Document ID: EPA-HQ-OPP-2004-0167-0021
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2004-05-20T04:00Z

UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES,
AND
TOXIC
SUBSTANCES
TXR
No.
0052264
MEMORANDUM
Date:
12/
3/
03
Subject:
2,4­
D:
Health
Effects
Division
(
HED)
Metabolism
Assessment
Review
Committee
(
MARC)
Decision
Document.
DP
Barcodes
D293119
and
D293128.
Chemical
I.
D.
No.
030001.
Case
No.
0073.
Meeting
date:
9/
3/
03.

From:
William
J
Hazel,
Ph.
D.,
Chemist,
Reregistration
Branch
3/
HED
(
7509C)
and
Linda
Taylor,
Ph.
D.,
Toxicologist,
Reregistration
Branch
3/
HED
(
7509C)

Through:
Richard
Loranger,
Ph.
D.,
HED
MARC
Chair
(
7509C)
and
Whang
Phang,
Ph.
D.,
Branch
Senior
Scientist,
Reregistration
Branch
3/
HED
(
7509C)

To:
Yan
Donovan,
HED
MARC
Executive
Secretary
(
7509C)

Introduction
The
MARC
met
on
9/
3/
03
to
discuss
the
2,4­
dichlorophenoxyacetic
acid
(
2,4­
D)
residues
of
concern
in
plants,
livestock,
rotational
crops,
and
drinking
water.

Material
Reviewed
A
briefing
document
(
D293119)
prepared
by
William
Hazel
(
RRB1),
Linda
Taylor
(
RRB1),
Mark
Corbin
(
EFED),
and
James
Hetrick
(
EFED).
The
briefing
document
is
attached
to
this
decision
document
as
Appendix
1;
the
briefing
document
was
not
filed
separately.

MARC
Members
in
Attendance:
Abdallah
Khasawinah,
Alberto
Protzel,
Christine
Olinger,
Yan
Donovan,
Richard
Loranger,
Leung
Cheng,
William
Wassell,
P.
V.
Shah,
Sheila
Piper,
Leonard
Keifer.

MARC
Members
in
Absentia:
John
Doherty
Alternate
Members
in
Attendance:
George
Kramer,
David
Soderberg,
and
Thuy
Nguyen.

Nonmembers
in
Attendance:
Mark
Corbin,
William
Hazel.
MARC
Decision
Table
The
MARC
recommendations
for
degradates
and
metabolites
to
be
included
in
the
dietary
risk
assessment
as
well
as
those
to
be
included
in
the
tolerance
expression
are
summarized
in
Table
1.
Table
2
presents
the
chemical
structures
identified
from
the
2,4­
D
plant
and
livestock
metabolism
studies
presently
available.
Table
3
provides
chemical
structures
of
environmental
degradates.

Table
1.
Summary
of
MARC
Decisions
for
2,4­
D.

Chemical:
2,4­
D
Date:
9/
3/
03
Residues
of
Concerna
Matrix
For
Risk
Assessment
For
Tolerance
Expression
Plants
­
primary
crops
2,4­
D,
both
free
and
conjugated,
determined
as
the
acid
2,4­
D,
both
free
and
conjugated,
determined
as
the
acid
Plants
­
rotational
crops
2,4­
D,
both
free
and
conjugated,
determined
as
the
acid
2,4­
D,
both
free
and
conjugated,
determined
as
the
acid
Livestock
­
ruminant
2,4­
D,
both
free
and
conjugated,
determined
as
the
acid
2,4­
D,
both
free
and
conjugated,
determined
as
the
acid
Livestock
­
poultry
2,4­
D,
both
free
and
conjugated,
determined
as
the
acid
2,4­
D,
both
free
and
conjugated,
determined
as
the
acid
Fish
and
shellfish
2,4­
D,
both
free
and
conjugated,
determined
as
the
acid
2,4­
D,
both
free
and
conjugated,
determined
as
the
acid
Water
Parent
N/
A
aThe
HED
Metabolism
Committee,
in
1993,
determined
that
2,4­
D
per
se
is
the
residue
of
concern
and
that
tolerances
listed
at
40
CFR
§
180.142
are
to
be
defined
as
"
residues
of
2,4­
D,
both
free
and
conjugated,
determined
as
the
acid"
(
R.
Perfetti,
6/
16/
93,
TXR
No.
0052001
and
clarification
by
W.
Smith,
12/
10/
93,
D197063).

Rationale:

Plants
­
treated
and
rotated:

$
In
treated
wheat
forage
and
straw,
2,4­
D
comprised
70­
80%
of
the
TRR,
three
hydroxylated
metabolites
comprised
11­
13%,
and
2,4­
dichlorophenol
(
2,4­
DCP)
contributed
0.5­
0.9%
TRR.
In
grain,
2,4­
D
was
the
only
compound
identified
at
6%
of
the
TRR.
The
majority
of
the
TRR
was
characterized
as
being
incorporated
into
endogenous
plant
compounds
such
as
cellulose,
protein,
and
starch
at
up
to
45%
TRR.
Refer
to
Table
2
for
chemical
structures.

$
In
lemon
treated
postharvest
with
2,4­
D
Isopropyl
ester
(
IPE),
the
IPE
was
rapidly
deesterified
resulting
in
up
to
69%
2,4­
D
after
20
weeks.
Hydroxylated
metabolites
and
2,4­
DCP
were
all
present
at
<
1%
TRR.

$
In
treated
potato,
50­
60%
TRR
was
2,4­
D.
The
remainder
of
the
TRR
existed
as
hydroxylated
metabolites
and
4­
6
unknown
polar
metabolites
together
accounting
for
42­
50%
of
the
TRR.

$
In
confined
rotational
crops
planted
into
soil
treated
at
1.1x
the
maximum
label
rate,
virtually
all
of
the
TRR
was
incorporated
into
natural
plant
constituents.
Only
traces
of
2,4­
D
and
2,4­
dichloroanisole
were
detected
in
radish
tops
each
at
0.0005
ppm
(
0.5%
TRR).

$
Minor
metabolites
such
as
hydroxylated
metabolites
and
2,4­
DCP
are
not
expected
to
be
significantly
more
toxic
than
the
parent.
Therefore,
MARC
concluded
that
for
plants,
parent
2,4­
D,
both
free
and
conjugated,
determined
as
the
acid,
are
the
residues
of
concern
for
risk
assessment
and
tolerance
expression.

Livestock:

$
The
major
residue
in
milk
and
tissues
was
2,4­
D,
accounting
for
47%
TRR
in
milk,
21%
TRR
in
liver,
53%
TRR
in
kidney,
45%
TRR
in
fat,
and
38%
TRR
in
muscle.

$
Minor
amounts
of
2,4­
DCP
were
tentatively
identified
in
milk
(
5%
TRR)
and
fat
(
2.3%
of
TRR),
and
4­
CPA
was
identified
in
milk
(
6.9%
TRR).
See
chemical
structure
in
Table
2.

$
Several
other
non­
polar
components
(
designated
NP1,
NP2,
and
NP3)
were
detected
in
tissues;
however,
these
metabolites
may
be
the
result
of
uptake
of
non­
polar
impurities
known
to
be
present
in
the
test
material.

$
In
poultry,
the
major
identified
component
in
eggs
and
tissues
was
2,4­
D,
accounting
for
23%
TRR
in
eggs,
25%
TRR
in
fat,
18%
TRR
in
liver,
and
76%
TRR
in
kidney.
Minor
amounts
of
2,4­
DCP
were
also
identified
in
eggs
(
7.3%
TRR)
and
liver
(
4.4%
TRR).

$
An
earlier
HED
Metabolism
Committee
decision
to
delete
2,4­
dichlorophenol
(
2,4­
DCP)
from
the
livestock
tolerance
expression
for
2,4­
D
(
R.
Perfetti,
6/
16/
93,
TXR
No.
0052001)
was
upheld
by
the
MARC,
i.
e.,
2,4­
DCP
is
not
of
concern
for
either
the
tolerance
expression
or
for
risk
assessment
at
the
levels
expected
in
livestock
tissues
and
considering
the
likely
lower
toxicity
of
2,4­
DCP
compared
to
2,4­
D.

Water:

$
The
major
degradates
in
the
aerobic
soil
metabolism
study
were
CO
2
(<
50%
of
applied
radioactivity,
AR)
and
bound
residues
(<
60%);
small
amounts
of
2,4­
DCP
(<
3.5%)
and
2,4­
DCA
(<
2.8%)
were
also
detected.
Refer
to
Table
3
for
chemical
structures.

$
Major
residues
under
aerobic
aquatic
conditions
were
chlorohydroquinone
(<
16%
of
AR),
CO
2
(<
16%),
and
bound
residues
(<
39%)
with
lesser
amounts
of
2,4­
DCP
(<
5%).

$
Under
anaerobic
aquatic
conditions,
the
major
residues
were
2,4­
DCP
(<
35%),
CO
2
(<
31%),
and
bound
residues
(<
41%)
as
well
as
lesser
amounds
of
4­
chlorophenol
(<
2%).

$
In
six
aquatic
field
dissipation
studies
(
three
each
with
the
BEE
ester
and
the
DMA
salt),
2,4­
D
was,
by
far,
the
predominant
residue.
These
studies
represent
"
real
world"
conditions.
2,4­
D
(
combined
with
small
amounts
of
the
parent
BEE
ester
form
in
three
studies)
comprised
92­
100%
of
the
detected
residues
which
included
2,4­
D,
2,4­
D
BEE
ester,
2,4­
dichlorophenol,
4­
chlorophenol,
and
4­
chlorophenoxyacetic
acid.
MARC
does
not
think
that
2,4­
dichlorophenol,
4­
chlorophenol,
or
4­
chlorophenoxyacetic
acid
will
potentially
be
significantly
more
toxic
than
the
parent;
therefore,
they
can
be
excluded
from
risk
assessment.
°
2,4­
DCP
is
the
major
residue
(<
35%)
only
under
anaerobic
aquatic
conditions
which
is
not
the
major
route
of
degradation;
2,4­
DCP
has
been
determined
not
to
be
of
concern
in
drinking
water
for
risk
assessment
at
the
levels
expected
in
water
and
considering
the
likely
lower
toxicity
of
2,4­
DCP
compared
to
2,4­
D.
°
Potential
concern
was
raised
regarding
1,2,4­
benzenetriol
and
chlorohydroquinone.
The
1,2,4­
benzenetriol
(
a
demonstrated
mutagen)
was
eliminated
from
concern
because
it
is
formed
only
via
aqueous
photolysis
which
is
expected
to
be
a
minor
route
of
2,4­
D
dissipation
in
the
environment.
The
MARC
determined
that
drinking
water
exposure
to
chlorohydroquinone
(
a
possible
carcinogen
based
on
similarity
to
hydroquinone,
a
carcinogen)
is
likely
to
be
low
since
it
formed
in
only
one
of
three
aerobic
aquatic
metabolism
studies,
it
formed
to
a
significant
extent
only
on
day
27,
and,
from
that
point,
dissipation
was
rapid
(
half­
life

5
days).

Database
Uncertainties:
None
identified.
4
cc:
W.
Hazel
(
HED),
L.
Taylor
(
HED),
M.
Corbin
(
EFED),
J.
Hetrick
(
EFED)
Reference:
MARC
briefing
document
­
D293119,
8/
27/
03
(
attached)
W.
Hazel:
wjh:
722J:
CM#
2:(
703)
305­
7677
5
O
Cl
Cl
O
O
CH
3
CH
3
O
Cl
Cl
OH
O
O
Cl
O
H
OH
O
Cl
O
Cl
Cl
OH
O
O
H
O
Cl
O
H
OH
O
Cl
OH
Cl
Cl
Table
2.
2,4­
D
and
its
metabolites/
degradates.

Chemical
Name
Substrate
MRID
Structure
Common
Name
°
(
2,4­
dichlorophenoxy)
acetic
acid,
2­
ethylhexyl
ester
wheat
forage
and
straw
42439701
2,4­
D
IOE
°
(
2,4­
dichlorophenoxy)
acetic
acid
wheat
forage,
straw,
and
grain
42439701
2,4­
D
°
(
4­
hydroxy­
2,5­
dichlorophenoxy)
acetic
acid
wheat
forage
and
straw
42439701
42615601
4­
OH­
2,5­
D
°
(
5­
hydroxy­
2,4­
dichlorophenoxy)
acetic
acid
wheat
forage
and
straw
42439701
42615601
5­
OH­
2,4­
D
°
(
4­
hydroxy­
2,3­
dichlorophenoxy)
acetic
acid
wheat
forage
and
straw
42439701
42615601
4­
OH­
2,3­
D
°
2,4­
dichlorophenol
wheat
forage
and
straw
42439701
2,4­
DCP
1
%
AR
=%
of
applied
radioactivity.

6
Table
3.
Environmental
Degradates
of
2,4­
D
Acid
Confirmed
Degradate
Lab
Results
Max
%
AR1
(
Study)
Chemical
Structure
1,2,4­
benzenetriol
37
(
aqueous
photolysis
at
pH
7)

2,4­
dichlorophenol
(
2,4­
DCP)
3.5
(
aerobic
soil)
33
(
anaerobic
aquatic
soil
metabolism,
water
+
sediment)
5
(
aerobic
aquatic
soil
metabolism,
sediment)

2,4­
dichloroanisole
(
2,4­
DCA)
2.8
(
aerobic
soil)

chlorohydroquinone
(
CHQ)
16
(
aerobic
aquatic
soil
metabolism,
water)

Bound
residues
1.0
(
soil
photolysis)
60
(
aerobic
soil)
41
(
anaerobic
aquatic
metabolism)
39
(
aerobic
aquatic
metabolism)

Carbon
Dioxide
25
(
aqueous
photolysis)
5
(
soil
photolysis)
50
(
aerobic
soil)
31
(
anaerobic
aquatic
metabolism)
16
(
aerobic
aquatic
soil
metabolism)
7
Volatile
compounds
4­
chlorophenol
2,4­
DCA
1.9
(
anaerobic
aquatic
metabolism)
1.9
(
anaerobic
aquatic
metabolism)
APPENDIX
1:
MARC
BRIEFING
DOCUMENT
8
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
MEMORANDUM
Subject:
2,4­
Dichlorophenoxyacetic
acid
(
2,4­
D).
Briefing
Memorandum
for
Meeting
of
HED's
Metabolism
Assessment
Review
Committee.

DP
Barcode:
D293119
Case
No.:
0073
PC
Code:
030001
Submission:
S331345
Trade
Names:
Statesman
®
,
DMA
®
6
Weed
Killer,
Grazon
®
P+
D,
Crossbow
®
,
Weed
Killer
4D,
Esteron
®
6E
EPA
Reg.
No.
:
Many
40
CFR
§
180.142
Class:
Herbicide
From:
William
J.
Hazel,
Ph.
D.,
Chemist
Linda
Taylor,
Ph.
D.,
Toxicologist
Reregistration
Branch
1
(
RRB1)
Health
Effects
Division
(
HED)
(
7509C)
and
Mark
Corbin,
Environmental
Scientist
James
Hetrick,
Ph.
D.,
Senior
Physical
Scientist
Environmental
Fate
&
Effects
Division
(
EFED)
(
7507C)

Through:
Whang
Phang,
Ph.
D.,
Branch
Senior
Scientist
RRB1/
HED
(
7509C)

To:
Yan
Donovan,
Executive
Secretary
Metabolism
Assessment
Review
Committee
Health
Effects
Division
(
7509C)

Introduction
2,4­
Dichlorophenoxyacetic
acid
(
2,4­
D)
is
an
alkylchlorophenoxy
herbicide
used
to
control
a
variety
of
broadle
weeds.
2,4­
D
may
also
occasionally
be
used
as
a
plant
growth
regulator
or
fungicide.
There
are
nine
active
ingredients
(
AIs)
in
2,4­
D
Reregistration
Case
0073
that
are
components
of
a
registered
pesticide
product
labe
for
use
on
a
food
or
feed
crop;
these
same
nine
AIs
are
also
being
supported
for
reregistration
by
the
Industr
Task
Force
II
on
2,4­
D
Research
Data
(
hereafter
referred
to
as
Task
Force
II).
Chemical
structures,
properties,
end­
use
products
of
these
AIs
are
listed
in
Tables
2­
4
and
include
the
acid
form
of
2,4­
D,
the
sodium
salt,
four
amine
salts,
and
three
esters.
The
members
of
Task
Force
II
currently
include
Agro­
Gor
Corp
(
jointly
owned
b
Attanor,
S.
A.
and
PBI­
Gordon
Corp.),
BASF,
Dow
AgroSciences,
and
Nufarm
USA.
In
addition,
USDA's
Interregional
Project
No.
4
(
IR­
4)
is
supporting
the
reregistration
of
a
number
of
minor
crop
uses
for
2,4­
D
and
California
Citrus
Quality
Council
(
CCQC)
is
supporting
selected
(
postharvest)
uses
of
2,4­
D
isopropyl
ester
(
IP
on
citrus
fruits.

