
or
LOAEL)
to
assess
the
total
risk
to
handlers
for
each
exposure
route
within
the
scenarios.
All
MOE
values
were
calculated
inhalation
exposure
levels
using
the
formula
below:

Where:

MOE
=
Margin
of
exposure,
value
used
by
HED
to
represent
risk
or
how
close
a
chemical
exposure
is
to
being
a
concern
(
unitless);
ADD
=
(
Average
Daily
Dose)
or
the
amount
as
absorbed
dose
received
from
exposure
to
a
pesticide
in
a
given
scenario
(
mg
pesticide
active
ingredient/
kg
body
weight/
day);
and
NOAEL
=
Dose
level
in
a
toxicity
study,
where
no
observed
adverse
effects
occurred
(
NOAEL
or
LOAEL)
in
the
study
9.1.3.2
Endothall
Risk
Summary
(
using
PHED
and
ORETF)

All
of
the
risk
calculations
for
occupational
endothall
handlers
completed
in
this
assessment
are
included
in
Tables
9.1.3.2a
and
9.1.3.2b.

.
Page
65
of
76
Table
9.1.3.2a
.
Summery
of
Endothall
Occupational
Short­
and
Intermediate­
Term
Inhalation
Handler
Risks
for
Agricultural
Crops
Uses
Exposure
Scenario
Crop
or
Target
Application
Ratea
(
lb
ai/
acre)
Area
Treated
Dailyb
(
acres)
Inhalation
MOEf,
g
(
Target
Short­
Term
MOE
=
100;
Target
Intermediate­
Term
MOE
=
300)

Baseline
Attirec
PPE
­
80%
Respiratord
Engineering
Controlse
Short­
term
Intermediateterm
Short­
term
Intermediateterm
Short­
term
Intermediate­
term
Mixer/
Loader
Mixing/
Loading
Emulsifiable
Concentrates
(
Liquids)
for
Aerial
Applications
Alfalfa
(
SLN)
1
1,200
390
83
2,000
420
5,700
1,200
Alfalfa
0.8
1,200
490
100
2,400
520
7,100
1,500
Potatoes
1
350
1,300
290
6,700
1,400
19,000
4,100
Clover
0.8
350
1,700
360
8,400
1,800
24,000
5,200
Cotton
(
SLN)
0.13
1,200
3,000
640
15,000
3,200
44,000
9,300
Cotton
0.1
1,200
3,900
830
20,000
4,200
57,000
12,000
Mixing/
Loading
Emulsifiable
Concentrates
(
Liquids)
for
Groundboom
Applications
Alfalfa
(
SLN)
1
200
2,400
500
12,000
2,500
34,000
7,200
Alfalfa
0.8
200
2,900
630
15,000
3,100
42,000
9,000
Potatoes
1
80
5,900
1,300
29,000
6,300
85,000
18,000
Hops
1
40
12,000
2,500
59,000
36,000
170,000
36,000
Clover
0.8
80
7,300
1,600
37,000
7,800
110,000
23,000
Cotton
(
SLN)
0.13
200
18,000
3,800
90,000
19,000
260,000
56,000
Cotton
0.1
200
24,000
5,000
120,000
25,000
340,000
72,000
Applicator
Applying
Sprays
via
Aerial
Equipment
Alfalfa
(
SLN)
1
1,200
No
Data
No
Data
No
Data
No
Data
6,900
1,500
Alfalfa
0.8
1,200
No
Data
No
Data
No
Data
No
Data
8,600
1,800
Potatoes
1
350
No
Data
No
Data
No
Data
No
Data
24,000
5,000
Clover
0.8
350
No
Data
No
Data
No
Data
No
Data
30,000
6,300
Cotton
(
SLN)
0.13
1,200
No
Data
No
Data
No
Data
No
Data
53,000
11,000
Cotton
0.1
1,200
No
Data
No
Data
No
Data
No
Data
69,000
15,000
Applying
Sprays
via
Groundboom
Equipment
Alfalfa
(
SLN)
1
200
3,800
810
19,000
4,100
66,000
14,000
Alfalfa
0.8
200
4,800
1,000
24,000
5,100
82,000
17,000
Potatoes
1
80
9,500
2,000
48,000
10,000
160,000
35,000
Hops
1
40
19,000
4,100
95,000
20,000
330,000
70,000
Clover
0.8
80
12,000
2,500
60,000
13,000
200,000
44,000
Exposure
Scenario
Crop
or
Target
Application
Ratea
(
lb
ai/
acre)
Area
Treated
Dailyb
(
acres)
Inhalation
MOEf,
g
(
Target
Short­
Term
MOE
=
100;
Target
Intermediate­
Term
MOE
=
300)

