UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
OFFICE
OF
PREVENTION,
PESTICIDES,
AND
TOXIC
SUBSTANCES
WASHINGTON,
D.
C.
20460
MEMORANDUM
DATE:
July
20,
2004
SUBJECT:
2,4­
DB
and
2,4­
DB­
DMA
Human
Health
Risk
Assessment
PC
Codes:
030801
(
2,4­
DB)
and
030819
(
2,4­
DB­
DMA)
DP
Barcode:
D290486
TO:
Mika
Hunter,
Chemical
Review
Manager
Special
Review
Branch
Special
Review
and
Reregistration
Division
(
7508C)

FROM:
Kit
Farwell,
D.
V.
M.
Reregistration
Branch
1
Health
Effects
Division
(
7509C)

THRU:
Whang
Phang,
Ph.
D.,
Senior
Scientist
Reregistration
Branch
1
Health
Effects
Division
(
7509C)

This
document
is
the
Health
Effects
Division
risk
assessment
for
the
reregistration
of
2,4­
DB
[
4­(
2,4­
dichlorophenoxy)
butyric
acid]
and
2,4­
DB­
DMA
(
2,4­
DB
dimethylamine
salt).
This
assessment
was
revised
in
response
to
error
only
comments
from
the
2,4­
DB
Task
Force.

Toxicologist:
Kit
Farwell,
D.
V.
M
Dietary
Exposure:
Felecia
Fort
Occupational
Exposure:
Timothy
Dole,
C.
I.
H.
Chemistry:
Danette
Drew
Water
Exposure:
Amer
Al­
Mudallal
Usage
Data:
Alan
Halvorson
Risk
Assessor:
Kit
Farwell,
D.
V.
M.
TABLE
OF
CONTENTS
1.0
EXECUTIVE
SUMMARY
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1
2.0
PHYSICAL/
CHEMICAL
PROPERTIES
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4
3.0
HAZARD
CHARACTERIZATION
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5
3.1
Hazard
Profile
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5
3.2
FQPA
Considerations
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7
3.3
Dose
Response
Assessment
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8
3.4
Endocrine
Disruption
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10
4.0
EXPOSURE
ASSESSMENT
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11
4.1
Summary
of
Registered
Uses
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11
4.2
Dietary
Exposure
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11
4.2.1
Residue
Profile
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11
4.2.2
Acute
and
Chronic
Dietary
Exposure
and
Risk
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13
4.3
Water
Exposure
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17
4.4
Residential
Exposure
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18
4.5
Aggregate
Exposure
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18
4.5.1
Acute
Aggregate
Risk
Assessment
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18
4.5.2
Chronic
Aggregate
Risk
Assessment
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19
4.6
Occupational
Exposure
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20
4.6.1
Handler
Exposure
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22
4.6.2
Postapplication
Exposure
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26
4.6.3
Incident
Report
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28
5.0
CUMULATIVE
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28
6.0
DATA
NEEDS
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29
7.0
TOXICITY
TABLES
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33
Table
22.
Acute
Toxicity
of
2,4­
DB
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33
Table
23.
Acute
Toxicity
of
2,4­
DB­
DMA
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33
Table
24.
Toxicology
Profile
of
2,4­
DB
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34
Table
25.
Toxicology
Profile
of
2,4­
DB­
DMA
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37
8.0
BIBLIOGRAPHY
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38
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
1
1.0
EXECUTIVE
SUMMARY
Uses:
2,4­
DB
is
a
plant
growth
regulator
and
herbicide
registered
for
use
on
alfalfa,
clover,
peanuts,
soybean,
peppermint,
spearmint,
and
trefoil.
It
is
manufactured
as
the
acid
and
the
dimethylamine
salt;
no
other
salt
or
ester
products
are
currently
registered.
End­
use
products
are
formulated
either
as
soluble,
emulsifiable,
or
flowable
concentrates.
2,4­
DB
can
be
applied
either
as
a
broadcast
application
early
season,
or
a
directed
spray
late
season.
Ground
or
aerial
applications
may
be
made.
Maximum
label
application
rates
for
food/
feed
crops
range
from
0.25
lb
ae
(
acid
equivalents)/
A
to
1.5
lb
ae/
A.
Total
annual
domestic
usage
of
2,4­
DB
is
approximately
326
thousand
pounds
active
ingredient.
There
are
no
current
residential
uses.

Because
of
similarities
in
metabolism
and
degradation
in
animals,
plants,
and
the
environment,
2,4­
DB
and
2,4­
DB­
DMA
were
considered
equivalent
in
this
risk
assessment.
An
exception
is
that
2,4­
DB­
DMA
is
a
severe
eye
irritant,
whereas
2,4­
DB
is
not
a
severe
eye
irritant.

Hazard:
Liver
toxicity,
which
occurred
in
all
the
subchronic
and
chronic
toxicity
studies,
included
increased
liver
weights,
changes
in
clinical
chemistry,
gross
changes
visible
at
necropsy,
and
microscopic
changes.
Kidney
toxicity
in
dog
and
rat
studies
included
changes
in
kidney
weights,
changes
in
clinical
chemistry,
and
microscopic
changes.
Decreased
hematological
parameters
occurred
in
dogs
and
rats.
No
systemic
toxicity
was
noted
in
dermal
studies,
although
dermal
irritation
occurred
with
2,4­
DB­
DMA.
No
neurotoxicity
was
attributed
to
treatment.
The
cancer
classification
is
"
not
likely
to
be
a
human
carcinogen".

FQPA
Assessment:
Developmental
toxicity
in
rats
occurred
at
doses
two­
fold
higher
than
the
doses
which
caused
maternal
toxicity,
and
included
decreased
fetal
body
weight,
skeletal
variations
and
malformations,
early
resorptions,
microphthalmia,
and
retroesophageal
aortic
arches.
No
developmental
toxicity
occurred
in
rabbits.
Offspring
toxicity
in
the
2­
generation
reproduction
study
included
mortality,
decreased
mean
litter
weight,
and
increased
incidence
of
necropsy
findings;
parental
toxicity
occurred
at
the
same
dose;
there
was
no
effect
upon
reproductive
parameters.
There
were
no
residual
uncertainties
for
pre­
and/
or
postnatal
toxicity
and
no
special
FQPA
Safety
Factor
was
applied
(
i.
e.
1X).

Dose­
Response:
An
acute
dietary
endpoint
was
selected
for
females
13­
50
years
of
age
based
on
developmental
abnormalities
in
rats;
no
acute
effects
were
applicable
to
any
other
subpopulations.
Chronic
and
long­
term
endpoints
were
based
on
decreased
body
weight
gain
and
food
consumption
in
female
rats.
Short­
term
incidental
oral
and
inhalation
endpoints
were
based
on
decreased
body
weight
and
related
changes
in
rats.
A
short­
term
dermal
endpoint
was
not
selected
because
no
systemic
toxicity
occurred
in
the
subchronic
dermal
toxicity
study.
Intermediate­
term
endpoints
were
based
on
decreased
body
weight
gain,
organ
weight
changes,
and
microscopic
changes
in
rats.

Tolerances:
Tolerances
for
residues
of
2,4­
DB
in
plant
commodities
are
currently
expressed
as
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
2
the
combined
residues
of
2,4­
DB
and
its
metabolite,
2,4­
D,
which
is
also
a
registered
active
ingredient.
Current
tolerance
levels
are
set
at
0.2
ppm
in
alfalfa;
clover;
mint,
hay;
peanut;
trefoil,
birdsfoot;
soybean;
and
soybean,
hay.
No
tolerances
in
livestock
commodities
or
food/
feed
processed
commodities
have
been
established.

The
reassessed
tolerances
for
plants
are:
alfalfa,
forage
(
0.70
ppm);
alfalfa,
hay
(
2.0
ppm);
clover,
forage
and
clover,
hay
(
insufficient
data
available);
peppermint,
tops
and
spearmint,
tops
(
0.20
ppm);
soybean,
seed
(
0.50
ppm),
soybean,
forage
(
0.70
ppm),
soybean,
hay
(
2.0
ppm);
peanut
(
0.05
ppm);
trefoil,
forage
(
0.70
ppm)
and
trefoil,
hay
(
2.0
ppm).
Sufficient
data
are
available
to
determine
that
residues
of
2,4­
DB
do
not
significantly
concentrate
in
any
peanut,
soybean
or
mint
processed
food/
feed
item;
thus,
tolerances
are
not
required
for
the
processed
commodities
of
these
crops.

For
livestock,
the
appropriate
tolerance
for
2,4­
DB
is
0.05
ppm
(
LOQ)
in
the
meat
byproducts
of
cattle,
goats,
hogs,
horses,
and
sheep.
There
is
no
reasonable
expectation
of
the
transfer
of
residues
of
2,4­
DB
from
feedstuffs
to
milk,
livestock
meat
or
fat,
poultry
tissues
or
eggs;
therefore,
these
commodities
should
be
classified
as
Category
3
under
40
CFR
180.6(
a)
and
tolerances
for
residues
of
2,4­
DB
in
milk,
poultry
tissues
and
eggs,
and
meat
and
fat
of
cattle,
goats,
hogs,
horses,
and
sheep
are
not
required.

The
HED
Metabolism
Committee
concluded
that
the
residue
to
be
regulated
in
plants
and
in
meat,
milk,
poultry
and
eggs
is
2,4­
DB
per
se,
and
that
2,4­
D
need
not
be
included
in
the
tolerance
expression
because
the
2,4­
D
metabolite
was
present
at
only
low
levels.

Dietary
Risk:
An
unrefined
acute
dietary
risk
assessment
(
tolerance
level
and
100%
crop
treated)
was
conducted
for
all
supported
2,4­
DB
food
uses.
Dietary
risk
estimates
are
provided
for
females
13
to
49
years
old,
the
population
subgroup
of
concern.
The
results
using
the
DEEM­
FCID
and
Lifeline
models
showed
risk
estimates
of
<
1%
of
the
aPAD
regardless
of
the
model
used
and
were
therefore
not
of
concern.
This
assessment
was
based
on
conservative
residue
estimates
and
could
be
further
refined,
however,
based
on
the
results
of
the
assessment,
further
refinements
are
not
warranted.

Tolerance
level
residues
and
100%
CT
information
were
also
used
to
determine
the
chronic
dietary
risk.
This
assessment
concludes
that
for
all
included
commodities,
the
chronic
risk
estimates
are
below
the
Agency's
level
of
concern
for
the
general
U.
S.
population
(<
1%
of
the
cPAD)
and
all
population
subgroups
(

2.2%
cpad)
when
using
the
DEEM­
FCID
or
Lifeline
models.
The
most
highly
exposed
population
subgroup
was
also
All
Infants
(<
1
years
old).

Residential
Risk:
There
are
no
residential
uses
for
2,4­
DB.
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
3
Drinking
Water:
2,4­
DB
was
classified
as
very
mobile
to
moderately
mobile
in
mineral
soils.
The
half­
life
of
2,4­
DB
in
terrestrial
field
dissipation
studies
was
2
to
6.7
days.
Although
2,4­
DB
has
been
detected
in
ground
and
surface
water,
there
were
not
enough
detections
for
the
results
to
be
used
in
risk
assessment.
Because
the
monitoring
data
could
not
be
used,
EFED
calculated
estimated
environmental
concentrations
(
EECs)
using
PRZM/
EXAMS
and
SCI­
GROW
modeling
software.