2,4­
D
is
currently
registered
by
Task
Force
II
members
for
food/
feed
uses
on
a
variety
of
field
and
orchard
cro
and
aquatic
sites.
The
2,4­
D
formulation
classes
registered
for
food/
feed
uses
include
wettable
powders
(
WP
granules
(
G),
soluble
concentrates
in
both
liquid
(
SC/
L)
and
solid
(
SC/
S)
forms,
and
emulsifiable
concentrates
(
EC).
These
formulations
are
typically
applied
as
broadcast,
banded,
of
directed
(
spray
or
wiper)
applications
APPENDIX
1:
MARC
BRIEFING
DOCUMENT
9
during
dormancy
or
preplant,
preharvest,
preemergence,
emergence,
postemergence,
or
postharvest
using
ground
or
aerial
equipment.
Tolerances
are
currently
established
forresidues
of
2,4­
D
per
se
in/
on:
numerou
raw
agricultural
commodity
(
RAC)
human
foods
derived
from
fruits,
grasses,
grains,
nuts,
vegetables,
sugarc
cotton,
hops,
and
asparagus
at
0.1
ppm
to
5
ppm;
processed
products
of
sugarcane
(
5
ppm)
and
grains
(
2
pp
fish
and
shellfish
at
1.0
ppm
and
potable
water
at
0.1
ppm
[
40
CFR
§
180.142(
a)
(
1)
to
­(
a)(
13)].
A
temporary
tolerance
of
0.02
ppm
for
2,4­
D
per
se
in/
on
soybean
seed
expired
12/
31/
01
and,
apparently,
has
been
extende
both
years
since
[
40
CFR
§
180.142(
a)(
11)].
A
time­
limited
tolerance
of
0.1
ppm
in/
on
wild
rice
established
und
FIFRA
Section
18
expired
12/
31/
02.
Tolerances
for
residues
in
livestock
commodities
are
currently
establishe
terms
of
residues
of
2,4­
D
and/
or
its
metabolite
2,4­
dichlorophenol
[
40
CFR
§
180.142(
a)(
8)].
The
HED
Metabol
Committee,
in
1993,
determined
that
2,4­
D
per
se
is
the
residue
of
concern
and
that
tolerances
listed
at
40
CFR
§
180.142
are
to
be
defined
as
"
residues
of
2,4­
D,
both
free
and
conjugated,
determined
as
the
acid"
(
R.
Perfett
memorandum
dated
6/
16/
93,
TXR
No.
0052001
and
clarification
in
the
W.
Smith
memorandum
dated
12/
10/
93,
D197063).

Issues
to
be
Considered:

°
Degradates
of
concern
in
plant
commodities
for
tolerance
expression
and
for
risk
assessment.
°
Degradates
of
concern
in
livestock
commodities
for
tolerance
expression
and
for
risk
assessment.
°
Degradates
of
concern
in
water
for
risk
assessment.

TEAM
PROPOSAL
TABLE
1.
Proposed
Residues
of
Concern
for
2,4­
D.

Matrix
Residues
included
in
Risk
Assessment
Residues
included
in
Tolerance
Expression
Plants
2,4­
D
2,4­
D
Livestock
2,4­
D
2,4­
D
Water
2,4­
D
Not
Applicable
Rationale
for
Selection
of
the
Residues
of
Concern:

Plants:

°
In
wheat
forage
and
straw,
2,4­
D
comprised
70­
80%
of
the
TRR,
three
hydroxylated
metabolites
comprised
13%,
and
2,4­
dichlorophenol
(
2,4­
DCP)
contributed
0.5­
0.9%
TRR.
In
grain,
2,4­
D
was
the
only
compound
identified
at
6%
of
the
TRR.
The
majority
of
the
TRR
was
characterized
as
being
incorporated
into
endoge
plant
compounds
such
as
cellulose,
protein,
and
starch
at
up
to
45%
TRR.
°
In
lemon
treated
postharvest
with
2,4­
D
Isopropyl
ester
(
IPE),
the
IPE
was
rapidly
deesterified
resulting
in
u
69%
2,4­
D
after
20
weeks.
Hydroxylated
metabolites
and
2,4­
DCP
were
all
present
at
<
1%
TRR.
°
In
potato,
50­
60%
TRR
was
2,4­
D.
The
remainder
of
the
TRR
existed
as
hydroxylated
metabolites
and
4­
6
unknown
polar
metabolites
together
accounting
for
42­
50%
of
the
TRR.

Livestock:

°
The
major
residue
in
milk
and
tissues
was
2,4­
D,
accounting
for
47%
TRR
in
milk,
21%
TRR
in
liver,
53%
TR
kidney,
45%
TRR
in
fat,
and
38%
TRR
in
muscle.
°
Minor
amounts
of
2,4­
DCP
were
tentatively
identified
in
milk
(
5%
TRR)
and
fat
(
2.3%
of
TRR),
and
4­
CPA
wa
identified
in
milk
(
6.9%
TRR).
°
Several
other
non­
polar
components
(
designated
NP1,
NP2,
and
NP3)
were
detected
in
tissues;
however,
th
metabolites
may
be
the
result
of
uptake
of
non­
polar
impurities
known
to
be
present
in
the
test
material.
°
In
poultry,
the
major
identified
component
in
eggs
and
tissues
was
2,4­
D,
accounting
for
23%
TRR
in
eggs
APPENDIX
1:
MARC
BRIEFING
DOCUMENT
10
TRR
in
fat,
18%
TRR
in
liver,
and
76%
TRR
in
kidney.
Minor
amounts
of
2,4­
DCP
were
also
identified
in
egg
(
7.3%
TRR)
and
liver
(
4.4%
TRR).

Water:

°
The
major
degradates
in
the
aerobic
soil
metabolism
study
are
CO
2
(<
50%
of
applied
radioactivity,
AR)
and
bound
residues
(<
60%);
small
amounts
of
2,4­
DCP
(<
3.5%)
and
2,4­
DCA
(<
2.8%)
were
also
detected.
°
Major
residues
under
aerobic
aquatic
conditions
are
chlorohydroquinone
(<
16%
of
AR),
CO
2
(<
16%),
and
bound
residues
(<
39%)
with
lesser
amounts
of
2,4­
DCP
(<
5%).
°
Under
anaerobic
aquatic
conditions,
the
major
residues
are
2,4­
DCP
(<
35%),
CO
2
(<
31%),
and
bound
residu
(<
41%)
as
well
as
lesser
amounds
of
4­
chlorophenol
(<
2%).
°
In
six
aquatic
field
dissipation
studies
(
three
each
with
the
BEE
ester
and
the
DMA
salt),
2,4­
D
was,
by
far,
predominant
residue.
These
studies
represent
"
real
world"
conditions.
2,4­
D
(
combined
with
small
amoun
of
the
parent
BEE
ester
form
in
three
studies)
comprised
100%
of
the
detected
residue
in
two
studies
and,
comparing
maximum
concentrations,
was
present
at
much
greater
concentrations
(
22x­
960x)
than
those
of
any
of
the
measured
metabolites
which
included
2,4­
dichlorophenol,
4­
chlorophenol,
and
4­
chlorophenoxyacetic
acid.

Rat/
dog:

°
In
the
rat,
2,4­
D
is
excreted
mainly
in
the
urine
and
basically
unchanged.
In
the
dog,
excretion
also
occurs
mainly
via
the
urine
but,
in
addition
to
intact
2,4­
D,
conjugates
of
2,4­
D
and
several
minor
metabolites
are
excreted.

Codex
Harmonization:

°
The
Codex
Alimentarius
Commission
has
established
several
maximum
residue
limits
(
MRLs)
for
residues
2,4­
D
in/
on
various
plant
and
animal
commodities.
The
Codex
MRLs
are
expressed
in
terms
of
2,4­
D
per
se
The
expression
of
residues
for
Codex
MRLs
and
U.
S.
tolerances
is
harmonized.

Analytical
Methodology:

°
Both
the
data
collection
method
and
the
enforcement
method
determine
any
salt,
any
ester,
and
conjugate
2,4­
D.
As
a
result
of
a
step
to
hydrolyze
the
esters
and
conjugates,
the
anionic
form
of
2,4­
D
is
released.
A
acidification
step
protonates
the
anionic
form
of
2,4­
D
which
results
in
the
more
nonpolar
acid
form
of
2,4­
for
quantitation.
These
steps
increase
the
quantitative
recovery
of
the
residues
of
concern
to
the
U.
S.
and
Codex.
APPENDIX
1:
MARC
BRIEFING
DOCUMENT
11
O
Cl
Cl
O
O­[
NH
2(
CH
2
CH
2
OH)
2]+
O
Cl
Cl
O
O­[
NH
2(
CH
2)
2]+
CHEMICAL
IDENTIFICATION
AND
PROPERTIES
Chemical
structures
and
other
information
are
presented
in
Table
2
for
2,4­
D
acid
and
those
salts
and
esters
w
registered
manufacturing­
use
and/
or
end­
use
products
(
MPs/
EPs).

Table
2.
2,4­
D
active
ingredients
with
registered
MPs/
EPs
2,4­
D
acid
Empirical
Formula:
C
8
H
6
Cl
2
O
3
Molecular
Weight:
221.0
CAS
Registry
No.:
94­
75­
7
PC
Code:
030001
2,4­
D
sodium
salt
(
Na)
Empirical
Formula:
C
8
H
5
Cl
2
NaO
3
Molecular
Weight:
243.03
CAS
Registry
No.:
2702­
72­
9
PC
Code:
030004
2,4­
D
diethanolamine
salt
(
DEA)
Empirical
Formula:
C
12
H
17
Cl
2
NO
5
Molecular
Weight:
326.18
CAS
Registry
No.:
5742­
19­
8
PC
Code:
030016
2,4­
D
dimethylamine
salt
(
DMA)
Empirical
Formula:
C
10
H
13
Cl
2
NO
3
Molecular
Weight:
266.13
CAS
Registry
No.:
2008­
39­
1
PC
Code:
030019
2,4­
D
isopropylamine
salt
(
IPA)
Empirical
Formula:
C
11
H
15
Cl
2
NO
3
Molecular
Weight:
280.04
CAS
Registry
No.:
5742­
17­
6
PC
Code:
030025
2,4­
D
triisopropanolamine
salt
(
TIPA)
Empirical
Formula:
C
17
H
27
Cl
2
NO
6
Molecular
Weight:
412.31
CAS
Registry
No.:
32341­
80­
3
PC
Code:
030035
APPENDIX
1:
MARC
BRIEFING
DOCUMENT
Table
2.
2,4­
D
active
ingredients
with
registered
MPs/
EPs
12
O
Cl
Cl
O
O
CH
3
CH
3
O
Cl
Cl
O
O
NH+(
CH
2
CHOHCH
3)
3
O
Cl
Cl
O
O
O
CH
3
Cl
Cl
O
O
O
­
[
NH
3
CH(
CH
3)
2]+

2,4­
D
2­
butoxyethyl
ester
(
BEE)
Empirical
Formula:
C
14
H
18
Cl
2
O
4
Molecular
Weight:
321.20
CAS
Registry
No.:
1929­
73­
3
PC
Code:
030053
2,4­
D
2­
ethylhexyl
ester
(
2­
EHE)
1
Empirical
Formula:
C
16
H
22
Cl
2
O
3
Molecular
Weight:
333.27
CAS
Registry
No.:
1928­
43­
4
PC
Code:
030063
2,4­
D
isopropyl
ester
(
IPE)
Empirical
Formula:
C
11
H
12
Cl
2
O
3
Molecular
Weight:
263.12
CAS
Registry
No.:
94­
11­
1
PC
Code:
030066
1
Formerly
identified
as
the
isooctyl
ester.

The
available
data
concerning
identification
and
some
basic
physicochemical
properties
of
the
active
ingred
are
summarized
in
Table
3
for
2,4­
D
acid,
salts,
and
esters
with
registered
Mps/
EPs.
13
Table
3.
Available
data
concerning
identification
of
the
active
ingredient.
1
Active
ingredient
(
PC
Code)
Color
Physical
State
Melting
Point/
Boiling
Point
Density/
Specific
Gravity
Octanol/
Water
Partition
Coeff.
Vapor
Pressu
2,4­
D
acid
(
030001)
white
crystalline
solid
m.
p.
138­
141
C
s.
g.=
1.416
at
25
C
674
1.4
x
10­
7
mm
H
at
25
C
2,4­
D
Na
salt
(
030004)
white
powder
m.
p.
200
C
bulk
=
42.2
lb/
ft3
at
25
C
N/
A
2;
salt
dissociates
to
acid
water
2,4­
D
DEA
salt
(
030016)
cream
powder
m.
p.
83
C
bulk
=
0.762
g/
cm3
at
25
C
2.24
x
10­
2
at
25
C
<
1.33
x
10­
5
Pa
25
C
2,4­
D
DMA
salt
(
030019)
amber
aqueous
liquid
m.
p.
118­
120
C
(
PAI)
s.
g.
=
1.23
at
20
C
N/
A;
salt
dissociates
to
acid
in
water
<
1
x
10­
7
mm
H
at
26
C
2,4­
D
IPA
salt
(
030025)
amber
aqueous
liquid
m.
p.
121
C
(
PAI)
s.
g.
=
1.15
at
20
C
N/
A;
salt
dissociates
to
acid
i
water
2,4­
D
TIPA
salt
(
030035)
amber
aqueous
liquid
m.
p.
87­
110
C
(
PAI)
s.
g.
=
1.21
at
20
C
N/
A;
salt
dissociates
to
acid
i
water
2,4­
D
BEE
(
030053)
dark
amber
liquid
b.
p.
98
C
s.
g.
=
1.225
at
20
C
log
=
4.13­
4.17
at
25
C
2.4
x
10­
6
mm
H
at
25
C
2,4­
D
2­
EHE
(
030063)
dark
amber
liquid
b.
p.
300
C
s.
g.
=
1.152
at
20
C
log
=
5.78
(
temp
N/
A)
3.6
x
10­
6
mm
H
(
temp
N/
A)

2,4­
D
IPE
(
030066)
pale
amber
liquid
b.
p.
240
C
s.
g.
=
1.252
at
25
C
253.8
±
44.4
(
temp
N/
A)
5.3
x
10­
6
mba
APPENDIX
1:
MARC
BRIEFING
DOCUMENT
14
1
Data
assembled
from
Agency
memoranda
and
comprehensive
review
documents
referenced
herein,
includin
the
2,4­
D
Reregistration
Standard.
2
N/
A
=
Not
available.
APPENDIX
1:
MARC
BRIEFING
DOCUMENT
15
Table
4.
Representative
2,4­
D
End­
Use
Products
being
Supported
by
the
2,4­
D
Task
Force
II
1.

