Document ID: EPA-HQ-OPP-2003-0124-0006
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2003-04-10T04:00Z

Page
1
of
9
Cl
O
OH
O
O
Cl
Cl
OH
O
Appendix
B:
Toxicity
Studies
with
4­
chlorophenoxyacetic
acid
(
4­
CPA)
and
Structures
Related
to
4­
CPA.

Structure
of
4­
chlorophenoxyacetic
acid
(
4­
CPA)
(
PC
019401)

The
following
are
brief
summaries
of
the
cancer
findings
for
each
of
the
structural
analogs
for
which
there
are
studies.
In
some
cases
the
Cancer
Assessment
Review
Committee
(
CARC)
has
not
evaluated
the
pesticide.
Comparison
of
the
results
from
toxicity
studies
are
made
for
4­
CPA
and
the
four
analogs,
2,4­
dichlorophenoxyacetic
acid,
2­
methyl­
4­
chlorophenoxyacetic
acid,
3­
chlorophenoxy­
2­
propionic
acid,
and
2­
methyl­
4­
chlorophenoxybutyric
acid
(
Table
1).
More
structurally
remote
chlorophenoxy
acid
pesticides
are:
(
1)
2,4­
dichlorophenoxybutyric
(
not
carcinogenic
in
rats
or
mice),
(
2)
2,4­
dichlorophenoxy­
2­
propionic
acid
(
not
carcinogenic
in
rats
or
mice),
(
3)
2,4,5­
trichlorophenoxyacetic
acid
(
evidence
of
carcinogenicity
in
total
tumors
in
female
mice,
but
not
rats),
and
(
4)
2,4,5­
trichlorophenoxy­
2­
propionic
acid
(
no
studies
available).
These
latter
pesticides
are
not
shown
and
not
summarized
further.
[
Information
from
Carcinogenicity
Peer
Review
(
4th)
of
2,4­
D,
1/
29/
97.]
______________________________________________________________________________

Although
there
are
no
carcinogenicity
studies
on
4­
CPA,
the
weight
of
the
evidence
does
not
suggest
that
4­
CPA
would
be
carcinogenic
in
life­
time
studies
at
reasonable
doses
not
causing
excessive
toxicity.

Structure
of
2,4­
dichlorophenoxyacetic
acid
(
2,4­
D)(
PC
030001)

The
following
is
a
summary
of
the
findings
from
the
fourth
and
last
cancer
assessment
of
2,4­
D.
This
pesticide
has
the
largest
toxicity
data
base
of
all
the
analogs.
The
Cancer
Peer
Review
Committee
(
CPRC)
concluded
that
2,4­
D
should
remain
classified
as
a
"
Group
D"
­
Not
classifiable
as
to
a
human
carcinogenicity.
That
is,
the
evidence
is
inadequate
and
cannot
be
interpreted
as
showing
either
the
presence
or
the
absence
of
a
carcinogenic
effect.
2,4­
D
was
initially
classified
as
a
possible
human
carcinogen,
based
on
a
significant
increased
trend
for
brain
astrocytomas
in
male
Fisher
344
rats
and
suggestive
to
weak
and
conflicting
evidence
of
non­
Hodgkin's
lymphoma
from
several
epidemiological
studies.
There
was
no
evidence
of
tumor
induction
in
female
rats
or
male
or
female
B6C3F1
mice,
however,
the
CPRC
concluded
that
the
highest
dose
tested
in
both
studies
was
sufficiently
toxic
to
adequately
test
for
carcinogenicity.
Repeat
studies
were
conducted
in
rats
and
mice
at
adequate
doses,
but
neither
study
showed
statistically
significantly
increased
tumor
incidence
in
either
species
or
sex.
Page
2
of
9
O
CH
3
Cl
OH
O
O
Cl
CH
3
O
ONa
Mutagenicity
studies
showed
consistently
negative
results
without
activation
and
positive
and
negative
result
with
activation.
The
CPRC
concluded
that
although
cytogenic
activity
was
seen,
there
was
no
concern
for
mutagenicity.
Metabolism
studies
in
the
rat
indicated
that
85
to
94%
of
the
parent
was
excreted
unchanged
in
the
urine
with
0%
­
1.3%
of
2
uncharacterized
compounds
and
4
to
10%
was
excreted
as
the
parent
in
feces.
Total
excretion
(
98
to
99.5%)
occurred
within
48
hours.
The
CPRC
and
SAP
agreed
on
a
"
Group
D"
classification.
[
Information
from
Carcinogenicity
Peer
Review
(
4th)
of
2,4­
D,
1/
29/
97.]