Aggregate
Risk:
Aggregate
exposure
included
food
and
water
exposure
only
because
there
are
no
residential
uses
for
2,4­
DB.
The
EECs
were
much
less
than
calculated
drinking
water
levels
of
comparison
(
DWLOCs)
and
there
were
no
concerns
for
aggregate
exposure
to
2,4­
DB
in
food
and
drinking
water.

Occupational
Risk:
MOEs
for
occupational
exposures
were
calculated
for
short­
term
inhalation
exposures
and
intermediate­
term
combined
dermal
and
inhalation
exposures;
quantification
of
short­
term
dermal
exposure
was
not
required
because
no
systemic
toxicity
developed
in
21­
day
dermal
toxicity
studies.
All
of
the
MOEs
for
short­
term
inhalation
exceeded
the
target
of
100
with
baseline
respiratory
protection
(
i.
e.
no
respirators
worn)
and
are
not
of
concern.
All
of
the
intermediate­
term
MOEs
exceeded
the
target
MOE
with
single
layer
PPE
for
mixer/
loaders
and
baseline
PPE
for
applicators.
However,
intermediate­
term
handler
exposures
are
unlikely
to
occur
because
2,4­
DB
is
applied
only
once
or
twice
per
season.

Many
of
the
labels
require
waterproof
gloves
instead
of
chemical
resistant
gloves.
It
is
not
known
if
these
gloves
provide
adequate
protection.
It
is
recommended
that
mixers
and
loaders
wear
chemical
resistant
gloves
made
of
waterproof
material
when
handling
2,4­
DB.
The
amine
salt
form
of
2,4­
DB
is
a
severe
eye
irritant
and
eye
protection
is
recommended.

Post­
Application
Exposure:
All
of
the
MOEs
are
above
100
on
Day
0
which
indicates
that
the
risks
are
not
of
concern.
The
post­
application
risk
estimates
are
highly
conservative
because
they
are
based
upon
intermediate­
term
exposure,
which
is
less
likely
to
occur
because
2,4­
DB
is
applied
only
once
or
twice
per
season.
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
4
O
Cl
Cl
O
OH
O
Cl
Cl
O
O
­

NH2(
CH3)
2
+
2.0
PHYSICAL/
CHEMICAL
PROPERTIES
As
shown
by
the
structures
below,
2,4­
DB
is
an
acid
and
2,4­
DB­
DMA
is
the
dimethyl
amine
salt
of
the
acid.

Table
1.
Physical
Properties
2,4­
DB
Acid
2,4­
DB­
DMA
Empirical
Formula
C10H10Cl2O3
C12H17Cl2NO3
Molecular
Weight
249.1
293.9
CAS
Registry
No.
94­
82­
6
2758­
42­
1
PC
Code
030801
030819
Color
off­
white
Light
orange/
brown
Physical
State
flakes/
powder
Viscous
liquid
Melting
Point
113.5­
117.5

C
­

Water
Solubility
46
ppm
Miscible
Vapor
Pressure
7x10­
7
mm
Hg
­

Log
KOW
3­
4
­

Table
2.
Chemical
Structures.

2,4­
DB
2,4­
DB­
DMA
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
5
3.0
HAZARD
CHARACTERIZATION
3.1
Hazard
Profile
2,4­
DB
is
manufactured
as
an
acid
and
the
dimethylamine
salt,
2,4­
DB­
DMA.
The
data
showed
that
2,4­
DB­
DMA
dissociates
to
2,4­
DB
in
rats,
after
which
they
shared
the
same
metabolic
pathway.
Urine
was
the
major
route
of
excretion;
2,4­
D
and
conjugated
dichlorophenol
were
the
major
metabolites
for
both
chemicals.
Most
toxicity
studies
were
conducted
with
2,4­
DB;
studies
with
2,4­
DB­
DMA
included
subchronic
feeding
in
rats,
developmental
toxicity
in
rats,
dermal
toxicity
in
rabbits,
mutagenicity,
and
metabolism.
The
toxicity
and
LOAELs
of
2,4­
DB
and
2,4­
DB­
DMA
were
similar
in
the
studies
which
were
conducted
with
both
chemicals.
For
the
above
reasons,
the
same
endpoints
were
selected
for
both
2,4­
DB
and
2,4­
DB­
DMA
and
the
database
was
adequate
for
establishing
toxicity
endpoints
for
risk
assessment.

A
minor
difference
in
toxicity
between
the
acid
and
DMA
salt
was
that
2,4­
DB­
DMA
was
more
irritating
than
2,4­
DB.
2,4­
DB­
DMA
caused
inflamed
lacrimal
glands
and
gastric
mucosal
irritation
in
the
subchronic
rat
feeding
study,
dermal
irritation
in
the
subchronic
dermal
toxicity
study,
and
eye
irritation
in
the
acute
eye
irritation
study;
these
effects
were
not
noted
with
2,4­
DB.

Some
form
of
liver
toxicity
was
noted
in
all
the
subchronic
and
chronic
toxicity
studies
with
2,4­
DB
and
in
the
subchronic
rat
study
with
2,4­
DB­
DMA.
Liver
weights
were
increased
in
subchronic
rat
studies
with
2,4­
DB
and
2,4­
DB­
DMA,
the
subchronic
dog
study,
and
the
mouse
carcinogenicity
study.
Liver
enzymes
(
ALT,
AST,
and/
or
alkaline
phosphatase)
were
elevated
in
the
subchronic
and
chronic
dog
studies
with
2,4­
DB
and
in
the
subchronic
rat
study
with
2,4­
DBDMA
Hepatocyte
hypertrophy
was
noted
in
the
subchronic
rat
study
with
2,4­
DB.
In
the
subchronic
dog
study
with
2,4­
DB,
BSP
retention
was
increased,
and
icterus
and
pale
livers
were
noted.

Kidney
toxicity
was
noted
in
several
studies.
Kidney
weights
were
increased
in
the
subchronic
dog
study
and
decreased
in
the
subchronic
and
chronic
rat
studies
with
2,4­
DB.
Kidney
infarcts
were
noted
in
the
chronic
rat
study.
Kidney
tubular
degeneration
was
noted
in
the
subchronic
rat
study
with
2,4­
DB­
DMA.
BUN
was
increased
in
the
subchronic
and
chronic
dog
studies
with
2,4­
DB.

Other
toxicity
included
decreased
hematological
parameters
in
the
chronic
rat
study
and
the
subchronic
and
chronic
dog
studies
with
2,4­
DB
and
in
the
subchronic
rat
study
with
2,4­
DBDMA
Heart
weights
were
decreased
in
the
subchronic
and
chronic
rat
studies
and
increased
in
the
mouse
carcinogenicity
study
with
2,4­
DB.
Light
foci
in
the
heart
were
also
noted
in
the
mouse
carcinogenicity
study.
Inflamed
lacrimal
glands
were
noted
in
the
subchronic
rat
study
with
2,4­
DB­
DMA.
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
6
No
systemic
toxicity
was
noted
in
21­
day
dermal
studies
in
rabbits
with
either
2,4­
DB
or
2,4­
DBDMA
although
local
dermal
irritation
occurred
in
the
dermal
study
with
2,4­
DB­
DMA.

Although
neurotoxicity
has
been
noted
with
other
phenoxy
herbicides,
clinical
signs
suggestive
of
neurotoxicity
with
2,4­
DB
and
2,4­
DB­
DMA
only
occurred
at
lethal
doses,
and
were
considered
agonal
in
nature.

Decreased
fetal
body
weight,
increased
incidence
of
skeletal
variations/
malformations,
early
resorptions,
microphthalmia,
and
retroesophageal
aortic
arches
occurred
in
developmental
rat
toxicity
studies
with
2,4­
DB
and/
or
2,4­
DB­
DMA.
Maternal
mortality
occurred
at
the
same
dose
as
did
the
developmental
toxicity.
No
developmental
toxicity
occurred
in
the
developmental
study
in
rabbits.

Offspring
toxicity
in
the
2­
generation
reproduction
study
with
2,4­
DB
included
mortality,
decreased
mean
litter
weight,
and
increased
incidence
of
necropsy
findings
(
small
thymus,
distended
bladder
with
bloody/
dark
urine
and
ocular
opacity);
parental
effects
at
the
same
dose
included
decreased
food
consumption
and
body
weight,
increased
food
conversion
ratio,
increased
water
consumption,
organ
weight
changes,
and
macroscopic
renal
findings
(
kidney
pallor
and
cortical
scarring).
There
was
no
effect
upon
reproductive
parameters.

Toxicity
endpoints
were
selected
from
rat
studies,
rather
than
dog
studies,
because
of
differences
in
elimination
of
phenoxyacetic
compounds
in
dogs
compared
to
other
mammalian
species.
The
dog
is
more
sensitive
to
toxicity
from
2,4­
DB
than
is
the
rat,
as
is
the
case
for
2,4­
D
and
MCPA.
Pharmacokinetic
data
on
dogs
are
not
available
for
2,4­
DB.
However,
compounds
closely
related
structurally
to
2,4­
DB,
including
2,4­
D,
triclopyr,
MCPA,
and
other
organic
acids
have
been
shown
to
have
a
decreased
clearance
in
dogs
relative
to
humans
and
rats.
Consequently,
effects
are
seen
at
lower
dose
levels
in
the
dog
than
in
other
species.
The
difference
in
the
elimination
pattern
between
dogs
and
humans
makes
the
rat
more
relevant
to
humans
than
the
dog.
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
7
3.2
FQPA
Considerations
There
are
acceptable
developmental
toxicity
studies
in
rats
with
2,4­
DB
and
2,4­
DB­
DMA
and
an
acceptable
developmental
study
in
rabbits
and
a
2­
generation
reproduction
study
in
rats
with
2,4­
DB.
The
HIARC
concluded
that
the
toxicology
database
for
2,4­
DB
and
2,4­
DB­
DMA
was
complete
for
evaluation
of
residual
concerns
under
FQPA.

Determination
of
Susceptibility:
There
was
no
indication
of
prenatal
susceptibility
in
the
developmental
rat
studies
with
2,4­
DB
and
2,4­
DB­
DMA;
with
both
chemicals,
developmental
effects
occurred
at
doses
two­
fold
higher
than
the
doses
that
caused
maternal
toxicity.
There
was
no
prenatal
susceptibility
in
the
rabbit
developmental
toxicity
study
with
2,4­
DB
because
no
developmental
toxicity
occurred.

There
was
qualitative,
but
not
quantitative
susceptibility
in
the
2­
generation
reproduction
study
with
2,4­
DB
because
offspring
mortality
occurred
at
a
dose
where
parental
toxicity
was
less
severe.
The
parental
NOAEL
was
30
mg/
kg/
day
and
the
parental
LOAEL
was
133
mg/
kg/
day
based
on
decreased
food
consumption
and
body
weight,
increased
food
conversion
ratio,
increased
water
consumption,
organ
weight
changes,
and
macroscopic
renal
findings
(
kidney
pallor
and
cortical
scarring).
The
offspring
NOAEL
was
30
mg/
kg/
day
and
the
offspring
LOAEL
was
133
mg/
kg/
day
based
on
mortality,
decreased
mean
litter
weight,
and
increased
incidence
of
necropsy
findings
(
small
thymus,
distended
bladder
with
bloody/
dark
urine
and
ocular
opacity).
There
was
no
effect
upon
reproductive
parameters.

Degree
of
Concern
Analysis
and
Residual
Uncertainties:
Since
there
was
evidence
of
increased
susceptibility
of
offspring
following
exposure
to
2,4­
DB
in
the
reproduction
study,
a
Degree
of
Concern
Analysis
was
performed
to:
1)
determine
the
level
of
concern
for
the
effects
observed
when
considered
in
the
context
of
all
available
toxicity
data;
and
2)
identify
any
residual
uncertainties
after
establishing
toxicity
endpoints
and
traditional
uncertainty
factors
to
be
used
in
the
risk
assessment
for
this
chemical.