EPA
Reg.
No.
Label
Acceptance
Date
2
Formulation
3
Product
name
2,4­
Dichlorophenoxyacetic
acid
(
030001)

228­
315
7/
16/
1996
0.76%
G
Sweet
Sixteen
Weed
&
Feed
with
Triplet
MC
DRI
538­
186
1/
28/
2002
0.75%
G
Fertilizer
Plus
Dicot
Weed
Control
III
2217­
579
1/
08/
2003
0.69%
G
Gordon's
Trimec
®
Weed
&
Feed
30
2217­
660
8/
23/
2002
0.76%
G
Gordon's
Trimec
®
Weed
&
Feed
33
½
62719­
218
4
3/
08/
2002
85%
WP
Statesman
®
62719­
330
5
3/
06/
2002
2.8
lb/
gal
EC
Esteron
638
71368­
3
5
3/
07/
2002
2.8
lb/
gal
EC
Weedone
®
638
Sodium
salt
2,4­
dichlorophenoxyacetate
(
030004)

5080­
2
11/
30/
1982
17.5%
P/
T
Aquacide
71368­
22
10/
27/
2000
76.8
SC/
S
2,4­
D
Sodium
Salt
Diethanolamine
2,4­
dichlorophenoxyacetate
(
030016)

2217­
703
7
11/
14/
2002
3.8
lb/
gal
EC
Hi­
Dep
®
Herbicide
2217­
813
3/
15/
2002
5.03
lb/
gal
EC
EH1330
Herbicide
Dimethylamine
2,4­
dichlorophenoxyacetate
(
030019)

228­
145
7/
31/
2001
3.8
lb/
gal
EC
Weedestory
®
AM­
40
Amine
Salt
228­
331
10/
20/
1997
0.83%
G
2,4­
D
Amine
Weed
&
Feed
228­
354
1/
21/
1999
19.2%
G
Depth
Charge
 
Aquatic
Herbicide
228­
260
7/
06/
1999
80.5%
SC/
S
Solution
Water
Soluble
®
2217­
2
3/
08/
2002
3.8
lb/
gal
EC
Amine
400
2,4­
D
Weed
Killer
2217­
543
7/
11/
2002
1.98
lb/
gal
SC/
L
Trimec
®
Herbicide
34707­
606
3/
04/
2002
78.9%
CR
Savage
Dry
Soluble
Herbicide
34707­
803
5/
29/
1999
3.8
lb/
gal
EC
Saber
Herbicide
42750­
21
6/
26/
1995
5.6
lb/
gal
EC
2,4­
D
Amine
6
Herbicide
62719­
1
6
11/
07/
2001
3.8
lb/
gal
EC
Formula
40
®
Herbicide
62719­
3
10/
13/
2000
3.8
lb/
gal
EC
DMA
4
71368­
1
10/
03/
2002
3.8
lb/
gal
EC
Weedar
®
64
Broadleaf
Herbicide
Isopropylamine
2,4­
dichlorophenoxyacetate
(
030025)

62719­
303
3/
06/
2002
3.8
lb/
gal
EC
IPA­
4
Triisopropaolamine
2,4­
dichlorophenoxyacetate
(
030035)

62719­
1
6
11/
07/
2001
3.8
lb/
gal
EC
Formula
40
®
herbicide
Butoxyethyl
2,4­
dichlorophenoxyacetate
(
030053)

228­
378
9/
21/
2000
19%
G
2,4­
D
Aquatic
Granules
62719­
50
9/
28/
2001
3.8
lb/
gal
EC
2,4­
D
BEE­
4
62719­
330
5
3/
06/
2002
2.8
lb/
gal
EC
Esteron
638
71368­
3
3/
07/
2002
2.8
lb/
gal
EC
Weedone
®
638
71368­
4
3/
12/
1980
19%
G
Aqua­
Kleen
2­
ethylhexyl
2,4­
Dichlorophenoxyacetate
(
030063)

228­
139
10/
11/
2002
3.84
lb/
gal
EC
2,4­
D
LV4
Ester
APPENDIX
1:
MARC
BRIEFING
DOCUMENT
EPA
Reg.
No.
Label
Acceptance
Date
2
Formulation
3
Product
name
16
228­
153
5/
27/
1993
0.66%
G
Fertilizer
Plus
2,4­
D
2217­
77
3/
26/
2002
3.8
lb/
gal
EC
LV
400
2,4­
D
Weed
Killer
5905­
529
7/
13/
2001
4.7
lb/
gal
EC
Barrage
®
HF
Low
Volatile
Herbicide
34704­
609
3/
18/
1997
5
lb/
gal
EC
Salvo
®
Postemergence
Broadleaf
Herbicide
42750­
20
11/
16/
2000
5.5
lb/
gal
EC
2,4­
D
LV6
Low
Volatile
Herbicide
62719­
9
6/
08/
2001
3.8
lb/
gal
EC
Weed
Killer
4D
71368­
11
2/
17/
2000
5.4
lb/
gal
EC
Weedone
®
LoVol
6
Broadleaf
Herbicide
Isopropyl
ester
2,4­
dichlorophenoxyacetate
(
030066)

5481­
145
12/
28/
2001
3.36
lb/
gal
EC
Citrus
Fix
 
35935­
21
4/
13/
1998
3.4
lb/
gal
EC
Alphaset
IPE
64864­
31
8/
18/
1998
3.3
lb/
gal
EC
Leffingwell
Hivol
44
1To
assist
in
developing
tables
of
uses
being
support
by
the
Industry
Task
Force
II
(
Agro­
Gor
Corp,
BASF,
Do
AgroSciences,
and
Nufarm
USA),
the
Task
Force
II
has
cited
labels
for
the
Agency
that
include
representative
D
active
ingredients
and
formulations.
2Date
of
the
most
recently
EPA­
approved
label
found
by
reviewer
on
the
Pesticide
Product
Label
System.
3The
active
ingredient
for
the
formulated
products
is
expressed
as
the
acid
equivalent.
For
formulations
containing
more
than
one
2,4­
D
a.
i.,
the
total
2,4­
D
acid
equivalents
is
presented.
5EPA
Reg.
Nos.
62719­
330
and
71368­
3
are
MAI
formulations
containing
both
the
acid
(
030001)
and
the
butoxyethyl
ester
of
2,4­
D
(
030053)
for
a
total
acid
equivalent
of
2.8
lb/
gal.
6EPA
Reg.
No.
62719­
1
is
a
MAI
formulation
containing
both
DMA
(
030019)
and
TIPA
(
030035)
salts
of
2,4­
D
for
total
acid
equivalent
of
3.8
lb/
gal.
7EPA
Reg.
No.
2217­
703
is
an
MAI
formulation
containing
both
DMA
(
030019)
and
DEA
(
030016)
salts
of
2,4­
D
f
total
acid
equivalent
of
3.8
lb/
gal.

DIRECTIONS
FOR
USE
There
are
numerous
2,4­
D
EPs
registered
under
FIFRA
Section
3
to
the
members
of
Task
Force
II.
To
indicate
what
uses
are
being
supported
by
Task
Force
II
members,
Task
Force
II
has
provided
the
Agency
with
a
Mast
Label
which
SRRD
agreed
to
have
the
science
divisions
use
as
the
universe
of
supported
uses
for
reregistrat
purposes.
For
each
use
site,
the
Master
Label
generally
summarizes
the
following
information:
forms
of
2,4­
being
supported
(
i.
e.
acid,
amine
salts,
and/
or
esters);
types
of
formulations
being
supported
(
i.
e.
EC,
WP,
etc
limitations
on
the
type
and
timing
of
application(
s);
allowed
application
equipment;
reentry
interval
(
REI);
maximum
single
and
seasonal
application
rates;
minimum
retreatment
interval
(
RTI);
regional
restrictions;
an
restrictions
on
the
preharvest
and
grazing
intervals
(
PHI
and
PGI).
The
Master
Label
does
not
provide
details
uses
on
labels
of
specific
EPs.
The
information
regarding
the
food/
feed
and
aquatic
use
sites
on
the
Master
L
is
summarized
in
Appendix
1
(
a
separate
electronic
attachment
to
accompany
this
MARC
briefing
memo).
A
v
brief
summary
of
several
representative
label
directions
for
use
on
major
crops
include:
(
i)
small
grains,
1.25
lb
ae/
A
postemergence
+
preharvest,
14­
d
PHI,
<
1.75
lb
ae/
A/
season;
(
ii)
field
corn,
1
+
0.5
+
1.5
lb
ae/
A
pre­
+
postemergence
+
preharvest,
7­
d
PHI,
<
3
lb
ae/
A/
season;
(
iii)
pasture
and
range,
2
lb
ae/
A
postemergence,
7­
d
precutting
interval;
(
iv)
grapes,
1.36
lb
ae/
A,
postbloom,
100­
d
PHI;
orchard
fruits
and
nuts,
2
x
2
lb
ae/
A
postemergence/
yr,
14­
d
PHI
for
pome
fruits,
40­
d
for
stone
fruits,
and
60­
d
PHI
for
nuts;
and
(
v)
citrus
plant
gr
regulator
use,
12­
200
ppm
foliar
application
with
7­
day
PHI,
500
ppm
postharvest
application
with
no
PHI.
APPENDIX
1:
MARC
BRIEFING
DOCUMENT
17
TOLERANCE
ENFORCEMENT
METHODOLOGY
For
the
purpose
of
reregistration,
adequate
methods
are
available
for
data
collection
and
the
enforcement
of
p
commodity
tolerances.
The
Pesticide
Analytical
Manual
(
PAM)
Vol.
II
lists
three
GC
methods
(
designated
as
Methods
A,
B,
and
C)
with
microcoulometric
detection
and
one
GC
method
(
designated
as
Method
D)
with
ele
capture
detection
(
ECD).
In
a
letter
dated
9/
3/
93
(
CBRS
No.
12270,
DP
Barcode
D193335,
9/
3/
93,
W.
Smith),
the
Task
Force
II
indicated
that
the
enforcement
methods
currently
listed
in
PAM
Vol.
II
are
unsuitable
for
determi
residues
of
2,4­
D
in
wheat
and
poultry
commodities.

Plant
Commodities:
The
Task
Force
II
submitted
an
adequate
proposed
enforcement
method
for
plants
(
designated
as
EN­
CAS
Method
No.
ENC­
2/
93,
described
below)
which
has
been
independently
validated.
Adequate
radiovalidation
data
have
been
submitted
and
evaluated
for
the
proposed
enforcement
method
usin
samples
from
the
wheat
metabolism
study.
The
proposed
enforcement
method
or
modifications
of
the
enforcement
method
were
used
for
data
collection
purposes.

Animal
Commodities:
The
Task
Force
II
submitted
two
separate
(
but
essentially
comparable)
proposed
enforcement
methods
for
determination
of
2,4­
D
in
livestock
commodities.
Adequate
radiovalidation
data
hav
been
submitted
for
the
method
using
samples
of
fat,
kidney,
and
milk
from
the
goat
metabolism
study
and
samples
of
eggs
from
the
poultry
metabolism
study.
The
Agency
concluded
that
the
methods
are
adequate
provided
the
registrants
satisfy
the
following
requests:
(
i)
submit
a
revised
method
which
combines
the
two
methods
into
a
single
method
and
once
an
adequate
revised
method
is
received
the
Agency
will
forward
the
method
to
EPA/
Beltsville
for
a
tolerance
method
validation;
(
ii)
delete
from
the
method
all
references
to
the
us
diazomethane
as
a
derivatizing
agent;
and
(
iii)
provide
complete
raw
data
and
sample
calculations
(
including
chromatograms
showing
peak
areas,
external
standard
linearity
curves
and
associated
data,
standard
calculations,
etc.).

For
the
GC/
ECD
method
ENC­
2/
93,
residues
are
extracted
from
plant
matrices
into
0.5
M
KOH
in
ethanol:
H
2
O
(
EtOH,
1:
1,
v/
v)
and
filtered.
The
resulting
extract
is
refluxed
for
1
hour
in
0.2
M
HCl.
Hydrolyzed
residues
are
cleaned
up
using
a
C
18
solid
phase
extraction
column
by
rinsing
with
water
and
hexane,
and
then
eluting
with
hexane:
ethyl
acetate
(
EtOAc,
1:
1,
v/
v).
Residues
are
then
partitioned
into
0.1
M
Na
2
HPO
4,
acidified,
and
partiti
into
diethyl
ether
(
Et
2
O).
Residues
are
concentrated
to
dryness
and
then
derivatized
to
the
methyl
ester
with
1
boron
trifluoride
in
methanol
(
MeOH).
For
samples
of
soybean
(
seed
and
forage),
sugarcane,
and
rice
straw,
derivatized
sample
is
then
oxidized
with
potassium
permanganate.
The
derivatized
residues
from
each
matrix
(
except
wheat
forage
and
grain)
are
then
partitioned
into
25%
toluene
in
hexane
and
cleaned
up
using
an
Alum
column
eluted
with
25%
toluene
in
hexane.
For
wheat
forage
and
grain
samples,
the
derivatized
residues
are
extracted
into
toluene,
diluted
with
hexane
(
toluene:
hexane,
1:
2,
v/
v),
and
cleaned
up
using
an
Alumina
colum
eluted
with
35%
toluene
in
hexane.
Methylated
residues
in
all
matrices
are
determined
by
GC/
ECD.
The
alkali
hydrolysis
step
is
expected
to
hydrolyze
any
2,4­
D
ester
that
may
be
present
as
well
as
conjugates
of
2,4­
D.

MULTIRESIDUE
METHODS
The
10/
97
edition
of
FDA
PAM
Volume
I,
Appendix
I
indicates
that
2,4­
D
is
partially
recovered
(
50­
80%)
using
Multiresidue
Methods
Section
402
E1
and
402
E2.

HAZARD
CHARACTERIZATION
(
From
2,4­
D
Toxicology
Chapter
of
the
RED
dated
8/
19/
03)

2,4­
Dichlorophenoxyacetic
acid
[
2,4­
D]
and
its
amine
salts
[
diethanolamine
(
DEA),
dimethylamine
(
DMA),
isopropylamine
(
IPA),
and
triisopropanolamine
(
TIPA)]
and
esters
[
butoxyethyl
ester
(
BEE),
ethylhexyl
ester
(
E
and
isopropyl
ester
(
IPE)]
are
not
acutely
toxic
via
the
oral,
dermal,
and
inhalation
routes
of
exposure
[
Toxicit
Category
III],
with
the
exception
of
DMA,
which
shows
moderate
[
Toxicity
Category
II]
toxicity
via
the
oral
and
dermal
routes.
2,4­
D
and
its
amine
salts
and
esters
are
not
skin
irritants
[
Toxicity
Categories
III
and
IV]
and
no
a
skin
sensitizer.
All
forms
of
2,4­
D
show
severe
eye
irritation
[
Toxicity
Category
I],
with
the
exception
of
BEE
APPENDIX
1:
MARC
BRIEFING
DOCUMENT
18
[
Toxicity
Category
III].

In
general,
2,4­
D
undergoes
limited
metabolism
primarily
involving
minor
conjugation
of
the
parent
acid
that
i
then
excreted
in
the
urine.
No
detectable
metabolites
of
2,4­
D
have
been
reported
in
the
rat;
i.
e.,
only
the
pare
acid
is
found
in
rat
urine.
In
addition
to
2,4­
D
itself,
2,4­
D
conjugates
have
been
found
in
the
urine
of
dogs,
humans,
mice,
and
hamsters
following
oral
exposure.
The
mechanisms
responsible
for
the
renal
clearance
of
D
have
been
investigated
in
several
species
also.
This
phenoxy
herbicide
is
actively
secreted
by
the
proximal
tubules
in
a
manner
similar
to
paraaminohippuric
acid
[
PAH],
and
this
mechanism
of
renal
clearance
for
2,4­
D
consistent
with
results
seen
with
other
phenoxy
acids.
It
has
been
suggested
that
the
observed
dose­
depend
non­
linear
pharmacokinetics
of
2,4­
D
are
primarily
due
to
the
saturation
of
this
renal
secretory
transport
syste
Due
to
a
limited
capacity
to
excrete
organic
acids,
the
dog
is
more
sensitive
to
the
effects
of
2,4­
D
than
the
ra
with
respect
to
repeated
dosing.

Following
subchronic
oral
exposure
at
dose
levels
of
2,4­
D
at
or
above
the
threshold
of
saturation
for
renal
clearance,
the
primary
target
organs
are
the
eye
[
retinal
degeneration,
cataract
formation],
thyroid
[
increased
thyroid
weight,
increased
T3/
decreased
T4,
and
follicular
cell
hypertrophy],
kidney
[
brush
border
loss
in
prox
tubule],
adrenals
[
hypertrophy],
and
ovaries/
testes
[
atrophy].
These
changes
are
also
observed
following
exposure
to
the
amine
salts
and
esters
of
2,4­
D.
Systemic
toxicity
was
not
observed
following
repeated
derma
exposure
to
2,4­
D,
EHE,
and
TIPA
at
or
above
the
limit
dose
or
following
repeated
dermal
exposure
to
BEE
an
at
the
highest
dose
tested.
Liver
toxicity
was
observed
following
repeated
dermal
exposure
to
DEA,
and
one
d
[
female]
occurred
following
dermal
exposure
to
DMA
at
a
high­
dose
level.