Structure
and
results
on
2­
methyl­
4­
chlorophenoxyacetic
acid
(
MCPA)
(
PC
030501)

MCPA
has
not
been
reviewed
by
the
CARC,
but
a
toxicology
reviewer
indicated
that
no
dose
related
tumors
were
seen
in
rats
or
mice
at
adequate
doses
to
test
for
carcinogenicity.
A
battery
of
mutagenicity
studies
shows
a
positive
study
for
chromosomal
aberrations
in
human
lymphocyte
cells
and
weakly
mutagenic
response
in
an
in
vivo
sister
chromatid
exchange
study.
The
remaining
6
in
vivo
and
in
vitro
mutagenicity
studies
conducted
were
negative.
The
metabolism
studies
in
the
rat
shows
that
MCPA
is
excreted
in
the
urine
(
74­
86%;
53%­
69%
as
the
parent
and
7­
13%
as
the
hydroxymethyl
metabolite
and
2­
5%
in
the
feces).
Total
excretion
occurred
within
192
hours
(
98%).
[
Information
from
the
1­
liners
and
Paul
Chin
reviewer].

Structure
and
results
on
sodium
3­
chlorophenoxy­
2­
propionate
(
cloprop,
sodium
salt)
(
PC
021201)

Life­
time
carcinogenicity
studies
have
been
conducted
with
cloprop,
but
there
are
no
definitive
conclusions.
There
was
a
statistically
significantly
increasing
trend
and
pair­
wise
comparison
with
control
for
mortality
in
male
and
female
rats
at
the
top
dose.
The
registrant
refused
to
submit
historical
control
data
on
morality
among
the
rats
used
in
the
carcinogenicity
study.
Consequently
the
Peer
Review
of
cloprop
was
canceled
and
the
pesticide
withdrawn.
In
the
mouse
study,
there
was
statistically
significantly
pair­
wise
comparison
of
male
liver
adenomas/
carcinomas
and
male
liver
carcinomas
at
the
highest
dose
tested
and
in
females
for
liver
adenomas
and
carcinomas
at
the
two
lowest
doses
tested,
but
not
at
the
highest
dose
tested.
One
reviewer
believed
that
there
was
no
evidence
for
carcinogenicity
in
mice,
however
another
reviewer
believed
there
was
evidence
of
liver
cancer
in
mice.
The
issue
has
never
been
resolved
because
the
pesticide
was
withdrawn.
Cloprop
is
negative
in
a
battery
of
mutagenicity
studies.
There
are
no
metabolism
studies
in
rats,
but
in
goats,
cloprop
is
excreted
as
the
parent.
[
Information
from
1­
liners
and
a
memorandum
from
John
Redden.]
Page
3
of
9
Cl
CH
3
O
OH
O
Structure
and
results
on
2­
methyl­
4­
chlorophenoxybutryic
acid
(
MCPB)
(
PC
019201)

No
life­
time
carcinogenicity
studies
have
been
conducted
with
MCPB.
A
battery
of
mutagenicity
studies
are
negative.
One
study
for
chromosomal
abnormalities
with
S9
produced
chromosomal
abnormalities
at
high
doses.
There
are
no
adequate
metabolism
studies,
but
a
reference
from
the
literature
suggest
that
bacteria
split
off
acetic
acid
from
the
butyric
acid
residue
in
plants
and
cows.
[
Information
from
1­
liners
and
DERs.]