It
was
concluded
that
there
was
low
concern
for
the
qualitative
susceptibility
because:
the
offspring
toxicity
was
well
characterized
and
was
accompanied
by
maternal
toxicity;
there
was
a
clear
NOAEL/
LOAEL
for
offspring
toxicity;
and
the
dose/
endpoint
selected
for
long­
term
risk
assessments
(
NOAEL
=
3mg/
kg/
day
based
on
decreased
body
weight
gain/
food
consumption
at
30
mg/
kg/
day)
was
considerably
lower
and
would
address
the
concerns
for
offspring
toxicity
seen
in
this
study.
Therefore,
there
were
no
residual
uncertainties
for
pre­
and/
or
postnatal
toxicity.

Special
FQPA
Safety
Factors:
Based
upon
the
above
analysis,
the
Hazard
Identification
Assessment
Review
Committee
(
HIARC)
determined
that
no
special
FQPA
Safety
Factor
was
needed
(
i.
e.
1X)
since
there
were
no
residual
uncertainties
for
pre­
and/
or
postnatal
toxicity.
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
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
8
potential
exposure
scenario
includes
all
metabolites
and/
or
degradates
of
concern
and
does
not
underestimate
the
potential
risk
for
infants
and
children.

3.3
Dose
Response
Assessment
Table
3.
Toxicological
Endpoints
for
2,4­
DB
(
Dietary)

Exposure
Scenario
Dose
for
Risk
Assessment
and
Uncertainty
Factor
Special
FQPA
Safety
Factor
and
Level
of
Concern
Study
and
Toxicological
Effects
Acute
Dietary
(
Females
13­
50
years
of
age)
NOAEL
=
62.5
mg/
kg/
day
UF
=
100
Acute
RfD
=
0.6
mg/
kg/
day
FQPA
SF
=
1X
aPAD
=
acute
RfD
FQPA
SF
=
0.6
mg/
kg/
day
Rat
developmental
toxicity.
LOAEL
=
125
mg/
kg/
day
based
on
skeletal
variations/
malformations,
microphthalmia,
post­
implantation
loss
Acute
Dietary
(
General
population
including
infants
and
children)
None
N/
A
No
appropriate
endpoint
attributable
to
a
single
dose
from
oral
toxicity
studies.

Chronic
Dietary
(
All
populations)
NOAEL=
3
mg/
kg/
day
UF
=
100
Chronic
RfD
=
0.03
mg/
kg/
day
FQPA
SF
=
1X
cPAD
=
chronic
RfD
FQPA
SF
=
0.03
mg/
kg/
day
Chronic/
carcinogenicity
study
in
rats.
LOAEL
=
30
mg/
kg/
day
based
on
decreased
body
weight
gain
and
food
consumption
in
females.

UF
=
uncertainty
factor,
FQPA
SF
=
Special
FQPA
safety
factor,
NOAEL
=
no
observed
adverse
effect
level,
LOAEL
=
lowest
observed
adverse
effect
level,
PAD
=
population
adjusted
dose,
(
a
=
acute,
c
=
chronic)
RfD
=
reference
dose,
MOE
=
margin
of
exposure,
LOC
=
level
of
concern,
NA
=
Not
Applicable
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
9
Table
4.
Toxicological
Endpoints
for
2,4­
DB
(
Non­
dietary)

Exposure
Scenario
Dose
for
Risk
Assessment
and
Uncertainty
Factor
Special
FQPA
Safety
Factor
and
Level
of
Concern
Study
and
Toxicological
Effects
Short­
Term
Dermal
(
1
to
30
days)
None
N/
A
Quantitation
not
required.
No
systemic
toxicity
via
the
dermal
route
and
there
are
no
developmental
concerns.

Intermediate­
Term
Dermal
(
1
to
6
months)
Oral
NOAEL
=
15.8
mg/
kg/
day
Residential
LOC
for
MOE
=
100
Occupational
=
100
Subchronic
rat
toxicity
(
2,4­
DB
study)
LOAEL
=
50
mg/
kg/
day
based
on
decreased
body
weight
gain,
increased
relative
liver/
kidney
weight,
and
microscopic
changes
Long­
Term
Dermal
(>
6
months)
Oral
NOAEL
=
3
mg/
kg/
day
(
dermal
absorption
=
23%)
Residential
LOC
for
MOE
=
100
Occupational
LOC
for
MOE
=
100
Chronic/
carcinogenicity
study
in
rats.
LOAEL
=
30
mg/
kg/
day
based
on
decreased
body
weight
gain
and
food
consumption
in
females.

Short­
Term
Inhalation
(
1
to
30
days)
Oral
NOAEL
=
31
mg/
kg/
day
(
inhalation
absorption
=
100%)
Residential
LOC
for
MOE
=
100
Occupational
LOC
for
MOE
=
100
Rat
developmental
toxicity.
LOAEL
=
62.5
mg/
kg/
day
based
on
decreased
maternal
body
weight,
body
weight
gain,
and
food
consumption,
and
clinical
signs
(
emaciation,
few
feces)

Intermediate­
Term
Inhalation
(
1
to
6
months)
Oral
NOAEL
=
15.8
mg/
kg/
day
(
inhalation
absorption
=
100%)
Residential
LOC
for
MOE
=
100
Occupational
LOC
for
MOE
=
100
Subchronic
rat
toxicity
(
2,4­
DB
study).
LOAEL
=
50
mg/
kg/
day
based
on
decreased
body
weight
gain,
increased
relative
liver/
kidney
weight,
and
microscopic
changes
Long­
Term
Inhalation
(>
6
months)
Oral
NOAEL
=
3
mg/
kg/
day
(
inhalation
absorption
=
100%)
Residential
LOC
for
MOE
=
100
Occupational
LOC
for
MOE
=
100
Chronic/
carcinogenicity
study
in
rats.
LOAEL
=
30
mg/
kg/
day
based
on
decreased
body
weight
gain
and
food
consumption
in
females.

Cancer
None
N/
A
Classified
"
not
likely
to
be
a
human
carcinogen".

UF
=
uncertainty
factor,
FQPA
SF
=
Special
FQPA
safety
factor,
NOAEL
=
no
observed
adverse
effect
level,
LOAEL
=
lowest
observed
adverse
effect
level,
PAD
=
population
adjusted
dose,
(
a
=
acute,
c
=
chronic)
RfD
=
reference
dose,
MOE
=
margin
of
exposure,
LOC
=
level
of
concern,
NA
=
Not
Applicable
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
10
3.4
Endocrine
Disruption
EPA
is
required
under
the
Federal
Food
Drug
and
Cosmetic
Act
(
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
the
recommendations
of
its
Endocrine
Disruptor
Screening
and
Testing
Advisory
Committee
(
EDSTAC),
EPA
determined
that
there
were
scientific
bases
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).

When
the
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency's
EDSP
have
been
developed,
2,4­
DB
and
2,4­
DB­
DMA
may
be
subjected
to
additional
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
11
4.0
EXPOSURE
ASSESSMENT
4.1
Summary
of
Registered
Uses
2,4­
DB
is
a
plant
growth
regulator
and
herbicide
registered
for
use
on
alfalfa,
clover,
peanuts,
soybean,
peppermint,
spearmint,
and
trefoil.
It
is
manufactured
as
the
acid
and
the
dimethylamine
salt;
no
other
salt
or
ester
products
are
currently
registered.
End­
use
products
are
formulated
either
as
soluble,
emulsifiable,
or
flowable
concentrates.
2,4­
DB
can
be
applied
either
as
a
broadcast
application
early
season,
or
a
directed
spray
late
season.
Ground
or
aerial
applications
may
be
made.
Maximum
label
application
rates
for
food/
feed
crops
range
from
0.25
lb
ae
(
acid
equivalents)/
A
to
1.5
lb
ae/
A
(
alfalfa).
Total
annual
domestic
usage
of
2,4­
DB
is
approximately
326
thousand
pounds
active
ingredient,
based
upon
pesticide
use
surveys
for
1992­
2000.
There
are
no
current
residential
uses.

4.2
Dietary
Exposure
Tolerances
for
residues
of
2,4­
DB
in
plant
commodities
are
currently
expressed
as
the
combined
residues
of
the
herbicide
4­(
2,4­
dichlorophenoxy)
butyric
acid
and
its
metabolite,
2,4­
D
(
2,4­
dichlorophenoxyacetic
acid),
which
is
also
a
registered
active
ingredient.
Current
tolerance
levels
are
set
at
0.2
ppm
(
based
on
negligible
residues)
in
alfalfa;
clover;
mint,
hay;
peanut;
trefoil,
birdsfoot;
soybean;
and
soybean,
hay.
No
tolerances
in
livestock
commodities
or
food/
feed
processed
commodities
have
been
established.

The
reassessed
tolerances
for
plants
are
listed
as
follows:
alfalfa,
forage
(
0.70
ppm);
alfalfa,
hay
(
2.0
ppm);
clover,
forage
and
clover,
hay
(
insufficient
data
available);
peppermint,
tops
and
spearmint,
tops
(
0.20
ppm);
soybean,
seed
(
0.50
ppm),
soybean,
forage
(
0.70
ppm),
soybean,
hay
(
2.0
ppm);
peanut
(
0.05
ppm);
trefoil,
forage
(
0.70
ppm)
and
trefoil,
hay
(
2.0
ppm).
For
livestock,
the
appropriate
tolerance
for
2,4­
DB
is
0.05
ppm
(
LOQ)
in
the
meat
byproducts
of
cattle,
goats,
hogs,
horses,
and
sheep.
There
is
no
reasonable
expectation
of
the
transfer
of
residues
of
2,4­
DB
from
feedstuffs
to
milk,
livestock
meat
or
fat,
poultry
tissues
or
eggs;
therefore,
these
commodities
should
be
classified
as
Category
3
under
40
CFR
180.6(
a)
and
tolerances
for
residues
of
2,4­
DB
in
milk,
poultry
tissues
and
eggs,
and
meat
and
fat
of
cattle,
goats,
hogs,
horses,
and
sheep
are
not
required.

4.2.1
Residue
Profile
Nature
of
the
Residue­
Plants:
The
qualitative
nature
of
the
2,4­
DB
residue
in
plant
commodities
is
adequately
understood
based
on
acceptable
metabolism
studies
in
alfalfa,
peanuts
and
soybeans.
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
12
2,4­
DB
is
metabolized
in
several
ways
including
side­
chain
degradation
[
to
form
2,4­
dichlorophenoxyacetic
acid
(
2,4­
D)
and
related
products],
ring
hydroxylation,
position
shift
of
the
chlorine
atoms
on
the
ring,
and
dechlorination.
Incorporation
of
radioactivity
into
sugar,
protein,
and
other
natural
constituents
also
resulted
from
metabolism
of
the
ring­
labeled
compound.
1,4­
benzoquinone
is
a
major
metabolite
in
soybean
hay,
pods,
and
vines.
However,
the
parent
is
the
primary
residue
found
in
most
crop
matrices.

The
HED
Metabolism
Committee
(
D.
Miller,
1/
29/
96)
concluded
that
the
residue
to
be
regulated
in
plants
is
2,4­
DB
per
se,
and
that
2,4­
D
need
not
be
included
in
the
tolerance
expression.
This
is
because
2,4­
DB
parent
was
the
major
compound
in
plant
matrices,
and
the
2,4­
D
metabolite
was
present
at
only
low
levels.
1,4­
benzoquinone
was
to
be
excluded
from
the
tolerance
expression
because
it
is
significant
only
in
certain
animal
feeds,
and
other
residues
were
excluded
because
they
each
comprise
only
a
small
portion
of
the
total
residue.
If
additional
crops
with
direct
human
consumption
are
registered,
additional
metabolism
studies
may
be
required.