There
are
no
repeated
inhalation
exposure
data
available
on
2,4­
D.
The
only
reliable
way
to
characterize
inhal
toxicity
and
to
quantify
inhalation
risk
is
through
the
use
of
inhalation
toxicity
studies.
Chemicals
tend
to
be
toxic
by
the
inhalation
route
than
by
the
oral
route
due
to
rapid
absorption
and
distribution,
bypassing
of
the
liver's
metabolic
protection
(
portal
circulation),
and
potentially
serious
portal­
of­
entry
effects,
such
as
irritatio
edema,
cellular
transformation,
degeneration,
and
necrosis.
An
inhalation
risk
assessment
that
is
based
on
o
data
generally
underestimates
the
inhalation
risk
because
it
cannot
account
for
these
factors.
Therefore,
a
subchronic
inhalation
study
is
required
for
2,4­
D.

Developmental
toxicity,
characterized
mainly
as
an
increased
incidence
of
skeletal
variations
in
the
rat,
was
observed
following
exposure
to
2,4­
D
and
its
amine
salts
and
esters.
Malformations
in
the
rat
were
observed
o
at
dose
levels
that
were
at
or
above
the
threshold
of
saturation
of
renal
clearance.
Developmental
toxicity
was
observed
in
the
rabbit
only
following
exposure
to
2,4­
D
[
abortions]
and
DEA
[
increased
number
of
litters
with
fetuses
with
7th
cervical
ribs].

Reproductive
toxicity,
characterized
as
an
increase
in
gestation
length,
was
observed
following
exposure
to
2
at
a
dose
level
above
the
threshold
of
saturation
of
renal
clearance.
A
repeat
2­
generation
reproduction
study
[
using
the
new
protocol]
is
required
to
address
concerns
for
endocrine
disruption
[
thyroid
and
immunotoxici
measures].

Neurotoxicity
was
demonstrated
following
exposure
to
2,4­
D
at
relatively
high
dose
levels.
Clinical
signs
of
neurotoxicity
[
ataxia,
decreased
motor
activity,
myotonia,
prostration,
lateral
recumbency,
and
impaired/
loss
the
righting
reflex,
cold
to
the
touch]
were
observed
in
pregnant
rabbits
following
exposure
to
2,4­
D
and
its
a
salts
and
esters.
Neuropathology
[
retinal
degeneration]
was
observed
following
2,4­
D
exposure
in
several
stu
in
female
rats.
Incoordination
and
slight
gait
abnormalities
(
forepaw
flexing
or
knuckling)
were
observed
follo
acute
dosing
and
increased
forelimb
grip
strength
was
observed
following
chronic
exposure
to
2,4­
D
at
dose
levels
that
exceeded
the
threshold
of
saturation
of
renal
clearance.
A
developmental
neurotoxicity
study
in
th
is
required
on
2,4­
D.

2,4­
D
is
classified
as
a
Group
D
chemical
[
not
classifiable
as
to
human
carcinogenicity].
Based
on
the
overall
pattern
of
responses
observed
in
both
in
vitro
and
in
vivo
genotoxicity
tests,
2,4­
D
was
not
mutagenic,
althou
some
cytogenic
effects
were
observed.

2,4­
D
affects
thyroid
hormone
homeostasis
following
oral
exposure,
and
there
is
a
concern
for
endocrine
disruption.
Effects
on
the
gonads
in
rats
[
decreased
testes
and
ovarian
weights,
atrophy
of
the
ovary,
uterus
testis,
degeneration
of
the
seminiferous
epithelium,
decreased
spermatozoa
in
epididymis,
testicular
degeneration,
increase
in
gestation
length]
and
dogs
[
increased
testes
weight,
juvenile
testes
and
prostate,
a
APPENDIX
1:
MARC
BRIEFING
DOCUMENT
19
hypospermatogenesis]
are
seen
following
exposure
to
2,4­
D
and/
or
its
amine
salts
and
esters.
Although
there
data
on
thyroid
hormone
levels
in
the
adult
animal,
there
are
no
data
with
respect
to
thyroid
hormones
in
the
young;
therefore,
there
is
no
information
on
whether
the
young
are
more
sensitive
with
respect
to
this
endpo
There
is
no
developmental
neurotoxicity
[
DNT]
study
available
on
2,4­
D,
and
the
HIARC
determined
previousl
a
DNT
study
is
required
[
HED
Document
No.
014234].
There
have
been
no
studies
on
2,4­
D
that
specifically
as
its
endocrine
disruption
potential,
and
there
are
no
data
on
other
hormonal
effects.
Thyroid
effects
[
increased
thyroid
weight,
increased
T3/
decreased
T4,
and
follicular
cell
hypertrophy]
have
been
observed
in
the
rat
follo
subchronic
exposure
to
2,4­
D
and
its
amine
salts
and
esters
and
following
chronic
exposure
to
2,4­
D
[
decreas
T4,
increased
thyroid
weight,
thyroid
masses,
and
follicular
cell
hyperplasia
(
males;
interim
sacrifice
only)/
hypertrophy
(
females;
interim
sacrifice
only)].
Additionally,
there
is
some
concern
for
immunotoxicity
following
exposure
to
2,4­
D.
There
are
clear
NOAELs
for
each
of
the
above­
mentioned
effects,
which
occur
on
high­
dose
levels;
above
the
doses
selected
for
overall
risk
assessment.
Therefore,
there
are
no
residual
uncertainties
with
regard
to
these
effects.
However,
the
HIARC
concluded
that
a
2­
generation
reproduction
st
using
the
current
protocol
is
required
to
address
both
the
concern
for
thyroid
effects
[
comparative
assessme
between
the
young
and
adult
animals]
and
immunotoxicity,
as
well
as
a
more
thorough
assessment
of
the
go
and
reproductive/
developmental
endpoints.
The
Task
Force
should
consult
the
Agency
on
the
protocol
for
th
study.

SUMMARY
OF
TOXICOLOGY
ENDPOINT
SELECTION
(
From
5/
1/
03
HIARC
report
of
4/
8/
03
HIARC
meeting
(
TXR
No.
0051866))

Table
5.
Summary
of
Toxicological
Dose
and
Endpoints
for
2,4­
D.

Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
(
Females
13­
50
years
of
age)
NOAEL
=
25
mg/
kg/
day
UF
=
1000
Acute
RfD
=
0.025
mg/
kg/
day
FQPA
SF
=
1X
aPAD
=
acute
RfD(
0.025)
FQPA
SF
(
1)

=
0.025
mg/
kg/
day
rat
developmental
toxicity
study
LOAEL
=
75
mg/
kg/
day
based
on
skeletal
malformations
and
skeletal
variations
Acute
Dietary
(
General
population
including
infants
and
children)
NOAEL
=
67
mg/
kg/
day
UF
=
1000
Acute
RfD
=
0.067
mg/
kg/
day
FQPA
SF
=
1X
aPAD
=
acute
RfD
(
0.067)
FQPA
SF
(
1)

=
0.067mg/
kg/
day
acute
neurotoxicity
study
in
rats
LOAEL
=
227
mg/
kg/
day
based
on
gait
abnormalities
APPENDIX
1:
MARC
BRIEFING
DOCUMENT
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
20
Chronic
Dietary
(
All
populations)
NOAEL=
5
mg/
kg/
day
UF
=
1000
Chronic
RfD
=
0.005
mg/
kg/
day
FQPA
SF
=
1X
cPAD
=
chronic
RfD
(
0.005)
FQPA
SF
(
1)

=
0.005
mg/
kg/
day
rat
chronic
toxicity
study
LOAEL
=
75
mg/
kg/
day
based
on
decreased
body­
weight
gain
(
females)
and
food
consumption
(
females),
alterations
in
hematology
[
decreased
RBC,
HCT,
and
HGB
(
females),
platelets
(
both
sexes)]
and
clinical
chemistry
parameters
[
increased
creatinine
(
both
sexes),
alanine
and
aspartate
aminotransferases
(
males),
alkaline
phosphatase
(
both
sexes),
decreased
T4
(
both
sexes),
glucose
(
females),
cholesterol
(
both
sexes),
and
triglycerides
(
females)],
increased
thyroid
weights
(
both
sexes
at
study
termination),
and
decreased
testes
and
ovarian
weights
.

Short­
Term
Incidental
Oral
(
1­
30
days)
NOAEL=
25
mg/
kg/
day
Residential
LOC
for
MOE
=
1000
Occupational
=
NA
rat
developmental
toxicity
study
LOAEL
=
75
mg/
kg/
day
based
on
decreased
maternal
body­
weight
gain
and
skeletal
malformations
and
skeletal
variations
Intermediate­
Term
Incidental
Oral
(
1­
6
months)
NOAEL
=
15
mg/
kg/
day
Residential
LOC
for
MOE
=
1000
Occupational
=
NA
subchronic
oral
toxicity
­
rat
LOAEL
=
100
mg/
kg/
day
based
on
decreased
body
weight/
bodyweight
gain,
alterations
in
some
hematology
[
decreased
platelets
(
both
sexes)]
and
clinical
chemistry
[
decreased
T3
(
females)
and
T4
(
both
sexes)]
parameters,
and
cataract
formation.

Short­
Term
Dermal
(
1
to
30
days)
Oral
study
NOAEL=
25
mg/
kg/
day
(
dermal
absorption
rate
=
5.8%)
Residential
LOC
for
MOE
=
1000
Occupational
LOC
for
MOE
=
100
rat
developmental
toxicity
study
LOAEL
=
75
mg/
kg/
day
based
on
decreased
maternal
body­
weight
gain
and
skeletal
malformations
and
skeletal
variations
Intermediate­
Term
Dermal
(
1
to
6
months)
Oral
study
NOAEL
=
15
mg/
kg/
day
(
dermal
absorption
rate
=
5.8%)
Residential
LOC
for
MOE
=
1000
Occupational
LOC
for
MOE
=
100
subchronic
oral
toxicity
­
rat
LOAEL
=
100
mg/
kg/
day
based
on
decreased
body
weight/
bodyweight
gain,
alterations
in
some
hematology
[
decreased
platelets
(
both
sexes)]
and
clinical
chemistry
[
decreased
T3
(
females)
and
T4
(
both
sexes)]
parameters,
and
cataract
formation.
APPENDIX
1:
MARC
BRIEFING
DOCUMENT
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
21
Long­
Term
Dermal
(>
6
months)
Oral
study
NOAEL=
5
mg/
kg/
day
(
dermal
absorption
rate
=
5.8%)
Residential
LOC
for
MOE
=
1000
Occupational
LOC
for
MOE
=
100
rat
chronic
toxicity
study
LOAEL
=
75
mg/
kg/
day
based
on
decreased
body­
weight
gain
(
females)
and
food
consumption
(
females),
alterations
in
hematology
[
decreased
RBC,
HCT,
and
HGB
(
females),
platelets
(
both
sexes)]
and
clinical
chemistry
parameters
[
increased
creatinine
(
both
sexes),
alanine
and
aspartate
aminotransferases
(
males),
alkaline
phosphatase
(
both
sexes),
decreased
T4
(
both
sexes),
glucose
(
females),
cholesterol
(
both
sexes),
and
triglycerides
(
females)],
increased
thyroid
weights
(
both
sexes
at
study
termination),
and
decreased
testes
and
ovarian
weights
.

Short­
Term
Inhalation
(
1
to
30
days)
Oral
study
NOAEL=
25
mg/
kg/
day
(
inhalation
absorption
rate
=
100%)
Residential
LOC
for
MOE
=
1000
Occupational
LOC
for
MOE
=
100
rat
developmental
toxicity
study
LOAEL
=
75
mg/
kg/
day
based
on
decreased
maternal
body­
weight
gain
and
skeletal
malformations
and
skeletal
variations
Intermediate­
Term
Inhalation
(
1
to
6
months)
Oral
study
NOAEL
=
15
mg/
kg/
day
(
inhalation
absorption
rate
=
100%)
Residential
LOC
for
MOE
=
1000
Occupational
LOC
for
MOE
=
100
subchronic
oral
toxicity
­
rat
LOAEL
=
100
mg/
kg/
day
based
on
decreased
body
weight/
bodyweight
gain,
alterations
in
some
hematology
[
decreased
platelets
(
both
sexes)]
and
clinical
chemistry
[
decreased
T3
(
females)
and
T4
(
both
sexes)]
parameters,
and
cataract
formation.

Long­
Term
Inhalation
(>
6
months)
Oral
study
NOAEL=
5
mg/
kg/
day
(
inhalation
absorption
rate
=
100%)
Residential
LOC
for
MOE
=
1000
Occupational
LOC
for
MOE
=
100
rat
chronic
toxicity
study
LOAEL
=
75
mg/
kg/
day
based
on
decreased
body­
weight
gain
(
females)
and
food
consumption
(
females),
alterations
in
hematology
[
decreased
RBC,
HCT,
and
HGB
(
females),
platelets
(
both
sexes)]
and
clinical
chemistry
parameters
[
increased
creatinine
(
both
sexes),
alanine
and
aspartate
aminotransferases
(
males),
alkaline
phosphatase
(
both
sexes),
decreased
T4
(
both
sexes),
glucose
(
females),
cholesterol
(
both
sexes),
and
triglycerides
(
females)],
increased
thyroid
weights
(
both
sexes
at
study
termination),
and
decreased
testes
and
ovarian
weights
.

Cancer
(
oral,
dermal,
inhalation)
Classification:
Group
D
[
not
classifiable
as
to
human
carcinogenicity]

UF
=
uncertainty
factor,
FQPA
SF
=
Special
FQPA
safety
factor,
NOAEL
=
no
observed
adverse
effect
level,
LO
=
lowest
observed
adverse
effect
level,
PAD
=
population
adjusted
dose
(
a
=
acute,
c
=
chronic),
RfD
=
referen
APPENDIX
1:
MARC
BRIEFING
DOCUMENT
22
dose,
MOE
=
margin
of
exposure,
LOC
=
level
of
concern,
NA
=
Not
Applicable
NOTE:
The
Special
FQPA
Safety
Factor
recommended
by
the
HIARC
assumes
that
the
exposure
databases
(
dietary
food,
drinking
water,
and
residential)
are
complete
and
that
the
risk
assessment
for
each
potential
exposure
scenario
includes
all
metabolites
and/
or
degradates
of
concern
and
does
not
underestimate
the
potential
risk
for
infants
and
children.

RESIDUE
CHEMISTRY
INFORMATION
PLANT
METABOLISM
EXCERPTS
FROM
24D.
003;
WHEAT
METABOLISM;
D181885
(
42439701)/
D186927
(
42615601).
In
the
wheat
metabolism
study,
[
14C]
2­
EHE
was
applied
to
plants
at
tillering
as
a
broadcast
application
at
1.5
lb
ae/
A
(

1x).
TRR
were
33.6
ppm
in/
forage
(
Table
6)
harvested
10
days
post­
treatment
and
55.7
ppm
in
straw
(
Table
7)
and
0.299
ppm
in
grain
(
Tab
harvested
at
maturity
(
49
days
post­
treatment).
Following
acid
hydrolysis,
2,4­
D
was
the
major
compound
identified
in
forage
(
68.0%
TRR)
and
straw
(
56.2%
TRR).
After
subsequent
base
hydrolysis,
another
8.8%
of
th
TRR
in
forage
and
16.1%
of
the
TRR
in
straw
was
identified
as
2,4­
D.
Minor
metabolites
(
each
<
10%
TRR)
identified
in
forage
and
straw
included:
4­
hydroxy­
2,5­
D;
4­
hydroxy­
2,3­
D;
5­
hydroxy­
2,4­
D;
and
2,4­
DCP.
The
only
compound
identified
in
grain
was
2,4­
D
(
6.0%
TRR).
The
majority
of
14C­
residues
in
grain
(
45%
TRR)
wer
characterized
as
being
incorporated
into
natural
plant
constituents,
such
as,
protein,
starch
and
cellulose.
R
to
Table
20
for
structures
of
plant
metabolites.