Structure
and
results
on
2(
4­
chlorophenoxy)­
2­
methylpropanoic
acid
ethyl
ester;
the
Drug
Clofibrate
(
lowers
plasma
triglycerides
and
cholesterol)

An
International
Agency
for
Research
on
Cancer
(
IARC)
Monograph
on
clofibrate
states
that
there
is
inadequate
evidence
in
humans
for
carcinogenicity
and
limited
evidence
in
animals
for
carcinogenicity.
Clofibrate
is
peroxisome
proliferator
and
is
excreted
rapidly
in
human
urine
as
the
parent.
(
http://
193.51.164.11/
htdocs/
monographs/
vol66/
clofibrate.
html).

Structure
and
results
on
mecoprop
[
2­(
2­
methyl­
4­
chlorophenoxy)
propionic
acid]
(
PC
031501)

The
acute
toxicity
of
mecoprop
is
similar
to
that
of
4­
CPA.
The
NOAEL/
LOAEL
in
the
rat
90­
day
feeding
study
was
lower
than
the
NOAEL/
LOAEL
in
rat
90­
day
neurotoxicity
study,
which
showed
no
neurotoxic
effects,
in
addition
to
being
lower
than
4­
CPA
in
a
rat
90­
day
feeding
study.
A
rabbit
developmental
toxicity
study
showed
a
maternal
NOAEL/
LOAEL
of
30/
75
mg/
kg/
day,
but
no
developmental
toxicity
at
the
highest
dose
tested.
The
rat
developmental
toxicity
study
showed
developmental
toxicity
in
the
form
of
decreased
crown­
rump
lengths,
decreased
ossification
of
sternebrae
and
increased
intrauterine
death
at
the
highest
dose
tested,
which
was
a
maternally
toxic
dose.
The
rat
developmental
effects
occurred
at
a
lower
dose
than
the
effects
from
4­
CPA
in
a
rat
developmental
toxicity
study.
No
90­
day
feeding
study
in
dogs
is
available.
Potential
carcinogenic
effects
have
not
been
fully
evaluated
as
yet,
but
there
is
suggestive
evidence
for
increased
liver
tumors
in
mice.
The
rat
carcinogenicity
study
was
negative.
A
reverse
gene
mutation
study
was
acceptable
and
negative
and
chromosomal
aberrations
study
was
acceptable
and
negative
for
clastogenicity
(
MRID#
41013909,
TXR#
009589).
The
remaining
mutagenicity
studies
were
unacceptable.
Page
4
of
9
Cl
O
OH
O
O
Cl
Cl
OH
O
O
CH
3
Cl
OH
O
O
Cl
CH
3
O
ONa
Cl
CH
3
O
OH
O
Table
1:
Comparison
of
toxicity
studies/
results
for
4­
chlorophenoxyacetic
acid
(
4­
CPA)
and
four
analogs
of
4­
CPA
Study/
Test
4­
chloro­
phenoxyacetic
acid
(
4­
CPA)

019401
Data
from
DERs
&

Peer
Rev
(
2,4­
dichlorophenoxy)­
2­

acetic
acid
(
2,4­
D)

030001
Data
from
1­
Liner
&
Peer
Rev
(
2­
methyl­
4­

chlorophenoxy
2­
acetic
acid
(
MCPA)

030501
Data
from
1­
Liner
&

Paul
Chin
sodium
(
3­
chlorophenoxy)
­
2­

propionate
(
cloprop,
sodium
salt)

021201
Data
from
1­
Liner
No
info
in
Archives
(
2­
methyl­
4­
chlorophenoxy)­
4­

butyric
acid
(
MCPB)

019201
Data
from
1­
Liner
Results
on
(
a.
i.)
Results
on
(
a.
i.)
Results
on
(
a.
i.)
Results
on
(
a.
i.)
Results
on
(
a.
i.)