Baseline
Attirec
PPE
­
80%
Respiratord
Engineering
Controlse
Short­
term
Intermediateterm
Short­
term
Intermediateterm
Short­
term
Intermediate­
term
Page
66
of
76
Cotton
(
SLN)
0.13
200
29,000
6,200
150,000
31,000
500,000
110,000
Cotton
0.1
200
38,000
8,100
190,000
140,000
660,000
140,000
Flagger
Flagging
for
Sprays
via
Aerial
Equipment
Alfalfa
(
SLN),

Potatoes
1
350
4,600
980
23,000
4,900
37,000
8,000
Alfalfa,
Clover
0.8
350
5,800
1,200
29,000
6,100
47,000
10,000
Cotton
(
SLN)
0.13
350
35,000
7,500
180,000
38,000
290,000
61,000
Cotton
0.1
350
46,000
9,800
230,000
49,000
370,000
80,000
Page
67
of
76
Table
9.1.3.2b.
Summery
of
Endothall
Short­
and
Intermediate­
Term
Occupational
Inhalation
Handler
Risks
for
Aquatic
Uses
Exposure
Scenario
Crop
or
Target
Application
Rate
Surface
Area
or
Length
of
Water
Body
(
acres
or
miles)
Depth
of
Water
Body
(
feet)
Width
of
Water
Body
(
feet)
Inhalation
MOE
(
Target
Short­
Term
MOE
=
100;
Target
Intermediate­
Term
MOE
=
300)

Baseline
Attire
PPE
­
80%
Respirator
Engineering
Controls
Short­
term
Intermediateterm
Short­
term
Intermediateterm
Short­
term
Intermediateterm
Mixer/
loader
Mixing/
loading
liquid
for
groundboom
application
(
subsurface
use)
Ponds/

Lakes
13.5
lb
ai/
A­
ft
30
Acres
5
NA
230
50
1150
250
500
(
half
face
respirator
90%

protection)
3150
670
Ponds/

Lakes
8
lb
ai/
A­
ft
30
Acres
5
NA
400
85
2000
425
4700
1000
Mixing/
Loading
Emulsifiable
Concentrate
with
Direct
Metering
(
PHED:

mixing/
loading
liquid
)
Flowing
Water
0.56
lb
ai
/
minute
at
50
cfs
300
minutes/
day
NA
NA
2800
600
14000
3000
40000
8600
Flowing
Water
0.15
lb
ai
/
minute
at
200
cfs
120
minutes/
day
NA
NA
26000
5500
130000
27500
380000
80000
Applicator
Applying
liquid
with
groundboom
(
subsurface
use)
Ponds/

Lakes
13.5
lb
ai/
A­
ft
30
Acres
5
NA
375
80
1900
400
NF
NF
Ponds/

Lakes
8
lb
ai/
A­
ft
30
Acres
5
NA
625
135
3150
675
NF
NF
Mixer/
Loader/
Applicator
Mixing/
Loading/
Applying
Emulsifiable
Concentrates
with
a
Handgun
Sprayer
(
LCO
ORETF
data)
Ponds/
Lakes
13.5
lb
ai/
A­
ft
10
Acres/
day
2
NA
1160
245
5900
1250
NF
NF
Ponds/
Lakes
8
lb
ai/
A­
ft
10
Acres/
day
2
NA
1880
400
9800
2100
NF
NF
Canals
1.7
lb
ai/
canal­­
1
mile
X
1
ft
wide
x
1
ft
deep
10
miles
long
2
20
470
100
2300
500
NF
NF
Canals
1.7
lb
ai/
canal­­
1
mile
X
1
ft
wide
x
1
ft
deep
10
miles
long
2
5
1880
400
9400
2000
NF
NF
Canals
1lb
ai/
canal­­
1
mile
X
1
ft
wide
x
1
ft
deep
10
miles
long
2
20
785
165
4000
850
NF
NF
Canals
1
lb
ai/
canal­­
1
mile
X
1
ft
wide
x
1
ft
deep
10
miles
long
2
5
3135
670
16000
3400
NF
NF
Table
9.1.3.2b.
Summery
of
Endothall
Short­
and
Intermediate­
Term
Occupational
Inhalation
Handler
Risks
for
Aquatic
Uses
Exposure
Scenario
Crop
or
Target
Application
Rate
Surface
Area
or
Length
of
Water
Body
(
acres
or
miles)
Depth
of
Water
Body
(
feet)
Width
of
Water
Body
(
feet)
Inhalation
MOE
(
Target
Short­
Term
MOE
=
100;
Target
Intermediate­
Term
MOE
=
300)