Table
6.
Distribution
of
14C­
residues
in
wheat
forage
following
a
single
over­
the­
top
spray
application
of
isooctyl
(
2­
ethylhexyl)
ester
of
[
14C]
2,4­
D
at
1.5
lb
ae/
A
(
1x
the
maximum
registered
seasonal
rate).

Extracts
and
Metabolites
[
14C]
2,4­
D
acid
equivalents
%
TRR
ppm
Composite
10­
Day
Forage
TRR
100.0
33.6
Ether
Extract
After
Hydrolysis
20.4
6.84
Ether
Extract
(
ETH­
1)
19.8
6.64
4­
Hydroxy­
2,5­
dichlorophenoxyacetic
acid
a
2.8
0.936
Hydroxydichlorophenoxyacetic
acid
(
HPLC
retention
time
15.0­
17.0
min.)
b
0.4
0.133
Hydroxydichlorophenoxyacetic
acid
(
HPLC
retention
time
19.0­
21.5
min.)
c
1.0
0.345
2,4­
D
d
12.5
4.21
2,4­
Dichlorophenol
a
0.2
0.066
Unknown
(
HPLC
retention
time
1.5­
3.5
min.)
0.3
0.113
Unknown
(
HPLC
retention
time
18.0­
18.5
min.)
<
0.1
0.007
Unknown
(
HPLC
retention
time
22.0­
24.0
min.)
0.2
0.080
Unknown
(
HPLC
retention
time
29.5­
37.0
min.)
0.6
0.206
Unknown
(
HPLC
retention
time
38.0­
43.0
min.)
e
1.2
0.405
Unknown
(
HPLC
retention
time
44.0­
54.0
min.)
0.4
0.133
Aqueous
Extract
(
AQ­
1)
0.6
0.198
Ether
Extract
(
ETH­
2)
0.4
0.131
4­
Hydroxy­
2,5­
dichlorophenoxyacetic
acid
a
<
0.1
0.016
2,4­
D
d
<
0.1
0.011
Unknown
(
HPLC
retention
time
1.5­
3.0
min.)
0.1
0.043
Unknown
(
HPLC
retention
time
17.5­
19.5
min.)
<
0.1
0.016
Unaccounted
<
0.1
0.045
Aqueous
Extract
(
AQ­
2)
0.1
0.032
Unaccounted
0.1
0.035
Ethanol
Extract
After
Hydrolysis
66.1
22.2
Ether
Extract
(
ETH­
1)
57.1
19.2
4­
Hydroxy­
2,5­
dichlorophenoxyacetic
acid
a
0.4
0.134
Hydroxydichlorophenoxyacetic
acid
0.2
0.058
2,4­
D
d
55.1
18.5
2,4­
Dichlorophenol
a
0.1
0.038
APPENDIX
1:
MARC
BRIEFING
DOCUMENT
Extracts
and
Metabolites
[
14C]
2,4­
D
acid
equivalents
%
TRR
ppm
23
Unknown
(
HPLC
retention
time
36.0­
39.0
min.)
1.1
0.0365
Aqueous
Extract
(
AQ­
1)
8.8
2.45
Ether
Extract
(
ETH­
2)
7.3
2.45
4­
Hydroxy­
2,5­
dichlorophenoxyacetic
acid
a
4.8
1.61
Hydroxydichlorophenoxyacetic
acid
(
HPLC
ret.
time
15.0­
17.0
min.)
b
1.5
0.519
Hydroxydichlorophenoxyacetic
acid
(
HPLC
ret.
time
19.0­
20.5
min.)
c
0.2
0.066
2,4­
D
d
0.4
0.120
2,4­
Dichlorophenol
a
0.2
0.059
Unknown
(
HPLC
retention
time
2.0­
3.0
min.)
0.1
0.034
Unknown
(
HPLC
retention
time
22.0­
23.0
min.)
0.1
0.037
Aqueous
Extract
(
AQ­
2)
1.5
0.496
KOH
Extract
12.2
4.09
Ether
Soluble
8.9
2.98
2,4­
D
d
8.8
2.95
Unknown
(
HPLC
retention
time
2.0­
3.0
min.)
0.1
0.027
Aqueous
Soluble­
3
1.6
0.540
Enzyme
Digestible
Cellulase
Digestible
0.3
0.098
Amylase
Digestible
0.1
0.045
Non­
extractable
0.4
0.140
a
Confirmed
by
GC/
MS.
b
Confirmed
by
GC/
MS
as
4­
hydroxy­
2,3­
dichlorophenoxyacetic
acid
in
the
supplemental
study
(
MRID
42615601).
c
Confirmed
by
GC/
MS
as
5­
hydroxy­
2,4­
dichlorophenoxyacetic
acid
in
the
supplemental
study
(
MRID
42615601).
d
Confirmed
by
one­
dimensional
TLC
and
GC/
MS.
e
Identification
by
GC/
MS
was
unsuccessful.
However,
the
presence
of
an
amino
acid
conjugate
of
2,4­
D
was
indicated.

Table
7.
Distribution
of
14C­
residues
in
wheat
straw
following
a
single
over­
the­
top
spray
application
of
isooc
(
2­
ethylhexyl)
ester
of
[
14C]
2,4­
D
at
1.5
lb
ae/
A
(
1x
the
maximum
registered
seasonal
rate).

Extracts
and
Metabolites
[
14C]
2,4­
D
acid
equivalents
%
TRR
ppm
Composite
49­
Day
Straw
TRR
100.0
55.7
Ether
Extract
After
Hydrolysis
14.3
7.95
Ether
Soluble
(
ETH­
1)
13.9
7.77
4­
Hydroxy­
2,5­
dichlorophenoxyacetic
acid
a
1.8
0.995
Hydroxydichlorophenoxyacetic
acid
(
HPLC
retention
time
15.0­
16.0
min.)
b
0.2
0.124
Hydroxydichlorophenoxyacetic
acid
(
HPLC
retention
time
18.5­
21.0
min.)
c
0.6
0.319
2,4­
D
d
8.1
4.51
2,4­
Dichlorophenol
a
0.4
0.241
Unknown
(
HPLC
retention
time
52.0­
54.0
min.)
0.3
0.140
Unknown
(
HPLC
retention
time
2.0­
3.5
min.)
0.2
0.093
Unknown
(
HPLC
retention
time
21.5­
23.0
min.)
0.2
0.101
Unknown
(
HPLC
retention
time
30.0­
36.0
min.)
0.3
0.163
Unknown
(
HPLC
retention
time
37.0­
42.0
min.)
0.5
0.256
Unknown
(
HPLC
retention
time
43.0­
51.0
min.)
0.4
0.218
Unknown
(
HPLC
retention
time
6.5­
12.0
min.)
0.9
0.482
Unknown
(
HPLC
retention
time
16.5­
18.0
min.)
0.1
0.039
Unknown
(
HPLC
retention
time
28.5­
29.5
min.)
0.1
0.031
Unknown
(
HPLC
retention
time
55.0­
60.0
min.)
0.1
0.054
Aqueous
Extract
(
AQ­
1)
0.3
1.75
Ether
Extract
(
ETH­
2)
0.3
0.158
4­
Hydroxy­
2,5­
dichlorophenoxyacetic
acid
a
<
0.1
0.022
2,4­
D
<
0.1
0.007
Unknown
(
HPLC
retention
time
2.0­
3.0
min.)
<
0.1
0.013
Unknown
(
HPLC
retention
time
17.5­
19.5
min.)
<
0.1
0.026
Unaccounted
0.2
0.091
Aqueous
Extract
(
AQ­
2)
<
0.1
0.017
Ethanol
Extract
After
Hydrolysis
62.5
34.8
Ether
Soluble
(
ETH­
1)
49.2
27.4
4­
Hydroxy­
2,5­
dichlorophenoxyacetic
acid
a
0.5
0.274
APPENDIX
1:
MARC
BRIEFING
DOCUMENT
Extracts
and
Metabolites
[
14C]
2,4­
D
acid
equivalents
%
TRR
ppm
24
Hydroxydichlorophenoxyacetic
acid
(
HPLC
retention
time
15.0­
16.0
min.)
b
0.1
0.055
Hydroxydichlorophenoxyacetic
acid
(
HPLC
retention
time
19.5­
20.5
min.)
c
0.2
0.110
2,4­
D
d
47.9
26.7
Unknown
(
HPLC
retention
time
2.0­
3.5
min.)
0.5
0.301
Aqueous
Extract
(
AQ­
1)
13.4
7.45
Ether
Extract
(
ETH­
2)
12.0
6.69
4­
Hydroxy­
2,5­
dichlorophenoxyacetic
acid
a
6.2
3.45
Hydroxydichlorophenoxyacetic
acid
(
HPLC
ret.
time
15.0­
16.0
min.)
b
2.2
1.2
Hydroxydichlorophenoxyacetic
acid
(
HPLC
ret.
time
19.0­
20.5
min.)
c
0.8
0.468
2,4­
D
d
0.2
0.127
2,4­
Dichlorophenol
a
0.5
0.301
Unknown
(
HPLC
retention
time
22.0­
23.0
min.)
0.2
0.114
Unaccounted
1.8
1.02
Aqueous
Extract
(
AQ­
2)
1.4
0.760
KOH
Extract
18.7
10.4
Ether
Extractable
After
Acidification
17.7
9.88
2,4­
D
a
16.1
8.95
Unknown
(
HPLC
retention
time
2.5­
6.5
min.)
1.5
0.85
Unknown
(
HPLC
retention
time
23.0­
26.0
min.)
0.2
0.089
Aqueous
Soluble
0.9
0.509
Enzyme
Digestible
Cellulase
Digestible
1.3
0.697
Amylase
Digestible
0.4
0.211
Non­
extractable
0.4
0.215
a
Confirmed
by
GC/
MS.
b
Confirmed
by
GC/
MS
as
4­
hydroxy­
2,3­
dichlorophenoxyacetic
acid
in
the
supplemental
study
(
MRID
42615601).
c
Confirmed
by
GC/
MS
as
5­
hydroxy­
2,4­
dichlorophenoxyacetic
acid
in
the
supplemental
study
(
MRID
42615601).
d
Confirmed
by
one­
dimensional
TLC
and
GC/
MS.

Grain
Table
8
indicates
that
only
6.0%
of
TRR
(
0.018
ppm)
was
identified
as
2,4­
D
in
all
fractions/
extracts
of
treated
g
A
significant
amount
of
bound
14C­
residues
remained
unidentified
even
after
organic
and
aqueous
extractions
enzyme
hydrolysis
of
the
solid
residues;
the
fractionation
procedures
resulted
in
extracts
with
TRR
values
an
concentrations
which
are
below
the
Agency
metabolism
trigger
values.
The
remaining
unidentified
radioactiv
includes:
(
i)
two
unknown
metabolites
(
combined
17.1%,
0.051
ppm),
(
ii)
aqueous­
soluble
metabolites
(
comb
21.4%,
0.064
ppm),
(
iii)
the
enzyme­
hydrolyzable
fractions
(
combined
10.1%,
0.03
ppm),
and
(
iv)
the
unaccoun
radioactivity
(
36.5%,
0.109
ppm).
Supplemental
characterization
indicates
that
ca.
45%
of
the
radioactivity
in
g
is
putatively
incorporated
into
plant
cell
constituents
such
as
protein,
starch
and
cellulose.

Table
8.
Distribution
of
14C­
residues
in
wheat
grain
following
a
single
over­
the­
top
spray
application
of
isooc
ethylhexyl)
ester
of
[
14C]
2,4­
D
at
1.5
lb
ae/
A.

Extracts
and
Metabolites
[
14C]
2,4­
D
acid
equivalents
Treated
Sample
Control
Sample
%
TRR
ppm
%
TRR
ppm
Composite
Grain
TRR
100.0
0.299
100.0
0.169
Acetonitrile:
Water
Extract
3.7
0.011
2.4
0.004
2,4­
D
1.3
0.004
­­
­­
Unknown
(
HPLC
retention
time
2.0­
3.0
min.)
0.3
0.001
­­
­­
Unknown
(
HPLC
retention
time
47.0­
49.0
min.)
0.3
0.001
­­
­­
Unaccounted
1.7
0.005
­­
­­

Aqueous
Extract
7.7
0.023
8.3
0.014
Ether
Extractable
After
Acid
Hydrolysis
1.3
0.004
­­
­­
Aqueous
Soluble
3.7
0.011
­­
­­
Unaccounted
2.7
0.008
­­
­­
APPENDIX
1:
MARC
BRIEFING
DOCUMENT
Extracts
and
Metabolites
[
14C]
2,4­
D
acid
equivalents
Treated
Sample
Control
Sample
25
KOH
Extract
28.4
0.085
18.9
0.032
Ether
Extract
(
ETH­
1)
5.4
0.016
3.0
0.005
2,4­
D
4.7
0.014
­­
­­
Unaccounted
0.7
0.002
­­
­­
Aqueous
Soluble
(
AQ­
2)
5.7
0.017
5.9
0.010
Precipitate
(
Acid­
Hydrolyzed)
17.4
0.052
9.5
0.017
Ether
Soluble
(
ETH­
2)
0.7
0.002
­­
­­
Aqueous
Soluble
(
AQ­
1)
12.0
0.036
­­
­­

Enzyme
Digestible
Amylase
Digested
2.3
0.007
2.4
0.004
Cellulase
Digested
4.7
0.014
4.7
0.008
Protease
Digested
3.0
0.009
2.4
0.004
Non­
Extractable
Solid
34.8
0.104
40.2
0.068
Acid
Hydrolysis/
Ether
1.3
0.004
1.2
0.002
Acid
Hydrolysis/
Aqueous
21.1
0.063
26.0
0.044
Unknown
(
HPLC
retention
time
2.0­
5.0
min.)
16.4
0.049
­­
­­
Unaccounted
for
HPLC
4.7
0.014
­­
­­
Unaccounted
After
Acid
Hydrolysis
3.7
0.011
­­
­­
Non­
extractable
8.9
0.027
11.2
0.019
Total
Extractable
and
Non­
Extractable
84.3
0.252
79.3
0.134
Lemons:

Proposed
metabolic
pathway
in
lemons
The
registrant
proposed
that
2,4­
D
IPE
is
rapidly
metabolized
in
lemons
treated
postharvest
by
ester
hydrolys
form
2,4­
D
and
small
amounts
of
2,4­
dichlorophenol,
which
are
subsequently
conjugated
and/
or
hydroxylated
the
phenyl
ring.

Lemon
metabolism
study
summary
The
qualitative
nature
of
2,4­
D
IPE
residues
in
stored
lemons
is
adequately
understood
based
on
the
submitte
study
reflecting
registered
use
as
a
plant
growth
regulator.
The
metabolism
in
lemons
is
similar
to
that
obser
in
wheat.
The
residue
to
be
regulated
in
citrus
is
proposed
to
be
2,4­
D.
Refer
to
Table
9
for
the
metabolic
pro
The
total
radioactive
residues
(
TRR,
expressed
as
[
14C]­
2,4­
D
IPE
equivalents)
found
in/
on
stored
lemons
sam
at
various
posttreatment
intervals
(
2
hours,
2
days,
and
1­
24
weeks)
following
postharvest
treatment
on
lemon
ranged
from
2.091
ppm
to
2.834
ppm.
The
extraction
procedures
indicate
that
the
majority
of
the
14C­
residue
w
found
in
the
peel
and
acetone
rinsate
(

95%
of
TRR
collectively)
at
all
sampling
intervals.
The
radioactivity
associated
with
pulp
and
juice
were
minimal
(

5%
of
TRR
collectively).

