Document ID: EPA-HQ-OPP-2005-0263-0007
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2005-10-26T04:00Z

Page
1
of
36
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
Date:
October
24,
2005
MEMORANDUM
SUBJECT:
MCPB:
Phase
II
Response
to
Error
Only
Comments
on
the
HED
Chapter
of
the
Reregistration
Eligibility
Decision
Document
(
RED).
PC
Code:
019201
(
MCPB
Acid)
and
019202
(
MCPB
Sodium
Salt)
DP
Barcode:
DP319763.

Regulatory
Action:
Phase
II
Reregistration
Action
Risk
Assessment
Type:
Single
Chemical
Aggregate
FROM:
Elizabeth
Méndez,
PhD
Reregistration
Branch
I
Health
Effects
Division
(
7509C)

AND
Kit
Farwell,
DVM
­
Toxicologist
Felecia
Fort
­
Chemist
Timothy
Dole,
CIH
­
ORE
Assessor
Reregistration
Branch
I
Health
Effects
Division
(
7509C)

THROUGH:
Whang
Phang,
PhD
­
Branch
Senior
Scientist
Reregistration
Branch
I
Health
Effects
Division
(
7509C)

TO:
Demson
Fuller
Reregistration
Branch
I
SRRD
(
7508C)
Page
2
of
36
The
Health
Effects
Division
(
HED)
of
EPA's
Office
of
Pesticide
Programs
has
evaluated
the
error
only
comments
received
from
MCPB
Task
Force
on
the
HED
Chapter
of
the
Reregistration
Eligibility
Decision
Document
(
RED)
as
well
as
the
Occupational
and
Residential
Exposure
and
Risk
Assessment
Chapter.
The
vast
majority
of
the
comments
reflected
typographical
and/
or
grammatical
errors
which
have
been
corrected
in
the
body
of
the
HED
chapters
and
will
not
be
addressed
further
in
this
document.
The
comments
listed
below
and
the
Agency's
responses,
however,
warrant
further
discussion.

Comment
1:
Chemical
name
needs
to
be
consistent
throughout
the
document
as
4­(
2­
methyl­
4­
chlorophenoxy)
butyric
acid.

The
Agency
acknowledges
the
comments
from
the
MCPB
Task
Force
and
has
replaced
the
chemical
name
4­(
4­
chloro­
o­
tolyloxy)
butyric
acid
with
the
nomenclature
recommended
by
the
Task
Force
throughout
the
body
of
the
document.
However,
for
the
IUPAC
names
and
CAS
names
listed
in
Table
2.2
the
Agency
has
reviewed
several
sources
including
the
Farm
Chemicals
Handbook,
Compendium
of
Pesticide
Common
Names,
and
the
Australian
Pesticide
and
Veterinary
Medicines
Authority.
All
of
these
sources
listed
the
official
IUPAC
and
CAS
names
for
MCPB
as
the
ones
used
in
Table
2.2.
Consequently,
the
nomenclature
used
in
the
table
will
remain
unchanged.

Comment
2:
Table
2.3
on
page
10
shows
vapor
pressure
of
4
x
10exp­
7
torr
at
25
°
C,
which
the
MCPB
Task
Force
member
Nufarm
reports
is
the
temperature
stated
in
the
Harold
Podall
memo.

The
Agency
acknowledges
the
comment
and
has
changed
all
references
to
the
vapor
pressure
to
reflect
a
temperature
of
25
°
C
rather
than
20
°
C.

Comment
3:
(
i)
MCPB
Task
Force
member
Nufarm
advises
that
the
Harold
Podall
memo
cites
a
density
of
1.33
for
the
technical
grade
of
MCPB
and
a
density
of
1.26
for
the
pure
active
ingredient.
(
ii)
UV/
vis
spectrum
should
be
clarified
as
an
absorbance
of
0.881
at
2229
nm.

The
Agency
concurs
with
the
registrant
and
has
included
the
density
of
the
pure
active
ingredient
as
well
as
the
technical
grade
active
ingredient.
The
Agency
has
also
stated
that
the
UV/
vis
spectrum
absorbance
of
0.881
was
at
229
nm.

Comment
4:
In
respect
to
the
requirement
for
an
enforcement
analytical
method
that
determines
both
MCPB
and
MCPA
in/
on
plant
commodities,
there
exists
an
unsubmitted
method
that
has
been
validated
and
independently
validated
for
MCPB,
MCPA
and
HMCPA
in
peas.

The
Agency
acknowledges
the
comment
by
the
Task
Force
and
encourages
submission
of
the
Page
3
of
36
afore
mentioned
validated
method
for
review
by
Agency
scientists.
Page
4
of
36
HUMAN
HEALTH
RISK
ASSESSMENT
MCPB
U.
S.
Environmental
Protection
Agency
Office
of
Pesticide
Programs
Health
Effects
Division
(
7509C)
Elizabeth
Méndez,
Ph.
D,
Risk
Assessor
Kit
Farwell,
D.
V.
M.,
Toxicologist
Felecia
Fort,
Chemist
Timothy
Dole,
CIH,
ORE
Risk
Assessor
Date:
August
4,
2005
Page
5
of
36
TABLE
OF
CONTENTS
1.0
Executive
Summary
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6
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35
2.0
Ingredient
Profile
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Page
8
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35
2.1
Summary
of
Registered/
Proposed
Uses
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Page
8
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35
2.2
Structure
and
Nomenclature
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Page
9
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35
2.3
Physical
and
Chemical
Properties
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Page
9
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35
3.0
Metabolism
Assessment
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Page
10
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35
3.1
Comparative
Metabolic
Profile
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Page
10
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35
3.2
Nature
of
the
Residue
in
Foods
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Page
11
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35
3.2.1.
Description
of
Primary
Crop
Metabolism
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Page
11
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35
3.2.2
Description
of
Livestock
Metabolism
.
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Page
11
of
35
3.2.3
Description
of
Rotational
Crop
Metabolism,
including
identification
of
major
metabolites
and
specific
routes
of
biotransformation
.
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Page
11
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35
3.3
Tabular
Summary
of
Metabolites
and
Degradates
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Page
12
of
35
3.4
Toxicity
Profile
of
Major
Metabolites
and
Degradates
.
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Page
13
of
35
3.5
Summary
of
Residues
for
Tolerance
Expression
and
Risk
Assessment
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Page
13
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35
3.5.1
Tabular
Summary
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Page
13
of
35
3.5.2
Rationale
for
Inclusion
of
Metabolites
and
Degradates
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Page
13
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35
4.0
Hazard
Characterization/
Assessment
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Page
14
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35
4.1
Database
Summary
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Page
14
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35
4.1.1
Toxicity
studies
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Page
14
of
35
4.1.2
Mode­
of­
action,
metabolism
and
toxicokinetic
data
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Page
14
of
35
4.1.3
Sufficiency
of
studies/
data
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Page
15
of
35
4.2
Toxicological
Effects
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Page
15
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4.3
Dose­
response
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Page
15
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35
4.4
FQPA
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Page
17
of
35
4.5
Datagaps
for
Toxicity
Studies
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Page
19
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35
4.6
Endocrine
disruption
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Page
20
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35
6.0
Exposure
Characterization/
Assessment
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Page
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6.1
Dietary
Exposure/
Risk
Pathway
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Page
21
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Page
6
of
36
6.1.1
Residue
Profile
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Page
21
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35
6.1.2
Acute
and
Chronic
Dietary
Exposure
and
Risk
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Page
21
of
35
6.2
Water
Exposure/
Risk
Pathway
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Page
23
of
35
6.3
Residential
(
Non­
Occupational)
Exposure/
Risk
Pathway
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Page
23
of
35
6.3.1
Spray
Drift
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Page
23
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35
7.0
Aggregate
Risk
Assessments
and
Risk
Characterization
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Page
24
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35
8.0
Cumulative
Risk
Characterization/
Assessment
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Page
25
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35
9.0
Occupational
Exposure/
Risk
Pathway
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Page
26
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35
9.1
Short/
Intermediate/
Long­
Term
Handler
Risk
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Page
26
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35
9.2
Short/
Intermediate­
Term
Postapplication
Risk
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Page
28
of
35
10.0
Data
Needs
and
Label
Requirements
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Page
29
of
35
10.1
Toxicology
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Page
29
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35
10.2
Residue
Chemistry
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Page
29
of
35
10.3
Occupational
and
Residential
Exposure
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Page
29
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35
APPENDIX
A
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Page
30
of
35
Page
7
of
36
1.0
Executive
Summary
The
Health
Effects
Division
(
HED)
of
EPA's
Office
of
Pesticide
Programs
has
evaluated
the
MCPB
[
4­(
2­
methyl­
4­
chlorophenoxy)
butyric
acid]
database
and
conducted
a
human
health
risk
assessment
for
the
reregistration
of
the
chemical.
This
assessment
supersedes
any
previous
assessments
issued
by
the
Agency.

MCPB
is
a
phenoxy
herbicide
produced
as
a
sodium
salt
and
an
acid.
It
is
used
as
a
postemergence
selective
weed
control
to
protect
pea
crops
from
a
variety
of
weeds
including
Canadian
thistle,
common
lambsquarters,
pigweed,
smartweed,
sowthistle,
and
morningglories.
Currently,
a
tolerance
of
0.1
ppm
is
established
for
negligible
residues
of
the
herbicide
4­(
2­
methyl­
4­
chlorophenoxy)
butyric
acid
in/
on
the
raw
agricultural
commodity
pea
(
CFR
§
180.318).
The
tolerance
expression
will
be
revised
in
accordance
with
current
residue
data.
This
chemical
is
registered
as
a
General
Use
Pesticide
(
GUP)
by
the
US
Environmental
Protection
Agency
(
US
EPA).
It
may
be
used
in
agricultural
settings
only;
there
are
no
registered
residential
uses.