870.1100
Acute
Oral
ToxicityLD50
870.1200
Acute
Dermal
Toxicity/
LD50
.
.
.
.
.
.
.
.

870.1300
Acute
Inhalation
Toxicity/
LC50
.
.
.
.
.
.
.
.

870.2400
Primary
Eye
Irritation
.
.

870.2500
Primary
Dermal
Irritation
870.2600
Dermal
Sensitization
.
.
.
2703
mg/
kg
>
2000
mg/
kg
>
5.25
mg/
L
Severe
Not
irritating
Not
sensitizing
3730mg/
kg
>
2000
mg/
kg
>
1.8
mg/
L
4hr
Mod/
Severe
None
Irritating
Not
sensitizing
3500
mg/
kg
>
2000mg/
kg
>
6.3
mg/
L
Mod/
Severe
Slight
Not
sensitizing
1567
mg/
kg
­

­­­­
1570
mg/
kg
1000
mg/
kg
1.1
mg/
L
(
acetone
vehicle)

Mod/
Severe
­­

870.3100
Oral
Subchronic
(
rat)
.
.
.
N/
L=
152/
517mkd,

Bwt
dec
&
urine
volume
inc,
liver
individual
cell
necrosis
N/
L=
15/
100mkd
testes,

liver,
thyroid
weight
inc
&
spleen
histop
N/
L=
50/
150ppm
N/
L=
2.5/
7.5
mkd
inc
kidney
weight
with
incr
creatinine
HDT,
no
histop
­
N/
L=
158/­
m/
k/
d
HDT
palatability
noted;

kidney
weight
incr,

histop
neg
870.3150
Oral
Subchronic
(
dog)
.
.
N/
L=
18.6/­
mkd
HDT
(
Peer
Rev);

N/
L=
3.3/
19mkd
bwt
&

food
decr;
no
histop
changes
seen
(
DER)
N/
L=
1.0/
3.0
mkd,
liver,

kidney
&
testes
histo
N/
L=
0.6/
2.4
mkd
liver
inflammation
&
clinical
chemistry
(
MCPADimethylamine
N/
L=
12.5/
50
mkd,

bwt
decr,
liver,

kidney
&
spleen
weight
incr
N/
L=
12/
40mkd
Inc
BSP
retention,
dec
spermatogenic
activity,

prostate
&
testes
tubular
atrophy
Cl
O
OH
O
O
Cl
Cl
OH
O
O
CH
3
Cl
OH
O
O
Cl
CH
3
O
ONa
Cl
CH
3
O
OH
O
Study/
Test
4­
chloro­
phenoxyacetic
acid
(
4­
CPA)

019401
Data
from
DERs
&

Peer
Rev
(
2,4­
dichlorophenoxy)­
2­

acetic
acid
(
2,4­
D)

030001
Data
from
1­
Liner
&
Peer
Rev
(
2­
methyl­
4­

chlorophenoxy
2­
acetic
acid
(
MCPA)

030501
Data
from
1­
Liner
&

Paul
Chin
sodium
(
3­
chlorophenoxy)
­
2­

propionate
(
cloprop,
sodium
salt)

021201
Data
from
1­
Liner
No
info
in
Archives
(
2­
methyl­
4­
chlorophenoxy)­
4­

butyric
acid
(
MCPB)

019201
Data
from
1­
Liner
Page
5
of
9
870.3200
21­
Day
Dermal
(
rabbit)
.

870.3250
90­
Day
Dermal
.
.
.
.
.
.
.

870.3465
90­
Day
Inhalation
.
.
.
.
.
­

­­
N/
L=
1000/­
mkd
­­
SystN/
L=
100/
1000mkd
Mineralization
kidney
tubules
IrritationN/
L=

10/
100mkd
­­
­

­­
­

­­

870.3700a
Developmental
Toxicity
(
rat)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
M
N/
L=
150/
300mkd
Bwt
dec
&
at
1000mkd
mortality,
tremors
&

uncoordinated
movements
D
N/
L=
150/
300mkd
sternebrae
unoss
M
N/
L=
25/
75mkd
decr
Bwt
D
N/
L=
25/
75mkd,
extra
rib,
dec
oss,
variations
M
N/
L=
60/
120
mkd
Bwt
D
N/
L=
60/
120
mkd
Dec
Bwt
&
dec
oss
M
N/
L=
400/­
mkd
HDT
D
N/
L=
400/­
mkd
UA,
OPP
added;