A
substantial
proportion
of
the
14C­
residues
in
the
peel
and
rinse
(

95%
of
TRR)
was
sufficiently
characterized
and
identified.
The
major
residue
identified
was
2,4­
D
(
24.16%­
67.46%
TRR,
0.623­
1.534
ppm)
which
noticeabl
increased
in
level
at
each
subsequent
sampling
interval.
The
test
substance,
2,4­
D
IPE
(
0.22%­
47.24%
TRR,
0.
1.339
ppm)
declined
at
subsequent
intervals
indicating
rapid
ester
hydrolysis
to
2,4­
D.
Other
minor
metabolit
(
each
<
1%
TRR)
identified
were
2,4­
dichlorophenol,
2,5­
dichloro­
4­
hydroxyphenoxyacetic
acid,
and
2,3­
dichlo
hydroxyphenoxyacetic
acid/
2,4­
dichloro­
5­
hydroxyphenoxyacetic
acid.
2,4­
D
Heptanone
ester
and
the
2,4­
D
dimer
were
identified
and
confirmed
but
not
quantitated.

The
qualitative
nature
of
2,4­
D
IPE
residues
in
stored
lemons
is
adequately
understood
based
on
the
submitte
study
reflecting
registered
use
as
a
plant
growth
regulator.
The
metabolism
in
lemons
is
similar
to
that
obser
in
wheat.
The
residue
recommended
to
be
regulated
in
citrus
is
2,4­
D.
APPENDIX
1:
MARC
BRIEFING
DOCUMENT
26
Excerpt
from
D205343;
MRID
43290501;
lemon
metabolism
following
postharvest
dip;
R.
Perfetti;
24D.
026
Table
9.
Summary
of
characterized/
identified
residues
in/
on
lemons
that
had
been
dipped
in
a
formulation
of
[
14C]­
2,4­
D
IPE
and
wax
and
rinsed
with
acetone.
a
2
hours
posttreatment
2
weeks
posttreatment
10
weeks
posttreatment
20
weeks
posttreatment
Metabolites/
Fractions
%
TRR
ppm
%
TRR
ppm
%
TRR
ppm
%
TRR
ppm
Identified
2,4­
D
IPE
47.24
1.339
0.33
0.008
0.22
0.005
0.22
0.005
2,4­
D
24.16
0.684
26.57
0.623
44.48
1.074
67.46
b
1.534
2,4­
Dichlorophenol
­­
­­
­­
­­
­­
­­
0.76
b
0.017
2,5­
D­
4­
OH
­­
­­
­­
­­
­­
­­
0.46
b
<
0.011
2,3­
D­
4­
OH/
2,4­
D­
5­
OH
­­
­­
­­
­­
­­
­­
0.59
b
<
0.014
2,4­
D
heptanone
ester
­­
­­
N/
Q
c
­­
­­
­­
­­
­­

2,4­
D
dimer
­­
­­
N/
Q
c
­­
­­
­­
­­
­­

Total
Identified
71.40
2.023
26.90
0.631
44.70
1.079
69.49
<
1.581
Characterized
Fraction
I
0.18
0.005
3.04
0.071
6.70
<
0.162
0.11
0.003
Fraction
II
0.76
0.021
3.11
0.073
4.67
<
0.114
3.19
<
0.072
Fraction
III
10.78
0.306
41.87
0.981
34.70
0.839
0.010
<
0.003
Fraction
V
4.89
0.139
5.63
0.133
0.51
0.012
0.99
0.023
Fraction
VII
11.06
0.314
15.66
0.367
3.22
<
0.078
1.57
0.036
Metabolite
A
­­
­­
­­
­­
­­
­­
3.97
0.090
Metabolite
B
­­
­­
­­
­­
­­
­­
5.22
0.119
Metabolite
C
­­
­­
­­
­­
­­
­­
2.73
0.062
Metabolite
D
­­
­­
­­
­­
­­
­­
1.11
0.025
Metabolite
E
­­
­­
­­
­­
­­
­­
0.41
0.009
Metabolite
F
­­
­­
­­
­­
­­
­­
1.48
0.034
Metabolite
G
­­
­­
­­
­­
­­
­­
3.09
0.070
Metabolite
H
­­
­­
­­
­­
­­
­­
0.46
0.010
Metabolite
K
­­
­­
­­
­­
­­
­­
0.83
0.019
EtOAc
soluble
­­
­­
­­
­­
­­
­­
1.71
0.039
Aqueous
soluble
­­
­­
­­
­­
­­
­­
0.73
0.017
Total
Identified/
Characterized
99.07
2.808
96.21
2.256
94.50
<
2.284
97.10
2.212
Non­
extractable
d
0.91
0.026
3.79
0.088
5.45
0.132
2.69
0.061
a
Totals
include
metabolites/
fractions
identified/
characterized
in
the
acetone
rinse.

b
Includes
conjugated
or
bound
analogs
identified
following
hydrolysis.

c
N/
Q
=
Not
quantified;
identification
of
2,4­
D
heptanone
ester
and
2,4­
D
dimer
in
Fraction
II
hydrolysate.

d
Includes
unextracted
juice
and
spent
pulp
from
the
2­
hour
and
2­
week
intervals.
APPENDIX
1:
MARC
BRIEFING
DOCUMENT
27
Potato:

In
the
potato
metabolism
study,
TRR
in
mature
vines
and
tubers
were
6.26
and
0.577
ppm,
respectively,
20
da
following
the
second
of
two
foliar
broadcast
applications
of
[
14C]
2,4­
D
2­
EHE
totaling
0.62
lb
ae/
A
(
4.4x
maxim
labeled
rate).
In
potato
tubers,
solvent
extractable
14C­
residues
accounted
for
>
95%
of
the
TRR.
The
largest
single
component
of
the
extractable
14C­
residues
was
identified
as
2,4­
D
(
42.8­
46.3%
TRR);
minor
portions
we
comprised
of
2,4­
D
EHE
(
0.5­
8.3%
TRR)
and
4­
hydroxy­
2,5­
D
(
6.4%
TRR).
The
remainder
of
the
extractable
radioactivity
was
comprised
of
4­
6
polar
unknowns
together
accounting
for
42.4­
50.4%
of
the
TRR.
Upon
acid
hydrolysis,
these
unknowns
were
converted
to
4­
hydroxy­
2,5­
D
(
14.6%
TRR)
and
4­
chlorophenoxy
acetic
acid
CPA,
24.4%
TRR).
Acid
hydrolysis
of
unextracted
14C­
residues
released
an
additional
8.7%
of
the
TRR,
the
ma
portion
of
which
was
comprised
of
2,4­
D
(
2.3%
TRR),
4­
CPA
(
1.6%
TRR),
and
4­
hydroxy­
2,5­
D
(
0.9%
TRR).
Ple
refer
to
Table
10.

Excerpt
from
D210592;
43496101;
potato
metabolism;
D.
Miller;
2/
22/
96;
24D.
045
Table
10.
Summary
of
characterization/
identification
of
14C­
residues
in
potato
tubers
from
plants
treated
twic
with
[
14C]
2,4­
D
2­
EHE
at
0.31
lb
ae/
A,
for
a
total
of
0.61
lb
ae/
A.

Metabolite
%
TRR
ppm
a
2,4­
D
2­
EHE
0.5
­
8.3
0.003
­
0.048
2,4­
D
acid
45.1
­
46.3
0.260
­
0.267
4­
hydroxy­
2,5­
D
b
15.5
0.089
4­
CPA
b
26.0
0.150
Total
identified
87.1
­
96.1
0.503
­
0.554
Polar
unknowns
b
10.5
c
0.060
Solids
5.4­
6.4
0.031­
0.037
a
Expressed
as
2,4­
D
acid
equivalents.
b
Metabolites
and
unknowns
isolated
following
acid
hydrolysis
of
ACN
extractable
residues
and
solvent
extracted
solids.
c
Comprised
of
at
least
nine
unknowns
each
accounting
for
0.2­
2.8%
of
the
TRR.

CONFINED
ROTATIONAL
CROPS
Excerpt
from
D207980
re:
Confined
rotational
crops/
D.
Miller/
24D.
040
Radioactive
residues
in
lettuce,
radishes,
and
wheat
were
<
0.001­
0.06
ppm
and
0.01­
0.084
ppm
from
plantings
made
30
and
139
days,
respectively,
following
an
application
of
[
14C]
2,4­
D
to
a
sandy
loam
soil
at
2.17
lb
ae/
A
the
maximum
label
rate).
Radioactive
residues
were
adequately
characterized
in
all
crop
matrices.
The
major
the
14C­
residues
were
characterized
as
either
aqueous­
soluble
or
unextractable
and
reflected
the
incorporatio
radioactivity
into
natural
components.
In
wheat
grain,
radioactivity
incorporated
into
starch
accounted
for
69
of
the
TRR,
and
6­
34.6%
of
the
TRR
was
associated
with
isolated
cellulose
and
lignin
fractions
from
lettuce,
ra
tops,
and
wheat
straw
from
the
30­
day
PBI
and
wheat
forage
and
straw
from
the
139­
day
PBI.
Acidic
organic
fractions,
which
would
have
contained
2,4­
D
residues,
were

0.004
ppm
in
all
matrices
from
both
PBIs
followi
either
direct
solvent
extraction
or
acid
hydrolysis
and
solvent
extraction.
Aqueous
EtOH
soluble
residues
we
0.003­
0.017
ppm,
and
were
only
>
0.01
ppm
in
radish
tops
(
30­
day
PBI)
and
wheat
straw
(
30­
and
139­
day
PBIs)
Organosoluble
residues
released
by
hydrolysis
of
solvent
extracted
solids
also
accounted
for
minor
amounts
radioactivity
(<
10%
TRR
and
<
0.01
ppm).
The
only
metabolites
detected
in
any
matrix
were
2,4­
D
and
2,4­
dichloroanisole,
which
were
each
detected
at
0.0005
ppm
following
acid
hydrolysis
of
EtOH/
H
2
O
soluble
residues
from
radish
tops.

LIVESTOCK
METABOLISM
APPENDIX
1:
MARC
BRIEFING
DOCUMENT
28
Ruminant
metabolism:

EXCERPT
FROM
D191013;
42749701;
RUMINANT
METABOLISM;
24D.
006
In
the
ruminant
metabolism
study,
a
lactating
goat
was
dose
orally
with
[
14C]
2,4­
D
for
three
consecutive
days
level
equivalent
to
483
ppm
in
the
diet
(~
0.6x
the
maximum
theoretical
dietary
burden).
At
sacrifice,
the
TRR
w
0.224
ppm
in
liver,
1.44
ppm
in
kidney,
0.037
ppm
in
muscle,
0.088
ppm
in
fat,
and
0.020
ppm
in
milk
(
Day
3).
major
residue
in
milk
and
tissues
was
2,4­
D,
accounting
for
47%
TRR
in
milk,
20.5%
TRR
in
liver,
52.7%
TRR
in
kidney,
45.4%
TRR
in
fat,
and
37.8%
TRR
in
muscle
(
Table
11).
Minor
amounts
of
2,4­
DCP
were
also
tentativel
identified
in
milk
(
5%
TRR)
and
fat
(
2.3%
of
TRR),
and
4­
CPA
was
identified
in
milk
(
6.9%
TRR).
Several
other
polar
components
(
designated
NP1,
NP2,
and
NP3)
were
detected
in
tissues;
however,
these
metabolites
may
the
result
of
uptake
of
non­
polar
impurities
known
to
be
present
in
the
test
material.

Table
11.
Summary
of
14C­
residue
identification/
characterization
in
goat
milk
and
tissues.

Milk
(
day­
3)
Liver
Kidney
Fat
Muscle
Component
%
TRR
ppm
%
TRR
ppm
%
TRR
ppm
%
TRR
ppm
%
TRR
ppm
2,4­
D
47.0
0.095
20.5
0.046
53.6
0.773
45.4
0.040
37.8
0.014
2,4­
dichloro­
phenol
5.0
0.010
­­
­­
­­
­­
2.3
0.002
­­
­­

p­
CPA
6.9
0.014
­­
­­
a
­­
­­
­­
­­
­­
­­

Total
identified
58.9
0.119
20.5
0.046
53.6
0.773
47.7
0.042
37.8
0.014
Nonpolar
1
1.0
0.002
14.7
0.033
10.3
0.148
3.4
0.003
2.7
0.001
Nonpolar
2
­­
­­
17.9
0.040
22.0
0.317
13.6
0.012
24.3
0.009
Nonpolar
3
­­
­­
5.4
0.012
4.1
0.059
­­
­­
­­
­­

Unknowns
5.5
0.011
6.7
0.015
­­
­­
3.3
0.003
­­
­­

Total
67.9
0.137
65.2
0.146
90.0
1.297
68.0
0.060
64.8
0.024
a
Detected
at
6.3%
(
0.014
ppm)
in
the
preliminary
liver
extraction.

Poultry
metabolism:

EXCERPT
FROM
D186732;
42605201;
POULTRY
METABOLISM;
24D.
004
In
the
poultry
metabolism
study,
laying
hens
were
dosed
orally
with
[
14C]
2,4­
D
for
seven
consecutive
days
at
levels
equivalent
to
18.3
ppm
in
the
diet
(
11.4x
the
maximum
theoretical
dietary
burden).
At
sacrifice,
the
TRR
were
0.0297
ppm
in
liver,
0.714
ppm
in
kidney,
<
0.002
ppm
in
breast
muscle,
0.008
ppm
in
thigh
muscle,
0.027
ppm
in
fat,
and
0.0178
ppm
in
eggs.
The
major
identified
component
in
eggs
and
tissues
was
2,4­
D,
accounti
23.0%
TRR
in
eggs,
25.1%
TRR
in
fat,
18.2%
TRR
in
liver,
and
75.6%
TRR
in
kidney
(
Tables
12­
15).
Minor
amou
of
2,4­
DCP
were
also
identified
in
eggs
(
7.3%
TRR)
and
liver
(
4.4%
TRR).

Table
12.
Distribution
of
14C­
residues
in
the
eggs
of
laying
hens
administered
[
14C]
2,4­
D.

Fractions
and
Metabolites
TRR,
[
14C]
2,4­
D
equivalents
%
ppm
Composited
Day­
7
Egg
TRR
100.0
0.0178
Initial
Ether
Extract
(
EO1)
84.8
0.0151
Acetonitrile
Extract
(
ACN­
HPLC)
51.7
0.0092
2,4­
D
23.0
0.0041
2,4­
dichlorophenol
7.3
0.0013
Unidentified
2.8
0.0005
Unaccounted
by
HPLC
19.1
0.0034
Ether­
soluble
(
POSTEO1)
24.2
0.0043
Unaccounted
following
Cleanup
9.0
0.0016
Post­
extract
Aqueous
Filtrate
(
EA2)
1.7
0.0003
APPENDIX
1:
MARC
BRIEFING
DOCUMENT
29
Tissue
Unextractable
(
PE)
16.3
0.0029
Total
Extractable
and
Unextractable
(
sum
of
EO1,
EA2,
and
PE)
102.8
0.0183
Total
Identified
a
30.3
0.0054
Total
Unidentified
a,
b
41.6
0.0079
Total
Unaccounted
a
28.1
0.0050
a
Calculated
by
the
study
reviewer.
b
Calculations
based
on
100%
recovery.

Table
13.
Distribution
of
14C­
residues
in
the
fat
of
laying
hens
administered
[
14C]
2,4­
D.

Fractions
and
Metabolites
TRR,
[
14C]
2,4­
D
equivalents
%
ppm
Composited
Fat
TRR
100.0
0.0271
Initial
Acetonitrile
Extract
(
EO1)
21.8
0.0059
Ether
(
EO2,
after
base
hydrolysis
of
EO1
aqueous
phase)
81.9
0.0222
Hexane
(
EO2­
Hex)
17.3
0.0047
Chloroform
(
EO2­
CH)
13.3
0.0036
Aqueous
(
EO2­
H
2
O)
8.9
0.0024
Acetonitrile
(
EO2­
ACN)
31.4
0.0085
2,4­
D
25.1
0.0068
Unaccounted
by
HPLC
6.3
0.0017
Non­
extractable
<
0.1
<
MQL
a
Total
Extractable
and
Non­
extractable
(
sum
of
EO1
and
EO2)
103.7
0.0281
Total
Identified
b
25.1
0.0068
Total
Unidentified
b,
c
68.6
0.0196
Total
Unaccounted
(
reported
by
registrant)
6.3
0.0017
a
MQL
=
Minimum
Quantifiable
Limit
by
LSS,
25.7
dpm.
b
Calculated
by
study
reviewer.
c
Calculations
based
on
100%
recovery.