MCPB
is
available
as
a
liquid
in
three
active
end
use
products
formulated
from
two
technical
products.
It
may
be
applied
to
pea
plants
only
once
during
the
growing
season
using
ground
and
aerial
equipment.
MCPB
may
be
applied
from
shoot
emergence
until
the
three
leaf
nodes
stage
preceding
flowering
.
Typically,
at
the
time
of
treatment
for
Canada
thistle,
pea
plants
are
at
the
6­
12
node
stage.
Applications
cannot
be
made
after
the
three
node
stage
prior
to
flowering
or
after
pea
flower
buds
appear.
In
general,
application
rates
range
from
0.5
to
1.5
lb
acid
equivalent/
acre
with
the
highest
rate
being
used
for
the
treatment
against
Canada
thistle
that
has
reached
the
bud
stage.

MCPB
has
a
low
to
moderate
acute
toxicity
profile
(
Toxicity
Category
IV
to
II).
The
currently
available
toxicological
database
for
MCPB
is
limited;
thus,
it
was
supplemented
with
the
closely
related
compound,
MCPA.
Structurally,
MCPB
and
MCPA
only
differ
in
that
the
side
chain
of
MCPB
contains
two
more
carbon
atoms
than
the
side
chain
of
MCPA.
In
both
animal
and
plant
metabolism
studies,
the
data
indicate
that
MCPB
is
readily
converted
to
MCPA.
It
would,
therefore,
not
be
unexpected
that
the
toxicity
profile
for
these
two
compounds
was
similar
at
sublethal
dose
levels.
Nephrotoxicity
and
hepatotoxicity
appear
to
be
the
most
prevalent
hazard
concerns
for
MCPB,
based
on
the
effects
seen
throughout
the
MCPA
database
and
the
limited
toxicity
data
set
available
for
MCPB.
Other
toxic
effects
reported
after
MCPB
or
MCPA
exposure
included
neurotoxicity.
Developmental
and
reproduction
toxicity
studies
conducted
in
MCPB
and/
or
MCPA
did
not
indicate
an
enhanced
sensitivity
or
susceptibility
to
the
young
as
developmental
effects
(
delayed
ossifications
and
decreased
fetal
or
pup
body
weight)
occurred
at
the
same
doses
eliciting
toxicity
in
the
parental
animals.

Although
the
dog
is
the
most
sensitive
species
to
the
effects
of
chlorophenoxy
herbicides
like
MCPB,
endpoint
selection
was
based
on
the
rodent
studies.
Unlike
rats
and
humans,
dogs
are
uniquely
sensitive
to
the
toxic
effects
of
this
class
of
compounds
due
to
their
decreased
ability
to
Page
8
of
36
excrete
organic
acids.
Thus,
the
rat
was
considered
to
be
a
more
suitable
animal
model
for
assessing
the
potential
risks
to
the
human
population
associated
with
MCPB
exposure.

For
both
acute
and
chronic
dietary
risk
assessments,
the
Health
Effects
Division
(
HED)
has
selected
endpoints
from
studies
available
in
the
MCPA
toxicology
database.
The
acute
risk
assessment
was
based
on
neurotoxicity
observed
in
the
Acute
Neurotoxicity
Study
in
Rats
while
the
chronic
assessment
was
based
on
liver
and
kidney
toxicity
reported
in
a
Chronic
Toxicity
Study
in
Rats.
Since
MCPB
has
been
classified
as
a
chemical
"
not
likely
to
be
carcinogenic
to
humans",
no
cancer
risk
assessment
was
conducted.
In
the
case
of
short/
intermediate­
term
dermal
exposures,
the
effects
of
concern
were
decreased
body
weight
gain
and
kidney
toxicity
reported
in
the
21­
Day
Dermal
Toxicity
Study
in
Rabbits
conducted
with
MCPA.
Given
that
neither
the
MCPB
nor
the
MCPA
database
contain
inhalation
studies
(
except
for
the
Acute
Inhalation
Lethality
Toxicity
Studies
[
LC
50]),
a
Developmental
Toxicity
Study
in
Rabbits
conducted
with
MCPB
was
used
for
short/
intermediate
inhalation
exposures
based
on
clinical
signs
and
maternal
mortality
as
the
critical
endpoints.
The
current
use
pattern
and
registered
use
for
MCPB
do
not
indicate
long­
term
occupational/
residential
exposure
risks.
Consequently,
longterm
risk
assessments
via
the
dermal
and/
or
inhalation
routes
were
not
conducted.

HED
has
concluded
that
the
special
FQPA
factor
could
be
reduced
to
1X
based
on
the
present
toxicological
database
and
adequacy
of
uncertainty
factors
assigned
to
chosen
endpoints.
Clear
NOAELs
were
identified
for
all
studies
used
for
endpoint
selection
and
their
dose­
response
relation
was
well
characterized.
A
FQPA
database
uncertainty
factor
(
UF
DB)
was
retained
to
account
for
the
lack
of
a
Developmental
Neurotoxicity
Study
in
Rats
(
DNT)
in
accordance
to
current
HED
policy.
A
10X
UF
DB
was
used
for
the
acute
dietary
risk
assessment
since
it
is
anticipated
that
the
DNT
may
yield
a
NOAEL
approximately
10X
lower
than
the
one
currently
used
for
the
risk
assessment.
For
the
chronic
dietary
risk
assessment,
the
UF
DB
was
reduced
to
3X
since
it
is
expected
that
the
DNT
could
yield
a
NOAEL
approximately
3X
lower
than
the
one
currently
used
for
this
risk
assessment.
No
additional
UF
DB
is
required
for
the
short/
intermediate
dermal
and
inhalation
risk
assessments
since
there
are
no
residential
exposure
scenarios
and
the
FQPA
UF
DB
has
not
been
historically
applied
to
occupational
risk
assessments.

Acute
and
chronic
dietary
risk
assessments
were
conducted
using
the
Dietary
Exposure
Evaluation
Model
(
DEEM­
FCID
 
,
Version
2.03)
which
uses
food
consumption
data
from
the
USDA's
Continuing
Surveys
of
Food
Intakes
by
Individuals
(
CSFII)
from
1994­
1996
and
1998.
An
unrefined
Tier
1
(
tolerance
level
and
100%
crop
treated
(%
CT))
acute
dietary
risk
assessment
was
conducted
for
all
supported
MCPB
food
uses.
This
assessment
showed
that
at
the
95th
percentile
of
exposure,
the
acute
risk
estimates
are
below
the
Agency's
level
of
concern
(<
100%
aPAD)
for
the
general
U.
S.
population
and
all
population
subgroups
(<
2%
of
the
aPAD).
Similarly,
tolerance
level
residues
and
100%
CT
were
used
to
determine
the
chronic
dietary
exposure
and
risk
estimates.
This
assessment
showed
that
for
all
included
commodities,
the
Page
9
of
36
chronic
risk
estimates
were
below
the
Agency's
level
of
concern
(<
100%
cPAD)
for
the
general
U.
S.
population
and
all
population
subgroups
(<
4%
cPAD).
Finally,
inclusion
of
surface
or
ground
water
modeling
residues
in
the
acute
and
chronic
assessments
indicates
that
HED's
level
of
concern
is
not
exceeded
(<
100%
aPAD
and
cPAD).

An
occupational
risk
assessment
has
been
conducted
for
handlers/
applicators
exposures
as
well
as
for
post­
application
exposures.
Since
chemical­
specific
handler
exposure
data
were
not
available,
the
analysis
for
exposure
was
performed
using
the
Pesticide
Handler
Exposure
Database
(
PHED).
The
calculations
of
handlers'
short­
and
intermediate­
term
inhalation
exposure
exceed
the
target
MOE
of
100
with
baseline
respiratory
protection
(
i.
e.,
no
respirators)
and
are,
therefore,
not
of
concern.
For
dermal
exposures,
all
the
MOEs
exceed
the
target
MOE
of
100
when
using
single
layer
personal
protective
equipment
(
PPE)
[
i.
e.
baseline
PPE
with
chemical
resistant
gloves].
HED
has
determined
that
workers
may
be
dermally
exposed
to
MCPB
upon
entering
previously
treated
areas
to
perform
specific
work
activities
(
e.
g.,
irrigation,
scouting,
etc.).
Inhalation
exposure
is
not
anticipated
for
the
post­
application
worker
scenarios
due
to
the
low
vapor
pressure
of
MCPB,
therefore,
only
dermal
exposure
risk
assessments
were
conducted.
All
MOEs
for
dermal
exposure
exceed
the
target
MOE
of
100
on
Day
0
indicating
that
the
post­
application
risks
are
not
of
concern.

2.0
Ingredient
Profile
MCPB
(
4­(
2­
methyl­
4­
chlorophenoxy)
butyric
acid
is
a
selective
phenoxy
herbicide
used
postemergence
as
a
broadcast
foliar
application
to
control
broad­
leaved
annual
and
perennial
weeds
(
Canada
thistle
)
in
peas.
The
end
use
products
are
sodium
salts.
Its
only
food/
feed
use
is
on
peas.

2.1
Summary
of
Registered/
Proposed
Uses
Table
2.1.
Summary
of
Directions
for
Use
of
MCPB.

Applic.
Timing,
Type,
and
Equip.
Applic.
Rate
(
lb
ai/
A)
Max.
No.
Applic.
per
Season
Max.
Seasonal
Applic.
Rate
(
lb
ai/
A)
PHI
(
days)
Use
Directions
and
Limitations
Groundboom
1.5
1
1.5
1
Use
single
layer
PPE
Aerial
1.5
1
1.5
1
Use
single
layer
PPE
Page
10
of
36
Cl
CH
3
O
OH
O
2.2
Structure
and
Nomenclature
The
chemical
structure
and
information
are
presented
below
for
MCPB.