Baseline
Attire
PPE
­
80%
Respirator
Engineering
Controls
Short­
term
Intermediateterm
Short­
term
Intermediateterm
Short­
term
Intermediateterm
Page
68
of
76
Loading/
Applying
Granulars
(
PHED:
open
loading
granulars)
Ponds/
Lakes
9.8
lb
ai/
A­
ft
30
Acres/
day
5
NA
230
48
1100
240
480
(
half
face
respirator
90%

protection)
NF
NF
Canals
1.6
lb
ai/
canal­­
1
mile
X
1
ft
wide
x
1
ft
deep
10
miles
long
5
20
208
45
1050
220
450
(
half
face
respirator
90%

protection)
NF
NF
Canals
1.6
lb
ai/
canal­­
1
mile
X
1
ft
wide
x
1
ft
deep
10
miles
long
5
5
860
180
4100
870
NF
NF
9.1.4
Cancer
Endothall
Handler
Exposure
and
Risk
Assessment
Page
69
of
76
No
occupational
handler
cancer
risk
assessment
is
needed
for
endothall,
since
no
cancer
endpoint
of
concern
was
identified.

9.1.5
Summary
of
Risk
Concerns
and
Data
Gaps
for
Occupational
Handlers
The
occupational
handler
scenarios
for
endothall
have
no
risks
associated
with
them
and
are
above
HED's
level
of
concern
for
inhalation
risk
assessments(
MOE
>
100).
The
assessment
involving
the
aquatic
herbicide
scenarios
uses
substitute
inhalation
unit
exposure
values,
since
no
data
are
available
for
assessing
inhalation
exposures
from
the
use
of
boat­
mounted
application
equipment.
These
occupational
handler
scenarios
for
endothall
could
be
better
refined
with
equipment­
specific
exposure
data.

9.1.5.1
Summary
of
Data
Gaps
Several
data
gaps
were
identified
for
endothall
in
many
different
aquatic
use
areas
that
include:

°
mixing/
loading/
applying
liquid
formulations
to
aquatic
areas
using
handheld
equipment;

$
loading/
applying
liquid
formulations
to
aquatic
areas
using
direct
metering;
and
$
loading/
applying
granular
formulations
to
aquatic
areas
using
centrifugal
or
blower­
type
equipment.

9.1.6
Recommendations
For
Refining
Occupational
Handler
Risk
Assessment
In
order
to
refine
this
occupational
risk
assessment,
data
on
actual
use
patterns
including
rates,
timing,
and
areas
treated
would
better
characterize
endothall
risks.
Exposure
studies
for
many
equipment
types
that
lack
data
or
that
are
not
well
represented
in
PHED
(
e.
g.,
because
of
low
replicate
numbers
or
data
quality)
should
also
be
considered
based
on
the
data
gaps
identified
above
and
based
on
a
review
of
the
quality
of
the
data
used
in
this
assessment.

9.2
Occupational
Postapplication
Exposures
and
Risks
Agricultural
Crop
Uses:

EPA
did
not
assess
occupational
postapplication
risks
to
agricultural
workers
following
treatments
to
agricultural
crops,
since
no
dermal
endpoint
of
concern
was
identified.

The
Environmental
Protection
Agency's
requirements
regarding
Restricted­
entry
Intervals
(
REIs)
are
included
in
the
40
CFR
156.208.
Guidance
on
applying
these
requirements
are
also
included
in
Chapter
11
of
the
Office
of
Pesticide
Programs'
Label
Review
Manual.
In
accordance
with
the
40
CFR
156.208,
the
REI
is
based
on
the
acute
toxicity
of
the
"
technical
active
ingredient
material".

The
toxicity
categories
of
the
active
ingredient
for
acute
dermal,
eye
irritation,
and
skin
irritation
potential
are
used
to
determine
the
interim
REI.
If
one
or
more
of
the
three
acute
toxicity
effects
are
in
toxicity
category
I,
the
interim
REI
is
established
at
48
hours.
If
none
of
the
acute
toxicity
effects
are
in
Page
70
of
76
category
I,
but
one
or
more
of
the
three
is
classified
as
category
II,
the
interim
REI
is
established
at
24
hours.
The
acute
toxicity
classification
for
primary
eye
irritation
of
endothall
is
category
I
which
requires
a
48­
hour
REI.