Residues
of
2,4­
DB
are
not
expected
to
be
taken
up
in
rotational
crops
based
on
confined
studies.
Therefore,
field
studies
and
tolerances
in
rotational
crops
are
not
required
and
dietary
exposure
to
2,4­
DB
in
rotational
crops
is
not
expected
to
occur.

Plant
metabolism
studies
for
2,4­
DB
utilized
the
acid
form
(
030801).
The
Agency
granted
a
waiver
(
5/
11/
94
Greybeard
Committee
memorandum)
for
metabolism
studies
for
the
DMA
salt
concluding
that
studies
for
the
acid
will
characterize
metabolism
for
both
the
salt
and
the
acid.

Nature
of
the
Residue
­
Livestock
The
qualitative
nature
of
the
residue
in
ruminants
and
poultry
is
adequately
understood
based
on
adequate
studies
in
dairy
cows
and
laying
hens.
In
the
hen
study,
the
highest
radioactivity
was
found
in
eggs,
fat,
and
liver.
Most
of
the
residue
was
identified
as
the
unchanged
parent
compound.
In
dairy
cows,
the
highest
radioactivity
was
found
in
milk,
liver,
and
kidney;
residues
in
muscle
and
fat
were
very
low.
Metabolites
included
the
glycine
conjugate
of
2,4­
DB,
2,4­
DB
per
se,
and
2,4­
dichlorophenol.

Based
on
these
data,
the
HED
Metabolism
Committee
(
D.
Miller,
11/
14/
95
and
1/
29/
96)
concluded
that
the
residue
to
be
regulated
in
meat,
milk,
poultry
and
eggs
is
2,4­
DB
per
se,
and
that
2,4­
D
need
not
be
included
in
the
tolerance
expression.
This
is
because
2,4­
DB
parent
was
the
major
compound
in
many
of
the
animal
matrices,
and
the
2,4­
D
metabolite
was
present
at
only
low
levels.
Other
metabolites
were
excluded
due
to
either
lower
potential
for
toxicity
or
relatively
insignificant
residue
levels.

Livestock
metabolism
studies
for
2,4­
DB
utilized
the
parent
compound
(
acid,
030801).
The
Agency
granted
a
waiver
(
5/
11/
94
Greybeard
Committee
memorandum)
for
metabolism
studies
for
the
DMA
salt
concluding
that
studies
for
the
acid
will
suffice
to
characterize
metabolism
for
both
the
salt
and
the
acid.
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
13
4.2.2
Acute
and
Chronic
Dietary
Exposure
and
Risk
Introduction:
Dietary
risk
assessment
incorporates
both
exposure
and
toxicity
of
a
given
pesticide.
The
risk
is
expressed
as
a
percentage
of
a
maximum
acceptable
dose
(
i.
e.,
the
dose
which
HED
has
concluded
will
result
in
no
unreasonable
adverse
health
effects).
This
dose
is
referred
to
as
the
population
adjusted
dose
(
PAD).
The
PAD
is
equivalent
to
the
Reference
Dose
(
RfD)
divided
by
the
special
FQPA
Safety
Factor.
HED
is
concerned
when
estimated
dietary
risk
exceeds
100%
of
the
PAD.

Exposure:
The
magnitude
of
the
residue
data
for
processed
commodities
of
food/
feed
crops
that
are
from
presently
registered
use
sites
have
been
evaluated
and
deemed
adequate.
Residues
of
2,4­
DB
do
not
significantly
concentrate
upon
processing.
Based
on
the
submitted
studies,
a
processing
factor
of
0.72x
was
used
for
peanut
oil
in
the
dietary
assessment
and
a
1x
processing
factor
was
used
for
mint
oil
and
soybean
oil.

Several
peer­
reviewed
programs
have
recently
been
emerging
for
modeling
dietary
exposure
to
pesticides.
For
technical
and
historical
reasons,
DEEM
 
was
the
preferred
program
for
EPA
through
2003.
Lifeline
 
,
which
is
capable
of
performing
a
probabilistic
aggregate
assessment
(
food,
water,
and
residential
exposure),
is
currently
being
evaluated
by
EPA.
This
evaluation
includes
the
comparison
of
dietary
exposure
estimates
for
a
given
chemical
using
both
DEEM
 
and
Lifeline
 
.
The
following
paragraphs
are
summaries
of
each
program.

2,4­
DB
acute
and
chronic
dietary
exposure
assessments
were
conducted
using
the
Dietary
Exposure
Evaluation
Model
software
with
the
Food
Commodity
Intake
Database
(
DEEMFCID
 
,
Version
1.30),
which
incorporates
consumption
data
from
USDA's
Continuing
Surveys
of
Food
Intakes
by
Individuals
(
CSFII),
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
For
chronic
dietary
exposure
assessment,
an
estimate
of
the
residue
level
in
each
food
or
foodform
(
e.
g.,
orange
or
orange
juice)
on
the
food
commodity
residue
list
is
multiplied
by
the
average
daily
consumption
estimate
for
that
food/
food
form.
The
resulting
residue
consumption
estimate
for
each
food/
food
form
is
summed
with
the
residue
consumption
estimates
for
all
other
food/
food
forms
on
the
commodity
residue
list
to
arrive
at
the
total
average
estimated
exposure.
Exposure
is
expressed
in
mg/
kg
body
weight/
day
and
as
a
percent
of
the
cPAD.
This
procedure
is
performed
for
each
population
subgroup.

For
acute
exposure
assessments,
individual
one­
day
food
consumption
data
are
used
on
an
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
14
individual­
by­
individual
basis.
The
reported
consumption
amounts
of
each
food
item
can
be
multiplied
by
a
residue
point
estimate
and
summed
to
obtain
a
total
daily
pesticide
exposure
for
a
deterministic
exposure
assessment,
or
"
matched"
in
multiple
random
pairings
with
residue
values
and
then
summed
in
a
probabilistic
assessment.
The
resulting
distribution
of
exposures
is
expressed
as
a
percentage
of
the
aPAD
on
both
a
user
(
i.
e.,
those
who
reported
eating
relevant
commodities/
food
forms)
and
a
per­
capita
(
i.
e.,
those
who
reported
eating
the
relevant
commodities
as
well
as
those
who
did
not)
basis.
In
accordance
with
HED
policy,
per
capita
exposure
and
risk
are
reported
for
all
tiers
of
analysis.
However,
for
tiers
1
and
2,
significant
differences
in
user
vs.
per
capita
exposure
and
risk
are
identified
and
noted
in
the
risk
assessment.

Acute
and
chronic
dietary
exposure
estimates
were
also
conducted
using
the
Lifeline
 
model
(
Version
2.0).
These
Lifeline
 
assessments
were
also
conducted
using
the
same
consumption
data
as
the
DEEM­
FCID
 
(
CSFII,
1994­
1996
and
1998
consumption
data
with
FCID).
Lifeline
 
uses
the
recipe
file
to
relate
RACs
to
foods
"
as­
eaten."
Lifeline
 
converts
the
RAC
residues
into
food
residues
by
randomly
selecting
a
RAC
residue
value
from
the
"
user
defined"
residue
distribution
(
created
from
the
residue,
percent
crop
treated,
and
processing
factors
data),
and
calculating
a
net
residue
for
that
food
based
on
the
ingredient's
mass
contribution
to
that
food
item.
For
example,
`
apple
pie'
will
have
a
residue
distribution
based
on
the
residues
provided
for
apples
(
adjusted
by
the
appropriate
processing
factors
and
percent
crop
treated),
as
well
as
the
residues
for
each
of
the
other
ingredients
in
the
apple
pie
recipe
for
which
there
may
be
tolerances.
Lifeline
 
calculates
dietary
exposure
from
`
apple
pie'
based
on
the
amount
eaten,
and
the
residue
drawn
from
the
`
apple
pie'
residue
distribution
for
that
eating
occasion.

Lifeline
 
models
the
individual's
dietary
exposures
over
a
season
by
selecting
a
new
CSFII
diary
each
day
from
a
set
of
similar
individuals
based
on
age,
season
and
socioeconomic
attributes
Lifeline
 
groups
CSFII
diaries
based
on
the
respondent's
age
and
the
season
during
which
the
food
diary
was
recorded.

An
unrefined
(
tolerance
level
and
100%
crop
treated)
dietary
risk
assessment
was
conducted
for
all
supported
2,4­
DB
food
uses
for
both
acute
and
chronic
dietary
risk.
There
was
high
confidence
in
the
residue
chemistry
database
and
the
required
studies
are
considered
confirmatory
data.
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
15
Acute
Dietary
Risk:
Dietary
risk
estimates
are
provided
for
females
13
to
49
years
old,
the
population
subgroup
of
concern.
The
results
using
the
DEEM­
FCID
and
Lifeline
models
showed
risk
estimates
at
the
95th
percentile
of
exposure
to
be
<
1%
of
the
aPAD
regardless
of
the
model
used
and
were
therefore
not
of
concern.

This
assessment
was
based
on
conservative
residue
estimates
(
tolerance
level
and
100%
crop
treated).
The
dietary
risk
estimate
could
be
further
refined
with
the
incorporation
of
anticipated
residues,
percent
crop
treated
data,
and
cooking/
processing
factors.
Based
on
the
results
of
the
assessment,
further
refinements
are
not
warranted.

Table
5.
Acute
Dietary
Exposure
and
Risk
Population
Subgroup
Acute
Dietary
(
95th
Percentile)

DEEM­
FCID
Lifeline
Dietary
Exposure
(
mg/
kg/
day)
%
aPAD
Dietary
Exposure
(
mg/
kg/
day)
%
aPAD
Females
13­
49
years
old
0.000467
0.08
0.000614
0.102
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
16
Chronic
dietary
risk:
The
chronic
risk
estimates
are
below
the
Agency's
level
of
concern
for
the
general
U.
S.
population
(<
1%
of
the
cPAD)
and
all
population
subgroups
(

2.2%
cPAD).
The
most
highly
exposed
population
subgroup
was
All
Infants
(<
1
years
old).
Similar
results
were
found
using
the
Lifeline
Model,
with
<
1%
of
the
cPAD
occupied
for
the
U.
S.
population.

This
assessment
was
based
on
conservative
residue
estimates
(
tolerance
level
and
100%
crop
treated).
The
dietary
risk
estimate
could
be
further
refined
with
the
incorporation
of
anticipated
residues,
percent
crop
treated
data,
and
cooking/
processing
factors.
Based
on
the
results
of
the
assessment,
further
refinements
are
not
warranted.

Table
6.
Chronic
Dietary
Exposure
and
Risk
Population
Subgroup*
Chronic
Dietary
DEEM­
FCID
Lifeline
Dietary
Exposure
(
mg/
kg/
day)
%
cPAD
Dietary
Exposure
(
mg/
kg/
day)
%
cPAD
General
U.
S.
Population
0.000242
0.8
0.000232
0.8
All
Infants
(<
1
year
old)
0.000661
2.2
0.000554
1.8
Children
1­
2
years
old
0.000548
1.8
0.000539
1.8
Children
3­
5
years
old
0.000535
1.8
0.000505
1.7
Children
6­
12
years
old
0.000373
1.2
0.000346
1.2
Youth
13­
19
years
old
0.000238
0.8
0.000224
0.7
Adults
20­
49
years
old
0.000197
0.7
0.000198
0.7
Adults
50+
years
old
0.000153
0.5
0.000191
0.6
Females
13­
49
years
old
0.000185
0.6
0.000228
0.8
*
*
The
values
for
the
highest
exposed
population
for
each
type
of
risk
assessment
are
bolded.
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
17
4.3
Water
Exposure
Environmental
Fate:
Because
2,4­
DB­
DMA
rapidly
dissociates
in
water
to
form
2,4­
DB,
EFED
used
ecotoxicity
data
for
2,4­
DB
as
bridging
data
for
2,4­
DB­
DMA.