TABLE
2.2.
Test
Compound
Nomenclature
Chemical
Structure
Empirical
Formula
C11H13ClO3
Common
name
MCPB
IUPAC
name
4­(
4­
chloro­
o­
tolyloxy)
butyric
acid
CAS
name
4­(
4­
Chloro­
2­
methylphenoxy)
butanoic
acid
CAS
Registry
Number
94­
81­
5
End­
use
product/
EP
Thistrol
Chemical
Class
phenoxy
herbicide
Known
Impurities
of
Concern
N/
A
2.3
Physical
and
Chemical
Properties
MCPB
is
a
brown
solid,
flake
with
a
melting
point
of
101.5­
103
C,
density
of
1.33
g/
ml
(
1.26
g/
mlfor
purif.
tech)
at
20

C,
octanol/
water
partition
coefficient
(
log
K
OW)
of
1.33
(
pH=
7),
and
vapor
pressure
of
4
x
10­
7
torr
at
25

C.
MCPB
is
soluble
in
water,
methanol,
acetone
and
other
organic
solvents.

It
is
very
similar
in
structure
to
MCPA
(
methyl­
chloro­
phenoxy
acetic
acid)
which
is
also
a
phenoxy
herbicide.
The
MCPB
side
chain
contains
two
more
carbons
than
MCPA.
Page
11
of
36
TABLE
2.3.
Physicochemical
Properties
of
MCPB
Parameter
Value
Reference
Molecular
Weight
228.6
g/
mol
D279212
(
H.
Podall,
3/
8/
02)

Melting
point/
range
101.5­
103.0
deg.
C
(
purif.
tech)
D279212
(
H.
Podall,
3/
8/
02)

pH
5.6
(
1%
w/
v)
D279212
(
H.
Podall,
3/
8/
02)

Density
D(
20/
4)
=
1.33
D(
20/
4)=
1.26(
for
purif.
tech)
D279212
(
H.
Podall,
3/
8/
02)

Water
solubility
(
20
C)
60.4
mg/
l
D279212
(
H.
Podall,
3/
8/
02)

Solvent
solubility
(
20
C)
n­
heptane
0.414
g/
l
xylene
37.6
g/
l
methylene
chloride
69.9
g/
l
methanol
>
250
g/
l
n­
octanol
71.6
g/
l
acetone
>
250
g/
l
ethyl
acetate
144
g/
l
D279212
(
H.
Podall,
3/
8/
02)

Vapor
pressure
(
25
C)
4x10exp­
7
torr
D279212
(
H.
Podall,
3/
8/
02)

Dissociation
constant,
pKa
pKa
=
4.6
D279212
(
H.
Podall,
3/
8/
02)

Octanol/
water
partition
coefficient,
logPOW
(
20
C)
pH
log
P(
o/
w)
4
3.45
7
1.33
10
­
0.21
D279212
(
H.
Podall,
3/
8/
02)

UV/
visible
absorption
spectrum
0.881
at
229
nm
D279212
(
H.
Podall,
3/
8/
02)

3.0
Metabolism
Assessment
3.1
Comparative
Metabolic
Profile
MCPB
and
MCPA
are
two
chlorophenoxy
herbicides
which
differ
only
in
that
MCPB
contains
two
additional
carbon
atoms
(
Table
3.1).
In
rat
metabolism
studies,
both
MCPB
and
MCPA
were
rapidly
absorbed
with
urine
being
the
major
route
of
excretion;
no
bioaccumulation
occurred
with
either
compound.
For
both
compounds,
the
major
urinary
metabolite
was
MCPA.
The
similarities
between
the
two
compounds
can
be
explained
because
metabolic
enzymes
typically
remove
carbons
two
at
a
time
during
degradation,
in
a
process
called
 ­
oxidation.
This
results
in
MCPB
being
converted
to
MCPA.
MCPB
was
also
shown
to
be
converted
to
MCPA
in
plant
metabolism
studies.
Page
12
of
36
3.2
Nature
of
the
Residue
in
Foods
3.2.1.
Description
of
Primary
Crop
Metabolism
The
nature
of
the
residue
in
peas
is
adequately
understood
based
on
metabolism
studies
conducted
in/
on
peas.
These
studies
have
shown
that
MCPB
is
converted
to
MCPA.
MCPA
undergoes
oxidation
of
the
phenyl
methyl,
and
the
resulting
hydroxymethyl
compound
forms
conjugates,
including
a
glucose
conjugate.
The
major
compound
identified
in
mature
pod
and
vine
was
parent,
MCPB,
40%
TRR
and
72%
TRR,
respectively.
The
compounds
identified
in
mature
seed
included
MCPA/
MCPA
ester,
11%
TRR,
and
the
glucose
conjugate
of
hydroxy
MCPA,
12.5%
TRR.
Polar
unknowns
comprised
27%
of
TRR.
The
Metabolism
Committee
decided
(
06/
08/
95)
that
the
residue
of
concern
for
both
tolerance
enforcement
and
for
dietary
risk
analysis
consists
of
MCPB
and
MCPA,
free
and
conjugated.

3.2.2
Description
of
Livestock
Metabolism
A
waiver
of
the
requirements
for
a
livestock
metabolism
study
was
granted
based
on
the
minor
nature
of
dried
peas
as
an
animal
feed
item
and
the
lack
of
MCPB
residues
found
in
the
pea
seeds
from
field
trials.

3.2.3
Description
of
Rotational
Crop
Metabolism,
including
identification
of
major
metabolites
and
specific
routes
of
biotransformation
A
rotational
crop
study
has
not
been
submitted
and
is
a
data
gap.
Page
13
of
36
Cl
CH
3
O
OH
O
O
Cl
OH
O
CH
3
3.3
Tabular
Summary
of
Metabolites
and
Degradates
Table
3.1
Tabular
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)

MCPB
Immature
Vine
66(
2.20)

Mature
Vine
72(
3.59)

Mature
Root
1(
0.0021)

Mature
Pod
40(
0.01)
Rotational
Crops
TBD
TBD
Ruminant
N/
A
N/
A
Poultry
N/
A
N/
A
Rat
0.1
MCPA
Mature
Seed
1.2(
0.0003)

Immature
Vine
6.0(
0.20)

Mature
Vine
5.8(
0.29)

Mature
Root
0.8(
0.0015)

Mature
Pod
0.8(
0.0002)

Rotational
Crops
TBD
TBD
Ruminant
N/
A
N/
A
Poultry
N/
A
N/
A
Rat
35
9
Peas,
MRID
42966301;
0.78
lb.
a.
i./
acre
(
0.4X);
10x
vegetative
growth
state;
60
Page
14
of
36
3.4
Toxicity
Profile
of
Major
Metabolites
and
Degradates
The
toxicity
database
for
MCPB
was
limited
and
was
supplemented
with
the
closely
related
compound,
MCPA.
MCPB
[
4­(
2­
methyl­
4­
chlorophenoxy)
butyric
acid)]
differs
from
MCPA
(
methyl­
chloro­
phenoxy
acetic
acid)
only
in
having
an
organic
acid
in
which
the
side
chain
contains
two
more
carbons
than
MCPA.
In
addition,
in
both
plant
and
animal
metabolism
studies,
the
results
indicated
that
MCPB
was
metabolized
to
MCPA.
Toxicity
was
very
similar
between
MCPB
and
MCPA
at
doses
below
a
lethal
dose.

3.5
Summary
of
Residues
for
Tolerance
Expression
and
Risk
Assessment
3.5.1
Tabular
Summary
Tolerances
are
currently
established
under
40
CFR
§
180.318
for
residues
of
MCPB
[
4­(
2­
methyl­
4­
chlorophenoxy)
butyric
acid)]
per
se
in/
on
peas
at
0.1
ppm.
The
Metabolism
Committee
decided
(
06/
08/
95)
that
the
residue
of
concern
for
both
tolerance
enforcement
and
for
dietary
risk
analysis
consists
of
MCPB
and
MCPA,
free
and
conjugated.
The
tolerance
expression
must
be
revised
in
accordance
with
these
recommendations.

Table
3.2
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
MCPB
and
MCPA
MCPB
and
MCPA
Rotational
Crop
Data
Gap
Data
GAp
Livestock
Ruminant
N/
A
N/
A
Poultry
N/
A
N/
A
3.5.2
Rationale
for
Inclusion
of
Metabolites
and
Degradates
The
metabolism
of
MCPB
in
peas
was
reviewed
(
S.
Funk,
Memorandum
of
Issues
to
Be
Presented
to
the
HED
Metabolism
Committee,
05/
25/
95).
The
Committee
decided
the
residue
of
concern
for
both
tolerance
and
risk
assessment
is
MCPB
and
MCPA,
free
and
conjugated.
Based
on
radiolabeled
compounds
identified
in
mature
rac's
and
immature
vines,
a
metabolism
pathway
was
proposed
that
involved
conversion
of
MCPB
to
MCPA,
hydroxylation
of
MCPA,
and
conjugation
of
the
resulting
4­
chloro­
2­
hydroxymethylphenoxy
acetic
acid.
Page
15
of
36
4.0
Hazard
Characterization/
Assessment
4.1
Database
Summary
The
toxicity
database
for
MCPB
was
limited
and
was
supplemented
with
the
closely
related
compound,
MCPA.
MCPB
[
4­(
2­
methyl­
4­
chlorophenoxy)
butyric
acid)
butyric
acid]
differs
from
MCPA
(
methyl­
chloro­
phenoxy
acetic
acid)
only
in
having
an
organic
acid
with
a
side
chain
that
is
two
carbons
longer
than
MCPA.
Toxicity
was
very
similar
between
MCPB
and
MCPA
at
doses
below
a
lethal
dose.
This
is
not
unexpected
as
MCPB
is
metabolized
to
MCPA
as
evidenced
in
both
plant
and
animal
metabolism
studies.