Aquatic
Uses:
Postapplication
occupational
exposures
following
endothall
application
to
aquatic
areas
is
likely
limited
to
persons
who
contact
the
treated
water
to
perform
tests,
such
as
testing
the
levels
of
endothall,
or
persons
such
as
agricultural
workers
or
irrigation
water
suppliers
who
contact
treated
water
in
irrigation
canals.
Worse­
case
postapplication
exposures
to
endothall
following
application
in
aquatic
sites
is
likely
to
be
to
persons
who
swim
in
the
treated
waters.
The
swimmer
exposure
to
endothall
followed
the
guidance
provided
in
the
Agency's
draft
SOP.
The
standard
exposure
factors
provided
in
the
residential
SOP
were
used
to
assess
noncompetitive
swimmer
exposure.
The
exposure
to
competitive
swimming
was
not
assessed
since
endothall
is
not
used
in
swimming
pools.

Refer
to
residential
postapplication
section
for
postapplication
exposure
assessment
to
aquatic
uses
of
endothall
for
noncompetitive
swimmers
(
i.
e.,
recreational).

10.0
Date
Needs
and
Label
Requirements
10.1
Toxicology
870.3700b
Developmental
Toxicity/
Teratology
(
rabbit)

870.3465
28­
Day
Inhalation
10.2
Residue
Chemistry,
Label
Needs,
Tolerance
Reassessment
Residue
Chemistry
Deficiencies
10.2.1.
Radiovalidation
data
to
determine
whether
the
current
enforcement
methods
for
plants
and
the
required
enforcement
methods
for
animals
and
fish
can
adequately
extract
and
convert
aged
residues
of
the
monomethyl
ester
to
endothall.

10.2.2.
Data
collection
and
regulatory
analytical
methods
for
the
determination
of
endothall,
per
se,
in
animal
commodities.

10.2.3.
Storage
stability
data
for
processed
plant
commodities,
animal
commodities,
and
fish.

10.2.4.
Livestock
(
ruminant
and
poultry)
feeding
studies
10.2.5.
Magnitude
of
the
residue
studies
in
irrigated
crops.

10.2.6.
Magnitude
of
the
residue
studies
in
potato,
alfalfa
seed,
cottonseed,
and
cotton
gin
byproducts.
Magnitude
of
the
residue
studies
in
the
RACs
of
sugar
beet
and
rice
if
the
registrant
intends
to
support
these
uses.
Page
71
of
76
10.2.7.
Processing
studies
on
apples,
corn
(
field),
grapes,
orange,
rice,
sorghum,
soybeans,
sugar
beet,
tomato,
and
wheat,
to
cover
irrigation
uses.

10.2.8.
Submission
of
analytical
reference
standards
for
dipotassium
and
mono­
N,
Ndimethylalkyl
amine
salts
of
endothall.

10.2.9.
An
acceptable
confined
rotational
crop
study,
or
in
lieu
of
a
confined
rotational
crop,
limited
rotational
crop
field
trials
may
be
performed
for
crops
with
TRR
exceeding
0.01
ppm
in
the
existing
confined
rotational
crop
study,
so
long
as
all
of
endothall
and
its
monoomethyl­
and
dimethyl
metabolites
are
tested.

Label
Needs
Labeling
on
the
Hydrothol
(
mono­
N,
N­
dimethylalkyl
amine
salt
of
endothall)
formulations
instructs
the
user
how
to
apply
the
product
at
5
ppm
of
the
free
acid
endothall
equivalents,
while
the
Aquathol
(
dipotassium
salt
of
endthall)
labels
instruct
the
user
how
to
apply
these
formulations
at
5
ppm
as
the
dipotassium
salt
of
endothall.
Thus,
while
the
application
rates
are
nominally
the
same,
5
ppm,
the
molecular
weight
difference
between
these
two
forms
of
endothall
causes
a
difference
to
exist
between
these
two
treatment
rates.
This
discrepancy
is
confusing
and
HED
recommends
that
the
labels
for
the
dipotassium
salt
(
Aquathol)
should
be
modified
to
include
a
description
of
the
application
rate
when
it
is
expressed
as
ppm
in
endothall,
acid
equivalents.

A
maximum
seasonal
application
rate
must
be
added
to
the
label
for
applications
to
irrigation
water.

Tolerance
Reassessment
Table
10.2.1.
Tolerance
Summary
for
Endothall.