The
mobility
of
2,4­
DB
in
mineral
soils
was
classified
as
very
mobile
to
moderately
mobile.
The
half­
life
of
2,4­
DB
in
terrestrial
field
dissipation
studies
was
2
to
6.7
days.
The
primary
route
of
dissipation
was
by
transformation,
major
transformation
products
being
2,4­
dichlorophenoxyacetic
acid
(
2,4­
D
acid,
5.0­
15
%
of
the
applied)
and
2,4­
D
Phenol
(
5.0­
27.3
%
of
the
applied).
2,4­
D
acid
has
been
identified
as
a
degradate
of
2,4­
DB
in
an
aerobic
soil
metabolism
study.

Monitoring
Data:
There
were
monitoring
data
for
2,4­
DB
from
the
United
States
Geological
Survey
(
USGS)
National
Water­
Quality
Assessment
(
NAWQA)
Program,
USEPA
STOrage
and
RETrieval
System
for
Water
and
Biological
Monitoring
Data
(
STORET),
and
from
the
USGS
Pilot
Reservoir
Monitoring
Study.
Frequency
of
detections
were
not
sufficient
to
calculate
time
weighted
means.

The
highest
annual
maximum
concentration
of
2,4­
DB
detected
in
surface
water
monitoring
data
was
0.83

g/
L
from
the
NAWQA
data
at
Reed
Wash
near
Mack,
Colorado
with
the
next
highest
being
0.81

g/
L
from
the
STORET
data
at
Big
Limestone
Creek
near
Limestone,
Tennessee.
2,4­
DB
was
reported
once
in
the
NAWQA
ground
water
data
at
a
concentration
of
0.06

g/
L
and
was
not
detected
in
the
STORET
data.

Modeling:
Modeling
of
surface
water
concentrations
of
2,4­
DB
was
performed
by
PRZM/
EXAMS
using
alfalfa,
peanuts,
and
soybean
applications.
Several
scenarios
for
each
crop
were
chosen
to
represent
a
geographically
dispersed
range
of
surface
water
concentrations
in
areas
representative
of
where
2,4­
DB
is
used.
EFED
recommended
using
318.68

g/
L
for
the
1
in
10
year
peak
concentration
(
acute)
and
72.40

g/
L
for
the
1
in
10
year
annual
daily
average
concentration
(
chronic­
non
cancer).
These
estimated
concentrations
were
from
the
Texas
alfalfa
IR/
PCA
scenario.

The
SCI­
GROW
model
estimated
the
concentration
of
2,4­
DB
in
drinking
water
from
shallow
ground
water
sources
to
be
0.51

g/
L.
This
concentration
can
be
used
for
both
acute
and
chronic
exposure.

No
degradation
products
of
2,4­
DB
were
included
in
this
assessment.
The
major
degradate
of
2,4­
DB
is
2,4­
D,
which
was
a
maximum
of
5.0­
15
%
of
applied
2,4­
DB
in
soil
dissipitation
studies.
The
annual
use
of
2,4­
DB
is
less
than
1%
of
the
annual
use
of
2,4­
D
(
326,000
pounds
vs
46
million
pounds).
According
to
data
from
the
US
Geographical
Survey
reported
in
the
EFED
water
memo,
2,4­
D
is
used
in
virtually
the
entire
country,
whereas
2,4­
DB
use
is
restricted
to
discrete
areas
of
the
country,
which
overlap
areas
of
2,4­
D
use.
Since
2,4­
DB
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
18
accounts
for
a
small
percentage
of
2,4­
D
water
exposure,
both
in
terms
of
usage
and
environmental
transformation,
water
exposure
to
2,4­
D
will
be
addressed
in
the
2,4­
D
RED.
For
more
information
on
2,4­
D
water
exposure,
see
the
EFED
water
memo
for
2,4­
D
(
D286666)
and
the
HED
risk
assessment
for
2,4­
D
(
D287199).

4.4
Residential
Exposure
There
are
no
residential
uses
for
2,4­
DB.

4.5
Aggregate
Exposure
Aggregate
exposure
to
a
pesticide
combines
exposure
from
food,
drinking
water,
and
residential
sources
of
exposure.
Since
there
are
no
residential
uses
for
2,4­
DB,
aggregate
assessments
included
exposure
via
food
and
drinking
water.

Drinking
water
levels
of
comparison
(
DWLOCs)
were
calculated
because
the
monitoring
data
for
2,4­
DB
did
not
have
enough
detects
to
calculate
means.
The
DWLOC
is
the
concentration
in
drinking
water
as
a
part
of
the
aggregate
acute
exposure
that
occupies
no
more
than
100%
of
the
PAD.
In
other
words,
the
DWLOC
for
2,4­
DB
is
the
maximum
potential
concentration
that
may
be
present
in
drinking
water
without
exceeding
a
level
of
concern
when
exposure
from
food
and
water
were
considered
together.

As
shown
below,
the
concentrations
of
2,4­
DB
estimated
in
water
were
less
than
the
DWLOCs
and
there
were
no
concerns
for
acute
or
chronic
aggregate
exposure.

4.5.1
Acute
Aggregate
Risk
Assessment
An
acute
DWLOC
was
calculated
only
for
females
13­
49
years
of
age
because
this
was
the
only
population
subgroup
for
which
an
endpoint
was
selected.
As
shown
below,
the
DWLOC
was
18,000
ug/
L
and
the
EEC
(
estimated
environmental
concentration)
was
0.51
ug/
L
for
ground
water
and
318
ug/
L
for
surface
water,
thus
there
were
no
concerns
for
acute
aggregate
exposure.

Table
7.
DWLOCs
for
Acute
Exposure
to
2,4­
DB
Population
Subgroup
Acute
PAD
mg/
kg/
day
Food
Exposure
mg/
kg/
day
Target
Max
Water
Exposure
mg/
kg/
day
Ground
Water
EEC

g/
L
Surface
Water
EEC

g/
L
DWLOC

g/
L
Females
13­
49
0.6
mg/
kg
0.000467
0.600
0.51
318.68
18,000
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
19
4.5.2
Chronic
Aggregate
Risk
Assessment
The
most
highly
exposed
population
subgroup
was
all
infants
<
1
year
old.
As
shown
below,
the
DWLOC
for
this
subgroup
was
290
ug/
L
and
the
EEC
for
ground
water
was
0.51
ug/
L
for
ground
water
and
was
72
ug/
L
for
surface
water,
thus
there
were
no
concerns
for
chronic
aggregate
exposure
for
any
population
subgroup.

Table
8.
DWLOCs
for
Chronic
Exposure
Population
Subgroup
Chronic
PAD
mg/
kg/
day
Food
Exposure
mg/
kg/
day
Target
Max
Water
Exposure
mg/
kg/
day
Ground
Water
EEC

g/
L
Surface
Water
EEC

g/
L
DWLOC

g/
L
U.
S.
Population
(
total)
0.03
0.000242
0.030
0.51
72.40
1050
All
infants
(<
1
year)
0.03
0.000661
0.029
0.51
72.40
290
Target
Maximum
Water
Exposure
=
PAD
­
food
exposure
DWLOC
=
maximum
water
exposure
(
mg/
kg/
day)
x
body
weight
(
kg)
water
consumption
(
L/
day)
x
10­
3
mg/

g
body
weight
=
70
kg
for
adult
males,
60
kg
for
adult
females,
10
kg
for
children
and
infants
water
consumption
=
2
L/
day
for
adult
males
and
females,
1
L/
day
for
children
and
infants
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
20
4.6
Occupational
Exposure
Ground
or
aerial
applications
may
be
made,
however,
labels
do
not
allow
chemigation.
BEAD
reports
that
only
one
application
is
typically
made
per
season,
although
labels
allow
two
applications
per
growing
season.
2,4­
DB
can
be
applied
either
as
a
broadcast
application
early
season,
or
a
directed
spray
late
season.
Maximum
label
application
rates
for
food/
feed
crops
range
from
0.25
to
1.5
lb
acid
equivalents/
acre.
For
most
crops,
post
emergent
applications
can
be
made
well
into
the
growing
season.
In
peanuts,
for
example,
applications
can
be
made
from
2
to
12
weeks
after
planting.
2,4­
DB
can
be
applied
over
the
top
to
all
the
labeled
crops,
however,
some
of
the
crops
such
as
soybeans
can
be
damaged
and
require
directed
sprays
when
the
higher
rates
are
used.
The
pre
harvest
interval
is
30
or
60
days
for
peanuts
and
60
days
for
soybeans.
The
pre
grazing
interval
for
alfalfa
and
forage
legumes
is
30
and
60
days,
respectively.

Chronic
occupational
exposures
to
2,4­
DB
are
not
expected
to
occur.
2,4­
DB
is
only
applied
once
or
twice
during
the
growing
season
and
rapidly
dissipates
from
the
foliage
Application
Rates:
The
label
application
rates
are
shown
in
Table
9
and
are
given
in
terms
of
acid
equivalent
(
ae)
which
is
based
upon
the
molecular
weight
of
the
acid
excluding
the
amine
salt.
The
average
application
rates
from
the
2,4­
DB
QUA
report
(
EPA
BEAD
2001)
are
shown
for
comparison.
The
QUA
data
indicate
that
only
one
application
is
typically
made
per
season.

Table
9.
2,4­
DB
Application
Rates
Crop
or
Site
Acid
Equivalent
Application
Rates
Per
Application
(
lb
ae/
acre)

Label
Application
Rate
Average
Rate1
Percent
Crop
Treated1
Alfalfa,
Clover
1.5
0.55
0.2%

Mint
0.75
0.80
1.0%

Peanuts
0.25
to
0.40
0.24
38%

Soybeans
0.40
0.13
0.4%

1.
Average
rate
and
PCT
from
2,4­
DB
QUA
Report
(
10/
31/
01)
which
includes
usage
data
from
1992
to
2000.
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
21
The
Phenoxy
Herbicide
NAPIAP
report
(
Burnside
et.
al.
1996)
has
some
information
regarding
the
use
of
2,4­
DB.
Selected
information
that
is
relevant
for
2,4­
DB
occupational
exposure
assessment
is
summarized
in
Table
10.

Table
10.
2,4­
DB
Use
Information
in
the
Phenoxy
Herbicide
NAPIAP
Report
Use
Site
NAPIAP
Findings
Alfalfa
The
only
phenoxy
used
on
alfalfa
is
2,4­
DB.

Peanuts
2,4­
DB
is
an
important
tool
in
peanut
production
and
was
used
on
83%
of
the
total
US
acreage
in
1992.
It
is
the
only
phenoxy
herbicide
used
on
peanuts.

Soybeans
There
is
little
use
of
2,4­
DB
prior
to
planting
no­
till
soybeans
because
there
is
little
to
no
advantage
over
2,4­
D
and
it
costs
more.
To
broaden
the
spectrum
of
control,
2,4­
DB
has
been
added
to
some
other
post
emergent
herbicides.
However,
because
of
some
risk
of
soybean
injury,
the
use
of
2,4­
DB
has
declined
as
more
selective
herbicides
have
been
introduced.