acceptable
with
rabbit
study
M
N/
L=
25/
100
mkd,
bwt;
D
N/
L=
25/
100mkd,
dec
oss
870.3700b
Developmental
Toxicity
(
rabbit)
.
.
.
.
.
.
.
.
.
.
.
.
.
M
N/
L=
25/
B
mkd,
D
N/
L=
10/
25mkd
fetal
wt
dec
ascribed
to
maternal
Bwt
dec.,
but
unsure
of
maternal
Bwt
dec
Rangefinding
(
5
rabbits/
group)
with
no
control
weight.
Invalid
study,
UA
M
N/
L=
30/
90mkd
ataxia,

motor
control,
dec
Bwt
D
N/
L=
90/­
mkd*
M
N/
L=
30/
60
mkd
Dec
Bwt,
food
consumption
D
N/
L=
60/­
mkd
M
N/
L=
100/
200
mkd
Bwt
dec
D
N/
L=
100/
200mkd
Misshapen,

compressed
&
small
cerebral
hemisphere
&
compressed
cranial
nerve
&

displaced
eye
M
N/
L=
5/
20mkd,

clinical
signs,
death
D
N/
L=>
20/­
mkd
HDT,

NC
Cl
O
OH
O
O
Cl
Cl
OH
O
O
CH
3
Cl
OH
O
O
Cl
CH
3
O
ONa
Cl
CH
3
O
OH
O
Study/
Test
4­
chloro­
phenoxyacetic
acid
(
4­
CPA)

019401
Data
from
DERs
&

Peer
Rev
(
2,4­
dichlorophenoxy)­
2­

acetic
acid
(
2,4­
D)

030001
Data
from
1­
Liner
&
Peer
Rev
(
2­
methyl­
4­

chlorophenoxy
2­
acetic
acid
(
MCPA)

030501
Data
from
1­
Liner
&

Paul
Chin
sodium
(
3­
chlorophenoxy)
­
2­

propionate
(
cloprop,
sodium
salt)

021201
Data
from
1­
Liner
No
info
in
Archives
(
2­
methyl­
4­
chlorophenoxy)­
4­

butyric
acid
(
MCPB)

019201
Data
from
1­
Liner
Page
6
of
9
870.3800
Reproduction
.
.
.
.
.
.
.
.
.
1
(
Partly
unreadable
1964­
5
study)
P
N/
L=
12.5/
B
mkd
Studied
at
too
low
of
dose.
No
effects
in
parents
or
offspring.

Since
parts
unreadable
N/
L
unverifiable
UA
P
N/
L=
5/
20mkd
kidney
Off
N/
L=
7.5/
20mkd,
Bwt
dec
(
same
ppm
dose
as
parents)*
P
N/
L=
225/­
mkd
Off
N/
L=
7.5/
225mkd
possible
pup
Bwt
dec
P
N/
L=
100/
400mkd
Off
N/
L=

100/
400mkdec
pup
Bwt
dec
­

870.4100a
Chronic
Toxicity
(
rodent)
­
­
­
­
­

870.4100b
Chronic
Toxicity
(
dog)
.
­
N/
L=
1/
5mkd,
liver
enzyme
inc,
histop
liver
&
kidney
N/
L=
6/
30mkd,
liver
histop
&
enzyme
inc,

histop
kidneys
­
­

870.4200a
Oncogenicity
(
rat)
.
.
.
.
.
­
­
­
­
­

870.4200b
Oncogenicity
(
mouse)
.
.
­
N/
L=
5/
62.5
mkd,
kidney
&
adrenal
weight
inc
Inadequate
doses
No
carcinogenicity.
N/
L=
15.7/
79.5mkd
histo
kidney
&
wt
&

calcification
No
carcinogenicity
N/
L=
75/
300
mkd
liver
pigmentation
Equivocal
oncogenicity,
UA
­

870.4300
Chronic/
Oncogenicity
(
rat)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
­
N/
L=
5/
75mkd,
Bwt
kidney,
liver,
liver
enz
&

thyroid
changes
Not
carcinogenicity
to
equivocal
N/
L=
1/
4.4mkd
liver
enzyme
inc.,
kidney
histop
No
carcinogenicity
N/
L=
25/
100mkd,

liver,
kid.
need
historical
control
to
confirm
carcinogenicity,

refused
submission
Not
carcinogenic.
­
Cl
O
OH
O
O
Cl
Cl
OH
O
O
CH
3
Cl
OH
O
O
Cl
CH
3
O
ONa
Cl
CH
3
O
OH
O
Study/
Test
4­
chloro­
phenoxyacetic
acid
(
4­
CPA)