4.1.1
Toxicity
studies:

°
Subchronic:
90­
day
rat
and
dog
feeding
studies
with
MCPB
and
MCPA;
21­
day
dermal
toxicity
study
in
rabbits
with
MCPA;
subchronic
neurotoxicity
study
with
MCPA
°
Developmental:
rat
and
rabbit
developmental
studies
with
MCPB
and
MCPA
°
Reproduction:
2­
generation
reproduction
study
with
MCPA
°
Chronic:
rat
and
mouse
cancer
studies
with
MCPA;
1­
year
dog
study
with
MCPA
°
Other:
mutagenicity
battery
for
MCPB
and
MCPA;
metabolism
studies
with
MCPA
and
MCPB;
acute
neurotoxicity
study
with
MCPA
4.1.2
Mode­
of­
action,
metabolism
and
toxicokinetic
data
The
pesticidal
action
of
chlorophenoxy
herbicides
is
due
to
mimicking
the
action
of
auxins,
plant
growth
hormones.
The
mode­
of­
action
for
toxicity
in
mammals
is
not
known.

In
rat
metabolism
studies,
both
MCPB
and
MCPA
were
rapidly
absorbed
with
urine
being
the
major
route
of
excretion;
no
bioaccumulation
occurred
with
either
compound.
For
both
MCPB
and
MCPA,
the
major
urinary
metabolite
was
MCPA.
The
similarities
between
the
two
compounds
can
be
explained
because
metabolic
enzymes
typically
remove
carbons
two
at
a
time
during
degradation,
in
a
process
called
 ­
oxidation.
This
results
in
MCPB
being
converted
to
MCPA.

Although
there
are
no
pharmacokinetic
data
in
dogs,
it
is
known
that
dogs
are
generally
more
sensitive
to
toxicity
from
chlorophenoxy
herbicides
than
rats
because
of
decreased
clearance
of
organic
acids
in
dogs
compared
to
humans
and
rats.
(
See
HIARC
reports
for
2,4­
D
and
MCPA
for
more
details.)

4.1.3
Sufficiency
of
studies/
data
Data
were
sufficient
for
endpoint
selection
for
each
exposure
scenario
and
for
FQPA
Page
16
of
36
evaluation
when
the
MCPA
database
is
included
with
the
MCPB
database.

4.2
Toxicological
Effects
Subchronic
studies
were
available
for
both
MCPB
and
MCPA.
MCPB
caused
liver
toxicity,
kidney
toxicity,
and
hematological
effects
in
rats
and
dogs;
and
small
testes,
prostate,
and
thymus
in
the
dog
study.
These
effects
are
seen
with
other
chlorophenoxy
herbicides,
and
at
similar
doses
in
the
subchronic
studies
with
MCPA.
Neurotoxicity
was
not
seen
in
the
MCPB
subchronic
studies
but
was
noted
in
MCPA
neurotoxicity
studies
(
decreased
arousal,
impaired
coordination
and
gait,
reduced
motor
activity,
reduced
grip
strength).
A
dermal
toxicity
study
was
available
only
for
MCPA;
this
study
found
microscopic
evidence
of
kidney
injury.

Chronic
studies
were
only
available
for
MCPA.
Liver
and
kidney
toxicity
occurred
in
chronic
rat
and
dog
studies
with
MCPA,
but
at
lower
doses
than
in
the
subchronic
studies.
There
was
no
increase
in
tumors
in
the
rat
or
mouse
carcinogenicity
studies
with
MCPA.
MCPB
was
negative
in
a
battery
of
mutagenicity
assays
except
for
a
positive
result
in
a
chromosomal
aberrations
in
CHO
cells
assay.
Similar
results
were
found
for
mutagenicity
testing
with
MCPA.
The
cancer
classification
for
MCPA
was
"
not
likely
to
be
carcinogenic
to
humans".

Developmental
studies
were
available
for
both
MCPB
and
MCPA.
In
the
developmental
rat
study
with
MCPB,
decreased
ossification
and
decreased
fetal
body
weights
occurred
at
the
same
dose
causing
decreased
maternal
body
weight.
Similar
effects
occurred
at
similar
doses
in
the
developmental
rat
study
with
MCPA.
No
toxicity
to
fetuses
occurred
in
the
MCPB
and
MCPA
rabbit
developmental
studies;
maternal
mortality
occurred
in
the
study
with
MCPB
but
not
with
MCPA.
A
reproduction
study
was
only
available
for
MCPA;
in
this
1986
study,
the
only
offspring
toxicity
was
decreased
weight
gain
while
nursing.

4.3
Dose­
response
Since
the
toxicity
database
for
MCPB
was
limited,
studies
with
the
closely
related
compound,
MCPA
were
used
to
select
toxicity
endpoints.
The
database
for
MCPA
acid
was
used
preferentially
instead
of
MCPA­
DMA
(
dimethyl
amine
salt)
and
MCPA­
EHE
(
ethyl
hexyl
ester)
because
there
are
no
DMA
or
EHE
formulations
with
MCPB,
as
is
the
case
with
MCPA.

Endpoints
were
selected
from
rat
studies,
rather
than
dog
studies
because
dogs
are
more
sensitive
to
toxicity
from
chlorophenoxy
herbicides
than
rats
and
other
species.
This
is
Page
17
of
36
because
dogs
have
decreased
ability
to
excrete
organic
acids
than
do
rats
and
humans,
which
results
in
higher
blood
levels
and
toxicity
at
lower
doses
in
dogs
than
in
other
species
(
see
MCPA
and
2,4­
D
HIARC
reports).

Endpoints
and
doses
are
shown
in
Table
4.1.

Acute
dietary:
The
endpoint
was
gait
impairment
in
an
acute
neurotoxicity
study
with
MCPA.
This
study
was
selected
because
the
toxicity
occurred
after
a
single
oral
dose
and
is
appropriate
for
exposure
of
this
duration.
The
endpoint
applies
to
the
general
population.
No
appropriate
endpoint
for
females
13+
years
was
identified.
The
MCPB
developmental
rat
study
was
not
used
because
decreases
in
skeletal
ossification
associated
with
decreased
fetal
weight
are
more
likely
to
occur
after
repeated
doses
rather
than
after
a
single
dose.

Chronic
dietary:
The
endpoint
is
liver
and
kidney
toxicity
from
the
chronic
rat
feeding
study
with
MCPA.
This
study
reported
clinical
chemistry
changes
as
well
as
gross
and
microscopic
lesions
of
chronic
progressive
kidney
disease.
This
study
was
selected
because
the
route
and
duration
of
exposure
are
appropriate
for
this
risk
assessment.

Incidental
oral
(
short
and
intermediate­
term):
The
endpoint
is
maternal
mortality
which
occurred
in
a
rabbit
developmental
study
with
MCPB.
No
deaths
occurred
in
the
rabbit
developmental
study
with
MCPA.

Dermal
(
short
and
intermediate­
term):
The
endpoint
was
kidney
toxicity
(
increased
renal
tubule
mineralization)
and
decreased
body
weight
gain
in
a
21­
day
dermal
toxicity
study
with
MCPA.

Dermal
(
long­
term):
The
endpoint
is
liver
and
kidney
toxicity
from
the
chronic
rat
feeding
study
with
MCPA
as
noted
above
for
the
chronic
dietary
endpoint.
The
duration
of
exposure
is
appropriate
for
this
risk
assessment.
A
dermal
absorption
factor
of
7%
shall
be
used
(
determined
from
MCPA
dermal
absorption
study).

Inhalation
(
short
and
intermediate
term):
The
endpoint
is
maternal
mortality
which
occurred
in
a
rabbit
developmental
study
with
MCPB.

Inhalation
(
long­
term):
The
endpoint
is
liver
and
kidney
toxicity
from
the
chronic
rat
feeding
study
with
MCPA.
This
study
reported
clinical
chemistry
changes
as
well
as
gross
and
microscopic
lesions
of
chronic
progressive
kidney
disease.
Page
18
of
36
Table
4.1
Toxicological
Doses
and
Endpoints
for
MCPB
Human
Risk
Assessment
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF
and
Level
of
Concern
UFDB
Study
and
Toxicological
Effects
Acute
Dietary
(
general
population)
NOAEL
=
200
mg/
kg/
day
UF
=
1000
acute
RfD
=
0.2
mg/
kg/
day
FQPA
SF
=
1x
acute
PAD
=
0.2
mg/
kg/
day
10
Acute
neurotoxicity
study
(
MCPA).
LOAEL
=
400
mg/
kg/
day
based
on
gait
impairment
in
males.

Chronic
Dietary
(
all
populations)
NOAEL=
4.4
mg/
kg/
day
UF
=
300
chronic
RfD
=
0.015
mg/
kg/
day
FQPA
SF
=
1X
chronic
PAD
=
0.015
mg/
kg/
day
3
Chronic
toxicity
study
in
rats
(
MCPA).
LOAEL
=
17.6
mg/
kg/
day
based
on
liver
and
kidney
toxicity.

Incidental
Oral
Short­
and
Intermediate­
Term
NOAEL
=
5
mg/
kg/
day
Residential
LOC
=
300
3
Developmental
toxicity
in
rabbits
(
MCPB).
LOAEL
=
20
mg/
kg/
day
based
on
maternal
mortality.

Dermal
Short­
and
Intermediate
Term
Dermal
NOAEL=
100
mg/
kg/
day
Residential
LOC
=
300
Occupational
LOC
=
100
3
21­
day
dermal
toxicity
study
(
MCPA).
LOAEL
=
1000
mg/
kg/
day
based
on
kidney
toxicity
and
decreased
body
weight
gain.

Dermal
Long­
Term
Oral
NOAEL=
4.4
mg/
kg/
day
Residential
LOC
=
300
Occupational
LOC
=
100
3
Chronic
toxicity
study
in
rats
(
MCPA).
LOAEL
=
17.6
mg/
kg/
day
based
on
liver
and
kidney
toxicity.

Inhalation
Short­
and
Intermediate
Term
Oral
NOAEL
=
5
mg/
kg/
day
Residential
LOC
=
300
Occupational
LOC
=
100
3
Developmental
toxicity
in
rabbits
(
MCPB).
LOAEL
=
20
mg/
kg/
day
based
on
maternal
mortality.