Commodity
Current
Tolerance
(
ppm)
Reassessed
Tolerance
(
ppm)
Comments
Tolerances
Listed
Under
40
CFR
§
180.293
(
a)(
1)

Cotton,
Undelinted
Seed
0.1
To
be
determined
(
TBD)
Additional
data
are
required.

Hop
0.1
TBD
Additional
data
are
required
Change
commodity
name
to
Hop,
Dried
Cones
Potato
0.1
TBD
Additional
data
are
required.
Commodity
Current
Tolerance
(
ppm)
Reassessed
Tolerance
(
ppm)
Comments
Page
72
of
76
Rice,
Grain
0.05(
N)
TBD
Although
there
are
presently
no
registered
uses
on
rice,
HED
recommends
for
the
retention
of
these
tolerances
until
the
registrant
has
submitted
the
requested
irrigation
crop
data
which
should
include
data
for
rice
commodities.
Rice,
Straw
0.05(
N)
TBD
Tolerance
Listed
Under
40
CFR
§
180.293
(
a)(
2)

Potable
Water
0.2
Revoke
Tolerance
OPP
no
longer
establishes
tolerances
in
drinking
water.
EPA's
Office
of
Water
has
established
an
MCL
for
endothall
at
0.10
ppm.

Tolerance
Listed
Under
40
CFR
§
180.319
Beet,
Sugar
0.2
TBD
Additional
data
are
required.
Although
there
are
presently
no
registered
uses
on
sugar
beets,
HED
recommends
for
the
retention
of
the
interim
tolerance
until
the
registrant
has
submitted
the
requested
irrigation
crop
data.
Residue
data
must
include
data
for
both
sugar
beet
root
and
tops.
Change
commodity
name
to
Beet,
sugar,
root
10.3
Occupational
and
Residential
Exposure
10.3.1
Summary
of
Data
Gaps
Several
data
gaps
were
identified
for
endothall
in
aquatic
use
areas
that
include:

1.04
mixing/
loading/
applying
liquid
formulations
to
aquatic
areas
using
handheld
equipment;
1.05
loading/
applying
liquid
formulations
to
aquatic
areas
using
direct
metering;
and
1.06
loading/
applying
granular
formulations
to
aquatic
areas
using
centrifugal
or
blower­
type
equipment.

10.3.2
Recommendations
For
Refining
Occupational
Handler
Risk
Assessment
Page
73
of
76
In
order
to
refine
the
occupational
risk
assessment,
data
on
actual
use
patterns
including
rates,
timing,
and
areas
treated
would
better
characterize
endothall
risks.
Exposure
studies
for
many
equipment
types
that
lack
data
or
that
are
not
well
represented
in
PHED
(
e.
g.,
because
of
low
replicate
numbers
or
data
quality)
should
also
be
considered
based
on
the
data
gaps
identified
above
and
based
on
a
review
of
the
quality
of
the
data
used
in
the
occupational
risk
assessment
Page
74
of
76
References:

Memo:
ENDOTHALL­
Report
of
the
Hazard
Identification
Assessment
Review
Committee.
June
14,
2004.
Robert
P.
Zendzian
PhD
Senior
Pharmacologist,
Toxicology
Branch,
Health
Effects
Division
(
7509C)

Memo:
Endothall.
Report
of
the
Health
Effects
Division
(
HED)
Risk
Assessment
Review
Committee
(
RARC).
4­
NOV­
2004
Jennifer
Tyler,
Executive
Secretary
RARC/
HED
Memo:
Endothall:
Toxicology
Disciplinary
Chapter
for
the
Reregistration
Eligibility
Decision
Document
(
RED).
Robert
P.
Zendzian
PhD,
Senior
Pharmacologist,
Toxicology
Branch,
Health
Effects
Division,
(
7509C)

Memo.
Endothall
and
its
Salts:
Product
Chemistry
Considerations
for
Reregistration
Eligibility
Decision.
Case
No.
2245
DP
Barcode
304026.
10
June
2004
David
Soderberg,
Chemist,
Reregistration
Branch
3,
Health
Effects
Division
(
7509C)

Memo.
Endothall
and
its
Salts:
Residue
Chemistry
Considerations
for
Reregistration
Eligibility
Decision.
Case
No.
2245.
29
November
2004
David
Soderberg,
Chemist,
Reregistration
Branch
3,
Health
Effects
Division
(
7509C)