Table
14.
Distribution
of
14C­
residues
in
the
liver
of
laying
hens
administered
[
14C]
2,4­
D.

Fractions
and
Metabolites
TRR,
[
14C]
2,4­
D
equivalents
%
ppm
Composited
Liver
TRR
100
0.0297
Initial
Ether
Extract
(
EO1)
53.9
0.0160
HPLC
Analyzable
(
chloroform
extract
after
repeated
fractionation
of
EO1)
34.7
0.0103
2,4­
D
a,
b
18.2
0.0054
2,4­
dichlorophenol
a
4.4
0.0013
Unaccounted
by
HPLC
11.8
0.0035
Aqueous­
soluble
(
EO1­
EA1,
sum
of
two
fractions
obtained
after
repeated
fractionation
of
EO1)
7.1
0.0021
Insoluble
Residue
c
2.0
0.0006
Unaccounted
after
Clean
up
9.8
0.0029
Ether
(
EO2,
following
acid
hydrolysis
of
unextractable
residues)
29.0
0.0086
Aqueous
(
EA1,
remaining
after
aqueous
partitioning
and
filtering
of
EO2)
d
­­
<
MQLe
Tissue
Non­
extractable
(
PE)
8.4
0.0086
Total
Extractable
and
Non­
extractable
(
sum
of
EO1,
EO2,
and
PE)
91.3
0.0271
Total
Identified
22.6
0.0067
Total
Unidentified
47.1
0.0140
Total
Unaccounted
(
reported
by
registrant)
21.6
0.0064
a
Identified
by
HPLC.
b
Identified
by
TLC.
c
Data
not
accounted
for
in
the
registrant's
flow
chart
but
were
included
in
the
registrant's
summary
table.
d
Data
not
listed
on
registrant's
summary
table
but
were
included
on
registrant's
flow
chart.
e
MQL
=
Minimum
Quantifiable
Limit
by
LSS,
25.7
dpm.
APPENDIX
1:
MARC
BRIEFING
DOCUMENT
30
Table
15.
Distribution
of
14C­
residues
in
the
kidney
of
laying
hens
administered
[
14C]
2,4­
D.

Fractions
and
Metabolites
TRR,
[
14C]
2,4­
D
equivalents
%
ppm
Composited
Kidney
TRR
100.0
0.7140
Initial
Ether
Extract
(
EO1)
11.6
0.0826
HPLC
Analyzable
(
after
TLC
purification)
a
2.6
0.0188
2,4­
D
b
0.1
0.0008
Three
Unknowns
c
0.4
0.0026
Unaccounted
by
HPLC
0.9
0.0063
Unaccounted
after
cleanup
8.9
0.0638
Ether
(
EO2,
following
acid
hydrolysis
of
aqueous
extract
of
EO1)
58.0
0.414
2,4­
D
b,
d,
e
57.3
0.4090
One
Unknown
0.7
0.0050
Ether
(
EO3,
following
base
hydrolysis
of
aqueous
extract
of
EO2)
16.7
0.119
2,4­
D
b
16.7
0.119
Ether
and
Acetonitrile
(
EO4
and
EO5)
4.5
0.0319
HPLC
Analyzable
(
after
acidification
and
chloroform
extraction)
1.5
0.0107
2,4­
D
b
1.5
0.0107
Aqueous­
soluble
(
EA45TL)
0.9
0.0062
Insoluble
Residue
(
45­
PE)
0.5
0.0034
Unaccounted
after
Cleanup
1.6
0.0116
Aqueous­
soluble
(
EA1
and
EA3,
combined
aqueous
filtrates
after
repeated
fractionation)
1.4
0.0102
Tissue
Unextractable
(
PE)
0.1
0.0009
Total
Extractable
and
Unextractable
(
sum
of
EO1,
EO2,
EO3,
EO4,
EO5,
and
PE)
92.3
0.659
Total
Identified
f
76.9
0.5487
Total
Unidentified
f
11.7
0.0836
Total
Unaccounted
(
reported
by
registrant)
11.4
0.0817
a
Data
not
accounted
for
in
the
registrant's
flow
chart
but
were
included
in
the
registrant's
summary
table.
b
Identified
by
HPLC.
c
Sum
of
three
unknowns
respectively
accounting
for
0.1%
of
TRR
(
0.0008
ppm),
0.1%
of
TRR,
(
0.0007
ppm),
and
0.2%
of
TRR
(
0.0011
ppm).
d
Identified
by
TLC.
e
Confirmed
by
GC­
MS.
f
Calculated
by
the
study
reviewer.

WATER,
FISH,
AND
IRRIGATED
CROPS
Nature
of
the
Residues
in
Fish
and
Shellfish.
In
summary,
the
metabolism
of
2,4­
D
in
fish
is
adequately
understood
(
Table
16).
The
TRR
was
0.406
ppm
in
bluegill
sunfish
fillets
exposed
to
10.6
ppm
of
[
14C]
2,4­
D
un
static
conditions
for
4
consecutive
days.
Approximately
95%
of
the
TRR
was
extractable
and
90%
of
the
TRR
identified/
characterized
by
HPLC.
The
principal
residue
was
2,4­
D,
accounting
for
80%
of
the
TRR
(
0.325
ppm
2,4­
DCP
accounted
for
8%
of
the
TRR
(
0.032
ppm).
The
identities
of
the
metabolites
were
confirmed
by
GC/
MS
The
registrant
also
tentatively
identified
radioactive
residues
in
fish
viscera.
In
viscera,
100%
of
the
TRR
was
extractable.
2,4­
D
and
2,4­
DCP
each
accounted
for
approximately
30%
of
the
TRR
and
a
mixture
of
CPAA
and
accounted
for
40%
of
the
TRR.
The
registrant
suggested
that
the
additional
metabolites
detected
in
the
visce
were
due
to
microbial
degradation.
Literature
was
cited
to
support
this
hypothesis.
The
2,4­
D
metabolic
path
in
fish
is
proposed
by
the
registrant
to
proceed
via
formation
of
2,4­
DCP
and
conjugates
of
2,4­
D
and
2,4­
DCP
Based
on
these
data,
the
residues
to
be
regulated
in
fish
and
shellfish
are
the
same
as
in
livestock
and
are
recommended
to
include
both
free
and
conjugated
2,4­
D.

Excerpt
from
D208093;
MRID
43378801;
fish
metabolism;
24D.
027;
R.
Perfetti
APPENDIX
1:
MARC
BRIEFING
DOCUMENT
31
Table
16.
Summary
of
characterization/
identification
of
14C­
residues
in
fillet
samples
from
bluegill
sunfish
do
with
[
14C]
2,4­
D
at
10.6
ppm
for
four
consecutive
days.

Metabolite/
Component
%
TRR
ppm
2,4­
D
80.0
0.325
2,4­
DCP
7.9
0.032
Total
identified
87.9
0.357
Polar
Unknowns
2.2
0.009
Solids
0.0
<
LOQ
Magnitude
of
Residues
in
Fish
and
Shellfish.
Adequate
studies
are
available
depicting
the
magnitude
of
2,4­
D
residues
in
catfish,
bluegill
sunfish,
crayfish,
and
clams
exposed
to
water
containing
6.0
ppm
of
2,4­
D
in
a
s
system.
The
maximum
supported
rate
for
aquatic
uses
of
2,4­
D
is
10.8
lb
ae/
acre
ft,
which
is
equivalent
to
a
concentration
of
4
ppm.
Therefore,
the
studies
were
conducted
at
1.5x
the
maximum
concentration.
In
the
tw
studies,
2,4­
D
residues
in
edible
tissues
plateaued
within
6
hours
for
both
species
of
fish,
12
hours
for
clams,
8
days
for
crayfish.
During
the
15­
day
exposure
in
one
test,
maximum
2,4­
D
residues
in
edible
tissues
were
0
ppm
in
catfish,
0.067
ppm
in
bluegill
sunfish,
and
1.1
ppm
in
crayfish.
During
the
28­
day
exposure
in
another
maximum
2,4­
D
residues
in
edible
tissues
were
0.59
ppm
in
clams
and
1.18
ppm
in
crayfish.
Based
on
exposu
6
ppm
(
1.5x),
these
studies
support
tolerances
for
2,4­
D
residues
in
fish
at
0.1
ppm
and
in
shellfish
at
1.0
ppm
Residues
in
Water.
The
Office
of
Ground
Water
and
Drinking
Water
has
established
a
Maximum
Contaminant
Level
of
0.07
ppm
for
2,4­
D
in
drinking
water.
The
aquatic
use
patterns
currently
being
supported
by
the
Task
Force
II
also
prohibit
the
use
of
2,4­
D
treated
water
for
use
as
potable
water
unless
an
approved
assay
indicat
that
2,4­
D
concentrations
are

0.07
ppm.

Data
pertinent
to
residues
in
water
were
reviewed
in
the
Residue
Chemistry
Chapter
of
the
1988
2,4­
D
Reregistration
Standard.
This
information
along
with
other
previous
reviews
was
summarized
in
an
HED
amended­
use
petition
review
(
CBTS
No.
9026,
3/
3/
92,
G.
Otakie).
In
studies
by
the
Department
of
the
Army,
application
of
the
DMA
salt
to
ponds
at
4
lb
ae/
A
resulted
in
2,4­
D
residues
of
0.39
ppm
1­
3
days
after
treatmen
0.4
ppm
after
7
days,
and
0.1
ppm
after
14
days.
Application
at
8
lb
ae/
A
resulted
in
2,4­
D
residues
of
0.69
ppm
days
after
treatment,
0.395
ppm
after
7
days,
and
0.013
ppm
after
14
days.
After
28
days
following
either
treatment,
residues
were
<
0.005
ppm.
In
another
study,
application
of
the
DMA
salt
to
two
TVA
reservoirs
at
4
ae/
A
resulted
in
residues
of
up
to
1.2
ppm
1
hour
post­
treatment,
4.8
ppm
at
8
hours,
1.8
ppm
at
24
hours,
and
0.67,
0.24,
and
0.018
ppm,
respectively,
at
2
weeks,
4
weeks,
and
2
months
after
treatment.
In
a
Bureau
of
Reclamation
study,
reservoir
water
treated
with
the
DMA
salt
or
butoxyethyl
ester
at
40
lb
ae/
A
had
residues
o
to
0.22
ppm
after
1
day,
0.09
ppm
after
4
days,
and
0.01
ppm
after
14
days.
Treatment
of
lakes
in
three
states
lb
ae/
A,
yielded
samples
containing
3.8
ppm
of
2,4­
D
one
day
after
treatment,
1.1
ppm
after
4
days,
and
0.052
p
after
7­
14
days,
and
at
reservoir
outlets,
maximum
residues
were
0.015
ppm
throughout
the
study.
The
1992
review
of
the
above
data
concluded
that
rates
of
up
to
40
lb
ae/
A
could
be
extended
to
sites
outside
the
TVA
system,
provided
that
use
is
restricted
to
Federal,
State,
or
local
agencies
or
applicators
under
their
control.
Official
Agency
oversight
of
this
aquatic
use
was
deemed
necessary
owing
to
the
relatively
high
2,4­
D
concentrations
in
water
observed
initially
after
treatment
and
the
need
to
control
treatment
and
subsequent
w
uses.

Irrigated
Crops:
The
Residue
Chemistry
Chapter
of
the
2,4­
D
Reregistration
Standard
previously
determined
that
residues
of
2,4­
D
at
up
to
0.5
ppm
are
expected
in
irrigation
water
derived
from
2,4­
D
treated
ponds,
lakes
reservoirs.
Citing
the
data
from
numerous
studies
on
crops
irrigated
with
2,4­
D
treated
water,
the
Agency
tentatively
concluded
that
tolerances
for
irrigated
crops
should
be
established
at
1
ppm
for
crop
groups
and
the
individual
miscellaneous
crops.
However,
the
aquatic
use
patterns
currently
being
supported
by
the
Task
Force
II
prohibit
the
use
of
2,4­
D
treated
water
for
irrigation
unless
an
approved
assay
indicates
that
2,4­
D
concentrations
are

0.1
ppm.

RAT
METABOLISM
APPENDIX
1:
MARC
BRIEFING
DOCUMENT
32
From
5/
8/
03
L.
Taylor
memo/
DER
(
TXR
No.
0051543)
re.
rat
and
dog
metabolism
and
pharmacokinetics:

EXECUTIVE
SUMMARY:
In
a
pharmacokinetics/
metabolism
study
(
MRID
45840901),
(
14C)
2,4­
D
[
98%%
a.
i.,
lot
#
45B;
(
14C)
batch
#
011022,
specific
radioactivity
9.206
MBq/
mg),
ring
labeled]
was
administered
to
18
male
and
female
Fischer­
strain
rats
[
CDF
Crl:
BR
(
F­
344)]
and
4
per
sex
pure­
bred
beagle
dogs
once
via
gavage
at
dose
levels
of
0,
5,
and
50
mg/
kg.

There
were
no
overt
signs
of
toxicity
in
either
species
or
sex
at
either
dose
level.
Essentially
all
of
the
radiolab
was
recovered
from
the
rats,
while
approximately
half
was
recovered
from
the
dogs
[
dog
carcasses
were
not
monitored].
Plasma
levels
of
radiolabel
reached
maximum
concentration
at
1hour
[
low
dose]
and
2
hours
[
hig
dose]
post
dose
in
rats
of
both
sexes.
Maximum
plasma
concentrations
of
radiolabel
in
the
dog
were
attained
5.5
hours
[
males]/
6.0
hours
[
females]
at
the
low
dose
and
8.0
hours
[
males]/
10
hours
[
females]
at
the
high­
dos
both
the
rat
and
dog,
clearance
of
radiolabel
from
plasma
was
slightly
more
prolonged
in
females
than
in
mal
both
dose
levels.
In
the
rat,
pharmacokinetic
parameters
were
not
linear
with
respect
to
dose
level.
A
10­
fold
increase
in
dose
resulted
in
an

60­
fold
increase
in
AUC
and
an

20­
fold
increase
in
C
max,
suggesting
that
a
clearance
mechanism
was
saturated
at
the
high­
dose
level
in
the
rat.
In
contrast,
the
pharmacokinetic
parame
in
the
dog
were
essentially
proportional
with
the
10­
fold
increase
in
dose
level,
with
a
similar
increase
in
both
and
C
max.

The
majority
of
the
radiolabel
was
excreted
in
the
urine
of
both
male
[
low

77%/
high

73%]
and
female
[
low

73%/
high
57%]
rats
at
both
dose
levels
and
both
sexes
of
dogs
at
the
low­
dose
level
[
males
35%/
females
36%
Of
the
amount
excreted
via
the
urine,
greater
than
90%
was
excreted
by
12
hours
post
dose
in
the
low­
dose
ra
[
both
sexes]
and
high­
dose
male
rats,
while
the
high­
dose
female
rats
excreted
only
79%
by
12
hours
post
do
[
96%
by
24
hours
post
dose].
In
the
dog,
of
the
amount
excreted
via
the
urine,
less
than
15%
was
excreted
by
hours
post
dose.
Elimination
of

80%
of
the
dose
via
the
urine
by
the
dogs
was
not
attained
until
96
hours
po
dose
in
both
sexes
and
both
dose
levels
[
low
males
84%/
females
83%;
high
males
80%/
females
84%].
Less
tha
2.5%
of
the
radiolabel
was
excreted
in
the
feces
of
male
rats
at
both
dose
levels,
and
the
low­
dose
female
rats
excreted

3.4%
via
the
feces.
High­
dose
female
rats
excreted

8.4%
via
the
feces.
Of
the
amount
of
radiolabel
excreted
via
the
feces,
the
majority
was
excreted
by
12
hours
post
dose
in
both
the
low­
[
76%]
and
high­
[
66%
dose
male
rats.
Of
the
amount
of
radiolabel
excreted
via
the
feces
in
the
low­
dose
females,
only
9%
was
eliminated
by
12
hours
post
dose;
83%
was
eliminated
by
the
24­
hour
timepoint.
For
the
high­
dose
female
rat
52%
was
excreted
by
the
12­
hour
time
point
and
27%
by
the
24­
hour
time
point.
In
the
dogs,
excretion
via
the
feces
occurred
throughout
the
duration
of
the
study.
Low­
dose
male
[
13.03%]
and
female
[
10.08%]
dogs
excre
about
half
the
amount
of
radiolabel
via
the
feces
as
did
the
high­
dose
male
[
25%]
and
female
[
21.27%]
dogs.
A
120
hours
post
dose,
the
amount
eliminated
via
the
feces
[
both
sexes]
was
15%
at
the
low
dose
and
11%
[
males]/
13%
[
females]
at
the
high
dose.
At
the
high­
dose
level,
the
greatest
amount
excreted
via
the
feces
occurred
at
the
48­
and
72­
hour
timepoints
post
dose
in
both
sexes
of
the
dog.
At
the
low­
dose
level,
the
grea
amount
excreted
via
the
feces
also
occurred
at
the
48­
and
72­
hour
timepoints
post
dose
in
the
male
dogs,
wh
comparable
amounts
[

20%]
were
excreted
at
the
24­,
48,
and
72
hour
timepoints
in
the
low­
dose
females.
Females
of
both
sexes
displayed
a
slower,
more
prolonged
clearance
from
the
plasma
than
the
males,
althoug
the
difference
between
the
sexes
was
more
pronounced
in
the
rat
than
in
the
dog.