Inhalation
Long­
Term
Oral
NOAEL=
4.4
mg/
kg/
day
Residential
LOC
=
300
Occupational
LOC
=
100
3
Chronic
toxicity
study
in
rats
(
MCPA).
LOAEL
=
17.6
mg/
kg/
day
based
on
liver
and
kidney
toxicity.

Cancer
Classification:
Not
likely
to
be
carcinogenic
to
humans.

UF
=
uncertainty
factor,
FQPA
SF
=
Special
FQPA
safety
factor,
NOAEL
=
no
observed
adverse
effect
level,
LOAEL
=
lowest
observed
adverse
effect
level,
a
RfD
=
acute
reference
dose
=
NOAEL/
UF,
cRfD
=
chronic
RfD
=
NOAEL/
UF,

MOE
=
margin
of
exposure,
LOC
=
level
of
concern,
NA
=
Not
Applicable,
PAD
=
population
adjusted
dose
=
RfD/
FQPA
SF,
UFDB
=
database
uncertainty
factor
Dermal
absorption
=
7%

4.4
FQPA
The
database
was
adequate
for
FQPA
assessment
when
the
database
for
MCPA
was
included.
There
were
acceptable
rat
and
rabbit
developmental
studies
with
both
MCPB
and
MCPA.
There
were
also
a
two­
generation
reproduction
study
and
neurotoxicity
Page
19
of
36
studies
with
MCPA.

There
was
no
indication
of
quantitative
or
qualitative
sensitivity
noted
in
developmental
rat
studies
with
MCPB
or
MCPA.
In
the
developmental
rat
studies
with
MCPB
and
MCPA,
decreased
ossification
and
decreased
fetal
body
weights
occurred
at
the
same
dose
causing
decreased
maternal
body
weight.
No
toxicity
to
fetuses
occurred
in
the
MCPB
and
MCPA
rabbit
developmental
studies.
A
reproduction
study
was
only
available
for
MCPA;
in
this
1986
study,
the
only
offspring
toxicity
was
decreased
weight
gain
while
nursing.

The
Special
FQPA
Safety
Factor
for
MCPB
can
be
removed
(
1x)
because
there
is
no
evidence
of
quantitative
or
qualitative
susceptibility
to
offspring
seen
in
the
developmental
rat
and
rabbit
studies
with
MCPB
or
MCPA,
or
in
the
two­
generation
reproduction
study
with
MCPA.

Neurotoxicity
was
not
seen
in
the
MCPB
subchronic
studies
(
clinical
signs
in
rabbit
developmental
study
occurred
on
the
day
of
or
day
prior
to
death
or
moribund
sacrifice
and
were
attributed
to
agonal
death).
Neurotoxicity
was
noted
in
MCPA
neurotoxicity
studies
in
rats
(
decreased
arousal,
impaired
coordination
and
gait,
reduced
motor
activity,
reduced
grip
strength).
Similar
signs
of
neurotoxicity
can
be
expected
with
MCPB
and
a
developmental
neurotoxicity
study
(
DNT)
is
therefore
required
for
MCPB.
This
datagap
can
be
satisfied
with
a
developmental
neurotoxicity
study
with
MCPA
if
this
study
becomes
available.

As
was
the
case
with
MCPA,
since
there
is
a
datagap
for
a
DNT
study,
a
dose
analysis
was
conducted,
following
procedures
described
in
the
policy
document,
Change
in
Dose
Analysis
Procedure,
7/
20/
04.
It
was
assumed
that
doses
for
the
DNT
study
will
be
based
upon
the
reproduction
study
or
the
subchronic
neurotoxicity
study
and
that
a
NOAEL
will
be
determined.
If
a
NOAEL
of
2.5
mg/
kg/
day
(
from
the
reproduction
study)
is
determined
from
the
DNT
study,
then
the
database
uncertainty
factors
named
below
should
be
used.
Page
20
of
36
Exposure
Scenario
Dose
Selected
mg/
kg/
day
Estimated
NOAEL
of
DNT,
mg/
kg/
day
Database
Uncertainty
Factor
Acute
Dietary
200
2.5
The
DNT
NOAEL
may
be
lower
than
the
dose
selected
for
risk
assessment:
UFDB
of
10x
is
required.

Chronic
Dietary
4.4
2.5
The
DNT
NOAEL
may
be
slightly
lower
than
the
dose
selected
for
risk
assessment:
UFDB
of
3x
is
required.

Short­
and
Intermediate­
Term
Incidental
Oral
5
2.5
The
DNT
NOAEL
may
be
slightly
lower
than
the
dose
selected
for
risk
assessment:
UFDB
of
3x
is
required.

Short­
and
Intermediate­
Term
Dermal
dermal
NOAEL
=
100
2.5
The
DNT
NOAEL
may
be
slightly
lower
than
the
dose
selected
for
risk
assessment
when
7%
dermal
absorption
is
considered:
UFDB
of
3x
is
required.

Long­
Term
Dermal
oral
NOAEL
=
4.4
2.5
The
DNT
NOAEL
may
be
slightly
lower
than
the
dose
selected
for
risk
assessment:
UFDB
of
3x
is
required.

Short­
and
Intermediate­
Term
Inhalation
oral
NOAEL
=
5
2.5
The
DNT
NOAEL
may
be
slightly
lower
than
the
dose
selected
for
risk
assessment:
UFDB
of
3x
is
required.

Long­
Term
Inhalation
oral
NOAEL
4.4
2.5
The
DNT
NOAEL
may
be
slightly
lower
than
the
dose
selected
for
risk
assessment:
UFDB
of
3x
is
required.

4.5
Datagaps
for
Toxicity
Studies
The
following
studies
are
required
for
MCPB.
These
studies
are
also
required
for
MCPA
and
may
be
satisfied
by
studies
with
MCPA.

1.
Developmental
neurotoxicity
study
in
rats.

2.
Twenty
eight
(
28)­
day
inhalation
study
in
rats
(
abbreviated
90­
day
protocol).
This
study
is
required
because
there
is
the
potential
for
repeated
occupational
exposure
via
this
route.
Page
21
of
36
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).

In
the
available
toxicity
database
for
MCPB
there
was
no
evidence
of
estrogen,
androgen,
and/
or
thyroid
mediated
toxicity.
When
additional
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency's
EDSP
have
been
developed,
MCPB
may
be
subjected
to
further
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.

5.0
Public
Health
Data
A
single
case
of
MCPB
sodium
salt
poisoning
was
reported
involving
a
35
year­
old
adult
male
with
a
minor
medical
outcome
who
was
seen
in
a
health
care
facility.
This
case
reported
headache
and
one
other
unspecified
miscellaneous
symptom.
There
were
no
other
reports
involving
MCPB
or
its
salts
among
the
over
one
million
exposures
reported
to
Poison
Control
Centers
participating
in
TESS
from
1993
through
2003
or
any
other
databases
such
as
OPP
Incident
Data
System
(
IDS),
California
Department
of
Pesticide
Regulation,
National
Pesticide
Information
Center
(
NPIC),
National
Institute
of
Occupational
Safety
and
Health's
Sentinel
Event
Notification
System
for
Occupational
Risks
(
NIOSH
SENSOR).
Page
22
of
36
6.0
Exposure
Characterization/
Assessment
6.1
Dietary
Exposure/
Risk
Pathway
6.1.1
Residue
Profile
The
nature
of
the
residue
in
plants
is
adequately
understood
based
on
metabolism
studies
conducted
in/
on
peas.
HED
(
9/
2/
04)
has
determined
that
the
residues
to
be
regulated
for
both
tolerance
and
risk
assessment
purposes
in
plant
commodities
are
free
and
conjugated
MCPB
and
MCPA.
Residues
of
concern
are
not
likely
to
be
detected
in
livestock
tissues,
milk
and
eggs,
and
HED
has
recommended
against
establishing
tolerances
due
to
the
minor
nature
of
dried
peas
as
an
animal
feed
item
and
the
lack
of
MCPB
residues
found
in
the
pea
seeds
from
field
trials.

Tolerances
are
currently
established
under
40
CFR
§
180.318
for
residues
of
MCPB
4­(
2­
methyl­
4­
chlorophenoxy)
butyric
acid)
per
se
in/
on
peas
at
0.1
ppm.
The
tolerance
expression
will
be
revised.

The
reregistration
requirements
for
magnitude
of
the
residue
in/
on
peas
are
not
fulfilled.
Residue
studies
must
be
submitted
depicting
the
magnitude
of
both
MCPB
and
MCPA
residues
in/
on
peas.
New
data
were
also
required
because
much
of
the
residues
were
generated
by
Craven
Laboratories.
In
the
previously
submitted
residue
studies
in/
on
peas,
MCPB
residues
were
nondetectable.
An
enforcement
analytical
method
is
also
required
that
determines
both
MCPB
and
MCPA
in/
on
plant
commodities.

No
Codex
MRLs
have
been
established
for
MCPB;
therefore,
issues
of
compatibility
between
Codex
MRLs
and
U.
S.
tolerances
do
not
exist.
Additionally,
no
Canadian
or
Mexican
MRLs
have
been
established
for
MCPB.