019401
Data
from
DERs
&

Peer
Rev
(
2,4­
dichlorophenoxy)­
2­

acetic
acid
(
2,4­
D)

030001
Data
from
1­
Liner
&
Peer
Rev
(
2­
methyl­
4­

chlorophenoxy
2­
acetic
acid
(
MCPA)

030501
Data
from
1­
Liner
&

Paul
Chin
sodium
(
3­
chlorophenoxy)
­
2­

propionate
(
cloprop,
sodium
salt)

021201
Data
from
1­
Liner
No
info
in
Archives
(
2­
methyl­
4­
chlorophenoxy)­
4­

butyric
acid
(
MCPB)

019201
Data
from
1­
Liner
Page
7
of
9
870.5100
Mutagenicity
C
Gene
Mutation
­
bacterial
870.5100
Mutagenicity
C
Gene
Mutation
­
bacterial
.
.
.
.
Neg
Neg
Neg
Neg
Neg
Neg
Neg
870.5300
Mutagenicity
C
Gene
Mutation
­
mammalian
.
Neg
Pos
Neg
Neg
870.5375
Mutagenicity
C
Structural
Chromosomal
Aberrations
.
.
.
.
.
.
.
.
.
.
­
­
­
­
­

Nonguideline
Chromosomal
aberrations
(
human
lymphocytes)............
­
One
pos
+/
one
neg
­
Pos.
­
­

Nonguideline
Recom/
Convers
Assay
(
Saccharomyces)
­
­
­
Neg
­

Nonguideline
Recomb/
Convers
Assay
(
Mouse).................
­
­
­
Neg
­

870.
5395
Mutagenicity
C
Structural
Chromosomal
Aberrations.
Neg
Neg
Neg
Neg
­

870.5450
Rodent
Dominant
Lethal
­
­
­
NOAEL>
400
mg/
kg
Neg
­

870.5915
Sister
Chromatid
Exchange.......................
­
Neg
+
S9/
Pos
­
S9
Weakly
Pos.
­
­
Cl
O
OH
O
O
Cl
Cl
OH
O
O
CH
3
Cl
OH
O
O
Cl
CH
3
O
ONa
Cl
CH
3
O
OH
O
Study/
Test
4­
chloro­
phenoxyacetic
acid
(
4­
CPA)

019401
Data
from
DERs
&

Peer
Rev
(
2,4­
dichlorophenoxy)­
2­

acetic
acid
(
2,4­
D)

030001
Data
from
1­
Liner
&
Peer
Rev
(
2­
methyl­
4­

chlorophenoxy
2­
acetic
acid
(
MCPA)

030501
Data
from
1­
Liner
&

Paul
Chin
sodium
(
3­
chlorophenoxy)
­
2­

propionate
(
cloprop,
sodium
salt)

021201
Data
from
1­
Liner
No
info
in
Archives
(
2­
methyl­
4­
chlorophenoxy)­
4­

butyric
acid
(
MCPB)

019201
Data
from
1­
Liner
Page
8
of
9
870.5550
Mutagenicity
C
Other
Genotoxic
Effects
.
.
.
.
.
­
Neg
­
­
­

870.6100a
Acute
Delayed
Neurotox.

(
hen)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

870.6100b
90­
Day
Neurotoxicity
(
hen)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
­­
­­
­­
­­
­­

870.6200a
Acute
Neurotox.