At
the
50
mg/
kg
dose
level,
clearance
was
clearly
reduced
[
males
41

g/
g/
females
21

g/
g]
compared
to
the
5
mg/
kg
dose
level
[
males
238

g/
g;
females
88

g/
g]
in
both
sexes
of
rat,
suggesting
that
a
clearance
mechanis
was
saturated
at
the
higher
dose
level
in
the
rat.
The
dogs
displayed
comparable
clearance
at
both
dose
level
indicating
that
both
dose
levels
saturated
a
clearance
mechanism
[
males
1.0

g/
g
at
low;
1.5

g/
g
at
high
dos
Metabolism
was
minimal
in
the
rat,
with
2,4­
D
being
excreted
in
the
urine
basically
unchanged.
In
the
dog,
numerous,
minor,
metabolites
of
2,4­
D
were
excreted
in
the
urine,
with
the
main
metabolic
route
being
by
conjugation.
The
major
components
in
the
dog
urine
were
the
glycine
conjugate
and
the
parent
compound.
T
other
identified
metabolites
were
the
glutamic
acid,
serine,
and
taurine
conjugates
of
2,4­
D,
the
sulphate
and
glucuronide
conjugates
of
the
de­
acetylated
parent
compound,
and
the
cysteine
conjugate
of
the
de­
chlorina
and
de­
acetylated
parent.

This
metabolism/
pharmacokinetics
study
in
the
rat
and
dog
is
classified
acceptable/
non­
guideline.
The
study
designed
specifically
to
(
1)
compare
the
rat
and
dog
with
respect
to
the
excretion
of
2,4­
D
and
(
2)
address
the
APPENDIX
1:
MARC
BRIEFING
DOCUMENT
33
issue
of
the
relevancy
of
the
dog
data
for
risk
assessment.
As
such,
the
study
fulfilled
its
objectives.
However
did
not
satisfy
the
guideline
requirement
for
a
metabolism/
pharmacokinetics
study
[
OPPTS
870.7485,
OECD
4
in
rats
[
and
dogs].
It
was
classified
non­
guideline
because
no
tissues
were
monitored,
other
than
plasma/
bloo
and
the
carcass
of
the
dogs
was
not
monitored.

DRINKING
WATER
RESIDUE
CHARACTERIZATION:

EFED
RESPONSES
TO
MARC
MEETING
QUESTIONNAIRE
In
order
to
determine
which
degradates,
if
any,
should
be
included
in
the
human
drinking
water
exposure
assessment,
please
answer
the
following
questions
to
the
best
of
your
ability
and
create
tables
using
the
for
provided
below.

1.
What
is
the
name
of
the
pesticide
and
what
uses
are
being
considered
in
this
assessment?

2,4­
D
is
an
herbicide
used
on
a
wide
variety
of
crops.
EECs
from
aquatic
exposure
modeling
for
terrestrial
use
2,4­
D
was
performed
by
modeling
with
PRZM/
EXAMS.
Specific
uses
chosen
for
aquatic
exposure
modeling
include
sugarcane
in
Florida,
turf
in
Florida
and
Pennsylvania,
spring
wheat
in
North
Dakota,
winter
wheat
in
Oregon,
corn
in
Illinois
and
California,
sorghum
in
Kansas
and
Texas,
soybean
in
Mississippi,
pasture
in
Nor
Carolina,
apples
in
North
Carolina,
Oregon,
and
Pennsylvania,
and
filberts
in
Oregon.
Although
this
only
represents
a
portion
of
the
crops
for
which
2,4­
D
has
a
labeled
use,
it
does
represent
crops
with
higher
application
rates
and
crops
which
have
a
large
percentage
of
their
total
acreage
treated
with
2,4­
D.
Some
crop
with
large
total
acreage
treated
were
also
included
as
modeled
scenarios.
These
crops
were
also
chosen
to
represent
a
wide
geographic
area,
thus
encompassing
a
variety
of
environmental
conditions.
By
encompassin
crops
with
large
percentages
of
acreage
treated
with
2,4­
D
and
a
large
geographic
area,
some
crops
with
lowe
maximum
application
rates
were
also
covered
in
the
set
of
scenarios.

2.
Briefly
describe
the
environmental
persistence
of
the
pesticide.
What
are
expected
to
be
the
major
routes
degradation
in
the
environment
(
e.
g.
aerobic
soil
metabolism,
soil
photolysis,
etc)?
What
is
the
expected
persistence
in
soil
and
water
(
provide
available
half
lives)?

2,4­
D
is
non­
persistent
(
t
1/
2=
6.2
days)
in
terrestrial
environments,
moderately
persistent
(
t
1/
2=
45
days)
in
aerobi
aquatic
environments,
and
highly
persistent
(
t
1/
2=
231
days)
in
anaerobic
terrestrial
and
aquatic
environments
3.
Briefly
describe
the
expected
mobility
of
the
pesticide.
Is
the
pesticide
volatile?
Does
the
pesticide
bind
s
sediment
strongly
(
please
provide
Kd
or
Koc)?

Because
2,4­
D
will
be
anionic
(
X­
COO­
H+)
under
most
environmental
conditions,
it
is
expected
to
be
highly
m
(
K
oc=
41)
in
soil
and
aquatic
environments.

4.
Briefly
describe
the
degradates
of
the
pesticide.
Identify
major
and
minor
degradates.
Provide
available
information
regarding
degradate
stability
and
mobility.

The
2,4­
D
degradates
detected
in
the
various
fate
studies
were
1,2,4­
benzenetriol,
2,4­
dichlorophenol
(
2,4­
DC
2,4­
dichloroanisole
(
2,4­
DCA),
chlorohydroquinone
(
CHQ),
4­
chlorophenol,
volatile
organics,
bound
residues,
carbon
dioxide.
See
Tables
18
and
19
for
chemical
name,
structure,
and
maximum
percents
of
applied
radioactivity
contributed
by
each
degradate
in
several
environmental
fate
laboratory
studies.

5.
If
possible,
describe
the
effects
of
water
treatment
on
the
pesticide
and
degradates
that
may
reach
drinking
water
sources.
APPENDIX
1:
MARC
BRIEFING
DOCUMENT
34
EFED
is
in
the
process
of
evaluating
whether
there
are
treatment
effects
for
2,4­
D
or
any
of
its
degradates.

6.
Provide
any
other
pertinent
information
(
e.
g.
monitoring
data).

Monitoring
data
considered
in
the
assessment
were
the
NAWQA
groundwater
and
surface
water
database,
USGS/
EPA
reservoir
monitoring
database,
National
Drinking
Water
Contaminant
Occurrence
Database
(
NCOD
and
STORET.
A
preliminary
review
of
the
databases
was
conducted
to
provide
peak
and
median
concentrati
and
is
summarized
in
Table
17.
A
more
extensive
review
of
the
data
is
presented
in
the
sections
which
follow
Additionally,
the
quality
of
data
(
especially
with
STORET)
needs
to
be
evaluated
for
targeting
pesticide
use
ar
detection
limits,
and
analytical
recoveries.

The
monitoring
data
indicates
2,4­
D
is
detected
in
ground
and
surface
water.
Also,
2,4­
D
is
detected
in
finish
drinking
water.
Maximum
concentrations
of
2,4­
D
in
surface
source
water
and
ambient
ground
water
are
58
u
and
14.8
ug/
l,
respectively.
The
highest
2,4­
D
concentrations
(
20000
ug/
l)
determined
to
be
present
in
the
preliminary
analysis
from
the
STORET
database
reflect
the
detection
limit
rather
than
actual
concentrations.
highest
detection
in
STORET
reported
above
the
detection
limit
without
qualification
is
7500
ug/
l
in
groundwa
however,
this
value
is
of
questionable
validity
and
is
not
recommeded
for
use
in
the
risk
assessment.
The
hig
median
2,4­
D
concentration
of
1.18
ug/
l
was
derived
from
finished
water
samples
in
the
NCOD
database.
The
highest
TWM
concentration
was
1.45
ug/
l
from
the
NAWQA
data.
It
is
important
to
note
the
maximum
contam
level
(
MCL)
for
2,4­
D
is
70
ug/
l.

Table
17:
Preliminary
Analysis
of
Available
Monitoring
Data
Data
Source
Peak
Concentration
(
ug
ae/
L)
Median
Concentration
(
ug
ae/
L)
TWM
Concentration
(
ug
ae/
L)

Groundwater
NAWQA
14.8
0.035
NA
NCOD
(
finished)
8
0.87
NA
STORET
7500*
0.1
NA
Surface
Water
NAWQA
15
0.035
1.45
USGS/
EPA
Reservoir
Raw
Water
0.414
0.077
0.15
Finish
Water
0.634
0.077
0.12
NCOD
(
finished)
58
1.18
NA
STORET
330*
0.01
NA
*
Maximum
values
in
STORET
are
not
recommended
for
exposure
estimates
given
uncertainty
in
data
quality.
Values
rep
are
for
comparison
with
model
estimates
and
other
monitoring
data
only.

7.
Complete
the
table
for
the
pesticide
and
degradates.

Table
18.
Environmental
Degradates
of
2,4­
D
Acid
APPENDIX
1:
MARC
BRIEFING
DOCUMENT
2
%
AR
=%
of
applied
radioactivity.

35
Confirmed
Degradate
Lab
Results
Max
%
AR2
(
Study)
Chemical
Structure
1,2,4­
benzenetriol
37
(
aqueous
photolysis
at
pH
7)

2,4­
dichlorophenol
(
2,4­
DCP)
3.5
(
aerobic
soil)
33
(
anaerobic
aquatic
soil
metabolism,
water
+
sediment)
5
(
aerobic
aquatic
soil
metabolism,
sediment)

2,4­
dichloroanisole
(
2,4­
DCA)
2.8
(
aerobic
soil)

chlorohydroquinone
(
CHQ)
16
(
aerobic
aquatic
soil
metabolism,
water)

Bound
residues
1.0
(
soil
photolysis)
60
(
aerobic
soil)
41
(
anaerobic
aquatic
metabolism)
39
(
aerobic
aquatic
metabolism)

Carbon
Dioxide
25
(
aqueous
photolysis)
5
(
soil
photolysis)
50
(
aerobic
soil)
31
(
anaerobic
aquatic
metabolism)
16
(
aerobic
aquatic
soil
metabolism)
APPENDIX
1:
MARC
BRIEFING
DOCUMENT
36
Volatile
compounds
4­
chlorophenol
2,4­
DCA
1.9
(
anaerobic
aquatic
metabolism)
1.9
(
anaerobic
aquatic
metabolism)

Table
19.
Profiles
of
2,4­
D
and
Its
Degradates
from
Several
Environmental
Fate
Studies.

Confirmed
Degradate
Maximum
%
of
Applied
Radioactivity
Aqueous/
soil
photolysis
(
two
studies)
Aerobic
aquatic
metabolism
Anaerobic
aquatic
met.
+
volatile
Aerobic
soil
metabolism
1,2,4­
benzenetriol
37/­­
 
 
 
2,4­
dichlorophenol
 
5
33
+
1.9
3.5
2,4­
dichloroanisole
 
 
 
2.8
chlorohydroquinone
 
16
 
 
Carbon
dioxide
25/
5
16
31
+
0
50
4­
chlorophenol
 
 
0
+
1.9
 
Bound
residues
 
/
1.0
39
41
+
0
60
AQUATIC
FIELD
DISSIPATION
STUDIES
In
order
to
determine
the
relative
maximum
observed
concentrations
of
2,4­
D
compared
to
those
of
the
water
soil
degradates
occurring
in
the
"
real
world",
EFED
provided
brief
summaries
of
several
aquatic
field
dissipat
studies.
These
are
summarized
below.
Note
that
2­
butoxyethanol
and
dimethylamine
were
not
analyzed
in
th
studies.

2,4­
D
BEE
(
MRID
4425001):

NC
Study
2,4­
D
BEE
(
40.4
ug/
L)­
parent
compound
2,4­
D
(
2,750
ug/
L)­
hydrolysis
product
of
2,4­
D
BEE
2,4­
dichlorophenol­
(
4.0
ug/
L)
4­
chlorophenol­
(
127
ug/
L)
4­
chlorophenoxyacetic
acid­
(
122
ug/
L)

MN
Study
2,4­
D
BEE
(
8.3
ug/
L)­
parent
compound
2,4­
D
(
109
ug/
L)­
hydrolysis
product
of
2,4­
D
BEE
4­
chlorophenoxyacetic
acid­
(
4.2ug/
L)

WA
Study
2,4­
D
BEE
(
8.3
ug/
L)­
parent
compound
2,4­
D
(
117
ug/
L)­
hydrolysis
product
of
2,4­
D
BEE
APPENDIX
1:
MARC
BRIEFING
DOCUMENT
37
O
Cl
Cl
O
O
CH
3
CH
3
O
Cl
Cl
OH
O
O
Cl
O
H
OH
O
Cl
O
Cl
Cl
OH
O
O
H
2,4­
D
DMA:

SD
Study
(
MRID
43908302)
2,4­
D
(
4,800
ug/
L)­
dissociation
product
of
2,4­
D
DMA
2,4­
dichlorophenol­
(
10.0
ug/
L)
4­
chlorophenoxyacetic
acid­
(
5
ug/
L)

NC
Study
(
MRID
43954701)
2,4­
D
(
2,800
ug/
L)­
dissociation
product
of
2,4­
D
DMA
2,4­
dichlorophenol­
(
6.0
ug/
L)
4
chlorophenol­
(
3
ug/
L)
4­
chlorophenoxyacetic
acid­
(
12
ug/
L)

LA
Study
(
MRID
43491601)
2,4­
D
(
1,371
ug/
L)­
dissociation
product
of
2,4­
D
DMA
Table
20.
2,4­
D
and
its
metabolites
in
plants.

Chemical
Name
Substrate
MRID
Structure
Common
Name
0
(
2,4­
dichlorophenoxy)
acetic
acid,
2­
ethylhexyl
ester
wheat
forage
and
straw
42439701
2,4­
D
IOE
(
2,4­
dichlorophenoxy)
acetic
acid
wheat
forage,
straw,
and
grain
42439701
2,4­
D
(
4­
hydroxy­
2,5­
dichlorophenoxy)
acetic
acid
wheat
forage
and
straw
42439701
42615601
4­
OH­
2,5­
D
(
5­
hydroxy­
2,4­
dichlorophenoxy)
acetic
acid
wheat
forage
and
straw
42439701
42615601
5­
OH­
2,4­
D
(
4­
hydroxy­
2,3­
dichlorophenoxy)
acetic
acid
APPENDIX
1:
MARC
BRIEFING
DOCUMENT
Chemical
Name
Substrate
MRID
Structure
Common
Name
38
O
Cl
O
H
OH
O
Cl
OH
Cl
Cl
wheat
forage
and
straw
42439701
42615601
4­
OH­
2,3­
D
2,4­
dichlorophenol
wheat
forage
and
straw
42439701
2,4­
DCP