6.1.2
Acute
and
Chronic
Dietary
Exposure
and
Risk
In
determining
exposure
and
risk
from
use
of
MCPB
in/
on
food,
HED
used
the
Dietary
Exposure
Evaluation
Model
(
DEEM­
FCID
 
,
Version
2.03)
which
uses
food
consumption
data
from
the
USDA's
Continuing
Surveys
of
Food
Intakes
by
Individuals
(
CSFII)
from
1994­
1996
and
1998.
The
1994­
96,
98
data
are
based
on
the
reported
consumption
of
more
than
20,000
individuals
over
two
non­
consecutive
survey
days.
Foods
"
as
consumed"
(
e.
g.,
apple
pie)
are
linked
to
EPA­
defined
food
commodities
(
e.
g.
apples,
peeled
fruit
­
cooked;
fresh
or
N/
S;
baked;
or
wheat
flour
­
cooked;
fresh
or
N/
S,
baked)
using
publicly
available
recipe
translation
files
developed
jointly
by
USDA/
ARS
and
EPA.
For
chronic
exposure
assessment,
consumption
data
are
averaged
for
the
entire
U.
S.
population
and
within
population
subgroups,
but
for
acute
exposure
assessment
are
retained
as
individual
consumption
events.
Based
on
analysis
of
the
1994­
96,
98
CSFII
Page
23
of
36
consumption
data,
which
took
into
account
dietary
patterns
and
survey
respondents,
HED
concluded
that
it
is
most
appropriate
to
report
risk
for
the
following
population
subgroups:
the
general
U.
S.
population,
all
infants
(<
1
year
old),
children
1­
2,
children
3­
5,
children
6­
12,
youth
13­
19,
adults
20­
49,
females
13­
49,
and
adults
50+
years
old.

Acute
Dietary
Exposure
Results
and
Characterization
An
unrefined
Tier
1
(
tolerance
level
and
100%
crop
treated
(%
CT))
acute
dietary
risk
assessment
was
conducted
for
all
supported
MCPB
food
uses
(
Table
6.1).
Dietary
risk
estimates
are
provided
for
the
general
U.
S.
population
and
various
population
subgroups.
This
assessment
showed
that
at
the
95th
percentile
of
exposure,
the
acute
risk
estimates
are
below
the
Agency's
level
of
concern
(<
100%
aPAD)
for
the
general
U.
S.
population
and
all
population
subgroups
(<
2%
of
the
aPAD).
The
highest
exposed
population
subgroup
was
infants
(<
1
years
old).

Chronic
Dietary
Exposure
Results
and
Characterization
Tolerance
level
residues
and
100%
CT
were
also
used
to
determine
the
chronic
dietary
exposure
and
risk
estimates
(
Table
6.1).
This
assessment
showed
that
for
all
included
commodities,
the
chronic
risk
estimates
were
below
the
Agency's
level
of
concern
(<
100%
cPAD)
for
the
general
U.
S.
population
and
all
population
subgroups
(<
4%
cPAD).
The
highest
exposed
population
subgroup
was
infants
(<
1
years
old).

MCPB
has
been
classified
as
"
not
likely
to
be
carcinogenic
to
humans".
A
quantitative
carcinogenic
dietary
analysis
is
not
required.

Table
6.1
Summary
of
Dietary
Exposure
and
Risk
for
MCPB.

Population
Subgroup
a
Acute
Dietary
(
95th
Percentile)
Chronic
Dietary
aPAD,
mg/
kg
Exposure,
mg/
kg/
day
b
%
aPAD
cPAD,
mg/
kg/
day
Exposure,
mg/
kg/
day
b
%
cPAD
General
U.
S.
Population
0.2
0.000754
0.4
0.015
0.000128
0.9
All
Infants
(<
1
yr)
0.2
0.003971
2.0
0.015
0.000568
3.8
Children
1­
2
yrs
0.2
0.002701
1.4
0.015
0.000410
2.7
Children
3­
5
yrs
0.2
0.001653
0.8
0.015
0.000251
1.7
Children
6­
12
yrs
0.2
0.000803
0.4
0.015
0.000141
0.9
Youth
13­
19
yrs
0.2
0.000440
0.2
0.015
0.000081
0.5
Adults
20­
49
yrs
0.2
0.000614
0.3
0.015
0.000094
0.6
Adults
50+
yrs
0.2
0.000817
0.4
0.015
0.000125
0.8
Females
13­
49
yrs
0.2
0.000581
0.3
0.015
0.000090
0.6
a
The
values
for
the
population
with
the
highest
risk
for
each
type
of
risk
assessment
are
bolded.
Page
24
of
36
b
Reported
to
2
significant
figures.

6.2
Water
Exposure/
Risk
Pathway
The
OPP
Environmental
Fate
and
Effects
Division
(
EFED)
prepared
the
drinking
water
assessment
for
MCPB.
The
surface
water
residues
provided
by
the
Environmental
Fate
and
Effects
Division
(
Alex
Clem,
email
correspondence,
1/
27/
05)
are
from
a
PRZMEXAMS
analysis.
For
groundwater,
EDWCs
were
generated
from
a
Tier
I
SCI­
GROW
analysis.
These
results
have
been
characterized
as
conservative,
though
not
unreasonable
estimates
of
possible
concentrations
in
drinking
water.
A
point
estimate
was
used
for
the
two
commodities
"
Water,
direct,
all
sources"
and
"
Water,
indirect,
all
sources"
in
the
residue
file
editor
for
DEEM­
FCID
(
Table
6.2).
These
results,
were
in
turn
used
for
the
aggregate
(
food
+
water)
risk
assessment.

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

Exposure
Duration
MCPB
Surface
Water
Conc.,
ppb
a
Ground
Water
Conc.,
ppb
b
Acute
54.7
0.86
Chronic
(
non­
cancer)
13.5
0.86
a
From
the
Tier
II
PRZM­
EXAMS
­
Index
Reservoir
model.
Input
parameters
are
based
on
use
of
MCPB
applied
once
a
year
at
1.5
lbs
ai/
A
to
peas.
b
From
the
SCI­
GROW
model
assuming
a
maximum
seasonal
use
rate
of
1.5
lbs
ai/
A
6.3
Residential
(
Non­
Occupational)
Exposure/
Risk
Pathway
Occupational
and
residential
exposure
and
risk
assessments
are
required
for
an
active
ingredient
if:
(
1)
certain
toxicological
criteria
are
triggered
and
(
2)
there
is
potential
exposure
to
handlers
during
use,
or
to
field
workers
entering
treated
areas
after
application
is
completed.
MCPB
[
4­(
2­
methyl­
4­
chlorophenoxy)
butyric
acid];
CAS
#
94­
81­
5
meets
both
criteria.
However,
in
the
case
of
MCPB
there
are
no
residential
uses.
Nonetheless,
spray
drift
is
a
potential
source
of
exposures
for
bystanders
since
the
MCPB
labels
allow
for
aerial
application.

6.3.1
Spray
Drift
Spray
drift
is
always
a
potential
source
of
exposure
to
residents
nearby
to
spraying
operations.
This
is
particularly
the
case
with
aerial
application,
but,
to
a
lesser
extent,
could
also
be
a
potential
source
of
exposure
from
the
ground
application
method
employed
for
MCPB.
The
Agency
has
been
working
with
the
Spray
Drift
Task
Force,
EPA
Regional
Offices
and
State
Lead
Agencies
for
pesticide
regulation
and
other
parties
to
develop
the
best
spray
drift
management
practices.
On
a
chemical
by
chemical
basis,
the
Agency
is
now
requiring
interim
mitigation
measures
for
aerial
applications
that
must
Page
25
of
36
be
placed
on
product
labels/
labeling.
The
Agency
has
completed
its
evaluation
of
the
new
data
base
submitted
by
the
Spray
Drift
Task
Force,
a
membership
of
U.
S.
pesticide
registrants,
and
is
developing
a
policy
on
how
to
appropriately
apply
the
data
and
the
AgDRIFT
computer
model
to
its
risk
assessments
for
pesticides
applied
by
air,
orchard
airblast
and
ground
hydraulic
methods.
After
the
policy
is
in
place,
the
Agency
may
impose
further
refinements
in
spray
drift
management
practices
to
reduce
off­
target
drift
with
specific
products
with
significant
risks
associated
with
drift.

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

No
residential
uses
are
supported
for
MCPB.
Moreover,
MCPB
has
been
classified
as
"
not
likely
to
be
carcinogenic
to
humans."
Consequently,
only
acute
and
chronic
dietary
aggregate
exposure
risk
assessments
(
i.
e.,
food
+
water)
were
conducted
(
Table
7.1).
When
surface
or
ground
water
modeling
residues
are
included
in
the
acute
and
chronic
assessments,
HED's
level
of
concern
is
not
exceeded
(<
100%
aPAD
and
cPAD).
For
surface
water,
the
most
highly
exposed
population
subgroup
was
all
infants
(<
1
yr
old)
at
approximately
6%
aPAD
(
95th
%
ile)
and
10%
cPAD,
respectively.
For
ground
water,
all
infants
were
also
the
most
highly
exposed
population
subgroup.
For
infants,
<
2
or
4%
of
the
aPAD
and
cPAD,
respectively
were
occupied
in
the
acute
and
chronic
aggregate
assessment,
respectively.
Page
26
of
36
Table
7.1.
Results
of
Acute
and
Chronic
Dietary
Exposure
Analyses
for
Food
and
Drinking
Water
Population
Subgroup
Acute
Chronic
Surface
Water
Ground
Water
Surface
Water
Ground
Water
Exposure
(
mg/
kg/
day)
%
aPAD
Exposure
(
mg/
kg/
day)
%
aPAD
Exposure
(
mg/
kg/
day)
%
cPAD
Exposure
(
mg/
kg/
day)
%
cPAD
General
U.
S.
Population
0.003356
1.7
0.000772
0.4
0.000414
2.8
0.000148
1.0
All
Infants
(<
1
year
old)*
0.011869
5.9
0.004018
2.0
0.001501
10
0.000627
4.2
Children
1­
2
years
old
0.006060
3.0
0.002724
1.4
0.000833
5.6
0.000437
2.9
Children
3­
5
years
old
0.005061
2.5
0.001678
0.8
0.000647
4.3
0.000276
1.8
Children
6­
12
years
old
0.003316
1.7
0.000817
0.4
0.000413
2.8
0.000158
1.1
Youth
13­
19
years
old
0.002588
1.3
0.000447
0.2
0.000287
1.9
0.000094
0.6
Adults
20­
49
years
old
0.002993
1.5
0.000630
0.3
0.000359
2.4
0.000110
0.7
Adults
50+
years
old
0.002764
1.4
0.000841
0.4
0.000404
2.7
0.000143
1.0
Females
13­
49
years
old
0.002987
1.5
0.000602
0.3
0.000355
2.4
0.000107
0.7
*
Values
for
highest
exposed
population
are
bolded
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
MCPB
and
any
other
substances
and
MCPB
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
MCPB
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/.
1
Memorandum
from
Timothy
Dole
to
Liz
Méndez
dated
July
6th,
2005
(
D291215)