Application
Methods
:
The
2,4­
DB
labels
allow
ground
and
aerial
application,
however,
they
do
not
allow
chemigation.
A
listing
of
application
methods
and
amounts
of
acreage
treated
per
8
hour
day
is
included
in
Table
11.

Table
11.
2,4­
DB
Application
Methods
Application
Method
Typical
Crops
Treated
Treated
Areaa
1
­
Groundboom
Alfalfa,
Mint,
Peanuts,
Soybeans
200
2
­
Fixed
Wing
Aircraft
Same
as
above
1200
a.
Based
upon
HED
ExpoSAC
SOP
#
9
"
Standard
Values
for
Daily
Acres
Treated
in
Agriculture",
Revised
July
5,
2000
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
22
4.6.1
Handler
Exposure
The
following
assumptions
and
factors
were
used
in
order
to
complete
the
exposure
and
risk
assessments
for
occupational
handlers/
applicators:


The
average
work
day
was
8
hours.


The
daily
acreage
treated
was
taken
from
EPA
Science
Advisory
Council
for
Exposure
Standard
Operating
Procedure
#
9
"
Standard
Values
for
Daily
Acres
Treated
in
Agriculture,"
Revised
July
5,
2000.


The
maximum
label
application
rates
were
used
to
assess
short­
term
risks
because
it
is
possible
that
these
rates
could
be
used
for
one
to
thirty
consecutive
days.


The
average
application
rates
were
used
to
assess
intermediate­
term
risks
because
it
is
highly
unlikely
that
maximum
label
rates
would
be
used
for
more
than
thirty
consecutive
days.


A
body
weight
of
70
kg
was
assumed
because
the
endpoint
is
not
gender
specific.


The
inhalation
absorption
rate
is
100%.


Baseline
PPE
includes
long
sleeve
shirts,
long
pants
and
no
gloves
or
respirator.\


Single
Layer
PPE
includes
baseline
PPE
with
chemical
resistant
gloves.


Aerial
applicators
utilize
closed
cockpit
aircraft
and
do
not
wear
chemical
resistant
gloves.

Exposure
Data
Sources:
Exposure
analyses
were
performed
using
the
Pesticide
Handlers
Exposure
Database
(
PHED)
as
tabulated
in
the
PHED
Surrogate
Exposure
Guide
of
August
1998.
The
unit
exposure
values
calculated
by
PHED
generally
range
from
the
geometric
mean
to
the
median
of
the
selected
data
set.
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
23
Risks:
The
target
Margin
of
Exposure
(
MOE)
for
occupational
populations
is
100,
which
includes
the
standard
safety
factors
of
10X
for
intraspecies
variability
(
i.
e.
differences
among
humans)
and
10X
for
interspecies
variability
(
differences
between
humans
and
animals).

The
MOEs
for
occupational
exposures
were
calculated
for
short­
term
inhalation
exposures
and
for
intermediate­
term
combined
dermal
and
inhalation
exposures
and
are
summarized
in
Tables
12
and
13.
All
of
the
short­
term
inhalation
MOEs
exceed
100
at
baseline
and
respiratory
protection
is
not
needed.
All
of
the
intermediate­
term
mixer/
loader
combined
MOEs
exceed
100
if
single
layer
PPE
(
i.
e.
baseline
clothing
with
chemical
resistant
gloves)
is
worn.
The
intermediate­
term
MOEs
for
applicators
exceed
100
with
baseline
PPE.

Occupational
Handler
Risk
Characterization:
Intermediate­
term
handler
exposures
are
less
likely
to
occur
because
2,4­
DB
is
applied
only
once
or
twice
per
season.
Metabolism
studies
in
rats
also
indicated
that
most
of
the
2,4­
DB
dose
is
excreted
within
24
hours
through
the
urine
and
feces.

Many
of
the
labels
require
waterproof
gloves
instead
of
chemical
resistant
gloves.
It
is
not
known
if
these
gloves
provide
adequate
protection.
It
is
recommended
that
mixers
and
loaders
wear
chemical
resistant
gloves
made
of
waterproof
material
when
handling
2,4­
DB.

The
amine
salt
form
of
2,4­
DB
is
a
severe
eye
irritant
and
eye
protection
is
recommended.
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
24
Table
12.
2,4­
DB
Short­
Term
MOEs
for
Handlers
Exposure
Scenario
Crop
Label
Application
Rate
(
lb
ae/
acre)
Acres/
Day
Baseline
Inhalation
MOE
Mix/
Load
Liquids
for
Aerial
Alfalfa,
Clover
Mint
Peanuts
(
SW),
Soybeans
Peanuts
(
SE)
1.5
0.75
0.4
0.25
1200
1200
1200
1200
1,000
2,000
3,800
6,000
Mix/
Load
Liquids
for
Groundboom
Alfalfa,
Clover,
CRPA
Mint
Peanuts
(
SW),
Soybeans
Peanuts
(
SE)
1.5
0.75
0.4
0.25
200
200
200
200
6,000
12,000
23,000
36,000
Aerial
Application
Alfalfa,
Clover
Mint
Peanuts
(
SW),
Soybeans
Peanuts
(
SE)
1.5
0.75
0.4
0.25
1200
1200
1200
1200
18,000
35,000
66,000
110,000
Groundboom
Application
Alfalfa,
Clover,
CRPA
Mint
Peanuts
(
SW),
Soybeans
Peanuts
(
SE)
1.5
0.75
0.4
0.25
200
200
200
200
9,800
20,000
37,000
59,000
Flag
Aerial
Application
Alfalfa,
Clover
Mint
Peanuts
(
SW),
Soybeans
Peanuts
(
SE)
1.5
0.75
0.4
0.25
1200
1200
1200
1200
3,400
6,900
13,000
21,000
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
25
Table
13.
2,4­
DB
Intermediate­
Term
MOEs
for
Handlers
Exposure
Scenario
Crop
Average
Application
Rate
(
lb
ae/
acre)
Acres/
Day
Baseline
Combined
Dermal/
Inhala
tion
MOE
Single
Layer
Combined
MOE
Mix/
Load
Liquids
for
Aerial
Alfalfa,
Clover
Mint
Peanuts
Soybeans
0.55
0.75
0.24
0.13
1200
1200
1200
1200
2.5
1.8
5.7
11
260
190
590
1100
Mix/
Load
Liquids
for
Groundboom
Alfalfa,
Clover
Mint
Peanuts
Soybeans
0.55
0.75
0.24
0.13
200
200
200
200
15
11
34
64
1500
1100
3600
6600
Aerial
Application
Alfalfa,
Clover
Mint
Peanuts
Soybeans
0.55
0.75
0.24
0.13
1200
1200
1200
1200
1400
1000
3200
5800
NA
NA
NA
NA
Groundboom
Application
Alfalfa,
Clover
Mint
Peanuts
Soybeans
0.55
0.75
0.24
0.13
200
200
200
200
2500
1900
5800
11000
2500
1900
5800
11000
Flag
Aerial
Application
Alfalfa,
Clover
Mint
Peanuts
Soybeans
0.55
0.75
0.24
0.13
1200
1200
1200
1200
580
430
1300
2500
540
400
1200
2300
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
26
4.6.2
Postapplication
Exposure
Post­
application
2,4­
DB
exposures
can
occur
in
the
agricultural
environment
when
workers
enter
fields
recently
treated
with
2,4­
DB
to
conduct
tasks
such
as
scouting
and
irrigation.
Postapplication
exposure
to
re­
entry
workers
is
possible
because
2,4­
DB
can
be
applied
over
the
top
to
most
of
the
labeled
crops.

Occupational
Post­
Application
Exposure
Scenarios:
Broadcast
applications
can
be
made
to
the
labeled
crops,
which
are
tolerant
of
2,4­
DB.
Because
2,4­
DB
is
typically
applied
once
or
twice
per
season
it
is
anticipated
that
2,4­
DB
exposures
would
be
primarily
short­
term.
Because
there
is
no
endpoint
for
short­
term
dermal
exposures,
short­
term
post­
application
risks
were
not
assessed.
To
address
the
limited
possibility
that
intermediate
exposures
could
occur,
intermediate­
term
risks
were
assessed
using
the
intermediate­
term
dermal
endpoint.
Potential
inhalation
exposures
are
not
anticipated
for
the
post­
application
worker
scenarios
because
of
the
low
vapor
pressure
of
2,4­
DB
(
7.1e­
07
mm
Hg
at
23.6o
C).

Assumptions
and
Transfer
Coefficients
for
Post­
Application:
There
were
no
data
submitted
for
2,4­
DB,
therefore,
standard
values
and
assumptions
were
used
as
discussed
below.
The
following
assumptions
were
made
regarding
occupational
post­
application:


The
average
application
rates
were
used
because
it
is
highly
unlikely
workers
would
be
exposed
to
day
zero
residues
for
more
than
thirty
consecutive
days
following
the
application
of
maximum
label
rates.


The
risks
for
alfalfa,
peanuts
and
soybeans
were
assessed
using
average
rates
as
reported
in
the
QUA
report.
The
risks
for
mint
were
assessed
at
the
maximum
label
rate
of
0.75
lb
ai/
acre
which
is
slightly
less
than
the
rate
of
0.8
lb
ai/
acre
reported
in
the
QUA
report.


The
transfer
coefficients
as
listed
in
Table
14
are
from
an
interim
transfer
coefficient
policy
developed
by
HED's
Science
Advisory
Council
for
Exposure
using
proprietary
data
from
the
Agricultural
Re­
entry
Task
Force
(
ARTF)
database
(
US
EPA,
August
7,
2001).


The
initial
percent
of
application
rate
as
Dislodgeable
Foliar
Residue
(
DFR)
was
assumed
to
be
20%
for
all
crops.
This
a
standard
value.
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
27
Table
14.
Post­
Application
Exposure
Scenarios
and
Transfer
Coefficients
for
2,4­
DB
Crop
Transfer
Coefficient
Group
Post­
Application
Exposure
Scenarios
Transfer
Coefficient
(
cm2/
hr)

Alfalfa
Field/
row
crop,
low/
medium
Low
Exposure
Scenarios
­
Irrigation,
scouting,
immature
plants
Medium
Exposure
Scenarios
­
Scouting
mature
plants
100
1500
Mint
Field/
row
crop,
low/
medium
Low
Exposure
Scenarios
­
Scouting,
immature
plants
Medium
Exposure
Scenarios
­
Scouting
mature
plants
100
1500
Peanuts,
Soybeans
Field/
row
crop,
low/
medium
Low
Exposure
Scenarios
­
Scouting,
immature
plants
Medium
Exposure
Scenarios
­
Scouting
mature
plants
100
1500
Calculation
Methodology
for
Post­
Application
Exposures:
The
calculations
used
to
estimate
the
exposures
for
the
post­
application
scenarios
are
similar
to
those
described
previously
for
the
handler/
applicator
scenarios.
Daily
dermal
exposure
is
calculated
by
multiplying
the
residue
level
(
ug/
cm2
of
leaf
area)
times
a
transfer
coefficient
(
amount
of
leaf
area
contacted
per
unit
time).
The
MOEs
are
then
calculated
using
the
intermediate­
term
dermal
NOAEL.
It
should
be
noted
that
MOEs
were
not
calculated
for
short­
term
exposures
because
there
was
no
short­
term
dermal
endpoint.