Memo:
Endothall
and
its
Salts.
Chronic
Dietary
Exposure
Assessment
for
the
Reregistration
Eligibility
Decision.
29
November
2004.
David
Soderberg,
Chemist,
Reregistration
Branch
3,
Health
Effects
Division
(
7509C)

Memo:
Occupational
and
Residential
Exposure
Assessment
and
Recommendations
for
the
Reregistration
Eligibility
Decision
Document
for
Endothall.
November
15,
2004.
Seyed
Tadayon,
Chemist,
Reregistration
Branch
2,
Health
Effects
Division
(
7509C)

Memo:
Drinking
Water
Assessment
for
Endothall
for
both
Terrestrial
and
Aquatic
Uses.
Registrant:
Cerexagri.
May
5,
2004.
James
Breithaupt,
Agronomist
Environmental
Risk
Branch
II
Environmental
Fate
and
Effects
Division
(
7507C)

Memo:
Review
of
Endothall
(
and
salts)
Incident
Reports.
DP
Barcode
DP304467,
Chemical#
038901
(
and
salts
038902­
11).
June
24,
2004.
Jerome
Blondell,
Ph.
D.,
Health
Statistician
Chemistry
and
Exposure
Branch
Health
Effects
Division
(
7509C)
and
Monica
S.
Hawkins,
M.
P.
H.,
Environmental
Health
Scientist
Chemistry
and
Exposure
Branch
Health
Effects
Division
(
7509C
Page
75
of
76
Appendices
1.0
TOXICOLOGY
DATA
REQUIREMENTS
The
requirements
(
40
CFR
158.340)
for
food
use
for
endothall
are
in
Table
1.
Use
of
the
new
guideline
numbers
does
not
imply
that
the
new
(
1998)
guideline
protocols
were
used.

Table
1
Toxicology
Data
Requirements
for
Endothall
Test
Technical
Required
Satisfied
870.1100Acute
Oral
Toxicity
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.1200Acute
Dermal
Toxicity
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.1300Acute
Inhalation
Toxicity
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.2400
Primary
Eye
Irritation
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.2500
Primary
Dermal
Irritation
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.2600
Dermal
Sensitization
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
870.3100
Oral
Subchronic
(
rodent)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.3150
Oral
Subchronic
(
nonrodent)
.
.
.
.
.
.
.
.
.
.
.
.
870.3200
21­
Day
Dermal
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.3250
90­
Day
Dermal
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.3465
90­
Day
Inhalation
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
yes
yes
yes
yes
yes
yes
yes
yes
yes
no
870.3700a
Developmental
Toxicity
(
rodent)
.
.
.
.
.
870.3700b
Developmental
Toxicity
(
nonrodent)
.
.
.
870.3800Reproduction
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
yes
yes
yes
yes
no
yes
870.4100a
Chronic
Toxicity
(
rodent)
.
.
.
.
.
.
.
.
.
.
.
870.4100b
Chronic
Toxicity
(
nonrodent)
.
.
.
.
.
.
.
.
870.4200a
Oncogenicity
(
rat)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.4200b
Oncogenicity
(
mouse)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.4300Chronic/
Oncogenicity
.
.
.
.
.
.
.
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.
.
.
.
.
.
.
.
.
.
yes
yes
yes
yes
yes
chronic/
onco
yes
chronic/
onco
yes
yes
870.5100Mutagenicity
 
Gene
Mutation
­
bacterial
.
.
.
870.5300Mutagenicity
 
Gene
Mutation
­
mammalian
870.5xxxMutagenicity
 
Structural
Chromosomal
Aberrations
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.5xxxMutagenicity
 
Other
Genotoxic
Effects
.
.
.
.
yes
yes
yes
yes
yes
yes
yes
yes
Test
Technical
Required
Satisfied
Page
76
of
76
870.6100a
Acute
Delayed
Neurotox.
(
hen)
.
.
.
.
.
.
870.6100b
90­
Day
Neurotoxicity
(
hen)
.
.
.
.
.
.
.
.
.
870.6200a
Acute
Neurotox.
Screening
Battery
(
rat)
870.6200b
90
Day
Neurotox.
Screening
Battery
(
rat)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.6300
Developmental
Neurotoxicity
.
.
.
.
.
.
.
.
.
.
.
.
no
no
no
no
no
­
­
­
­
­

870.7485
General
Metabolism
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.7600
Dermal
Penetration
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
yes
no
yes
yes
Special
Studies
for
Ocular
Effects
Acute
Oral
(
rat)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
Subchronic
Oral
(
rat)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
Six­
month
Oral
(
dog)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
no
no
no
­
­
­