Page
27
of
36
9.0
Occupational
Exposure/
Risk
Pathway
As
previously
described
in
the
Residential
(
Non­
Occupational)
Exposure/
Risk
Pathway
section
of
this
document,
an
occupational
exposure
risk
assessment
is
required
for
MCPB.
The
MCPB
labels
allow
for
both
aerial
and
ground
applications,
however,
they
do
not
allow
for
chemigation.
MCPB
may
be
used
only
on
agricultural
settings
once
during
the
growing
season
to
protect
pea
crops
from
a
variety
of
weeds
including
Canada
thistle,
lambsquarters,
pigweed,
smartweed,
sowthistle,
and
morningglories.
It
may
be
applied
from
shoot
emergence
until
the
three
leaf
nodes
stage
preceding
flowering
.
Typically,
at
the
time
of
treatment
for
Canada
thistle,
pea
plants
are
at
the
6­
12
node
stage.
Applications
cannot
be
made
after
the
three
node
stage
prior
to
flowering
or
after
pea
flower
buds
appear.
In
general,
application
rates
range
from
0.5
to
1.5
lb
acid
equivalent/
acre
with
the
highest
rate
being
used
for
the
treatment
against
Canada
thistle
that
has
reached
the
bud
stage.
For
risk
assessment
purposes,
the
maximum
application
rate
allowed
in
the
label
(
1.5
acid
equivalent/
acre)
was
used.
A
listing
of
application
methods
and
amounts
of
acreage
treated
per
8
hour
day
is
included
in
Table
9.1.
For
further
details
please
refer
to
the
disciplinary
chapter
"
MCPB:
Occupational
and
Residential
Exposure
and
Risk
Assessment
for
the
Reregistration
Eligibility
Decision
(
RED)."
1
Table
9.1
­
MCPB
Application
Methods
Application
Method
Typical
Crops
Treated
Treated
Areaa
1
­
Groundboom
peas
200
2
­
Fixed
Wing
Aircraft
peas
350
a.
Based
upon
HED
ExpoSAC
SOP
#
9
"
Standard
Values
for
Daily
Acres
Treated
in
Agriculture",
Revised
July
5,
2000
9.1
Short/
Intermediate/
Long­
Term
Handler
Risk
HED
has
determined
that
pesticide
handlers/
applicators
are
likely
to
be
exposed
during
MCPB
use
resulting
in
short
(
1
day
to
1
month)
and
intermediate­
term
(
1
to
6
months)
exposures.
Chronic
exposures
(
longer
than
6
months)
are
not
expected
because
MCPB
is
used
only
once
a
year.
Based
upon
the
application
methods
shown
in
Table
9.1,
the
following
exposure
scenarios
were
assessed.

Mix/
Load
Liquid
Formulations
Aerial
Application
Groundboom
Application
Flag
Aerial
Application
Page
28
of
36
The
MOEs
for
occupational
exposures
were
calculated
for
short/
intermediate
term
dermal
and
inhalation
exposures
using
standard
assumptions
and
unit
exposure
data.
The
unit
exposure
data
were
taken
from
Pesticide
Handlers
Exposure
Database
(
PHED)
data.
To
calculate
the
risk,
the
application
rates,
number
of
acres
treated
per
day,
body
weight
of
handlers,
and
frequency
of
application
are
needed
to
complete
the
assessment.
The
amount
of
active
ingredient
handled
per
day
is
based
upon
the
number
of
acres
treated
and
the
application
rate.
These
values
and
the
unit
exposure
values
are
used
to
calculate
the
daily
exposure
to
the
handler.

The
Agency
initially
calculates
the
handler's
risk
using
the
least
amount
of
protective
measures.
This
is
called
the
baseline
assessment.
For
individuals
involved
in
applications,
this
assessment
normally
accounts
for
an
individual's
normal
work
clothing
(
e.
g.,
long
sleeve
shirt
and
long
pants),
no
gloves,
and
no
respirator.
If
there
is
a
concern
at
this
level,
the
Agency
requires
the
use
of
protective
measures
(
e.
g.,
personal
protective
equipment
and
engineering
controls)
to
lower
the
risk.
Personal
protective
equipment
(
PPE)
can
include
an
additional
layer
of
clothing,
chemically­
resistant
gloves,
and
respirator.
Common
examples
of
engineering
controls
include:
enclosed
tractor
cabs,
closed
loading
systems,
and
water­
soluble
packaging.

Currently,
the
MCPB
labels
require
waterproof
gloves
instead
of
chemical
resistant
gloves.
It
is
unknown
if
these
gloves
provide
adequate
protection.
Therefore,
it
is
recommended
that
mixers
and
loaders
wear
chemical
resistant
gloves
when
handling
this
product.

For
MCPB,
the
target
Margin
of
Exposure
(
MOE)
for
occupational
exposures
is
100,
which
includes
the
default
uncertainty
factors
(
UFs)
for
interspecies
extrapolation
and
intraspecies
variation.
The
MOEs
for
handlers
are
summarized
in
Table
9.2.
All
of
the
MOEs
for
dermal
exposure
are
greater
than
100
if
single
layer
PPE
(
i.
e.,
baseline
PPE
with
chemical
resistant
gloves)
is
worn.
All
inhalation
MOEs
exceed
the
target
MOE
of
100
with
baseline
PPE
(
i.
e.,
respirators
not
needed).
Page
29
of
36
Table
9.2
­
MCPB
MOEs
for
Handlers
Exposure
Scenario
Crop
Application
Rate
(
lb
ae/
acre)
Acres/
Day
Baseline
Dermal
MOE
Single
Layer
Dermal
MOE
Baseline
Inhalation
MOE
Mix/
Load
Liquids
for
Aerial
Peas
1.5
350
5
580
560
Mix/
Load
Liquids
for
Groundboom
Peas
1.5
200
8
1000
970
Aerial
Application
Peas
1.5
350
2700
N/
A
9800
Groundboom
Application
Peas
1.5
200
1700
1700
1600
Flag
Aerial
Application
Peas
1.5
350
1200
1100
1900
9.2
Short/
Intermediate­
Term
Postapplication
Risk
Post­
application
MCPB
exposures
can
occur
when
workers
enter
pea
fields
recently
treated
with
MCPB
to
conduct
tasks
such
as
scouting
and
irrigation.
Based
on
the
MCPB
use
pattern
(
once
per
season
application
to
pea
plants
until
the
three
nodes
stage
before
flowering),
it
is
expected
that
exposures
to
this
compound
would
be
of
short/
intermediateterm
duration.
Consequently,
long­
term
exposures
were
not
assessed.
Moreover,
inhalation
exposures
are
not
anticipated
and
were
not
assessed
for
this
post­
application
worker
assessment
given
the
low
vapor
pressure
for
MCPB
(
7.1e­
07
mm
Hg
at
23.6o
C).

Since
no
chemical­
specific
data
were
available
for
MCPB,
standard
values
and
assumptions
were
used
in
this
risk
assessment
(
e.
g.,
maximum
application
rates,
Dislodgeable
Foliar
Residue
[
DFR]
of
20%,
etc.).

A
summary
of
worker
risks
for
post­
application
exposures
is
presented
in
Table
9.3.
All
of
the
MOEs
are
above
100
on
Day
0
which
indicate
that
the
risks
are
not
of
concern.

Table
9.3
­
MCPB
Post­
Application
Worker
Risks
Crop
Application
Rate
(
lb
ae/
acre)
Task
Transfer
Coefficient
(
cm2/
hr)
Day
0
Dermal
MOE
Peas
1.5
Irrigation,
scouting,
immature
plants
Scouting
mature
plants
100
1500
2600
170
Page
30
of
36
10.0
Data
Needs
and
Label
Requirements
10.1
Toxicology
The
following
studies
are
required
for
MCPB.
These
studies
are
also
required
for
MCPA
and
may
be
satisfied
by
studies
with
MCPA.

1.
Developmental
neurotoxicity
study
in
rats.

2.
Twenty
eight
(
28)­
day
inhalation
study
in
rats
(
abbreviated
90­
day
protocol).
This
study
is
required
because
there
is
the
potential
for
repeated
occupational
exposure
via
this
route.