Occupational
Post­
Application
Risk
Estimates:
A
summary
of
the
worker
risks
for
intermediateterm
post­
application
exposures
is
given
in
Table
15.
All
of
the
MOEs
are
above
100
on
Day
0
which
indicates
that
the
risks
are
not
of
concern.

Occupational
Post­
Application
Risk
Characterization:
The
post­
application
risk
estimates
are
highly
conservative
because
they
are
based
upon
an
intermediate­
term
endpoint.
Intermediateterm
exposures
are
unlikely
to
occur
because
2,4­
DB
is
applied
only
once
or
twice
per
season.
Turf
Transferable
residue
data
for
the
other
phenoxy
herbicides
such
as
2,4­
D
and
MCPA
have
indicated
that
the
dissipation
is
fairly
rapid.

Table
15.
2,4­
DB
Post­
Application
Worker
Risks
Crop
Transfer
Coefficient
Group
Application
Rate
(
lb
a.
i./
acre)
Intermediate­
term
MOE
on
Day
0
Low
Exposure
Scenarios
*
Medium
Exposure
Scenarios*
High
Exposure
Scenarios*

Alfalfa
Field/
row
crop,
low/
medium
0.55
4900
325
NA
Mint
Field/
row
crop,
low/
medium
0.75
3600
240
NA
Peanuts
Field/
row
crop,
low/
medium
0.24
11000
740
NA
Soybeans
Field/
row
crop,
low/
medium
0.13
22000
1500
NA
*
Task
descriptions
for
each
crop
and
exposure
scenario
are
included
in
Table
14.
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
28
4.6.3
Incident
Report
The
incident
report
is
being
prepared
under
a
separate
memo
by
Monica
Spann,
M.
P.
H.
and
Jerome
Blondell,
PhD.
of
the
Office
of
Pesticide
Programs.
No
incidents
were
reported
in
California.

5.0
CUMULATIVE
Section
408(
b)(
2)(
D)(
v)
of
the
FFDCA
requires
that,
when
considering
whether
to
establish,
modify,
or
revoke
a
tolerance,
the
Agency
consider
"
available
information"
concerning
the
cumulative
effects
of
a
particular
pesticide's
residues
and
"
other
substances
that
have
a
common
mechanism
of
toxicity."

2,4­
DB
is
a
member
of
the
alkylphenoxy
herbicide
class
of
pesticides.
This
class
also
includes
MCPA,
2,4­
D,
and
2,4­
DP.
A
cumulative
risk
assessment
has
not
been
performed
as
part
of
this
human
health
risk
assessment
because
the
Agency
has
not
yet
made
a
determination
as
to
which
compounds
humans
may
be
exposed,
if
any,
and
whether
or
not
these
compounds
have
a
common
mechanism
of
toxicity.
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
29
6.0
DATA
NEEDS
Toxicology
Data
Gap:
A
28­
day
inhalation
study
is
required
because
the
use
pattern
indicates
potential
repeated
exposure
via
this
route.
This
study
should
be
conducted
with
2,4­
DB­
DMA
because
of
irritancy
from
this
compound.

Residue
Chemistry
Deficiencies
Labels
for
EPA
Reg.
No.
56077­
26
(
now
66222­
76)
and
EPA
Reg
No.
56077­
52
(
now
66222­
80)
only
prohibit
the
grazing
of
forage
or
feeding
of
hay
within
60
days
of
the
application
of
a
tank
mix
with
Lorax
50W
application,
and
there
is
no
indication
of
any
restriction
when
2,4­
DB
is
applied
alone.
The
restriction
should
be
against
feeding/
grazing
soybean
forage
and
harvesting
hay
for
60
days
following
any
2,4­
DB
application.

The
submitted
plant
analytical
methods
are
adequate
for
data
collection
but
must
be
adequately
validated
for
each
study
for
which
it
is
used.
If
any
of
the
submitted
analytical
methods
for
plant
commodities
are
proposed
as
a
2,4­
DB
tolerance
enforcement
method
then
the
method
should
be
modified
to
include
determination
of
free
and
conjugated
2,4­
DB.
An
ILV
should
be
performed.

The
submitted
methods
for
livestock
commodities
are
adequate
for
data
collection.
If
the
submitted
method
is
proposed
as
the
enforcement
method
for
determining
2,4­
DB
in
livestock
commodities
then
an
ILV
of
the
method
should
be
performed.

Additional
field
trials
on
clover
forage
and
hay
are
required
at
the
maximum
label
rate
(
1.3
lb
ae/
A)
with
a
60­
day
PHI
to
reassess
the
2,4­
DB
tolerances.
Ten
additional
trials
are
recommended
in
the
following
regions:
1
(
Region1),
1
(
Region
2),
1
(
Region
4),
3
(
Region
5),
1
(
Region
6),
1
(
Region
7),
1
(
Region
8),
1
(
Region
9).

Analytical
reference
standards
must
be
supplied
as
requested
by
the
EPA
National
Pesticide
Standards
Repository
for
2,4­
DB.

Product
Chemistry
Deficiencies
There
are
a
number
of
product
chemistry
deficiencies
for
various
registrants
which
are
listed
in
the
following
tables
16­
21.
Registrants
should
also
submit
required
data
for
dibenzo­
p­
dioxins
and
dibenzofurans,
and
either
certify
that
the
suppliers
of
beginning
materials
and
the
manufacturing
process
for
the
2,4­
DB
products
have
not
changed
since
the
last
comprehensive
product
chemistry
review
or
submit
a
complete
updated
product
chemistry
data
package.
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
30
Table
16.
Product
Deficiency:
Aceto
Agricultural
Chemicals
Corp.
2,4­
DB:
98%
T
(
EPA
Reg.
No.
2749­
93)

Guideline
Requirement
830.1550
Product
identity
and
composition,

830.1600
Description
of
materials
used
to
produce
the
product
830.1620
Description
of
production
process
830.1670
Discussion
of
formation
of
impurities
830.1700
Preliminary
analysis
830.1750
Certified
limits
830.1800
Enforcement
analytical
method
Table
17.
Product
Deficiency:
Drexel
Chemical
Co.
2,4­
DB:
98%
T
(
EPA
Reg.
No.
19713­
124)

Guideline
Requirement
830.1550
Product
identity
and
composition
830.1600
Description
of
materials
used
to
produce
the
product
830.1620
Description
of
production
process
830.1670
Discussion
of
formation
of
impurities
830.1700
Preliminary
analysis
830.1750
Certified
limits
830.1800
Enforcement
analytical
method
830.6302
Color
830.6303
Physical
state
830.6304
Odor
830.6313
Stability
to
normal
and
elevated
temperatures,
metals,
and
metal
ions
830.6314
Oxidation/
reduction:
chemical
incompatibility
830.6316
Explodability
830.6317
Storage
stability
830.6320
Corrosion
characteristics
830.7000
pH
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
31
830.7050
UV/
visible
absorption
830.7200
Melting
point/
melting
range
830.7300
Density/
relative
density/
bulk
density
830.7370
Dissociation
constant
30.7550/
7560/
7570
Partition
coefficient
(
n­
octanol/
water)

830.7840/
7860
Water
solubility
830.7950
Vapor
pressure
Table
18.
Product
Deficiency:
Atanor
S.
A..
2,4­
DB:
98%
T
(
EPA
Reg.
No.
46146­
1)

Guideline
Requirement
830.6316
Explodability
830.6317
Storage
stability
830.6320
Corrosion
characteristics
Table
19.
Product
Deficiency:
Makhteshim­
Agan
of
North
America
Inc
2,4­
DB:
97%
T
(
EPA
Reg.
No.
66222­
78)

Guideline
Requirement
830.1550
Product
identity
and
composition
830.1600
Description
of
materials
used
to
produce
the
product
830.1620
Description
of
production
process
830.1670
Discussion
of
formation
of
impurities
830.1700
Preliminary
analysis
830.1750
Certified
limits
830.1800
Enforcement
analytical
method
830.6302
Color
830.6303
Physical
state
830.6304
Odor
830.6313
Stability
to
normal
and
elevated
temperatures,
metals,
and
metal
ions
830.6314
Oxidation/
reduction:
chemical
incompatibility
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
32
830.6316
Explodability
830.6317
Storage
stability
830.6320
Corrosion
characteristics
830.7000
pH
830.7050
UV/
visible
absorption
830.7200
Melting
point/
melting
range
830.7300
Density/
relative
density/
bulk
density
830.7370
Dissociation
constant
830.7550/
7560/
7570
Partition
coefficient
(
n­
octanol/
water)

830.7840/
7860
Water
solubility
830.7950
Vapor
pressure
Table
20.
Product
Deficiency:
Makhteshim­
Agan
of
North
America.
2,4­
DB:
75%
T
(
EPA
Reg.
No.
66222­
80;
transferred
from
Cedar
Chemical
Co
2/
3/
03,
EPA
Reg.
No.
56077­
85)

Guideline
Requirement
830.1750
Certified
limits
Table
21.
Product
Deficiency:
A.
H.
Marks
&
Co.
Ltd
2,4­
DB­
DMA:
49.2%
FI
(
EPA
Reg.
No.
15440­
33)

Guideline
Requirement
830.6302
Color
830.6304
Odor
830.6317
Storage
stability
830.7000
pH
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
33
7.0
TOXICITY
TABLES
Table
22.
Acute
Toxicity
of
2,4­
DB
Technical.

Guideline
No.
Study
Type
MRID
#
s
Results
Toxicity
Category
81­
1
Acute
Oral
00128854
0092159
LD50
=
1935
mg/
kg
LD50
=
1715
mg/
kg
III
81­
2
Acute
Dermal
0128854
LD50
=
>
2000
mg/
kg
III
81­
3
Acute
Inhalation
41774001
LC50
>
2.3
mg/
L
IV
81­
4
Primary
Eye
Irritation
0128854
00092160
Eye
irritation
with
complete
clearing
by
day
7
III
81­
5
Primary
Skin
Irritation
0128854
No
irritation
IV
81­
6
Dermal
Sensitization
43593904
Under
review
 
Table
23.
Acute
Toxicity
of
2,4­
DB­
DMA
(
26%)

Guideline
No.
Study
Type
MRID
#
Results
Toxicity
Category
81­
1
Acute
Oral
41224401
LD50
=
3583
mg/
kg
III
81­
2
Acute
Dermal
(
rabbit)
41224402
LD50
>
2000
mg/
kg
III
81­
3
Acute
Inhalation
41370101
LC50
>
7.98
mg/
L
IV
81­
4
Primary
Eye
Irritation
41958001
Persistent
corneal
opacity,
iritis,
erythema
I
81­
5
Primary
Skin
Irritation
250871
Irritation
score
=
0.99
IV
81­
6
Dermal
Sensitization
43968911
Under
review
 
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
34
Table
24.
Toxicology
Profile
of
2,4­
DB
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
870.3100
90­
Day
oral
toxicity
rats
00104739
(
1969)
acceptable/
guideline
0,
316,
1000
or
3160
ppm
(
0,
15.8,
50
or
158
mg/
kg/
day
LOAEL
=
1000
ppm
(
50
mg/
kg/
day).,
based
on
decreased
body
weight
gain,
increased
relative
liver
and
kidney
weight,
microscopic
alterations
in
the
liver,
kidneys
and
stomach.

NOAEL
=
316
ppm
(
15.8
mg/
kg/
day)

870.3150
90­
Day
oral
toxicity
dogs
00092165
(
1969)
acceptable/
guideline
capsules
at
8,
25
or
80
mg/
kg/
day;
group
of
4
dogs/
sex
was
also
treated
with
capsules
at
2.5
mg/
kg/
day
for
three
months.
LOAEL
=
25
mg/
kg/
day,
based
on
death
(
sacrifice
in
extremis),
clinical
signs
of
toxicity,
decreased
body
weight,
decreased
hematology
parameters,
altered
clinical
chemistry
parameters,
increased
relative
weight
of
liver,
kidney
and
spleen,
and
gross
and
microscopic
necropsy
evidence
of
generalized
toxicity.