Screening
Battery
(
rat)
.
.
­
N/
L=
67/
227mkd
altered
FOB,
dec
coordination
SystN/
L=
227/­
mkd
N/
L=
200/
400mkd
impaired
gait
males
­
­

870.6200b
90
Day
Neuro.
Screening
Battery
(
rat)
.
.
.
.
.
.
.
.
.
.
­
­
N/
L=
34/
177mkd
dec
motor
activity,
grip
strength,
liver
histo.
­
­

870.6200
One­
year
Neuro.
Toxicity
study
(
rat)
­
N/
L=
75/
150mkd
incr
relative
forelimb
grip
strength
­
­
­

870.6300
Develop.
Neuro
.
.
.
.
.
.
.
­
­
­
­
­
Cl
O
OH
O
O
Cl
Cl
OH
O
O
CH
3
Cl
OH
O
O
Cl
CH
3
O
ONa
Cl
CH
3
O
OH
O
Study/
Test
4­
chloro­
phenoxyacetic
acid
(
4­
CPA)

019401
Data
from
DERs
&

Peer
Rev
(
2,4­
dichlorophenoxy)­
2­

acetic
acid
(
2,4­
D)

030001
Data
from
1­
Liner
&
Peer
Rev
(
2­
methyl­
4­

chlorophenoxy
2­
acetic
acid
(
MCPA)

030501
Data
from
1­
Liner
&

Paul
Chin
sodium
(
3­
chlorophenoxy)
­
2­

propionate
(
cloprop,
sodium
salt)

021201
Data
from
1­
Liner
No
info
in
Archives
(
2­
methyl­
4­
chlorophenoxy)­
4­

butyric
acid
(
MCPB)

019201
Data
from
1­
Liner
Page
9
of
9
870.7485
General
Metabolism
(
Lab#

152/
517)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

870.7600
Dermal
Penetration
.
.
.
­
­
Excreted
as
parent
in
urine
(
86­
94%),
4­
11%
in
the
feces
Small
amounts
of
metabolites
(
0.6%­
1.3%).

98­
99.5%
recovered
within
48
hr.

Excreted
mostly
unmetabolized
­
Mostly
excreted
as
MCPA,
7­
13%

hydroxylated
methyl
MCPA.
98%
excreted
within
192
hr.

Excreted
mostly
unmetabolized
­
Excreted
as
parent,

mostly
unmetabolized
in
the
goat
UC
­
Lit.;
Bact­
Splits
off
acetic
acid
from
the
butyric
acid
residue
in
plants
and
cows
UA
­

Carcogenicity
Classification.......................................
No
studies
"
D"
not
classifiable
as
a
human
carcinogen
Not
likely
to
be
a
human
carcinogen,
but
no
HIARC
or
CARC
review
yet
Rats
(
historical
control
required)
Chem
withdrawn
Mice
increased
pairwise
hepatocellular
carcinomas
at
HDT
Unclassified
by
CARC
No
carcinogenicity
studies
1
This
3­
generation
reproduction
study
with
4­
CPA
is
reasonably
well
conducted
but
the
doses
were
too
low
(
the
highest
dose
tested
was
12.5%
of
the
NOAEL
from
the
90­
day
subchronic
study
in
rats.).
The
highest
dose
tested
was
250
ppm
and
the
NOAEL
in
a
90­
day
rat
study
was
2000
ppm.
In
addition,
the
colony
showed
respiratory
problems
with
weight
loss
with
recovery
and
related
marked
cannibalism,
and
pup
death
due
to
maternal
death.
The
material
tested
appeared
to
be
reasonably
pure
from
acid
equivalent
measurements,
but
since
no
units
were
reported,

this
cannot
be
verified.
The
study
was
conducted
prior
to
GLPs
and
the
test
material
in
the
diet
was
not
measured.
Therefore
the
study
is
unacceptable/
not
upgradable.

N/
L
=
NOAEL/
LOAEL
followed
by
effects
at
LOAEL
unless
otherwise
specified;
mkd
=
mg/
kg/
day.
­
=
No
study
conducted
or
available;
UA
=
Unacceptable
study;
UC
=
Unclassified
study;
a.
i.
=
active
ingredient.
inc=
increase;
dec=
decrease;
histop=
histopathology;
DER=
data
evaluation
record;
neg=
negative;
pos=
positive;
Syst=
systemic;
HDT=
highest
dose
tested;

mod=
moderate;
Bwt=
body
weight;
unoss=
unossified;
oss=
ossification;
M=
maternal;
D=
developmental;
UA=
unacceptable;
P=
parental;
Off=
offspring;
FOB=
Functional
Observation
Battery;

CARC=
Cancer
Assessment
Review
Committee.