10.2
Residue
Chemistry
The
following
studies
are
required
for
MCPB
and/
or
MCPA
(
where
indicated):

1.
Magnitude
of
Residues
in
Plants
­
MCPB
and
MCPA
2.
Enforcement
Analytical
Methods
­
MCPB
and
MCPA
3.
Confined
Accumulation
in
Rotational
Crops
Study
10.3
Occupational
and
Residential
Exposure
No
additional
data
requirements.
Page
31
of
36
APPENDIX
A
TOXICITY
PROFILE
Page
32
of
36
Table
A­
1.
Acute
Toxicity
Profile
­
MCPB
Guideline
No.
Study
Type
MRID
Results
Toxicity
Category
870.1100
Acute
oral
­
rat
116340
LD50
=
1570
mg/
kg
III
870.1100
Acute
oral
­
rat
144801
LD50
=
4300
mg/
kg
III
870.1200
Acute
dermal
­
rabbit
116342
LD50
>
10000
mg/
kg
IV
870.1200
Acute
dermal
­
rat
144799
LD50
>
2000
mg/
kg
II
870.1300
Acute
inhalation
­
rat
41630001
LC50
>
1.14
mg/
L
III
870.2400
Acute
eye
irritation
­
rabbit
116343
Moderately
irritating
II
870.2400
Acute
eye
irritation
­
rabbit
144797
Mildly
irritating
III
870.2500
Acute
dermal
irritation
­
rabbit
144798
Non­
irritating
IV
870.2600
Skin
sensitization
­
guinea
pig
144800
Negative
IV
Table
A­
2.
Subchronic
and
Chronic
Toxicity
Profile
Guideline
MRID
(
year)
/
Doses
Results
870.3100
90­
Day
oral
toxicity
(
Rat)
42883602
(
1993)
Acceptable/
guideline
0,
100,
500,
2500
ppm
(
0,
6,
32,
158
mg/
kg/
day)
NOAEL
=
158
mg/
kg/
day
LOAEL
>
158
mg/
kg/
day
870.3150
90­
Day
oral
toxicity
(
Dog)
42883603
(
1993)
Acceptable/
guideline
0,
12,
80,
800,
1800
ppm
(
0,
0.4,
2,
25,
44
mg/
kg/
day
NOAEL
=
2
mg/
kg/
day
LOAEL
=
25
mg/
kg/
day
based
on
small
prostate
and
clinical
chemistry
(
elevated
BUN)

870.3200
21­
Day
dermal
toxicity
(
Rabbit)
116346
(
1970)
Supplementary.
NOAEL
/
LOAEL
could
not
be
determined.

870.3465.
Inhalation
tox
N/
A
N/
A
870.3700a
Prenatal
Developmental
(
Rat)
40865402
(
1988)
Acceptable/
guideline
0,
25,
100,
225
mg/
kg/
day
Maternal
NOAEL
=
25
mg/
kg/
day
LOAEL
=
100
mg/
kg/
day
based
on

BW
gain
Developmental
NOAEL
=
25
mg/
kg/
day
LOAEL
=
100
mg/
kg/
day
based
on

fetal
BW
and

ossification
Table
A­
2.
Subchronic
and
Chronic
Toxicity
Profile
Guideline
MRID
(
year)
/
Doses
Results
Page
33
of
36
870.3700b
Prenatal
Developmental
(
Rabbit)
40865401
(
1988)
Acceptable/
guideline
0,
1,
5,
20
mg/
kg/
day
Maternal
NOAEL
=
5
mg/
kg/
day
LOAEL
=
20
mg/
kg/
day
based
on
mortality
Developmental
NOAEL
=
20
mg/
kg/
day
LOAEL
>
20
mg/
kg/
day,
highest
dose
tested
870.3800.
Reproductiona
N/
A
N/
A
870.4100
Chronic
toxicitya
N/
A
N/
A
870.4200
Carcinogenicitya
N/
A
N/
A
870.5100
Gene
Mutation:
Ames
assay
Gene
Mutation:
HGPRT
40564302
(
1988)
Acceptable/
guideline
40564303
(
1988)
Acceptable/
guideline
No
increase
in
mutant
colonies.

No
increase
in
mutant
colonies.

870.5375
Cytogenetics:
Chromosomal
Aberrations
in
CHO
Cells
40564301
(
1988)
Acceptable/
guideline
Evidence
of
chromosomal
aberrations
at
cytotoxic
concentration
with
S9.

870.5550
Other
Genotoxic
Effects:
UDS
40564304
(
1987)
Acceptable/
guideline
No
evidence
of
unscheduled
DNA
synthesis
870.6200a
Acute
Neurotoxicity
Study
N/
A
N/
A
870.6200b
Subchronic
Neurotoxicity
N/
A
N/
A
870.6300
D.
T.
N/
A
N/
A
870.7485
Metabolism
44818101
(
1998)
Acceptable/
guideline
Oral:
5
mg/
kg
and
100
mg/
kg
MCPB
was
well
absorbed
(~
90%),
urine
was
major
route
of
excretion
(~
87%),
most
excreted
by
48
hr
with
no
bioaccumulation.
MCPA
was
major
metabolite
(~
36%).

870.7600
Dermal
Absorption
N/
A
N/
A
Page
34
of
36
Table
A­
3.
Comparative
MCPB
and
MCPA
Tox
Profiles
Study
MCPB
MCPA
90­
Day
Rat
0,
100,
500,
2500
ppm
(
0,
6,
32,
158
mg/
kg/
day)

6:

abs
kidney
wt
(+
10%
M)

32:

abs
kidney
wt
(+
22%
M),


rel
to
brain
kidney
wt
(+
20%
M)

158:

abs
kidney
wt
(+
9%
M)


rel
to
brain
kidney
wt
(+
13%
M)


rel
to
BW
kidney
wt
(+
28%/
+
16%
M/
F)

BW
(­
15%/­
17%),

FC
(­
18%/­
15%)

platelets
(
M)


ALT
(+
60%
M)

1993.
Hazleton,
VA.
SD
rats.
MRID
42883602.
0,
50,
150,
450
ppm
(
0,
4,
11,
33
mg/
kg/
day)

11:

abs
kidney
wt
(+
8%
M)


rel
kidney
wt
(+
6%
M)

33:

abs
kidney
wt
(+
13%
M)


rel
kidney
wt
(+
14%
M)
slight

crystals
in
urine

clotting
time
(
M)

1985.
BASF,
German.
Wistar
rats.
MRID
00165471
Subchronic
Neurotoxicty
Not
available
0,
50,
500,
and
2500
ppm
(
0,
3,
34,
or
177
mg/
kg/
day
)

34:

rel
kidney
wt
(+
13%
M)

177:
1
F
death
on
day
57
(
cachectic)

BW
(­
27%/­
20%)

abs,
rel
kidney
wt
anemia

grip
strength,
landing
splay,
MA

liver
enzymes,
and
creatinine,
small
testes,
atrophy
1994.
BASF,
Germany.
Wistar
rats.
MRID
43562601
Table
A­
3.
Comparative
MCPB
and
MCPA
Tox
Profiles
Study
MCPB
MCPA
Page
35
of
36
90­
Day
Dog
0,
12,
80,
800,
1800
ppm
(
0,
0.4,
2,
25,
44
mg/
kg/
day
2:

25:

BUN
(+
76%/+
83%
M/
F)

44:

BUN
(+
146%/+
125%
M/
F)

BW
(­
30%/­
16%),

FC
(­
39%/­
19%)
M/
F

Hct:
(
34%
vs
47%
for
M
controls)
small
testes,

thymic
wt
with
lymphoid
depletion
1993.
Hazleton,
VA.
MRID
42883603
0,
8,
25,
77,
300,
1198
ppm
(
0,
0.3,
1,
3,
12,
48
mg/
kg/
day)
1:
3:

phenol
red
retention
12:

BW
(­
7%/­
14%
M/
F)


clotting
time
in
females
(
PT,
+
16%)
variable

BUN
(+
103%/+
54%
M/
F)


ALT
(+
242%/+
102%
M/
F)
kidney:

phenol
red
retention
(+
321%/+
423%)
liver:

BSP
retention
(+
85%/+
100%
M/
F)
(

thymus
wt
in
28­
day
study
at
30
mg/
kg/
day)

48:
7/
8
deaths,
skin
lesions,
icterus
1980.
Germany.
MRID
00106595.
2
studies.

Developmental
Rat
0,
25,
100,
225
mg/
kg/
day
Maternal:
100:

BW
(­
5%)
and
gain
225:

BW
(­
10%)
and
gain
Develop:
100:
unossified
cervical
centrum
#
5

fetal
BW
(­
5%
M)
225:
unossified
cervical
centrum
#
5,
6,
7

fetal
BW
(­
18%

1998.
Bushy
Run,
PA.
CD
rats.
MRID
40865402.
15,
60,
120
mg/
kg/
day
Maternal:
120:

BW
gain,
FC
Develop:
120:

fetal
body
weights
(­
13%)


skeletal
retardation
1993.
Germany.
Wistar
rats.
MRID
42723801
Developmental
Rabbit
0,
1,
5,
20
mg/
kg/
day
Maternal
20:
3/
20
does
died
Developmental
No
developmental
toxicity
noted.

1988.
Bushy
Run,
PA.
NZW
rabbits.
MRID
40865401.
15,
30,
60
mg/
kg/
day
Maternal
60:

BW
and
FC,
stomach
ulcers
Developmental
No
developmental
toxicity
noted.

1993.
Germany.
Himalayan
rabbits.
42723802
Gene
Mutation
Ames
assay:
No
increase
in
mutant
colonies.
HGPRT:
No
increase
in
mutant
colonies.
Ames
assay:
No
increase
in
mutant
colonies.
HGPRT:
No
increase
in
mutant
colonies.
Table
A­
3.
Comparative
MCPB
and
MCPA
Tox
Profiles
Study
MCPB
MCPA
Page
36
of
36
Cytogenetics:
Chrom
Aberr
in
CHO
Cells:
Pos
at
cytotoxic
dose
+
S9
Sister
chromatid
exchange:
weakly
positive.
Chrom
aberr
Chinese
Hamster
bone
marrow:
neg
Cytogenetics
in
human
lymphocytes:
positive
Other
Muta
No
evidence
of
unscheduled
DNA
synthesis
Metabolism
Oral:
5
mg/
kg
and
100
mg/
kg
In
both
dose
groups,
MCPB
was
well
absorbed
(~
90%),
urine
was
major
route
of
excretion
(~
87%),
most
excreted
by
48
hr
with
no
bioaccumulation.
MCPA
was
major
metabolite
(~
36%),
HMCPA
(
5­
9%).
Oral:
5
mg/
kg.
MCPA
was
rapidly
absorbed,
metabolized
and
eliminated
in
urine
(>
85%)
with
no
bioaccumulation.
MCPA
was
major
metabolite
(~
60%);
also
HMCPA
(~
10%).

Doses
in
mg/
kg
basis
from
feeding
studies
shown
only
for
males.