NOAEL
=
8
mg/
kg/
day
870.3200
21­
day
dermal
­
rabbit
41551301
(
1989)
acceptable/
guideline
0,
500,
1000,
2000
mg/
kg/
day
The
LOAELs
for
systemic
toxicity
and
dermal
irritation
were
not
established.
The
NOAELs
for
systemic
toxicity
and
dermal
irritation
were
2000
mg/
kg/
day
(
HDT).
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
Table
24.
Toxicology
Profile
of
2,4­
DB
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
35
870.3700a
Prenatal
developmental
in
rats
MRID
41382701
(
1990)
acceptable/
guideline
0,
31.25,
62.5
or
125
mg/
kg/
day
Maternal
LOAEL
=
62.5
mg/
kg
bw/
day,
based
on
decreased
body
weight
(
days
6­
16)
and
body
weight
gain
(
days
0­
20).
One
maternal
death
was
attributed
to
treatment
at
125
mg/
kg/
day.
Maternal
NOAEL
=
31.25
mg/
kg
bw/
day.

Developmental
LOAEL
=
125
mg/
kg
bw/
day,
based
on
decreased
fetal
body
weight,
skeletal
malformations/
variations,
microphthalmia,
retroesophageal
aortic
arches.
Developmental
NOAEL
=
62.5
mg/
kg
bw/
day.

870.3700b
Prenatal
developmental
in
rabbits
MRID
41529902
(
1990)
acceptable/
guideline
0,
15,
30
or
60
mg/
kg/
day
Maternal
LOAEL
=
60
mg/
kg
bw/
day,
based
on
mortality,
clinical
signs
of
toxicity
and
decreased
body
weight
gains.
Maternal
NOAEL
=
30
mg/
kg
bw/
day.

Developmental
LOAEL
was
not
determined.
Developmental
NOAEL
=
60
mg/
kg/
day
(
HDT).

870.3800
Reproduction
and
fertility
effects
MRID
40257503
(
1986)
acceptable/
guideline
0,60,
300
or
1500
ppm
(
Males:
0,
5,
25
or
112
mg/
kg/
day
and
Females:
0,
6,
30
and
133
mg/
kg/
day)
Parental
LOAEL
=
1500
ppm
(
112
mg/
kg/
day
in
males
and
133
mg/
kg/
day
in
females),
based
on
increased
water
consumption,
decreased
food
consumption
and
body
weight,
increased
food
conversion
ratio,
organ
weight
changes
and
macroscopic
renal
findings.
Parental
NOAEL
=
300
ppm
(
25
mg/
kg/
day
in
males
and
30
mg/
kg/
day
in
females).

Offspring
LOAEL
=
1500
ppm
(
112
mg/
kg/
day
in
males
and
133
mg/
kg/
day
in
females),
based
on
increased
mortality,
decreased
mean
litter
weight
and
increased
incidence
of
necropsy
findings
(
small
thymus,
distended
bladder
with
bloody/
dark
urine
and
ocular
opacity).
Offspring
NOAEL
=
300
ppm
(
25
mg/
kg/
day
in
males
and
30
mg/
kg/
day
in
females).

No
effect
upon
reproductive
parameters.
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
Table
24.
Toxicology
Profile
of
2,4­
DB
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
36
870.4100b
Chronic
toxicity
in
dogs
MRID
42006301
(
1990)
acceptable/
guideline
0,
75,
225
or
450
(
reduced
from
675
ppm
after
week
6)
(
0,
2.39,
6.07
and
12.94
mg/
kg/
day
for
males;
2.15,
7.06
and
14.16
mg/
kg/
day
for
females)
LOAEL
=
75
ppm
(
2.39
and
2.15
mg/
kg/
day
in
males
and
females,
respectively)
based
on
clinical
pathology
changes
(
increased
BUN,
ALT
and
AST),
decreased
liver
and
kidney
weights
(
females)
and
microscopic
changes
in
the
kidney.
NOAEL
has
not
been
established.

870.4200
Carcinogenicity
in
mice
40257502
(
1987)
acceptable/
guideline
0,
25,
250
or
750
ppm
(
equivalent
to
0,
3.75,
37.5
and
112.5
mg/
kg
bw/
day
based
on
7
ppm
in
the
diet
equals
1
mg/
kg/
day)
LOAEL
=
750
ppm
(
112.5
mg/
kg/
day),
based
on
increased
mortality
in
males
and
increased
absolute
and
relative
organ
weights
(
liver
and
kidney
in
both
sexes,
heart
in
males),
gross
pathological
changes
in
liver
and
kidney
(
males)
and
increased
amyloidosis
and
hepatocellular
enlargement
(
males).

NOAEL
=
250
ppm
(
37.5
mg/
kg/
day)

870.4300
Chronic
Toxicity/
Carcinogenicity
in
rats
MRID
40257501(
1987)
acceptable/
guideline
0,
60,
600
or
1800
ppm
(
equivalent
to
0,
3,
30
or
90
mg/
kg
bw/
day
based
on
1
ppm
equals
0.05
mg/
kg)
LOAEL
in
males
=
1800
ppm
(
90
mg/
kg/
day)
based
on
decreased
body
weight,
body
weight
gain
and
food
consumption,
clinical
pathology
changes
and
necropsy
alterations
(
decreased
kidney
weights,
increased
incidence
of
kidney
foci
and
infarcts
and
liver
mononuclear
infiltration
and
spongy
degeneration).
LOAEL
in
females
=
600
ppm
(
30
mg/
kg/
day),
based
on
decreased
body
weight
gain
and
food
consumption.
NOAEL
in
males
=
600
ppm
(
30
mg/
kg/
day)
NOAEL
in
females
=
60
ppm
(
3
mg/
kg/
day)
.

870.7485
Metabolism
and
pharmacokinetics
in
rats
41981601
(
1991)
acceptable/
guideline
Single
i.
v.
and
oral
doses
and
multiple
oral
dosing.
Radioactivity
recovery
in
urine
was
71.5­
97.6%
of
dose
and
3.5­
13.8%
in
feces.
Major
metabolites
were
2,4­
D
and
conjugated
2,4­
DCP.

870.7485
Metabolism
and
pharmacokinetics
in
rats
MRID
44774101(
1999)
acceptable/
guideline
Single
oral
dose
and
2
bile­
duct
cannulated
males.
Biliary
excretion
and
enterohepatic
recirculation
occurred.
Metabolite
G
was
identified
4­(
2,4­
dichlorophenoxy)­
3­
hydroxybutyric
acid.
The
distribution
of
metabolites
in
the
present
study
was
comparable
to
the
distribution
observed
in
the
previous
rat
metabolism
study.
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
37
Table
25.
Toxicology
Profile
of
2,4­
DB­
DMA
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
870.3200
21­
day
dermal
­
rabbit
41529901
(
1990)
acceptable/
guideline
0,
250,
750
or
1500
mg/
kg
bw/
day
The
systemic
LOAEL
was
not
established.
The
systemic
NOAEL
was
1500
mg/
kg/
day.
The
dermal
irritation
LOAEL
was
750
mg/
kg/
day
based
on
erythema,
desquamation
and
fissuring
which
were
more
severe
than
control
lesions.
The
dermal
NOAEL
was
250
mg/
kg/
day.

870.3100
90­
Day
oral
toxicity
rodents
41775401
(
1990)
acceptable/
guideline
0,
60,
600
or
1800
ppm
(
0,
4.16,
41.86
and
130.37
mg/
kg/
day
for
males
and
0,
4.96,
51.36
and
153.64
mg/
kg/
day
for
females)
The
LOAEL
is
600
ppm
(
41.86
mg/
kg/
day
in
males
and
51.36
mg/
kg/
day
in
females),
based
on
decreased
body
weight
and
body
weight
gain
(
females),
increased
kidney
weights
and
increased
incidence
of
tubular
degeneration
(
females).
The
NOAEL
is
60
ppm
(
4.16
mg/
kg/
day
in
males
and
4.96
mg/
kg/
day
in
females).

870.3700a
Prenatal
developmental
in
rats
42536101,
42595201
(
1991)
acceptable/
guideline
0,
31.25,
62.5
or
125
mg/
kg/
day
The
maternal
LOAEL
was
62.5
mg/
kg
bw/
day,
based
on
emaciation
and
decreased
body
weight
gain
and
food
consumption.
There
were
3
maternal
deaths
attributed
to
treatment
at
125
mg/
kg/
day.
The
maternal
NOAEL
was
31.25
mg/
kg
bw/
day.

The
developmental
LOAEL
was
125
mg/
kg/
day
based
on
an
increase
in
early
resorptions
per
dam,
skeletal
malformations,
microphthalmia,
and
a
decrease
in
fetal
weight.
The
developmental
NOAEL
was
62.5
mg/
kg/
day.
Human
Health
Risk
Assessment
for
2,4­
DB
and
2,4­
DB­
DMA
July
20,
2004
38
8.0
BIBLIOGRAPHY
Toxicology:
2,4­
DB
and
2,4­
DB­
DMA.
Toxicology
Chapter
for
RED.
Kit
Farwell,
D.
V.
M.
July
11,
2003.
TXR
0052015.

Hazard
Identification:
2,4­
DB
and
2,4­
DB­
DMA
­
Report
of
the
Hazard
Identification
Assessment
Review
Committee.
Kit
Farwell,
D.
V.
M.
June
13,
2003.
TXR
0051956.

Chemistry:
2,4­
DB
[
4­(
2,4­
dichlorophenoxy)
butyric
acid]
and
2,4­
DB
dimethylamine
salt
(
PC
Codes
030801,
030819):
Product
Chemistry
and
Residue
Chemistry
Summary
Documents
for
the
Reregistration
Eligibility
Decision
Document
(
RED).
Danette
Drew,
Chemist.
December
11,
2003.
D290793.

Metabolism:
2,4­
DB.
Results
of
the
1/
16/
96
Meeting
of
the
HED
Metabolism
Committee.
David
J.
Miller,
HSO,
US
Public
Health
Service.
January
29,
1996.
TXR
0051087.

2,4­
DB.
Metabolism
Committee
Question
Re:
Regulation
of
Metabolites
in
Plant
and
Animal
Commodities.
1995.
D220888.

Dietary
Exposure:
2,4­
DB
Acute
and
Chronic
Dietary
Exposure
Assessments
for
the
Reregistration
Eligibility
Decision.
Felecia
Fort.
April
20,
2004.
D300627.

Water
Exposure:
2,4­
DB
 
Drinking
Water
Assessment
for
the
Health
Effects
Division
(
HED)
Reregistration
Eligibility
Decision
Document.
Amer
Al­
Mudallal,
Chemist.
July
8,
2003.
D279637.

Environmental
Fate
and
Effects
Division's
Risk
Assessment
for
the
Reregistration
Eligibility
Document
for
4­(
2,4­
dichlorophenoxy)
Butyric
Acid
(
2,4­
DB)
and
Dimethylamine
4­(
2,4­
dichlorophenoxy)
butyrate
(
2,4­
DB­
DMAS).
Amer
Al­
Mudallal
and
Lewis
Brown.

Occupational
Exposure:
2,4­
DB:
Occupational
and
Residential
Exposure
and
Risk
Assessments
for
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